Clinician Reviews

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

SAN DIEGO — The investigative oral Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib shows promise in patients with moderate to severe hidradenitis suppurativa (HS), results from a randomized 16-week phase 2 trial showed.

“Research shows that the TNF-alpha and IL-17 signaling pathways have important roles in HS,” lead investigator Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center, Boston, said at the annual meeting of the American Academy of Dermatology. “However, several additional pathways are thought to contribute to disease pathogenesis.”

“We will see if phase 3 trials with more balanced demographics across remibrutinib and placebo arms will reproduce these outcomes,” she continued, “It is exciting to see this potential new medication for HS under continued investigation, especially in light of the current gap in oral therapeutic options for the HS patient community.” Dr. Hsiao was not involved with the study.

Dr. Kimball disclosed numerous conflicts of interest from various pharmaceutical companies, including the receipt of research grants and consulting fees from Novartis. Dr. Hsiao disclosed that she is a member of the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

The results of a recent study suggest that biologics and small molecule inhibitors (SMIs) do not impair the protective effect of COVID-19 vaccine against hospitalization in patients with psoriasis and hidradenitis suppurativa (HS).

METHODOLOGY:

• It remains unknown whether immunomodulatory therapies impair COVID-19 vaccine efficacy and increase hospitalization rates linked to COVID-19 in patients with inflammatory skin conditions such as psoriasis or HS.
• Researchers conducted a cross-sectional study using data from the Epic Cosmos database from January 2020 to October 2023, identifying 30,845 patients with psoriasis or HS.
• Overall, 22,293 patients with documented completion of their primary COVID-19 vaccine series were included in the analysis.
• Of the vaccinated patients, they compared 7046 patients with psoriasis on SMIs and 2033 with psoriasis or HS on biologics with 13,214 patients who did not receive biologics or SMIs.
• The primary outcome was the COVID-19 hospitalization rate.
• Treatment with biologics did not increase COVID-19-related hospitalization rates in vaccinated patients with psoriasis or HS (hospitalization rate, 6.0% for both those taking and those not taking a biologic; P > .99).
• Similarly, hospitalization rates did not significantly differ between vaccinated patients who received SMIs vs those who did not (7.1% vs 6.0%; P = .0596).

IN PRACTICE:

These findings “encourage dermatologists to continue treating [psoriasis]/HS confidently despite the ongoing COVID-19 pandemic,” the authors concluded.

SOURCE:

The study led by Bella R. Lee from Ohio State University Wexner Medical Center, Columbus, was published online on March 13, 2024, in the Journal of the American Academy of Dermatology. 

LIMITATIONS:

Multivariable adjustments could not be performed in this study due to unavailability of individual-level data, and hospital admissions that occurred outside the Epic system were not captured.

DISCLOSURES:

The study did not receive any funding. All authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

The risk for type 2 diabetes (T2D) was higher in individuals who followed a pro-inflammatory diet and had a high habitual salt intake than in those who followed an anti-inflammatory diet and used less salt.

METHODOLOGY:

• High scores on the dietary inflammatory index (DII) — a scoring system that measures the inflammatory potential of an individual’s diet — and high salt intake are associated with increased cardiovascular disease risk; however, studies investigating the association between DII and salt intake with incident T2D risk are scarce.
• Researchers investigated the association between a pro-inflammatory diet, habitual salt intake, and the risk for T2D among 171,094 participants from the UK Biobank (mean age, 55.98 years; 40.7% men).
• Participants were free of diabetes at baseline, had completed at least one dietary recall questionnaire, and were followed up for a median period of 13.5 years.
• The energy-adjusted DII was calculated on the basis of 28 food and nutrient parameter-specific scores, while habitual salt intake was assessed through self-reported frequency of adding salt to foods.
• Any newly diagnosed cases of T2D were considered the first occurrences of health outcomes.

TAKEAWAY:

• Incident cases of T2D were reported in 6216 individuals over the median follow-up period.
• The risk of developing T2D was 18% higher in individuals who followed a pro-inflammatory vs anti-inflammatory diet (adjusted hazard ratio [HR], 1.18; 95% CI, 1.11-1.25); the risk for T2D was elevated by 4% for each one-point increment in the energy-adjusted DII.
• Compared with participants who never or rarely added salt to foods, the risk for T2D increased gradually in those who sometimes (HR, 1.10; 95% CI, 1.04-1.16), usually (HR, 1.14; 95% CI, 1.05-1.24), and always (HR, 1.30; 95% CI, 1.15-1.47) added salt to foods.
• The risk for T2D was the highest in participants who followed a pro-inflammatory diet and always added salt to foods (HR, 1.60; 95% CI, 1.32-1.90) compared with those who followed an anti-inflammatory diet and never or rarely added salt to foods.

