Osteoarthritis

HARROGATE, ENGLAND — To better understand the genetic components of osteoporosis, a University of Edinburgh researcher is planning to study the relationship between the two in the isolated population of the Orkney Islands.

Dr. Stuart Ralston, professor of rheumatology and head of the school of molecular and clinical medicine at University of Edinburgh, said research has shown that bone mineral density (BMD) in osteoporosis patients is almost certainly regulated by genetic signals.

Genetic factors explain 60%–85% of the variance in BMD, including type I collagen affecting bone structure, vitamin D receptors affecting mineralization, estrogen receptors affecting hormone action, and interleukin-1 and interleukin −6 affecting inflammation. However, the effects of individual genes appear to be small and may be magnified only by the interactions of multiple genes.

Orkney—an archipelago of 70 or so islands about 10 miles off the northern tip of Scotland—is one of the more isolated regions of Europe, and it has good genealogical records, making it possible for researchers to get a clearer picture of the way genetics affects bone health, Dr. Ralston said.

Dr. Ralston said colleagues were already planning to test the Orkney Islands population for genetic factors related to cardiovascular disease, so he asked them to tack on the factors for osteoporosis as well.

“Linking studies conducted in general isolated populations are good,” Dr. Ralston said June 26 during a workshop at the annual conference of the National Osteoporosis Society.

“If you're going to study osteoporosis or any other complex disease, I would study an isolated population because you're more likely to find something,” Dr. Ralston said.

One study of the Icelandic population showed that a variation in the gene BMP2 in chromosome 20 was correlated to osteoporosis. That study found that variation was present in 5% of people with low BMD at spine or hip or a fracture, compared with 1% in the control population.

Dr Ralston said he confirmed that work with an isolated population in northeast Scotland, where 3% of fracture patients had that same variation, compared with 0.04% of the control population.

“It's still rare,” Dr. Ralston explained. “One of the advantages of studying an isolated population is that you're more likely to discover a gene. One of the disadvantages of this is, is it applicable for the rest of the world?”

The study will go beyond the BMP2 gene to include the entire human genome for correlations to osteoporosis. But even with research into the genetic components of osteoporosis, identifying a single marker that will help physicians identify likely hip fracture patients may be impossible, he said.

HARROGATE, ENGLAND — To better understand the genetic components of osteoporosis, a University of Edinburgh researcher is planning to study the relationship between the two in the isolated population of the Orkney Islands.

Dr. Stuart Ralston, professor of rheumatology and head of the school of molecular and clinical medicine at University of Edinburgh, said research has shown that bone mineral density (BMD) in osteoporosis patients is almost certainly regulated by genetic signals.

Genetic factors explain 60%–85% of the variance in BMD, including type I collagen affecting bone structure, vitamin D receptors affecting mineralization, estrogen receptors affecting hormone action, and interleukin-1 and interleukin −6 affecting inflammation. However, the effects of individual genes appear to be small and may be magnified only by the interactions of multiple genes.

Orkney—an archipelago of 70 or so islands about 10 miles off the northern tip of Scotland—is one of the more isolated regions of Europe, and it has good genealogical records, making it possible for researchers to get a clearer picture of the way genetics affects bone health, Dr. Ralston said.

Dr. Ralston said colleagues were already planning to test the Orkney Islands population for genetic factors related to cardiovascular disease, so he asked them to tack on the factors for osteoporosis as well.

“Linking studies conducted in general isolated populations are good,” Dr. Ralston said June 26 during a workshop at the annual conference of the National Osteoporosis Society.

“If you're going to study osteoporosis or any other complex disease, I would study an isolated population because you're more likely to find something,” Dr. Ralston said.

One study of the Icelandic population showed that a variation in the gene BMP2 in chromosome 20 was correlated to osteoporosis. That study found that variation was present in 5% of people with low BMD at spine or hip or a fracture, compared with 1% in the control population.

Dr Ralston said he confirmed that work with an isolated population in northeast Scotland, where 3% of fracture patients had that same variation, compared with 0.04% of the control population.

“It's still rare,” Dr. Ralston explained. “One of the advantages of studying an isolated population is that you're more likely to discover a gene. One of the disadvantages of this is, is it applicable for the rest of the world?”

The study will go beyond the BMP2 gene to include the entire human genome for correlations to osteoporosis. But even with research into the genetic components of osteoporosis, identifying a single marker that will help physicians identify likely hip fracture patients may be impossible, he said.

HARROGATE, ENGLAND — To better understand the genetic components of osteoporosis, a University of Edinburgh researcher is planning to study the relationship between the two in the isolated population of the Orkney Islands.

Dr. Stuart Ralston, professor of rheumatology and head of the school of molecular and clinical medicine at University of Edinburgh, said research has shown that bone mineral density (BMD) in osteoporosis patients is almost certainly regulated by genetic signals.

Genetic factors explain 60%–85% of the variance in BMD, including type I collagen affecting bone structure, vitamin D receptors affecting mineralization, estrogen receptors affecting hormone action, and interleukin-1 and interleukin −6 affecting inflammation. However, the effects of individual genes appear to be small and may be magnified only by the interactions of multiple genes.

Orkney—an archipelago of 70 or so islands about 10 miles off the northern tip of Scotland—is one of the more isolated regions of Europe, and it has good genealogical records, making it possible for researchers to get a clearer picture of the way genetics affects bone health, Dr. Ralston said.

