Sherry Boschert

Major Finding: In adults with diabetes, the presence of obstructive sleep apnea predicted a 3.6-fold greater risk for sight-threatening retinopathy and a threefold greater risk for diabetic peripheral neuropathy, compared with patients without obstructive sleep apnea.

Data Source: Two separate prospective, observational cross-sectional studies of 224 patients in the retinopathy study and 231 patients in the neuropathy study who were recruited from a hospital-based, outpatient diabetes clinic.

Disclosures: Dr. Tahrani reported having no conflicts of interest.

SAN DIEGO – Obstructive sleep apnea in patients with type 2 diabetes predicted a three- to fourfold higher risk for diabetic peripheral neuropathy or sight-threatening retinopathy, separate analyses have found.

The results suggest that obstructive sleep apnea may play a role in the development of peripheral neuropathy and sight-threatening retinopathy in people with diabetes, Dr. Abd Tahrani and his associates reported at the meeting. Ongoing studies are exploring possible mechanisms involved.

Further study is warranted on the possibility that treating obstructive sleep apnea might affect the development or progression of retinopathy or neuropathy, added Dr. Tahrani of the University of Birmingham (England), where he is a research fellow for the U.K. National Institute for Health Research.

The prospective studies recruited random patients from a hospital-based, outpatient diabetes clinic in the United Kingdom. Subjects were excluded if they had a known respiratory disorder, including obstructive sleep apnea. Patients had a mean age of 59 years and a mean 11-year history of diabetes, and 48% were white. They underwent one night of home-based multichannel respiratory monitoring and were considered to have obstructive sleep apnea if they had an apnea-hypopnea index of at least 5 events per hour.

In 224 patients who also were assessed for sight-threatening retinopathy, 63% had obstructive sleep apnea and 38% had sight-threatening retinopathy. Patients with obstructive sleep apnea were significantly more likely to have sight-threatening retinopathy (48%) than were patients without obstructive sleep apnea (20%).

The study defined sight-threatening retinopathy as the presence of preproliferative or proliferative retinopathy, maculopathy, or the need for laser treatment.

After adjustment for possible confounders, patients with obstructive sleep apnea were 3.6 times more likely to have sight-threatening retinopathy, 5 times more likely to have advanced diabetic retinopathy, and 4.4 times more likely to have maculopathy than were patients without obstructive sleep apnea.

In a separate study by the same researchers of 231 patients assessed for obstructive sleep apnea and peripheral neuropathy, 65% had obstructive sleep apnea and 45% had diabetic peripheral neuropathy. Patients with obstructive sleep apnea reported more neuropathic symptoms. Among patients with obstructive sleep apnea, 60% had diabetic peripheral neuropathy, compared with 27% of patients without sleep apnea.

Obstructive sleep apnea conferred a significant threefold higher risk for peripheral neuropathy after adjustment for potentially confounding variables, Dr. Tahrani reported. The severity of peripheral neuropathy correlated with the severity of obstructive sleep apnea.

Obstructive sleep apnea was prevalent in 75% and 52% of white and South Asian patients, respectively. Likewise, diabetic peripheral neuropathy was more prevalent in whites (56% vs. 40%). Both differences were significant.

The lower prevalence of obstructive sleep apnea in the South Asian patients might be one reason for the lower prevalence of diabetic peripheral neuropathy, the investigators suggested.

Major Finding: In adults with diabetes, the presence of obstructive sleep apnea predicted a 3.6-fold greater risk for sight-threatening retinopathy and a threefold greater risk for diabetic peripheral neuropathy, compared with patients without obstructive sleep apnea.

Data Source: Two separate prospective, observational cross-sectional studies of 224 patients in the retinopathy study and 231 patients in the neuropathy study who were recruited from a hospital-based, outpatient diabetes clinic.

Disclosures: Dr. Tahrani reported having no conflicts of interest.

SAN DIEGO – Obstructive sleep apnea in patients with type 2 diabetes predicted a three- to fourfold higher risk for diabetic peripheral neuropathy or sight-threatening retinopathy, separate analyses have found.

The results suggest that obstructive sleep apnea may play a role in the development of peripheral neuropathy and sight-threatening retinopathy in people with diabetes, Dr. Abd Tahrani and his associates reported at the meeting. Ongoing studies are exploring possible mechanisms involved.

Further study is warranted on the possibility that treating obstructive sleep apnea might affect the development or progression of retinopathy or neuropathy, added Dr. Tahrani of the University of Birmingham (England), where he is a research fellow for the U.K. National Institute for Health Research.

The prospective studies recruited random patients from a hospital-based, outpatient diabetes clinic in the United Kingdom. Subjects were excluded if they had a known respiratory disorder, including obstructive sleep apnea. Patients had a mean age of 59 years and a mean 11-year history of diabetes, and 48% were white. They underwent one night of home-based multichannel respiratory monitoring and were considered to have obstructive sleep apnea if they had an apnea-hypopnea index of at least 5 events per hour.

In 224 patients who also were assessed for sight-threatening retinopathy, 63% had obstructive sleep apnea and 38% had sight-threatening retinopathy. Patients with obstructive sleep apnea were significantly more likely to have sight-threatening retinopathy (48%) than were patients without obstructive sleep apnea (20%).

The study defined sight-threatening retinopathy as the presence of preproliferative or proliferative retinopathy, maculopathy, or the need for laser treatment.

After adjustment for possible confounders, patients with obstructive sleep apnea were 3.6 times more likely to have sight-threatening retinopathy, 5 times more likely to have advanced diabetic retinopathy, and 4.4 times more likely to have maculopathy than were patients without obstructive sleep apnea.

In a separate study by the same researchers of 231 patients assessed for obstructive sleep apnea and peripheral neuropathy, 65% had obstructive sleep apnea and 45% had diabetic peripheral neuropathy. Patients with obstructive sleep apnea reported more neuropathic symptoms. Among patients with obstructive sleep apnea, 60% had diabetic peripheral neuropathy, compared with 27% of patients without sleep apnea.

Obstructive sleep apnea conferred a significant threefold higher risk for peripheral neuropathy after adjustment for potentially confounding variables, Dr. Tahrani reported. The severity of peripheral neuropathy correlated with the severity of obstructive sleep apnea.

Obstructive sleep apnea was prevalent in 75% and 52% of white and South Asian patients, respectively. Likewise, diabetic peripheral neuropathy was more prevalent in whites (56% vs. 40%). Both differences were significant.

The lower prevalence of obstructive sleep apnea in the South Asian patients might be one reason for the lower prevalence of diabetic peripheral neuropathy, the investigators suggested.

Major Finding: In adults with diabetes, the presence of obstructive sleep apnea predicted a 3.6-fold greater risk for sight-threatening retinopathy and a threefold greater risk for diabetic peripheral neuropathy, compared with patients without obstructive sleep apnea.

Data Source: Two separate prospective, observational cross-sectional studies of 224 patients in the retinopathy study and 231 patients in the neuropathy study who were recruited from a hospital-based, outpatient diabetes clinic.

Disclosures: Dr. Tahrani reported having no conflicts of interest.