IN PRACTICE:

“Our findings indicate that a pro-inflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes,” the authors wrote.

SOURCE:

This study was led by Wenqui Shen, MD, from the Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Data from a 24-hour dietary recall questionnaire were used to calculate the energy-adjusted DII, which might have led to incidences of incorrect reporting. This study could not measure all components of the DII score. Unmeasured variables and residual confounders might also be present, which were not considered in this analysis.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Project of Biobank from the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, and other sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients who undergo surgery for carpal tunnel syndrome (CTS) may have an increased risk of developing incident diabetes, showed a recent study.

METHODOLOGY:

• Diabetes has been shown to be a risk factor for CTS, the most common entrapment neuropathy, but it remains unclear whether CTS is associated with subsequent diabetes.
• Researchers used data from Danish national registries to evaluate the odds of developing diabetes in 83,466 patients (median age, 54 years; 67% women) who underwent surgery for CTS between January 1996 and December 2018.
• The study compared the risk of developing diabetes in patients who had CTS surgery with that of an age- and sex-matched cohort of individuals from the general population in a 1:5 ratio (n = 417,330).
• Patients were followed (median of 7.6 years) until either a diagnosis of diabetes during hospitalization or a prescription of a glucose-lowering drug, or until either death, emigration, or the end of the study period.
• Cause-specific Cox proportional hazard models were used to compare the odds of developing diabetes between the two groups.

TAKEAWAY:

• The cumulative incidence of diabetes was higher in the CTS group than in the age-matched controls (16.8% vs 10.3%).
• Patients who underwent surgery for CTS were at a higher risk of developing diabetes within 1 year of surgery (hazard ratio [HR], 1.72) and during the rest of the study period (> 1 year: HR, 1.66).
• The risk for incident diabetes after CTS surgery was higher among younger patients aged 18-39 years (adjusted HR, 2.77) than among older patients aged 70-79 years (adjusted HR, 1.29).
• Also, patients who had bilateral surgery had a higher risk of developing diabetes than the matched control population (adjusted HR, 1.86).

IN PRACTICE:

“Identifying patients who are at risk of DM [diabetes mellitus] may mediate earlier initiation of preventive strategies. However, other factors, such as obesity and A1c levels, may affect the association,” the authors wrote.

SOURCE:

The study led by Jeppe Ravn Jacobsen, MB, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, was published online in Diabetes, Obesity, and Metabolism .

LIMITATIONS:

The study did not find an association between CTS and a future diagnosis of type 1 diabetes, which may be attributed to the fact that patients younger than 18 years were excluded. A proportion of the patients who underwent CTS may have had undetected prediabetes or diabetes at the time of CTS surgery. Moreover, the registry lacked information on potential confounders such as body mass index, smoking history, and blood samples. The association between CTS and diabetes may be attributable to shared risk factors for both, such as obesity.

DISCLOSURES:

The study was funded by an internal grant from the Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients who undergo surgery for carpal tunnel syndrome (CTS) may have an increased risk of developing incident diabetes, showed a recent study.

METHODOLOGY:

• Diabetes has been shown to be a risk factor for CTS, the most common entrapment neuropathy, but it remains unclear whether CTS is associated with subsequent diabetes.
• Researchers used data from Danish national registries to evaluate the odds of developing diabetes in 83,466 patients (median age, 54 years; 67% women) who underwent surgery for CTS between January 1996 and December 2018.
• The study compared the risk of developing diabetes in patients who had CTS surgery with that of an age- and sex-matched cohort of individuals from the general population in a 1:5 ratio (n = 417,330).
• Patients were followed (median of 7.6 years) until either a diagnosis of diabetes during hospitalization or a prescription of a glucose-lowering drug, or until either death, emigration, or the end of the study period.
• Cause-specific Cox proportional hazard models were used to compare the odds of developing diabetes between the two groups.

TAKEAWAY:

• The cumulative incidence of diabetes was higher in the CTS group than in the age-matched controls (16.8% vs 10.3%).
• Patients who underwent surgery for CTS were at a higher risk of developing diabetes within 1 year of surgery (hazard ratio [HR], 1.72) and during the rest of the study period (> 1 year: HR, 1.66).
• The risk for incident diabetes after CTS surgery was higher among younger patients aged 18-39 years (adjusted HR, 2.77) than among older patients aged 70-79 years (adjusted HR, 1.29).
• Also, patients who had bilateral surgery had a higher risk of developing diabetes than the matched control population (adjusted HR, 1.86).