Dr. Ralston said colleagues were already planning to test the Orkney Islands population for genetic factors related to cardiovascular disease, so he asked them to tack on the factors for osteoporosis as well.

“Linking studies conducted in general isolated populations are good,” Dr. Ralston said June 26 during a workshop at the annual conference of the National Osteoporosis Society.

“If you're going to study osteoporosis or any other complex disease, I would study an isolated population because you're more likely to find something,” Dr. Ralston said.

One study of the Icelandic population showed that a variation in the gene BMP2 in chromosome 20 was correlated to osteoporosis. That study found that variation was present in 5% of people with low BMD at spine or hip or a fracture, compared with 1% in the control population.

Dr Ralston said he confirmed that work with an isolated population in northeast Scotland, where 3% of fracture patients had that same variation, compared with 0.04% of the control population.

“It's still rare,” Dr. Ralston explained. “One of the advantages of studying an isolated population is that you're more likely to discover a gene. One of the disadvantages of this is, is it applicable for the rest of the world?”

The study will go beyond the BMP2 gene to include the entire human genome for correlations to osteoporosis. But even with research into the genetic components of osteoporosis, identifying a single marker that will help physicians identify likely hip fracture patients may be impossible, he said.

CHICAGO — A nasal spray formulation of the osteoporosis drug, teriparatide, has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of teriparatide nasal spray on 4 subsequent days. Two nasal formulations at two dose levels were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg and formulation No. 2 at 500 mcg and 1,000 mcg. Blood samples were collected up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, the bioavailability of the nasal formulation No. 1 was only about 5%–8% and 12%–15% for the second formulation.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing. “I think the take-home is that contrary to what you might think, the nasal spray in fact doesn't result in markedly greater variability than an injection,” he said.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia following any nasal spray dosing.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced. In a separate poster at the same meeting, cost and side effects were identified as significant barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more.

CHICAGO — A nasal spray formulation of the osteoporosis drug, teriparatide, has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of teriparatide nasal spray on 4 subsequent days. Two nasal formulations at two dose levels were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg and formulation No. 2 at 500 mcg and 1,000 mcg. Blood samples were collected up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, the bioavailability of the nasal formulation No. 1 was only about 5%–8% and 12%–15% for the second formulation.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing. “I think the take-home is that contrary to what you might think, the nasal spray in fact doesn't result in markedly greater variability than an injection,” he said.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia following any nasal spray dosing.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced. In a separate poster at the same meeting, cost and side effects were identified as significant barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more.

CHICAGO — A nasal spray formulation of the osteoporosis drug, teriparatide, has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of teriparatide nasal spray on 4 subsequent days. Two nasal formulations at two dose levels were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg and formulation No. 2 at 500 mcg and 1,000 mcg. Blood samples were collected up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, the bioavailability of the nasal formulation No. 1 was only about 5%–8% and 12%–15% for the second formulation.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing. “I think the take-home is that contrary to what you might think, the nasal spray in fact doesn't result in markedly greater variability than an injection,” he said.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia following any nasal spray dosing.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced. In a separate poster at the same meeting, cost and side effects were identified as significant barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more.

A large, randomized, placebo-controlled trial has confirmed that calcium supplementation in women above the age of 70 can reduce osteoporotic fractures, but the investigators concluded that it would be ineffective as a public health measure since almost half the women were not compliant.

The study's intent-to-treat analysis demonstrated no overall benefit from calcium supplementation of 1,200 mg per day. But when the analysis was restricted to women who took at least 80% of their tablets, calcium supplementation resulted in a statistically significant 34% decrease in fracture incidence, compared with placebo, Dr. Richard L. Prince of the University of Western Australia, Nedlands, and his colleagues reported (Arch. Intern. Med. 2006;166:869–75).

This figure corresponds to an absolute risk reduction of 10.2% in the calcium group vs. 15.4% in the placebo group.

The 5-year study involved 1,460 women with an average age of 75 years who were randomized to receive 600 mg calcium carbonate twice per day or an identical placebo.

Investigators collected data on incident osteoporotic fractures, vertebral deformity, dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, peripheral quantitative computed tomography of the distal radius, and adverse events.

A total of 236 individuals (16%) sustained 297 incident osteoporotic fractures. After adjustment for age, body mass index, and prevalent baseline fractures, the intent-to-treat analysis revealed that calcium supplementation did not significantly reduce fracture risk.

Medication compliance was checked by counting returned tablets in each 12-month review, and average yearly compliance of less than 80% was classified as noncompliant. By this measure, 630 participants (43%) were noncompliant.

When the analysis was restricted to the 830 participants who were compliant, the investigators demonstrated a reduction in all-site clinical fractures (hazard ratio 0.66), appendicular fractures (hazard ratio 0.65), and upper-limb fractures (hazard ratio 0.44).

The investigators recorded 92,000 adverse events, but only constipation was significantly higher in the calcium group (13%), compared with the placebo group (9%).

The investigators concluded that individuals who are compliant, especially if they are under the care of a clinician, can benefit from calcium supplementation. However, they also concluded, “These data should give pause to those who consider that public health policy in this area should be based on epidemiological or surrogate end point data.”

A large, randomized, placebo-controlled trial has confirmed that calcium supplementation in women above the age of 70 can reduce osteoporotic fractures, but the investigators concluded that it would be ineffective as a public health measure since almost half the women were not compliant.