SAN DIEGO – Obstructive sleep apnea in patients with type 2 diabetes predicted a three- to fourfold higher risk for diabetic peripheral neuropathy or sight-threatening retinopathy, separate analyses have found.

The results suggest that obstructive sleep apnea may play a role in the development of peripheral neuropathy and sight-threatening retinopathy in people with diabetes, Dr. Abd Tahrani and his associates reported at the meeting. Ongoing studies are exploring possible mechanisms involved.

Further study is warranted on the possibility that treating obstructive sleep apnea might affect the development or progression of retinopathy or neuropathy, added Dr. Tahrani of the University of Birmingham (England), where he is a research fellow for the U.K. National Institute for Health Research.

The prospective studies recruited random patients from a hospital-based, outpatient diabetes clinic in the United Kingdom. Subjects were excluded if they had a known respiratory disorder, including obstructive sleep apnea. Patients had a mean age of 59 years and a mean 11-year history of diabetes, and 48% were white. They underwent one night of home-based multichannel respiratory monitoring and were considered to have obstructive sleep apnea if they had an apnea-hypopnea index of at least 5 events per hour.

In 224 patients who also were assessed for sight-threatening retinopathy, 63% had obstructive sleep apnea and 38% had sight-threatening retinopathy. Patients with obstructive sleep apnea were significantly more likely to have sight-threatening retinopathy (48%) than were patients without obstructive sleep apnea (20%).

The study defined sight-threatening retinopathy as the presence of preproliferative or proliferative retinopathy, maculopathy, or the need for laser treatment.

After adjustment for possible confounders, patients with obstructive sleep apnea were 3.6 times more likely to have sight-threatening retinopathy, 5 times more likely to have advanced diabetic retinopathy, and 4.4 times more likely to have maculopathy than were patients without obstructive sleep apnea.

In a separate study by the same researchers of 231 patients assessed for obstructive sleep apnea and peripheral neuropathy, 65% had obstructive sleep apnea and 45% had diabetic peripheral neuropathy. Patients with obstructive sleep apnea reported more neuropathic symptoms. Among patients with obstructive sleep apnea, 60% had diabetic peripheral neuropathy, compared with 27% of patients without sleep apnea.

Obstructive sleep apnea conferred a significant threefold higher risk for peripheral neuropathy after adjustment for potentially confounding variables, Dr. Tahrani reported. The severity of peripheral neuropathy correlated with the severity of obstructive sleep apnea.

Obstructive sleep apnea was prevalent in 75% and 52% of white and South Asian patients, respectively. Likewise, diabetic peripheral neuropathy was more prevalent in whites (56% vs. 40%). Both differences were significant.

The lower prevalence of obstructive sleep apnea in the South Asian patients might be one reason for the lower prevalence of diabetic peripheral neuropathy, the investigators suggested.

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

Controversy surrounds the Institute of Medicine's November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” an update of 1997 guidelines. Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her patients. As a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a the meeting.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU vitamin D/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

But many experts think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30–32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients accordingly.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815–22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels. The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629–37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve of mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was statistically not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30–40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day for those who are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day in older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200–1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction (MI) or vascular calcification (Circulation 2007;115:846–54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262–6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19:342:d2040).

There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted. “Whether this truly represents an increased risk or not is unclear,” she said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added. The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010;341:c3691). “It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said. “I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU/day of vitamin D to reach 'sufficient' serum levels in the 30–32-ng/mL range.

Source DR. SELLMEYER

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

Controversy surrounds the Institute of Medicine's November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” an update of 1997 guidelines. Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her patients. As a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a the meeting.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU vitamin D/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

But many experts think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30–32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients accordingly.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815–22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels. The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629–37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve of mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was statistically not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30–40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day for those who are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day in older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200–1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction (MI) or vascular calcification (Circulation 2007;115:846–54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262–6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19:342:d2040).

There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted. “Whether this truly represents an increased risk or not is unclear,” she said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added. The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010;341:c3691). “It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said. “I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU/day of vitamin D to reach 'sufficient' serum levels in the 30–32-ng/mL range.

Source DR. SELLMEYER

SAN FRANCISCO – Updated national guidelines on calcium and vitamin D intake should be followed loosely, cautioned Dr. Deborah E. Sellmeyer, director of the Metabolic Bone Center at Johns Hopkins University, Baltimore.

Controversy surrounds the Institute of Medicine's November 2010 report, “Dietary Reference Intakes for Calcium and Vitamin D,” an update of 1997 guidelines. Dr. Sellmeyer uses the latest IOM report as a starting point and then tailors the recommendations to meet the needs of her patients. As a result, the amounts of vitamin D and calcium that her patients take usually vary from the guidelines, she said at a the meeting.

There is uncertainty about the cutoff level of serum vitamin D that's considered adequate and the potential side effects from ingesting too much calcium, she said.

The IOM recommends that adults take 600 IU vitamin D/day through age 50 and 800 IU/day for those aged 51 years and older, with a suggested upper tolerability limit of 4,000 IU/day. Those are the intake amounts that generally would be needed to reach a serum level of 20 ng/mL.

But many experts think that physiologic and fracture data suggest that a “sufficient” serum level should be in the 30–32-ng/mL range, she said. “It takes most people about 1,200 IU/day to reach that” serum level, said Dr. Sellmeyer, who advises her patients accordingly.

A 2010 study of high-dose vitamin D and fracture risk caused “a lot of consternation,” she noted. The double-blind trial randomized 2,256 older women to a once-yearly oral dose of 500,000 IU cholecalciferol or placebo, and found higher rates of falls and fractures in the vitamin D group (JAMA 2010;303:1815–22).

“It's almost a moot point because you wouldn't give 500,000 IU once a year, but it did raise the idea that there may be some administration techniques, some regimens that would not be beneficial,” Dr. Sellmeyer said.

The IOM committee that compiled the 2010 report expressed a great deal of concern about a potentially higher mortality risk with excessively high vitamin D serum levels. The concern was sparked by the committee's interpretation of an analysis of data from the Third National Health and Nutrition Examination Survey. Overall, that survey documented higher mortality rates in patients in the lowest quartile of serum vitamin D levels (Arch. Intern. Med. 2008;168:1629–37). However, the IOM committee noticed a statistically nonsignificant dip in mortality risk between the highest and second-highest quartiles of serum vitamin D before the mortality risk increased in each of the two lowest quartiles, constituting what some saw as a J-shaped curve of mortality risk.

Numerically, the lowest mortality was in patients with 24-32 ng/mL of serum vitamin D, but this was statistically not significantly different than in patients with a serum level greater than 32 ng/mL.

“I'm really not sure that there is a higher mortality,” Dr. Sellmeyer said. “I think there is enough evidence to suggest that we probably ought to be a little more in the 30–40-ng/mL range.”

The IOM recommends that adult males get 1,000 mg/day of calcium through age 70 years and 1,200 mg/day for those who are older. Adult women should get 1,000 mg/day through age 50 and 1,200 mg/day in older ages. The maximum tolerability limits were set at 2,500 mg/day for adults younger than 50 years or 2,000 mg/day for older adults.