IN PRACTICE:

“Identifying patients who are at risk of DM [diabetes mellitus] may mediate earlier initiation of preventive strategies. However, other factors, such as obesity and A1c levels, may affect the association,” the authors wrote.

SOURCE:

The study led by Jeppe Ravn Jacobsen, MB, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, was published online in Diabetes, Obesity, and Metabolism .

LIMITATIONS:

The study did not find an association between CTS and a future diagnosis of type 1 diabetes, which may be attributed to the fact that patients younger than 18 years were excluded. A proportion of the patients who underwent CTS may have had undetected prediabetes or diabetes at the time of CTS surgery. Moreover, the registry lacked information on potential confounders such as body mass index, smoking history, and blood samples. The association between CTS and diabetes may be attributable to shared risk factors for both, such as obesity.

DISCLOSURES:

The study was funded by an internal grant from the Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients who undergo surgery for carpal tunnel syndrome (CTS) may have an increased risk of developing incident diabetes, showed a recent study.

METHODOLOGY:

• Diabetes has been shown to be a risk factor for CTS, the most common entrapment neuropathy, but it remains unclear whether CTS is associated with subsequent diabetes.
• Researchers used data from Danish national registries to evaluate the odds of developing diabetes in 83,466 patients (median age, 54 years; 67% women) who underwent surgery for CTS between January 1996 and December 2018.
• The study compared the risk of developing diabetes in patients who had CTS surgery with that of an age- and sex-matched cohort of individuals from the general population in a 1:5 ratio (n = 417,330).
• Patients were followed (median of 7.6 years) until either a diagnosis of diabetes during hospitalization or a prescription of a glucose-lowering drug, or until either death, emigration, or the end of the study period.
• Cause-specific Cox proportional hazard models were used to compare the odds of developing diabetes between the two groups.

TAKEAWAY:

• The cumulative incidence of diabetes was higher in the CTS group than in the age-matched controls (16.8% vs 10.3%).
• Patients who underwent surgery for CTS were at a higher risk of developing diabetes within 1 year of surgery (hazard ratio [HR], 1.72) and during the rest of the study period (> 1 year: HR, 1.66).
• The risk for incident diabetes after CTS surgery was higher among younger patients aged 18-39 years (adjusted HR, 2.77) than among older patients aged 70-79 years (adjusted HR, 1.29).
• Also, patients who had bilateral surgery had a higher risk of developing diabetes than the matched control population (adjusted HR, 1.86).

IN PRACTICE:

“Identifying patients who are at risk of DM [diabetes mellitus] may mediate earlier initiation of preventive strategies. However, other factors, such as obesity and A1c levels, may affect the association,” the authors wrote.

SOURCE:

The study led by Jeppe Ravn Jacobsen, MB, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, was published online in Diabetes, Obesity, and Metabolism .

LIMITATIONS:

The study did not find an association between CTS and a future diagnosis of type 1 diabetes, which may be attributed to the fact that patients younger than 18 years were excluded. A proportion of the patients who underwent CTS may have had undetected prediabetes or diabetes at the time of CTS surgery. Moreover, the registry lacked information on potential confounders such as body mass index, smoking history, and blood samples. The association between CTS and diabetes may be attributable to shared risk factors for both, such as obesity.

DISCLOSURES:

The study was funded by an internal grant from the Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A recent study linking a niacin derivative to an increased risk for cardiovascular events has raised questions about the safety of this B vitamin, which is added to many food staples in the Western diet and taken in the form of supplements.

The findings, which were published in Nature Medicine, may also help explain why taking niacin, which lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol, did not lead to a reduction in cardiovascular events in major clinical trials.

But could this essential micronutrient really have an adverse effect on cardiovascular risk, and what are the implications for niacin intake?

Senior author of the new study Stanley Hazen, MD, believes some prudence on excessive niacin intake may be justified.

“I’m not suggesting we should completely avoid niacin — it is an essential nutrient, but our results suggest that too much may be harmful,” Dr. Hazen said.

Niacin supplements are also sold with claims of antiaging effects, arthritis relief, and boosting brain function, although none of these claims have been proven. And the related compound, nicotinamide, is recommended to prevent skin cancer in high-risk patients; however, a recent study questioned that guidance.