The study's intent-to-treat analysis demonstrated no overall benefit from calcium supplementation of 1,200 mg per day. But when the analysis was restricted to women who took at least 80% of their tablets, calcium supplementation resulted in a statistically significant 34% decrease in fracture incidence, compared with placebo, Dr. Richard L. Prince of the University of Western Australia, Nedlands, and his colleagues reported (Arch. Intern. Med. 2006;166:869–75).

This figure corresponds to an absolute risk reduction of 10.2% in the calcium group vs. 15.4% in the placebo group.

The 5-year study involved 1,460 women with an average age of 75 years who were randomized to receive 600 mg calcium carbonate twice per day or an identical placebo.

Investigators collected data on incident osteoporotic fractures, vertebral deformity, dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, peripheral quantitative computed tomography of the distal radius, and adverse events.

A total of 236 individuals (16%) sustained 297 incident osteoporotic fractures. After adjustment for age, body mass index, and prevalent baseline fractures, the intent-to-treat analysis revealed that calcium supplementation did not significantly reduce fracture risk.

Medication compliance was checked by counting returned tablets in each 12-month review, and average yearly compliance of less than 80% was classified as noncompliant. By this measure, 630 participants (43%) were noncompliant.

When the analysis was restricted to the 830 participants who were compliant, the investigators demonstrated a reduction in all-site clinical fractures (hazard ratio 0.66), appendicular fractures (hazard ratio 0.65), and upper-limb fractures (hazard ratio 0.44).

The investigators recorded 92,000 adverse events, but only constipation was significantly higher in the calcium group (13%), compared with the placebo group (9%).

The investigators concluded that individuals who are compliant, especially if they are under the care of a clinician, can benefit from calcium supplementation. However, they also concluded, “These data should give pause to those who consider that public health policy in this area should be based on epidemiological or surrogate end point data.”

A large, randomized, placebo-controlled trial has confirmed that calcium supplementation in women above the age of 70 can reduce osteoporotic fractures, but the investigators concluded that it would be ineffective as a public health measure since almost half the women were not compliant.

The study's intent-to-treat analysis demonstrated no overall benefit from calcium supplementation of 1,200 mg per day. But when the analysis was restricted to women who took at least 80% of their tablets, calcium supplementation resulted in a statistically significant 34% decrease in fracture incidence, compared with placebo, Dr. Richard L. Prince of the University of Western Australia, Nedlands, and his colleagues reported (Arch. Intern. Med. 2006;166:869–75).

This figure corresponds to an absolute risk reduction of 10.2% in the calcium group vs. 15.4% in the placebo group.

The 5-year study involved 1,460 women with an average age of 75 years who were randomized to receive 600 mg calcium carbonate twice per day or an identical placebo.

Investigators collected data on incident osteoporotic fractures, vertebral deformity, dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, peripheral quantitative computed tomography of the distal radius, and adverse events.

A total of 236 individuals (16%) sustained 297 incident osteoporotic fractures. After adjustment for age, body mass index, and prevalent baseline fractures, the intent-to-treat analysis revealed that calcium supplementation did not significantly reduce fracture risk.

Medication compliance was checked by counting returned tablets in each 12-month review, and average yearly compliance of less than 80% was classified as noncompliant. By this measure, 630 participants (43%) were noncompliant.

When the analysis was restricted to the 830 participants who were compliant, the investigators demonstrated a reduction in all-site clinical fractures (hazard ratio 0.66), appendicular fractures (hazard ratio 0.65), and upper-limb fractures (hazard ratio 0.44).

The investigators recorded 92,000 adverse events, but only constipation was significantly higher in the calcium group (13%), compared with the placebo group (9%).

The investigators concluded that individuals who are compliant, especially if they are under the care of a clinician, can benefit from calcium supplementation. However, they also concluded, “These data should give pause to those who consider that public health policy in this area should be based on epidemiological or surrogate end point data.”

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

DESTIN, FLA. — Patients with rheumatic disease and osteoporosis or low-impact fracture might benefit from early sequential therapy with anabolic and antiresorptive drugs to build and maintain bone, Dr. Nancy Lane reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

“Although the exact treatment recommendation is still unclear, you could use parathyroid hormone for a year or two to change the bone architecture in a positive way and then maintain those gains with an antiresorptive agent—either a bisphosphonate or a selective estrogen receptor modulator,” Dr. Lane said.

The continuous inflammation of diseases like systemic lupus erythematosus and rheumatoid arthritis appears to adversely affect bone health by increasing bone resorption and decreasing formation. Even premenopausal patients with relatively normal bone density are at high risk for skeletal problems, said Dr. Lane, director, the Center for Healthy Aging at the University of California, Davis.

In a study of vertebral fractures in 70 patients with systemic lupus erythematosus who were compared with 22 matched healthy controls, no bone mineral density differences were found between the two groups. However, 21% of the lupus group had at least one thoracic or lumbar spine fracture, compared with no subjects in the control group. The study included premenopausal women with a mean age of 31.5 years (Lupus 2005;14:529–33).

The first step is to address the problem of systemic inflammation, Dr. Lane said. But it's also critical to be aggressive in identifying and treating those who are at risk for fracture. Glucocorticoid therapy can also induce osteoporotic changes. Initiating therapy early is important, Dr Lane said at the meeting, also sponsored by the International Society for Clinical Densitometry and the Alabama Chapter of the Arthritis Foundation.