It's important to remember that the recommended level includes both dietary and supplemental sources of calcium, she emphasized. “We see a lot of women who are taking 1,200–1,500 mg/day in supplements and also drinking two glasses of milk a day,” she said. “Those [are the patients who] can get into trouble.”

There are no data to suggest that ingesting more than 1,200 mg/day is better for skeletal health, and high doses of calcium increase the risk of developing kidney stones, studies show.

The most controversial aspect of calcium supplementation in recent years has been some preliminary evidence of a possible increased risk for vascular calcification with higher doses.

Initially, an analysis of data on 36,282 participants in the Women's Health Initiative (WHI) who were randomized to take 500 mg calcium carbonate with 200 IU vitamin D twice daily found no effect on risk of myocardial infarction (MI) or vascular calcification (Circulation 2007;115:846–54).

Then a randomized, controlled trial of 1,471 healthy women found that the group taking 1 g/day of calcium citrate showed a doubling in risk for MI and a trend toward higher risk of angina, compared with the placebo group (BMJ 2008;336:262–6). The investigators in that study reanalyzed the WHI data and found a 22% increase in risk for MI in women who at baseline had no personal calcium use (BMJ 2011;19:342:d2040).

There were significant differences in the comparison groups in the reanalysis, including differences in personal history of MI, Dr. Sellmeyer noted. “Whether this truly represents an increased risk or not is unclear,” she said.

Another study by some of the same investigators “got a ton of press” even though it was a relatively small meta-analysis, she added. The attempted meta-analysis of 190 trials of calcium supplementation yielded 15 eligible trials, but most of the data came from 5 trials. The meta-analysis reported a 31% increase in risk for MI in calcium supplement users, with possibly a higher risk in those taking more than 1,600 mg/day (BMJ 2010;341:c3691). “It's really hard to know at this point” whether the risk of vascular calcification from supplementation is significant, Dr. Sellmeyer said. “I think it does behoove us to be judicious with our calcium and not let people consume more calcium than we think is really beneficial.”

Dr. Sellmeyer said she has no relevant conflicts of interest.

Most people need about 1,200 IU/day of vitamin D to reach 'sufficient' serum levels in the 30–32-ng/mL range.

Source DR. SELLMEYER

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at a conference on osteoporosis sponsored by the University of California, San Francisco.

The findings have been submitted for publication. The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine, epidemiology and biostatistics at the university.

The original FREEDOM study enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All of the subjects had bone mineral density T scores that were less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756–65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said.

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5, more than twice that of patients on denosumab in the extension study.

A separate study highlighted another advantage of denosumab that it shares with zoledronic acid – greater adherence rates compared with oral therapies, he added. An open-label study of 250 women with untreated osteoporosis found an 87% adherence rate in the first year in patients randomized to get a denosumab injection every 6 months, compared with a 77% adherence rate for patients randomized to weekly oral alendronate therapy. Alendronate use was monitored by electronic bottle caps (Osteoporos. Int. 2011;22:1725–35).

The study's 2-year results, which have not yet been published, show that the difference in adherence rates between groups continues to widen, Dr. Cummings said.

Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly & Co.

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at a conference on osteoporosis sponsored by the University of California, San Francisco.

The findings have been submitted for publication. The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine, epidemiology and biostatistics at the university.

The original FREEDOM study enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All of the subjects had bone mineral density T scores that were less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756–65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said.

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5, more than twice that of patients on denosumab in the extension study.

A separate study highlighted another advantage of denosumab that it shares with zoledronic acid – greater adherence rates compared with oral therapies, he added. An open-label study of 250 women with untreated osteoporosis found an 87% adherence rate in the first year in patients randomized to get a denosumab injection every 6 months, compared with a 77% adherence rate for patients randomized to weekly oral alendronate therapy. Alendronate use was monitored by electronic bottle caps (Osteoporos. Int. 2011;22:1725–35).

The study's 2-year results, which have not yet been published, show that the difference in adherence rates between groups continues to widen, Dr. Cummings said.

Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly & Co.

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at a conference on osteoporosis sponsored by the University of California, San Francisco.

The findings have been submitted for publication. The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine, epidemiology and biostatistics at the university.

The original FREEDOM study enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All of the subjects had bone mineral density T scores that were less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756–65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said.

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5, more than twice that of patients on denosumab in the extension study.

A separate study highlighted another advantage of denosumab that it shares with zoledronic acid – greater adherence rates compared with oral therapies, he added. An open-label study of 250 women with untreated osteoporosis found an 87% adherence rate in the first year in patients randomized to get a denosumab injection every 6 months, compared with a 77% adherence rate for patients randomized to weekly oral alendronate therapy. Alendronate use was monitored by electronic bottle caps (Osteoporos. Int. 2011;22:1725–35).

The study's 2-year results, which have not yet been published, show that the difference in adherence rates between groups continues to widen, Dr. Cummings said.

Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly & Co.

SAN FRANCISCO – Bariatric surgery can be beneficial for obese people, but it also can lead to significant bone loss.

The limited data so far suggest that decreased bone mineral density after bariatric surgery is a real problem that increases the risk for fracture, Dr. Anne Schafer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The extent of bone loss within a year after the most common bariatric surgery, Roux-en-Y gastric bypass, can be equivalent to “what you would expect in the first 5 years of menopause” in some women, said Dr. Schafer of the division of endocrinology at the University of California, San Francisco.

A 2011 study not yet published by the Mayo Clinic, Rochester, Minn., compared fracture rates in 277 patients undergoing bariatric surgery with local age- and sex-matched fracture rates. The surgeries occurred in 1985-2004, and 94% were gastric bypasses. The retrospective chart study found 138 fractures in 82 patients since the surgery, with a standardized incidence ratio of 2.1 for any fracture and 1.9 for fractures of the hip, spine, wrist, or arm after bariatric surgery, she said.

Dr. Schafer incorporated her own clinical experience with recommendations from the Endocrine Society and from Tufts University in advising clinicians to take the following steps in managing patients undergoing bariatric surgery.

Prior to surgery, check serum 25-hydroxyvitamin D (25[OH]D) levels and prescribe preoperative treatment to augment vitamin D in patients with low levels. After surgery, all patients should take two multivitamins per day to make sure their micronutrient needs are met.

After malabsorptive bariatric surgery, such as gastric bypass, patients also should take calcium supplements, although there are not enough data to pinpoint the best dose or to identify which patients might most need the calcium, Dr. Schafer said. She recommended 1,200–2,000 mg/day (preferably in citrate form) after malabsorptive surgery and possibly after restrictive bariatric surgery such as adjustable gastric banding.

Based on the preoperative vitamin D level, prescribe 800-2,000 IU/day of vitamin D₃ supplementation after malabsorptive surgery and possibly after restrictive bariatric surgery. “I've had people who need more” than that dose range, she added.

For postoperative surveillance, check calcium homeostasis laboratory tests every 6 months for the first 2 years and then annually after malabsorptive surgery and possibly after any bariatric surgery. The tests include calcium, albumin, phosphate, creatinine, 25(OH)D, and parathyroid hormone.

If the parathyroid hormone level is high, but the 25(OH)D level is low, treat with vitamin D supplementation. If the parathyroid hormone level is high and the 25(OH)D level is ideal, check the patient's 24-hour urinary calcium, and if that is low, increase calcium intake.