“I would say to the general public that avoiding supplements containing niacin or related compounds could be a sensible approach at present, while these findings are investigated further.”

Other experts are unsure if such action is justified on the basis of this single study.
 

Residual Cardiovascular Risk

Dr. Hazen, who is chair of the Department of Cardiovascular & Metabolic Sciences, at the Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, explained to this news organization that they did not set out to study niacin.

“It began as a study to look for novel pathways involved in residual cardiovascular disease risk — the risk for cardiovascular events after adjusting for traditional risk factors such as cholesterol, blood pressure, and diabetes.”

The researchers began looking for compounds in plasma that predicted future adverse cardiovascular events in individuals undergoing elective diagnostic cardiac evaluation. Two of the leading candidates identified were niacin derivatives — 2PY and 4PY — that are only formed in the presence of excess niacin.

They then developed assays to measure 2PY and 4PY and conducted further studies in two validation cohorts — 2331 US individuals and a European cohort of 832 individuals. In both cohorts, elevated plasma levels of 2PY and 4PY predicted future adverse cardiovascular events, with a doubling in cardiovascular risk seen in those with levels in the highest vs the lowest quartile.

To move beyond these observational studies and to explore a potentially causal relationship, Dr. Hazen’s team went on to perform genome-wide association studies and found that genetic variants that tracked with higher levels of 4PY also linked to levels of the inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1).

And in cell culture and animal studies, they found that 4PY was a driver of inflammation, upregulating VCAM-1 and eliciting vascular inflammation responses.

“So, we have shown in several different ways that the niacin derivative, 4PY, is linked to increased cardiovascular risk,” Dr. Hazen commented.
 

Significant Health Implications?

Dr. Hazen believed these findings could have significant health implications.

He noted that Western populations have been consuming large amounts of niacin ever since World War 2 when we began to fortify many foods with essential vitamins to avoid diseases caused by deficiencies. Niacin was added to foods to prevent pellagra — a disease characterized by inflamed skin, diarrhea, and dementia, that was often fatal.

“While we may have eliminated pellagra, have we, as a consequence, increased the prevalence of cardiovascular disease many years later?” Dr. Hazen asked.

This may be a clue to why niacin does not lower cardiovascular risk as much as would be expected from the degree of cholesterol lowering it brings about. “This is the niacin paradox and has led to the thought that there could be some kind of adverse effect that niacin is promoting. I think we may have found something that contributes to the niacin paradox,” he said.

However, the niacin pathway is complicated. Niacin is the major source of nicotinamide adenine dinucleotide (NAD), an integral molecule that allows cells to create energy. “Because it is so important, our bodies are designed to salvage and retain NADs, but once storage capacity is exceeded, then these 4PY and 2PY derivatives are generated,” Dr. Hazen explained. “But you have to really eat a lot of niacin-rich foods for this to happen.”

He is not claiming that niacin causes cardiovascular disease. “It is 4PY that appears to be the driver of vascular inflammation. And 4PY is a breakdown product of niacin. But there is more than one pathway that could lead to 4PY generation. There is a whole interconnecting network of compounds that interchange with each other — known as the niacin pool — any one or more of these compounds can be ingested and raise pool levels and ultimately 4PY levels. However, by far and away, niacin is one of the major sources,” Dr. Hazen commented.
 

Are High-Protein Diets Also Implicated?

Other sources of NADs include tryptophan, present in protein. And one of the genetic variants linked to changes in 4PY levels is connected to how dietary protein is directed into the niacin pool, raising the possibility that a high-protein diet may also raise cardiovascular risk in some people, Dr. Hazen noted.

Dr. Hazen estimated that about 3% of the niacin pool in a normal diet comes from protein intake, but that the percentage could increase substantially in very high–protein diets.

“Our data support the concept that if we lower our 4PY level long-term, then that would result in a reduction in cardiovascular disease. But this is still just a hypothesis. If we lower niacin intake, we will lower 4PY,” Dr. Hazen stated.

He said that this research is at too early a stage to give firm recommendations in what this means for the consumer.

“Based on these findings, I would advise people to avoid taking niacin or nicotinic acid or nicotinamide supplements and to eat a sensible balanced diet — maybe not to overdo the high protein–type diets. That’s all we can really say at the moment.”

Noting that niacin can also be one of the major components in energy drinks, he suggested it may be prudent to limit consumption of these products.
 

What Is the Optimum Niacin Intake?

Dr. Hazen noted that the recommended dietary allowance (RDA) for niacin is well known — between 14 and 18 mg, but he said the average American ingests four times that amount, and some people have substantially higher intakes — up to 50 times the RDA if taking supplements.