DESTIN, FLA. — Patients with rheumatic disease and osteoporosis or low-impact fracture might benefit from early sequential therapy with anabolic and antiresorptive drugs to build and maintain bone, Dr. Nancy Lane reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

“Although the exact treatment recommendation is still unclear, you could use parathyroid hormone for a year or two to change the bone architecture in a positive way and then maintain those gains with an antiresorptive agent—either a bisphosphonate or a selective estrogen receptor modulator,” Dr. Lane said.

The continuous inflammation of diseases like systemic lupus erythematosus and rheumatoid arthritis appears to adversely affect bone health by increasing bone resorption and decreasing formation. Even premenopausal patients with relatively normal bone density are at high risk for skeletal problems, said Dr. Lane, director, the Center for Healthy Aging at the University of California, Davis.

In a study of vertebral fractures in 70 patients with systemic lupus erythematosus who were compared with 22 matched healthy controls, no bone mineral density differences were found between the two groups. However, 21% of the lupus group had at least one thoracic or lumbar spine fracture, compared with no subjects in the control group. The study included premenopausal women with a mean age of 31.5 years (Lupus 2005;14:529–33).

The first step is to address the problem of systemic inflammation, Dr. Lane said. But it's also critical to be aggressive in identifying and treating those who are at risk for fracture. Glucocorticoid therapy can also induce osteoporotic changes. Initiating therapy early is important, Dr Lane said at the meeting, also sponsored by the International Society for Clinical Densitometry and the Alabama Chapter of the Arthritis Foundation.

DESTIN, FLA. — Patients with rheumatic disease and osteoporosis or low-impact fracture might benefit from early sequential therapy with anabolic and antiresorptive drugs to build and maintain bone, Dr. Nancy Lane reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

“Although the exact treatment recommendation is still unclear, you could use parathyroid hormone for a year or two to change the bone architecture in a positive way and then maintain those gains with an antiresorptive agent—either a bisphosphonate or a selective estrogen receptor modulator,” Dr. Lane said.

The continuous inflammation of diseases like systemic lupus erythematosus and rheumatoid arthritis appears to adversely affect bone health by increasing bone resorption and decreasing formation. Even premenopausal patients with relatively normal bone density are at high risk for skeletal problems, said Dr. Lane, director, the Center for Healthy Aging at the University of California, Davis.

In a study of vertebral fractures in 70 patients with systemic lupus erythematosus who were compared with 22 matched healthy controls, no bone mineral density differences were found between the two groups. However, 21% of the lupus group had at least one thoracic or lumbar spine fracture, compared with no subjects in the control group. The study included premenopausal women with a mean age of 31.5 years (Lupus 2005;14:529–33).

The first step is to address the problem of systemic inflammation, Dr. Lane said. But it's also critical to be aggressive in identifying and treating those who are at risk for fracture. Glucocorticoid therapy can also induce osteoporotic changes. Initiating therapy early is important, Dr Lane said at the meeting, also sponsored by the International Society for Clinical Densitometry and the Alabama Chapter of the Arthritis Foundation.

TORONTO — Risk factors for fractures in later life are already present in middle age, and their early identification can provide a window of opportunity for intervention, Dr. Anna H. Holmberg said at a world congress on osteoporosis.

Diabetes and mental health problems were among the factors found to be predictive of an increased likelihood of later-life fractures in the Malmö Preventive Project, which was a prospective study that followed 22,444 men and 10,902 women from 1974 through 1999. The primary focus of the project was cardiovascular health, but the investigators also collected data on all low-energy, or fragility, fractures as well as fractures of the forearm, vertebrae, proximal humerus, and ankle, said Dr. Holmberg of the department of orthopedics, Malmö (Sweden) University Hospital.

During follow-up, which averaged 19 years for men and 15 years for women, 1,262 men (5.6%) had 1,975 low-energy fractures, while 1,257 women (11.5%) had 1,805 low-energy fractures.

Among men, the risk factor with the highest impact on later fragility fracture was diabetes, with a relative risk (RR) of 2.38. Other strong risk factors among men were prior hospitalization for mental health problems (RR 1.92), poor appetite (RR 1.72), sleep disturbances (RR 1.53), and poor self-rated health (RR 1.25).

An indirect measure of alcohol consumption, serum γ-glutamyl transferase level, also was associated with an increased fracture risk in men at all sites except the forearm. High body mass index in men was protective against fractures in general (RR 0.88), Dr. Holmberg said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Diabetes also was a strong risk factor for fractures in general among women (RR 1.87), and specifically was a significant risk factor for vertebral, ankle, and hip fractures. Previous fracture also was a risk factor for fracture in general (RR 2.00), and for all fracture types except that of the proximal humerus. Hormone therapy decreased fracture risk by 30%, she noted.

TORONTO — Risk factors for fractures in later life are already present in middle age, and their early identification can provide a window of opportunity for intervention, Dr. Anna H. Holmberg said at a world congress on osteoporosis.

Diabetes and mental health problems were among the factors found to be predictive of an increased likelihood of later-life fractures in the Malmö Preventive Project, which was a prospective study that followed 22,444 men and 10,902 women from 1974 through 1999. The primary focus of the project was cardiovascular health, but the investigators also collected data on all low-energy, or fragility, fractures as well as fractures of the forearm, vertebrae, proximal humerus, and ankle, said Dr. Holmberg of the department of orthopedics, Malmö (Sweden) University Hospital.