Because some of the etiology of bariatric surgery–induced bone loss may be the preferential loss of lean mass over fat mass, or changes in fat distribution, encourage patients to consume protein and to exercise, she said.

The Endocrine Society recommends dual-energy x-ray absorptiometry (DXA) at baseline and annually in people who are undergoing malabsorptive bariatric surgery. No data show that such monitoring actually improves outcomes, “but I do think that you should consider it for any people who can fit on the DXA scan before the operation,” Dr. Schafer said. The weight limit for the scanner is approximately 275–350 pounds.

Dr. Schafer also said that she advises a DXA scan 1-2 years postoperatively. Incorporate those results into “your clinical judgment and other risk factors like age or prior history of fractures to set up an individualized plan for monitoring bone density from there.”

In general, high body mass index has been associated with high bone mineral density, and either voluntary or involuntary weight loss is associated with bone loss and increased fracture risk. Bariatric surgery leads to loss of bone mass for multiple reasons, she said, including nutritional deficiencies from malabsorption, the body's signals about decreased skeletal loading with weight loss, and changes in fat-secreted hormone.

Most of the data on bone loss after bariatric surgery is for Roux-en-Y gastric bypass, which induces early and sustained increases in bone turnover and decreases in bone mineral density. Fewer data are available on other procedures, but a handful of studies suggest that another malabsorptive procedure, biliopancreatic diversion, may produce effects similar to those of gastric bypass, and that adjustable gastric banding may have less of an impact on bone, she said.

For gastric bypass, one study of 15 patients reported an 8% decrease in total hip bone mineral density within 9 months (J. Clin. Endocrinol. Metab. 2004;89:1061–5). Femoral neck bone density decreased by 9% within 1 year of gastric bypass in a separate study of 23 patients (J. Clin. Endocrinol. Metab. 2008;93:3735–40). A third study of 42 patients reported a 7% decrease in spine bone density and a 10% decrease in total hip bone density a year after gastric bypass (Obes. Surg. 2009;19:41–6).

Vitamin D deficiency can be a problem after bariatric surgery because many patients have low vitamin D levels before surgery, some of the surgeries are designed to create malabsorption, and patients eat less food and different kinds of food after surgery. In the worst cases, patients may develop secondary hyperparathyroidism or bone loss, and there have been case reports of osteomalacia.

All the studies used DXA scans to assess bone density after bariatric surgery, but DXA assessment may be biased in the setting of marked weight loss because of changes in soft tissue surrounding the bones. The informal consensus among experts is that the bone density losses reported by studies are real, “but we need nonbiased methods of assessing bone mineral density” for future studies of bariatric surgery's effects, she said.

Dr. Schafer said that she has no disclosures.

To watch an interview with Dr. Schafer, scan the QR code or visit www.rheumatologynews.com

SAN FRANCISCO – Bariatric surgery can be beneficial for obese people, but it also can lead to significant bone loss.

The limited data so far suggest that decreased bone mineral density after bariatric surgery is a real problem that increases the risk for fracture, Dr. Anne Schafer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The extent of bone loss within a year after the most common bariatric surgery, Roux-en-Y gastric bypass, can be equivalent to “what you would expect in the first 5 years of menopause” in some women, said Dr. Schafer of the division of endocrinology at the University of California, San Francisco.

A 2011 study not yet published by the Mayo Clinic, Rochester, Minn., compared fracture rates in 277 patients undergoing bariatric surgery with local age- and sex-matched fracture rates. The surgeries occurred in 1985-2004, and 94% were gastric bypasses. The retrospective chart study found 138 fractures in 82 patients since the surgery, with a standardized incidence ratio of 2.1 for any fracture and 1.9 for fractures of the hip, spine, wrist, or arm after bariatric surgery, she said.

Dr. Schafer incorporated her own clinical experience with recommendations from the Endocrine Society and from Tufts University in advising clinicians to take the following steps in managing patients undergoing bariatric surgery.

Prior to surgery, check serum 25-hydroxyvitamin D (25[OH]D) levels and prescribe preoperative treatment to augment vitamin D in patients with low levels. After surgery, all patients should take two multivitamins per day to make sure their micronutrient needs are met.

After malabsorptive bariatric surgery, such as gastric bypass, patients also should take calcium supplements, although there are not enough data to pinpoint the best dose or to identify which patients might most need the calcium, Dr. Schafer said. She recommended 1,200–2,000 mg/day (preferably in citrate form) after malabsorptive surgery and possibly after restrictive bariatric surgery such as adjustable gastric banding.

Based on the preoperative vitamin D level, prescribe 800-2,000 IU/day of vitamin D₃ supplementation after malabsorptive surgery and possibly after restrictive bariatric surgery. “I've had people who need more” than that dose range, she added.

For postoperative surveillance, check calcium homeostasis laboratory tests every 6 months for the first 2 years and then annually after malabsorptive surgery and possibly after any bariatric surgery. The tests include calcium, albumin, phosphate, creatinine, 25(OH)D, and parathyroid hormone.

If the parathyroid hormone level is high, but the 25(OH)D level is low, treat with vitamin D supplementation. If the parathyroid hormone level is high and the 25(OH)D level is ideal, check the patient's 24-hour urinary calcium, and if that is low, increase calcium intake.

Because some of the etiology of bariatric surgery–induced bone loss may be the preferential loss of lean mass over fat mass, or changes in fat distribution, encourage patients to consume protein and to exercise, she said.

The Endocrine Society recommends dual-energy x-ray absorptiometry (DXA) at baseline and annually in people who are undergoing malabsorptive bariatric surgery. No data show that such monitoring actually improves outcomes, “but I do think that you should consider it for any people who can fit on the DXA scan before the operation,” Dr. Schafer said. The weight limit for the scanner is approximately 275–350 pounds.

Dr. Schafer also said that she advises a DXA scan 1-2 years postoperatively. Incorporate those results into “your clinical judgment and other risk factors like age or prior history of fractures to set up an individualized plan for monitoring bone density from there.”

In general, high body mass index has been associated with high bone mineral density, and either voluntary or involuntary weight loss is associated with bone loss and increased fracture risk. Bariatric surgery leads to loss of bone mass for multiple reasons, she said, including nutritional deficiencies from malabsorption, the body's signals about decreased skeletal loading with weight loss, and changes in fat-secreted hormone.

Most of the data on bone loss after bariatric surgery is for Roux-en-Y gastric bypass, which induces early and sustained increases in bone turnover and decreases in bone mineral density. Fewer data are available on other procedures, but a handful of studies suggest that another malabsorptive procedure, biliopancreatic diversion, may produce effects similar to those of gastric bypass, and that adjustable gastric banding may have less of an impact on bone, she said.

For gastric bypass, one study of 15 patients reported an 8% decrease in total hip bone mineral density within 9 months (J. Clin. Endocrinol. Metab. 2004;89:1061–5). Femoral neck bone density decreased by 9% within 1 year of gastric bypass in a separate study of 23 patients (J. Clin. Endocrinol. Metab. 2008;93:3735–40). A third study of 42 patients reported a 7% decrease in spine bone density and a 10% decrease in total hip bone density a year after gastric bypass (Obes. Surg. 2009;19:41–6).