During follow-up, which averaged 19 years for men and 15 years for women, 1,262 men (5.6%) had 1,975 low-energy fractures, while 1,257 women (11.5%) had 1,805 low-energy fractures.

Among men, the risk factor with the highest impact on later fragility fracture was diabetes, with a relative risk (RR) of 2.38. Other strong risk factors among men were prior hospitalization for mental health problems (RR 1.92), poor appetite (RR 1.72), sleep disturbances (RR 1.53), and poor self-rated health (RR 1.25).

An indirect measure of alcohol consumption, serum γ-glutamyl transferase level, also was associated with an increased fracture risk in men at all sites except the forearm. High body mass index in men was protective against fractures in general (RR 0.88), Dr. Holmberg said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Diabetes also was a strong risk factor for fractures in general among women (RR 1.87), and specifically was a significant risk factor for vertebral, ankle, and hip fractures. Previous fracture also was a risk factor for fracture in general (RR 2.00), and for all fracture types except that of the proximal humerus. Hormone therapy decreased fracture risk by 30%, she noted.

TORONTO — Risk factors for fractures in later life are already present in middle age, and their early identification can provide a window of opportunity for intervention, Dr. Anna H. Holmberg said at a world congress on osteoporosis.

Diabetes and mental health problems were among the factors found to be predictive of an increased likelihood of later-life fractures in the Malmö Preventive Project, which was a prospective study that followed 22,444 men and 10,902 women from 1974 through 1999. The primary focus of the project was cardiovascular health, but the investigators also collected data on all low-energy, or fragility, fractures as well as fractures of the forearm, vertebrae, proximal humerus, and ankle, said Dr. Holmberg of the department of orthopedics, Malmö (Sweden) University Hospital.

During follow-up, which averaged 19 years for men and 15 years for women, 1,262 men (5.6%) had 1,975 low-energy fractures, while 1,257 women (11.5%) had 1,805 low-energy fractures.

Among men, the risk factor with the highest impact on later fragility fracture was diabetes, with a relative risk (RR) of 2.38. Other strong risk factors among men were prior hospitalization for mental health problems (RR 1.92), poor appetite (RR 1.72), sleep disturbances (RR 1.53), and poor self-rated health (RR 1.25).

An indirect measure of alcohol consumption, serum γ-glutamyl transferase level, also was associated with an increased fracture risk in men at all sites except the forearm. High body mass index in men was protective against fractures in general (RR 0.88), Dr. Holmberg said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Diabetes also was a strong risk factor for fractures in general among women (RR 1.87), and specifically was a significant risk factor for vertebral, ankle, and hip fractures. Previous fracture also was a risk factor for fracture in general (RR 2.00), and for all fracture types except that of the proximal humerus. Hormone therapy decreased fracture risk by 30%, she noted.

GLASGOW, SCOTLAND — Chemotherapy for lymphoma should be recognized as a risk factor for the development of osteoporosis, Dr. Bhaskar Dasgupta reported in a poster session at the annual meeting of the British Society for Rheumatology.

Patients with lymphoma have greatly improved survival rates because of advances in treatment, but their quality of life may be compromised by long-term complications of chemotherapy, reported Dr. Dasgupta, director of rheumatology, Southend Hospital NHS Trust, Westcliff on Sea, England. Osteoporosis is one such potential complication that can result from treatment with alkylating agents and the steroids that are often given with chemotherapy.

Height loss as a surrogate marker for vertebral osteoporosis was evaluated in a study of patients attending a lymphoma clinic. A total of 25 patients, 8 with Hodgkin's and 17 with non-Hodgkin's lymphoma, were enrolled. Mean age was 57.6 years, and 13 of the patients were female, reported Dr. Dasgupta.

Exclusion criteria included a previous osteoporosis diagnosis, lymphoma with spinal involvement, and previous corticosteroid treatment.

When baseline height was compared with height 24 months or more after chemotherapy, the mean loss was found to be 22.8 mm, according to Dr. Dasgupta.

The degree of height loss increased with age—every 10-year increase in age was associated with a 5.2-mm decrease in height, he reported. No association was seen between height loss and gender, and none of the patients had other risk factors for osteoporosis, according to questionnaires they had filled out.

Case notes were examined for cumulative steroid dose and the type of chemotherapy received, with no height loss association found. Patients whose height loss exceeded 40 mm were more likely to be symptomatic. Two patients whose height loss was 50 mm or more reported disabling back pain and poor quality of life.

Despite the fact that significant height loss was seen in this group of patients, none had received bisphosphonates or vitamin D, and only one patient was taking a calcium supplement, Dr. Dasgupta noted. Also, none of the patients had had a bone mineral density determination.

“Our findings suggest that larger studies of osteoporosis and its complications following chemo-therapy are needed, and that appropriate investigations and prophylactic management are indicated, especially in the elderly,” Dr. Dasgupta concluded.

GLASGOW, SCOTLAND — Chemotherapy for lymphoma should be recognized as a risk factor for the development of osteoporosis, Dr. Bhaskar Dasgupta reported in a poster session at the annual meeting of the British Society for Rheumatology.

Patients with lymphoma have greatly improved survival rates because of advances in treatment, but their quality of life may be compromised by long-term complications of chemotherapy, reported Dr. Dasgupta, director of rheumatology, Southend Hospital NHS Trust, Westcliff on Sea, England. Osteoporosis is one such potential complication that can result from treatment with alkylating agents and the steroids that are often given with chemotherapy.

Height loss as a surrogate marker for vertebral osteoporosis was evaluated in a study of patients attending a lymphoma clinic. A total of 25 patients, 8 with Hodgkin's and 17 with non-Hodgkin's lymphoma, were enrolled. Mean age was 57.6 years, and 13 of the patients were female, reported Dr. Dasgupta.

Exclusion criteria included a previous osteoporosis diagnosis, lymphoma with spinal involvement, and previous corticosteroid treatment.

When baseline height was compared with height 24 months or more after chemotherapy, the mean loss was found to be 22.8 mm, according to Dr. Dasgupta.

The degree of height loss increased with age—every 10-year increase in age was associated with a 5.2-mm decrease in height, he reported. No association was seen between height loss and gender, and none of the patients had other risk factors for osteoporosis, according to questionnaires they had filled out.

Case notes were examined for cumulative steroid dose and the type of chemotherapy received, with no height loss association found. Patients whose height loss exceeded 40 mm were more likely to be symptomatic. Two patients whose height loss was 50 mm or more reported disabling back pain and poor quality of life.

Despite the fact that significant height loss was seen in this group of patients, none had received bisphosphonates or vitamin D, and only one patient was taking a calcium supplement, Dr. Dasgupta noted. Also, none of the patients had had a bone mineral density determination.

“Our findings suggest that larger studies of osteoporosis and its complications following chemo-therapy are needed, and that appropriate investigations and prophylactic management are indicated, especially in the elderly,” Dr. Dasgupta concluded.

GLASGOW, SCOTLAND — Chemotherapy for lymphoma should be recognized as a risk factor for the development of osteoporosis, Dr. Bhaskar Dasgupta reported in a poster session at the annual meeting of the British Society for Rheumatology.

Patients with lymphoma have greatly improved survival rates because of advances in treatment, but their quality of life may be compromised by long-term complications of chemotherapy, reported Dr. Dasgupta, director of rheumatology, Southend Hospital NHS Trust, Westcliff on Sea, England. Osteoporosis is one such potential complication that can result from treatment with alkylating agents and the steroids that are often given with chemotherapy.

Height loss as a surrogate marker for vertebral osteoporosis was evaluated in a study of patients attending a lymphoma clinic. A total of 25 patients, 8 with Hodgkin's and 17 with non-Hodgkin's lymphoma, were enrolled. Mean age was 57.6 years, and 13 of the patients were female, reported Dr. Dasgupta.

Exclusion criteria included a previous osteoporosis diagnosis, lymphoma with spinal involvement, and previous corticosteroid treatment.

When baseline height was compared with height 24 months or more after chemotherapy, the mean loss was found to be 22.8 mm, according to Dr. Dasgupta.

The degree of height loss increased with age—every 10-year increase in age was associated with a 5.2-mm decrease in height, he reported. No association was seen between height loss and gender, and none of the patients had other risk factors for osteoporosis, according to questionnaires they had filled out.

Case notes were examined for cumulative steroid dose and the type of chemotherapy received, with no height loss association found. Patients whose height loss exceeded 40 mm were more likely to be symptomatic. Two patients whose height loss was 50 mm or more reported disabling back pain and poor quality of life.

Despite the fact that significant height loss was seen in this group of patients, none had received bisphosphonates or vitamin D, and only one patient was taking a calcium supplement, Dr. Dasgupta noted. Also, none of the patients had had a bone mineral density determination.

“Our findings suggest that larger studies of osteoporosis and its complications following chemo-therapy are needed, and that appropriate investigations and prophylactic management are indicated, especially in the elderly,” Dr. Dasgupta concluded.

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been demonstrated in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol/bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% versus 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days following the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been demonstrated in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol/bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% versus 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days following the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been demonstrated in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol/bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% versus 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days following the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

ATLANTA — Vitamin D supplementation should be considered for postmenopausal breast cancer patients treated with aromatase inhibitors, Dr. Per E. Lønning reported at the annual meeting of the American Society of Clinical Oncology.

“Low vitamin D status could be one of the factors predisposing patients to breast cancer,” said Dr. Lønning, a professor at Haukeland University in Bergen, Norway.

Postmenopausal breast cancer patients who were treated with exemestane and had vitamin D deficiency lost bone mineral density (BMD) at a higher rate than all other patients in a Norwegian trial, according to Dr. Lønning, who presented the trial's results.

The double-blind study enrolled early breast cancer patients at six sites between January 1999 and October 2001. Participants were postmenopausal with estrogen receptor-negative or progesterone receptor-positive breast cancer. Median patient age was 59.5 years, and all had a low risk of breast cancer recurrence after surgery.

Of the patients enrolled in the randomized, controlled trial, 128 of 147 (87%) had low levels of vitamin D, defined as 30 ng/mL or less.

Investigators randomized 73 women to 25 mg of oral exemestane daily and 74 women to a daily placebo for 2 years. Local guidelines did not routinely offer adjuvant endocrine therapy at the time of the study, the investigators noted. Mean vitamin D levels were reported as 21.6 ng/mL for the exemestane arm and 22.6 ng/mL for the control group.

Average patient change in femoral neck BMD was −4.7% after 2 years of treatment with exemestane, an aromatase inhibitor. Placebo patients with low vitamin D also had bone loss in the femoral neck, but the reduction was −3.0%.