Vitamin D deficiency can be a problem after bariatric surgery because many patients have low vitamin D levels before surgery, some of the surgeries are designed to create malabsorption, and patients eat less food and different kinds of food after surgery. In the worst cases, patients may develop secondary hyperparathyroidism or bone loss, and there have been case reports of osteomalacia.

All the studies used DXA scans to assess bone density after bariatric surgery, but DXA assessment may be biased in the setting of marked weight loss because of changes in soft tissue surrounding the bones. The informal consensus among experts is that the bone density losses reported by studies are real, “but we need nonbiased methods of assessing bone mineral density” for future studies of bariatric surgery's effects, she said.

Dr. Schafer said that she has no disclosures.

To watch an interview with Dr. Schafer, scan the QR code or visit www.rheumatologynews.com

SAN FRANCISCO – Bariatric surgery can be beneficial for obese people, but it also can lead to significant bone loss.

The limited data so far suggest that decreased bone mineral density after bariatric surgery is a real problem that increases the risk for fracture, Dr. Anne Schafer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The extent of bone loss within a year after the most common bariatric surgery, Roux-en-Y gastric bypass, can be equivalent to “what you would expect in the first 5 years of menopause” in some women, said Dr. Schafer of the division of endocrinology at the University of California, San Francisco.

A 2011 study not yet published by the Mayo Clinic, Rochester, Minn., compared fracture rates in 277 patients undergoing bariatric surgery with local age- and sex-matched fracture rates. The surgeries occurred in 1985-2004, and 94% were gastric bypasses. The retrospective chart study found 138 fractures in 82 patients since the surgery, with a standardized incidence ratio of 2.1 for any fracture and 1.9 for fractures of the hip, spine, wrist, or arm after bariatric surgery, she said.

Dr. Schafer incorporated her own clinical experience with recommendations from the Endocrine Society and from Tufts University in advising clinicians to take the following steps in managing patients undergoing bariatric surgery.

Prior to surgery, check serum 25-hydroxyvitamin D (25[OH]D) levels and prescribe preoperative treatment to augment vitamin D in patients with low levels. After surgery, all patients should take two multivitamins per day to make sure their micronutrient needs are met.

After malabsorptive bariatric surgery, such as gastric bypass, patients also should take calcium supplements, although there are not enough data to pinpoint the best dose or to identify which patients might most need the calcium, Dr. Schafer said. She recommended 1,200–2,000 mg/day (preferably in citrate form) after malabsorptive surgery and possibly after restrictive bariatric surgery such as adjustable gastric banding.

Based on the preoperative vitamin D level, prescribe 800-2,000 IU/day of vitamin D₃ supplementation after malabsorptive surgery and possibly after restrictive bariatric surgery. “I've had people who need more” than that dose range, she added.

For postoperative surveillance, check calcium homeostasis laboratory tests every 6 months for the first 2 years and then annually after malabsorptive surgery and possibly after any bariatric surgery. The tests include calcium, albumin, phosphate, creatinine, 25(OH)D, and parathyroid hormone.

If the parathyroid hormone level is high, but the 25(OH)D level is low, treat with vitamin D supplementation. If the parathyroid hormone level is high and the 25(OH)D level is ideal, check the patient's 24-hour urinary calcium, and if that is low, increase calcium intake.

Because some of the etiology of bariatric surgery–induced bone loss may be the preferential loss of lean mass over fat mass, or changes in fat distribution, encourage patients to consume protein and to exercise, she said.

The Endocrine Society recommends dual-energy x-ray absorptiometry (DXA) at baseline and annually in people who are undergoing malabsorptive bariatric surgery. No data show that such monitoring actually improves outcomes, “but I do think that you should consider it for any people who can fit on the DXA scan before the operation,” Dr. Schafer said. The weight limit for the scanner is approximately 275–350 pounds.

Dr. Schafer also said that she advises a DXA scan 1-2 years postoperatively. Incorporate those results into “your clinical judgment and other risk factors like age or prior history of fractures to set up an individualized plan for monitoring bone density from there.”

In general, high body mass index has been associated with high bone mineral density, and either voluntary or involuntary weight loss is associated with bone loss and increased fracture risk. Bariatric surgery leads to loss of bone mass for multiple reasons, she said, including nutritional deficiencies from malabsorption, the body's signals about decreased skeletal loading with weight loss, and changes in fat-secreted hormone.

Most of the data on bone loss after bariatric surgery is for Roux-en-Y gastric bypass, which induces early and sustained increases in bone turnover and decreases in bone mineral density. Fewer data are available on other procedures, but a handful of studies suggest that another malabsorptive procedure, biliopancreatic diversion, may produce effects similar to those of gastric bypass, and that adjustable gastric banding may have less of an impact on bone, she said.

For gastric bypass, one study of 15 patients reported an 8% decrease in total hip bone mineral density within 9 months (J. Clin. Endocrinol. Metab. 2004;89:1061–5). Femoral neck bone density decreased by 9% within 1 year of gastric bypass in a separate study of 23 patients (J. Clin. Endocrinol. Metab. 2008;93:3735–40). A third study of 42 patients reported a 7% decrease in spine bone density and a 10% decrease in total hip bone density a year after gastric bypass (Obes. Surg. 2009;19:41–6).

Vitamin D deficiency can be a problem after bariatric surgery because many patients have low vitamin D levels before surgery, some of the surgeries are designed to create malabsorption, and patients eat less food and different kinds of food after surgery. In the worst cases, patients may develop secondary hyperparathyroidism or bone loss, and there have been case reports of osteomalacia.

All the studies used DXA scans to assess bone density after bariatric surgery, but DXA assessment may be biased in the setting of marked weight loss because of changes in soft tissue surrounding the bones. The informal consensus among experts is that the bone density losses reported by studies are real, “but we need nonbiased methods of assessing bone mineral density” for future studies of bariatric surgery's effects, she said.

Dr. Schafer said that she has no disclosures.

To watch an interview with Dr. Schafer, scan the QR code or visit www.rheumatologynews.com

SAN FRANCISCO – Physicians know that corticosteroids are bad for bones. So bad that rheumatologist Jonathan D. Graf calls them “a case of skeletal cruelty.”

Given the bad reputation of chronic steroid use when it comes to bone health, one might expect physicians to be aware of the medical evidence for choosing a drug to prevent or treat glucocorticoid-induced osteoporosis. Many physicians may be unaware of the evidence, however, judging by a poll Dr. Graf conducted at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Nearly everyone present believed that there have been no comparative head-to-head studies of different medications to manage glucocorticoid-induced osteoporosis.

In reality, two of the approved drugs for managing glucocorticoid-induced osteoporosis – alendronate and risedronate – were shown to be effective in only placebo-controlled trials. But two others – zoledronic acid and teriparatide – showed some advantages over risedronate or alendronate, respectively, in head-to-head comparisons, said Dr. Graf of San Francisco General Hospital.