Women with normal vitamin D levels had similar outcomes whether they were treated with exemestane or placebo: reductions of −3.7% and −3.3%, respectively.

“It has not fully been examined that breast cancer patients on average have a poorer vitamin D status in comparison to the normal population in general,” he added, calling for further investigation of the relationship between vitamin D and breast cancer.

An annual BMD loss of 0.5% is normal for postmenopausal women, according to Dr. Lønning and his fellow investigators from the Norwegian Breast Cancer Screening Program. Interviewed during the poster session where he presented trial data, he said low vitamin D levels could be expected in about 50% of postmenopausal women in Norway.

However, he warned against assuming that low vitamin D levels are entirely explained by reduced sun exposure in northern latitudes, because people in other climates are spending more time indoors and out of the sun.

“You should not think of this as a preventive problem only in the far north,” he said. “This could be a problem to populations all over the world.”

While the investigators reported some significant differences in subgroups and “a trend toward higher loss of BMD in the femoral neck” among women with low vitamin D during the 2 years of exemestane treatment, low vitamin D did not appear to make as much of a difference in lumbar spine BMD.

The reductions were −3.4% for 52 vitamin D-deficient women who completed the study on exemestane and −2.5% for 59 women who stayed on placebo.

“Vitamin D has influence on compact bone, not trabecular bone,” Dr. Lønning said. “When you look at the low toxicity of vitamin D, you are not running much risk with supplementation,” he said. “However, I have to say for research purposes, we need more data.”

'Low vitamin D status could be one of the factors predisposing patients to breast cancer.' DR. LØNNING

LOS ANGELES — A prediction rule combining five easily obtainable risk factors distinguishes with high sensitivity women at high risk of developing osteoporotic fractures within the next 3 years, Dr. Idris Guessous reported at the annual meeting of the Society of General Internal Medicine.

The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study was a 3-year, prospective, multicenter study (n = 623) that computed a prediction score using low heel ultrasound stiffness index (SI), older age, fracture history, recent fall, and missed chair test to predict subsequent development of osteoporotic hip fractures and other nonvertebral fractures.

The objective of the study was to compute a prediction rule to identify women at high risk of osteoporotic fracture in general, or a hip fracture in particular, within the next 3 years, said Dr. Guessous of the University Hospital of Lausanne, Switzerland.

The heel bone ultrasonometer (Lunar Corp., Madison, Wisc.) was chosen because it is simple, inexpensive, noninvasive, and transportable. Of 7,114 Swiss women who responded to a mailed request to participate, 6,174 women between 70 and 85 years old were enrolled. Exclusion criteria included previous hip fracture, bilateral hip replacement, renal failure, active cancer, and dementia. The investigators calculated the bone SI using quantitative ultrasound of the heel, broadband ultrasound attenuation, and the speed of sound as the input parameters. The SI is expressed as a percentage of the values obtained by the manufacturer in a young adult population. Osteoporotic fractures were defined as hip, wrist, or arm breaks that occurred spontaneously or secondary to falling from standing height or lower despite a low level of trauma.

The investigators included baseline characteristics (age, weight, height, body mass index), known risk factors for osteoporosis (fracture history, history of maternal hip fracture, current smoking habits, early menopause, surgical menopause), fall (history of recent fall, missed chair test), and SI as parameters to develop a score that would predict risk of osteoporotic fracture. The investigators then used bootstrap methods to evaluate the stability of the score, Dr. Guessous said.

Mean follow-up was 2.8 years (17,546 person-years). Five risk factors were independent, significant predictors of the incidence of osteoporotic fractures: age older than 75, SI greater than 78%, history of any prior fracture, history of a fall during the last 12 months, and missed chair test (not being able to rise from a chair three successive times without using one's arms).

The investigators assigned a score to each of the five significant predictors: age, up to 3; SI, up to 7.5; history of fall within past 12 months, 1.5; fracture history, 1; and positive chair test, 1. Thus, the maximum prediction score is 14 points. The cutoff score to discriminate women at high risk of fracture with 90% sensitivity is 4.5. With this cutoff, 1,464 women (23.7%) were considered at low risk of hip fracture (score less than 4.5), and 4,710 (76.3%) were considered at high risk (score at least 4.5).

Among these high risk women, 60 (1.3%) experienced an osteoporotic hip fracture. In contrast, 6 (0.4%) of the low-risk women experienced such a fracture.

The main limitation of this predictor rule is that at a sensitivity of 90%, the specificity was only 24%. Ideally, a predictor rule should have high specificity as well. In addition, women aged older than 85 years were not included, but there are few data showing that very elderly women benefit from osteoporosis treatment, Dr. Guessous said.

LOS ANGELES — A prediction rule combining five easily obtainable risk factors distinguishes with high sensitivity women at high risk of developing osteoporotic fractures within the next 3 years, Dr. Idris Guessous reported at the annual meeting of the Society of General Internal Medicine.

The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study was a 3-year, prospective, multicenter study (n = 623) that computed a prediction score using low heel ultrasound stiffness index (SI), older age, fracture history, recent fall, and missed chair test to predict subsequent development of osteoporotic hip fractures and other nonvertebral fractures.

The objective of the study was to compute a prediction rule to identify women at high risk of osteoporotic fracture in general, or a hip fracture in particular, within the next 3 years, said Dr. Guessous of the University Hospital of Lausanne, Switzerland.