▸ Alendronate: A 48-week study randomized 477 patients who were taking at least 7.5 mg/day of prednisone (or the equivalent) to treatment with alendronate 5 mg/day or 10 mg/day or placebo. The 10-mg alendronate group showed significantly improved lumbar bone mineral density at 48 weeks compared with the placebo group. Bone density benefits were less impressive but statistically significant for the femoral neck, trochanter, and total body compared with placebo (N. Engl. J. Med. 1998;339:292–9).

The bone density improvements on 10 mg alendronate were seen in all subgroups of patients but especially in postmenopausal women who were not taking estrogen. The risk for fractures did not differ significantly between groups for the cohort as a whole, but postmenopausal women had a significantly lower risk of fracture if they were on 10 mg alendronate, compared with placebo (4% vs. 13%).

In an extension study that followed 208 of the patients on their same regimens for another 12 months, the difference in fracture risk became significant for the cohort as a whole at 2 years: 1% in the alendronate groups and 7% on placebo. All patients in the extension study received calcium and vitamin D supplementation (Arthritis Rheum. 2001;44:202-11).

▸ Risedronate: Two separate multicenter, double-blind studies randomized patients to 2.5 mg/day or 5 mg/day risedronate or placebo, and all received calcium and vitamin D supplementation.

In one study of 224 adults starting long-term glucocorticoid therapy, patients on risedronate maintained or improved bone mineral density, which decreased significantly in patients on placebo. There was a trend toward a lower rate of new vertebral fractures at 1 year on risedronate 5 mg (6%) than on placebo (17%), but the difference was not statistically significant (Arthritis Rheum. 1999;42:2309–18).

In a separate study of 290 adults who already had been using at least 7.5 mg/day of prednisone for at least 6 months, the rate of new vertebral fractures was significantly lower at 1 year in the combined risedronate groups (5%), compared with the placebo group (15%), while rates of adverse events did not differ significantly. The risedronate groups also showed significantly higher bone mineral density at the hip and spine, compared with the placebo group (J. Bone Miner. Res. 2000;15:1006–13).

▸ Zoledronic acid: A multicenter double-blind, double-dummy trial randomized 833 patients who were on steroid therapy to either a single intravenous infusion of 5 mg zoledronic acid or oral risedronate 5 mg/day. The cohort was “very representative of patients that I see” in practice, Dr. Graf said. Most were on 7.5 mg/day or more of prednisone daily, mostly for rheumatologic disorders.

Patients receiving zoledronic acid showed significantly better bone density at the lumbar spine after 1 year, compared with patients on risedronate (Lancet 2009;373:1253–63). The advantage was true both for preventing osteoporosis in “new” steroid users (less than 3 months use) and for treating chronic steroid users (more than 3 months).

“There are a whole bunch of issues with toxicity with zoledronic acid, compared with the other bisphosphonates, and there are cost issues and infusion issues,” Dr. Graf said. “Whether or not you should use it in your practice is your choice, but I think you have to be aware of the fact that this drug has been studied head to head.”

The study did not assess fracture risk. “Clinically speaking, we really don't know if this improves fracture risk, but we do know that there is a superior effect on bone mineral density,” he said.

▸ Teriparatide: A 3-year double-blinded trial randomized 428 adults who had been on the equivalent of 5 mg/day of prednisone for at least 3 months to treatment with 20 mcg/day of teriparatide or 10 mg/day of alendronate. These were high-risk patients with baseline bone mineral density T scores of less than −2.0 or less than −1.0 with a history of fragility fracture. In all, 20% in each group had a history of nonvertebral fragility fracture. The reason for taking glucocorticoids was rheumatologic disease in 75% of each group.

A quarter of patients in each group dropped out of the study. In intent-to-treat analyses, bone mineral densities were higher in the teriparatide group than in those on alendronate at 18 months or at 36 months. A highly significant difference emerged in radiographically identified vertebral fractures in the teriparatide group (1%), compared with the alendronate group (6%) at the interim 18-month analysis (N. Engl. J. Med. 2007;357: 2028–39).

By 36 months, the teriparatide group showed significantly lower rates of radiographic vertebral fractures (2%) and clinical vertebral fractures (0%), compared with the alendronate group (8% and 12%). No significant differences in nonvertebral fractures were seen at either time point.

“So, this primarily is of clinical benefit in the spine,” Dr. Graf said, “but the overall rate of clinical fractures is low in both groups.”

He suggested that clinicians consider teriparatide for patients with the most severe glucocorticoid-induced osteoporosis or patients at highest risk for fracture, such as those with previous fragility fractures.

▸ Denosumab: Although this drug is not yet approved for managing glucocorticoid-induced osteoporosis, a subgroup analysis from phase II trial data on 218 patients who were taking either glucocorticoids or bisphosphonates showed that adding denosumab significantly improved lumbar bone mineral density “on top of what you would normally see from the bisphosphonate,” Dr. Graf said (Ann. Rheum. Dis. 2010;69:872–5).

Dr. Graf said he has no conflicts of interest.

Consider teriparatide for patients with the most severe cases, or those at highest risk for fracture.

Source DR. GRAF

SAN FRANCISCO – Physicians know that corticosteroids are bad for bones. So bad that rheumatologist Jonathan D. Graf calls them “a case of skeletal cruelty.”

Given the bad reputation of chronic steroid use when it comes to bone health, one might expect physicians to be aware of the medical evidence for choosing a drug to prevent or treat glucocorticoid-induced osteoporosis. Many physicians may be unaware of the evidence, however, judging by a poll Dr. Graf conducted at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Nearly everyone present believed that there have been no comparative head-to-head studies of different medications to manage glucocorticoid-induced osteoporosis.

In reality, two of the approved drugs for managing glucocorticoid-induced osteoporosis – alendronate and risedronate – were shown to be effective in only placebo-controlled trials. But two others – zoledronic acid and teriparatide – showed some advantages over risedronate or alendronate, respectively, in head-to-head comparisons, said Dr. Graf of San Francisco General Hospital.

▸ Alendronate: A 48-week study randomized 477 patients who were taking at least 7.5 mg/day of prednisone (or the equivalent) to treatment with alendronate 5 mg/day or 10 mg/day or placebo. The 10-mg alendronate group showed significantly improved lumbar bone mineral density at 48 weeks compared with the placebo group. Bone density benefits were less impressive but statistically significant for the femoral neck, trochanter, and total body compared with placebo (N. Engl. J. Med. 1998;339:292–9).

The bone density improvements on 10 mg alendronate were seen in all subgroups of patients but especially in postmenopausal women who were not taking estrogen. The risk for fractures did not differ significantly between groups for the cohort as a whole, but postmenopausal women had a significantly lower risk of fracture if they were on 10 mg alendronate, compared with placebo (4% vs. 13%).

In an extension study that followed 208 of the patients on their same regimens for another 12 months, the difference in fracture risk became significant for the cohort as a whole at 2 years: 1% in the alendronate groups and 7% on placebo. All patients in the extension study received calcium and vitamin D supplementation (Arthritis Rheum. 2001;44:202-11).

▸ Risedronate: Two separate multicenter, double-blind studies randomized patients to 2.5 mg/day or 5 mg/day risedronate or placebo, and all received calcium and vitamin D supplementation.

In one study of 224 adults starting long-term glucocorticoid therapy, patients on risedronate maintained or improved bone mineral density, which decreased significantly in patients on placebo. There was a trend toward a lower rate of new vertebral fractures at 1 year on risedronate 5 mg (6%) than on placebo (17%), but the difference was not statistically significant (Arthritis Rheum. 1999;42:2309–18).

In a separate study of 290 adults who already had been using at least 7.5 mg/day of prednisone for at least 6 months, the rate of new vertebral fractures was significantly lower at 1 year in the combined risedronate groups (5%), compared with the placebo group (15%), while rates of adverse events did not differ significantly. The risedronate groups also showed significantly higher bone mineral density at the hip and spine, compared with the placebo group (J. Bone Miner. Res. 2000;15:1006–13).

▸ Zoledronic acid: A multicenter double-blind, double-dummy trial randomized 833 patients who were on steroid therapy to either a single intravenous infusion of 5 mg zoledronic acid or oral risedronate 5 mg/day. The cohort was “very representative of patients that I see” in practice, Dr. Graf said. Most were on 7.5 mg/day or more of prednisone daily, mostly for rheumatologic disorders.

Patients receiving zoledronic acid showed significantly better bone density at the lumbar spine after 1 year, compared with patients on risedronate (Lancet 2009;373:1253–63). The advantage was true both for preventing osteoporosis in “new” steroid users (less than 3 months use) and for treating chronic steroid users (more than 3 months).

“There are a whole bunch of issues with toxicity with zoledronic acid, compared with the other bisphosphonates, and there are cost issues and infusion issues,” Dr. Graf said. “Whether or not you should use it in your practice is your choice, but I think you have to be aware of the fact that this drug has been studied head to head.”

The study did not assess fracture risk. “Clinically speaking, we really don't know if this improves fracture risk, but we do know that there is a superior effect on bone mineral density,” he said.

▸ Teriparatide: A 3-year double-blinded trial randomized 428 adults who had been on the equivalent of 5 mg/day of prednisone for at least 3 months to treatment with 20 mcg/day of teriparatide or 10 mg/day of alendronate. These were high-risk patients with baseline bone mineral density T scores of less than −2.0 or less than −1.0 with a history of fragility fracture. In all, 20% in each group had a history of nonvertebral fragility fracture. The reason for taking glucocorticoids was rheumatologic disease in 75% of each group.

A quarter of patients in each group dropped out of the study. In intent-to-treat analyses, bone mineral densities were higher in the teriparatide group than in those on alendronate at 18 months or at 36 months. A highly significant difference emerged in radiographically identified vertebral fractures in the teriparatide group (1%), compared with the alendronate group (6%) at the interim 18-month analysis (N. Engl. J. Med. 2007;357: 2028–39).

By 36 months, the teriparatide group showed significantly lower rates of radiographic vertebral fractures (2%) and clinical vertebral fractures (0%), compared with the alendronate group (8% and 12%). No significant differences in nonvertebral fractures were seen at either time point.

“So, this primarily is of clinical benefit in the spine,” Dr. Graf said, “but the overall rate of clinical fractures is low in both groups.”

He suggested that clinicians consider teriparatide for patients with the most severe glucocorticoid-induced osteoporosis or patients at highest risk for fracture, such as those with previous fragility fractures.

▸ Denosumab: Although this drug is not yet approved for managing glucocorticoid-induced osteoporosis, a subgroup analysis from phase II trial data on 218 patients who were taking either glucocorticoids or bisphosphonates showed that adding denosumab significantly improved lumbar bone mineral density “on top of what you would normally see from the bisphosphonate,” Dr. Graf said (Ann. Rheum. Dis. 2010;69:872–5).

Dr. Graf said he has no conflicts of interest.

Consider teriparatide for patients with the most severe cases, or those at highest risk for fracture.

Source DR. GRAF

SAN FRANCISCO – Physicians know that corticosteroids are bad for bones. So bad that rheumatologist Jonathan D. Graf calls them “a case of skeletal cruelty.”

Given the bad reputation of chronic steroid use when it comes to bone health, one might expect physicians to be aware of the medical evidence for choosing a drug to prevent or treat glucocorticoid-induced osteoporosis. Many physicians may be unaware of the evidence, however, judging by a poll Dr. Graf conducted at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Nearly everyone present believed that there have been no comparative head-to-head studies of different medications to manage glucocorticoid-induced osteoporosis.

In reality, two of the approved drugs for managing glucocorticoid-induced osteoporosis – alendronate and risedronate – were shown to be effective in only placebo-controlled trials. But two others – zoledronic acid and teriparatide – showed some advantages over risedronate or alendronate, respectively, in head-to-head comparisons, said Dr. Graf of San Francisco General Hospital.

▸ Alendronate: A 48-week study randomized 477 patients who were taking at least 7.5 mg/day of prednisone (or the equivalent) to treatment with alendronate 5 mg/day or 10 mg/day or placebo. The 10-mg alendronate group showed significantly improved lumbar bone mineral density at 48 weeks compared with the placebo group. Bone density benefits were less impressive but statistically significant for the femoral neck, trochanter, and total body compared with placebo (N. Engl. J. Med. 1998;339:292–9).

The bone density improvements on 10 mg alendronate were seen in all subgroups of patients but especially in postmenopausal women who were not taking estrogen. The risk for fractures did not differ significantly between groups for the cohort as a whole, but postmenopausal women had a significantly lower risk of fracture if they were on 10 mg alendronate, compared with placebo (4% vs. 13%).

In an extension study that followed 208 of the patients on their same regimens for another 12 months, the difference in fracture risk became significant for the cohort as a whole at 2 years: 1% in the alendronate groups and 7% on placebo. All patients in the extension study received calcium and vitamin D supplementation (Arthritis Rheum. 2001;44:202-11).

▸ Risedronate: Two separate multicenter, double-blind studies randomized patients to 2.5 mg/day or 5 mg/day risedronate or placebo, and all received calcium and vitamin D supplementation.

In one study of 224 adults starting long-term glucocorticoid therapy, patients on risedronate maintained or improved bone mineral density, which decreased significantly in patients on placebo. There was a trend toward a lower rate of new vertebral fractures at 1 year on risedronate 5 mg (6%) than on placebo (17%), but the difference was not statistically significant (Arthritis Rheum. 1999;42:2309–18).

In a separate study of 290 adults who already had been using at least 7.5 mg/day of prednisone for at least 6 months, the rate of new vertebral fractures was significantly lower at 1 year in the combined risedronate groups (5%), compared with the placebo group (15%), while rates of adverse events did not differ significantly. The risedronate groups also showed significantly higher bone mineral density at the hip and spine, compared with the placebo group (J. Bone Miner. Res. 2000;15:1006–13).

▸ Zoledronic acid: A multicenter double-blind, double-dummy trial randomized 833 patients who were on steroid therapy to either a single intravenous infusion of 5 mg zoledronic acid or oral risedronate 5 mg/day. The cohort was “very representative of patients that I see” in practice, Dr. Graf said. Most were on 7.5 mg/day or more of prednisone daily, mostly for rheumatologic disorders.