The heel bone ultrasonometer (Lunar Corp., Madison, Wisc.) was chosen because it is simple, inexpensive, noninvasive, and transportable. Of 7,114 Swiss women who responded to a mailed request to participate, 6,174 women between 70 and 85 years old were enrolled. Exclusion criteria included previous hip fracture, bilateral hip replacement, renal failure, active cancer, and dementia. The investigators calculated the bone SI using quantitative ultrasound of the heel, broadband ultrasound attenuation, and the speed of sound as the input parameters. The SI is expressed as a percentage of the values obtained by the manufacturer in a young adult population. Osteoporotic fractures were defined as hip, wrist, or arm breaks that occurred spontaneously or secondary to falling from standing height or lower despite a low level of trauma.

The investigators included baseline characteristics (age, weight, height, body mass index), known risk factors for osteoporosis (fracture history, history of maternal hip fracture, current smoking habits, early menopause, surgical menopause), fall (history of recent fall, missed chair test), and SI as parameters to develop a score that would predict risk of osteoporotic fracture. The investigators then used bootstrap methods to evaluate the stability of the score, Dr. Guessous said.

Mean follow-up was 2.8 years (17,546 person-years). Five risk factors were independent, significant predictors of the incidence of osteoporotic fractures: age older than 75, SI greater than 78%, history of any prior fracture, history of a fall during the last 12 months, and missed chair test (not being able to rise from a chair three successive times without using one's arms).

The investigators assigned a score to each of the five significant predictors: age, up to 3; SI, up to 7.5; history of fall within past 12 months, 1.5; fracture history, 1; and positive chair test, 1. Thus, the maximum prediction score is 14 points. The cutoff score to discriminate women at high risk of fracture with 90% sensitivity is 4.5. With this cutoff, 1,464 women (23.7%) were considered at low risk of hip fracture (score less than 4.5), and 4,710 (76.3%) were considered at high risk (score at least 4.5).

Among these high risk women, 60 (1.3%) experienced an osteoporotic hip fracture. In contrast, 6 (0.4%) of the low-risk women experienced such a fracture.

The main limitation of this predictor rule is that at a sensitivity of 90%, the specificity was only 24%. Ideally, a predictor rule should have high specificity as well. In addition, women aged older than 85 years were not included, but there are few data showing that very elderly women benefit from osteoporosis treatment, Dr. Guessous said.

LOS ANGELES — A prediction rule combining five easily obtainable risk factors distinguishes with high sensitivity women at high risk of developing osteoporotic fractures within the next 3 years, Dr. Idris Guessous reported at the annual meeting of the Society of General Internal Medicine.

The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study was a 3-year, prospective, multicenter study (n = 623) that computed a prediction score using low heel ultrasound stiffness index (SI), older age, fracture history, recent fall, and missed chair test to predict subsequent development of osteoporotic hip fractures and other nonvertebral fractures.

The objective of the study was to compute a prediction rule to identify women at high risk of osteoporotic fracture in general, or a hip fracture in particular, within the next 3 years, said Dr. Guessous of the University Hospital of Lausanne, Switzerland.

The heel bone ultrasonometer (Lunar Corp., Madison, Wisc.) was chosen because it is simple, inexpensive, noninvasive, and transportable. Of 7,114 Swiss women who responded to a mailed request to participate, 6,174 women between 70 and 85 years old were enrolled. Exclusion criteria included previous hip fracture, bilateral hip replacement, renal failure, active cancer, and dementia. The investigators calculated the bone SI using quantitative ultrasound of the heel, broadband ultrasound attenuation, and the speed of sound as the input parameters. The SI is expressed as a percentage of the values obtained by the manufacturer in a young adult population. Osteoporotic fractures were defined as hip, wrist, or arm breaks that occurred spontaneously or secondary to falling from standing height or lower despite a low level of trauma.

The investigators included baseline characteristics (age, weight, height, body mass index), known risk factors for osteoporosis (fracture history, history of maternal hip fracture, current smoking habits, early menopause, surgical menopause), fall (history of recent fall, missed chair test), and SI as parameters to develop a score that would predict risk of osteoporotic fracture. The investigators then used bootstrap methods to evaluate the stability of the score, Dr. Guessous said.

Mean follow-up was 2.8 years (17,546 person-years). Five risk factors were independent, significant predictors of the incidence of osteoporotic fractures: age older than 75, SI greater than 78%, history of any prior fracture, history of a fall during the last 12 months, and missed chair test (not being able to rise from a chair three successive times without using one's arms).

The investigators assigned a score to each of the five significant predictors: age, up to 3; SI, up to 7.5; history of fall within past 12 months, 1.5; fracture history, 1; and positive chair test, 1. Thus, the maximum prediction score is 14 points. The cutoff score to discriminate women at high risk of fracture with 90% sensitivity is 4.5. With this cutoff, 1,464 women (23.7%) were considered at low risk of hip fracture (score less than 4.5), and 4,710 (76.3%) were considered at high risk (score at least 4.5).

Among these high risk women, 60 (1.3%) experienced an osteoporotic hip fracture. In contrast, 6 (0.4%) of the low-risk women experienced such a fracture.

The main limitation of this predictor rule is that at a sensitivity of 90%, the specificity was only 24%. Ideally, a predictor rule should have high specificity as well. In addition, women aged older than 85 years were not included, but there are few data showing that very elderly women benefit from osteoporosis treatment, Dr. Guessous said.