Patients receiving zoledronic acid showed significantly better bone density at the lumbar spine after 1 year, compared with patients on risedronate (Lancet 2009;373:1253–63). The advantage was true both for preventing osteoporosis in “new” steroid users (less than 3 months use) and for treating chronic steroid users (more than 3 months).

“There are a whole bunch of issues with toxicity with zoledronic acid, compared with the other bisphosphonates, and there are cost issues and infusion issues,” Dr. Graf said. “Whether or not you should use it in your practice is your choice, but I think you have to be aware of the fact that this drug has been studied head to head.”

The study did not assess fracture risk. “Clinically speaking, we really don't know if this improves fracture risk, but we do know that there is a superior effect on bone mineral density,” he said.

▸ Teriparatide: A 3-year double-blinded trial randomized 428 adults who had been on the equivalent of 5 mg/day of prednisone for at least 3 months to treatment with 20 mcg/day of teriparatide or 10 mg/day of alendronate. These were high-risk patients with baseline bone mineral density T scores of less than −2.0 or less than −1.0 with a history of fragility fracture. In all, 20% in each group had a history of nonvertebral fragility fracture. The reason for taking glucocorticoids was rheumatologic disease in 75% of each group.

A quarter of patients in each group dropped out of the study. In intent-to-treat analyses, bone mineral densities were higher in the teriparatide group than in those on alendronate at 18 months or at 36 months. A highly significant difference emerged in radiographically identified vertebral fractures in the teriparatide group (1%), compared with the alendronate group (6%) at the interim 18-month analysis (N. Engl. J. Med. 2007;357: 2028–39).

By 36 months, the teriparatide group showed significantly lower rates of radiographic vertebral fractures (2%) and clinical vertebral fractures (0%), compared with the alendronate group (8% and 12%). No significant differences in nonvertebral fractures were seen at either time point.

“So, this primarily is of clinical benefit in the spine,” Dr. Graf said, “but the overall rate of clinical fractures is low in both groups.”

He suggested that clinicians consider teriparatide for patients with the most severe glucocorticoid-induced osteoporosis or patients at highest risk for fracture, such as those with previous fragility fractures.

▸ Denosumab: Although this drug is not yet approved for managing glucocorticoid-induced osteoporosis, a subgroup analysis from phase II trial data on 218 patients who were taking either glucocorticoids or bisphosphonates showed that adding denosumab significantly improved lumbar bone mineral density “on top of what you would normally see from the bisphosphonate,” Dr. Graf said (Ann. Rheum. Dis. 2010;69:872–5).

Dr. Graf said he has no conflicts of interest.

Consider teriparatide for patients with the most severe cases, or those at highest risk for fracture.

Source DR. GRAF

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.

PARIS – Up to 24 months of dual antiplatelet therapy after coronary stent implantation was no more effective than was 6 months and significantly increased the risk of hemorrhage in a multicenter, randomized study of 1,970 patients.

In the Prolonging Dual Antiplatelet Treatment after Grading Stent-induced Intimal Hyperplasia Study (PRODIGY), 10% of the 983 patients who took clopidogrel plus aspirin for 6 months after stent implantation and 10% of 987 patients who took the dual antiplatelet therapy for up to 24 months died or had a nonfatal MI or a cerebrovascular accident.

Individual rates for death, MI, cerebrovascular accident, or stent thrombosis also did not differ significantly between groups, Dr. Marco Valgimigli and his associates reported at the annual congress of the European Society of Cardiology. Death rates were 10% in the 6-month group and 9% with prolonged therapy.

Among those on the longer dual antiplatelet therapy, however, the risk of type II, III or V bleeding was twice that of the 6-month therapy group during the 24 months of follow-up, said Dr. Valgimigli of University Hospital, Ferrara, Italy. Bleeds occurred in 7.4% of the extended-therapy group and in 3.5% of the 6-month therapy group.

The study used prespecified definitions of bleeding, including the recently proposed Bleeding Academic Research Consortium classification.

The risks of major bleeding defined by Thrombolysis in Myocardial Infarction (TIMI) also were significantly higher in the prolonged-therapy group (2% on prolonged therapy vs. 1% on 6-month therapy). Red blood cell transfusions were needed in 3% on prolonged therapy and 1% on 6-month therapy, a significant difference.

Adults who were scheduled for elective, urgent, or emergency coronary angioplasty were randomized in a 1:1:1:1 fashion to receive an everolimus-eluting stent, a paclitaxel-eluting stent, a zotarolimus-eluting stent, or a third-generation thin-strut bare-metal stent. Thirty days later, they were randomized again to either 6 or 24 months of clopidogrel as add-on therapy to aspirin.

Patients received stents due to chronic stable coronary artery disease or acute coronary syndromes including ST-elevation MI and non–ST-elevation MI.

Current guidelines call for at least 12 months of dual antiplatelet therapy in patients receiving drug-eluting stents, based mainly on data from registries.

With dual antiplatelet therapy lasting more than 6 months, "The risk of bleeding is surely higher than the possible benefit for ischemia," Dr. Valgimigli said. "We have not seen any signs suggesting that prolonged dual antiplatelet therapy is better than short."

Results Inform Antiplatelet Duration After Drug-Eluting Stents

"This all kind of stems from the only two big studies of bare-metal stents that address the question of how long to use dual antiplatelet therapy after somebody gets a stent: the PCI-CURE trial [Percutaneous Coronary Intervention–Clopidogrel in Unstable Angina to Prevent Recurrent Events, N. Engl. J. Med. 2001;345:494-502] and CREDO [Clopidogrel for the Reduction of Events During Observation, JAMA 2002;288:2411-20]," Dr. Gordon F. Tomaselli said in an interview.

The recommendations from American Heart Association guidelines in 2005 after looking at CURE-PCI and CREDO were that people should get at least a month and optimally a year of dual antiplatelet therapy for a bare-metal stent, he said.

"There wasn’t anything known initially about drug-eluting stents until we started to see some late stent thromboses. They’re rare, but with profound complications including death and MI, so preventing them was of paramount importance," said Dr. Tomaselli, chief of cardiology at Johns Hopkins University, Baltimore, and president of the American Heart Association. "We didn’t really know what the duration of dual antiplatelet therapy should be with drug-eluting stents. The recommendation that came out was that it should be at least a year. Whether or not that’s right, nobody has any clue. A randomized trial is the way to go."

The PRODIGY trial certainly is going to add to the information that can be used for a clinical trial update regarding duration of dual antiplatelet therapy, he said. "Will this be sufficient to change the recommendation? I’m not really sure, but it’s certainly something we need to think about considering the increased incidence of bleeding with longer duration therapy.

"It always is complicated for us because these patients have other problems that often require things like surgery. Getting them off of dual antiplatelet therapy earlier rather than later is usually a good thing."

Dr. Tomaselli said he has no relevant conflicts of interest.

Dr. Valgimigli’s university sponsored the study. He has received research funds from, or been an adviser or speaker for, Merck, Iroko, Eli Lilly, Medtronic, The Medicines Company, Daiichi Sankyo, St. Jude, Abbott Vascular, Cordis, CID, Terumo, and Accumetrics.

To watch a video interview of Dr. Tomaselli, go to http://www.youtube.com/watch?v=8vWiSqTK1Do.