While food fortification with niacin may have been useful in the past, Dr. Hazen questioned whether it should still be mandated.

“In the US, you cannot buy flour or cereal or rice that is not fortified. And if you look closely, some products have much higher levels than those that are mandated. The food companies advertise this as a benefit, but there is no good data in support of that. What if several decades of eating excessive amounts of niacin has led to an increase in cardiovascular disease?”

He does not propose stopping all niacin fortification, “but maybe, we could have the choice of selecting an unfortified option,” he said.
 

Causal Link Not Proven

Commenting for this news organization, John Guyton, MD, Professor Emeritus of Medicine, Duke University Medical Center, Durham, North Carolina, who has been involved in niacin research for many years, said the Nature Medicine study showed “interesting and important results,” but they do not at this point prove a causal link between niacin intake and risk for cardiovascular disease.

“These findings need to be investigated further, and more studies are certainly justified, but I don’t think that this study alone makes an adequate case for restricting niacin intake, or thinking about stopping niacin fortification of foodstuffs,” Dr. Guyton said.

Noting that niacin is present in large quantities in many fast foods, he suggested the researchers may have just picked up the consequences of eating an unhealthy diet.

“If you look at foods that contain high quantities of niacin, red meat is at the top of the list. And if you think of a hamburger, niacin is present in relatively large quantities both the burger and the bun. So, these findings may just be a reflection of an overall unhealthy diet,” he commented.

Dr. Guyton also pointed out that major clinical trials with niacin have shown mixed results, and its effect on cardiovascular risk is still not completely understood. While the HPS2-THRIVE and AIM-HIGH trials did not show benefits in reducing cardiovascular events, an earlier study, the Coronary Drug Project in which the agent was given with food, did show some positive effects with substantial reductions in myocardial infarction and stroke, and there was the suggestion of a reduction in long-term mortality in the niacin group several years after the trial had ended.
 

Nicotinamide in Skin Cancer Prevention

What about the use of nicotinamide in skin cancer prevention?

Addressing this question, Kristin Bibee, MD, assistant professor of dermatology at Johns Hopkins University School of Medicine, Baltimore, pointed out that nicotinamide, although closely related to niacin, may have different effects. “This study does not specifically address nicotinamide supplementation and 4PY levels,” she said.

Diona Damian, MD, professor of dermatology at the University of Sydney, Camperdown, Australia, told this news organization that it was hard to extrapolate these findings on basal levels of niacin in a cardiac cohort to the administration of supra-physiological doses of nicotinamide for skin cancer prevention.

There may be different effects of supplemental niacin compared to nicotinamide, which lacks the vasodilatory effects seen with niacin, Dr. Damian said, adding that it would be interesting to see the results from higher, therapeutic nicotinamide doses in patients with and without cardiac disease.

She pointed out that high vs low levels of nicotinamide supplementation can have different and even opposite effects on cellular processes, such as upregulating or inhibiting DNA repair enzymes. At high doses, nicotinamide is anti-inflammatory in skin.

Dr. Damian noted that two phase 3 studies (ONTRAC and ONTRANS) of nicotinamide 500 mg twice daily for skin cancer prevention did not find a significant increase in cardiovascular events compared to placebo over 12 months.

“Oral nicotinamide has been shown to reduce nonmelanoma skin cancer by about a quarter in patients with normal immunity and multiple skin cancers. The doses used for skin cancer prevention are well above daily dietary levels, and treatment needs to be ongoing for the protective effects to continue. Nicotinamide should not be recommended as a preventive agent for people who have not had multiple skin cancers but should be reserved for those with a heavy burden of skin cancers,” she commented.

“For now, it would be reasonable to balance the benefits of skin cancer reduction against possible effects on inflammatory markers in patients with cardiac risk factors, when helping patients to decide whether or not nicotinamide therapy is appropriate for them,” she added.

Meanwhile, Dr. Hazen said the most exciting part of this new research is the discovery of a new pathway that contributes to cardiovascular disease and potentially a new target to treat residual cardiovascular risk.

“I believe our results show that we should be measuring 4PY levels and individuals with high levels need to be extra vigilant about lowering their cardiovascular risk.”

The next step will be to confirm these results in other populations and then to develop a diagnostic test to identify people with a high 4PY level, he said.

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — After 24 weeks of treatment with subcutaneously administered sonelokimab 120 mg, about 43% of patients with moderate to severe hidradenitis suppurativa (HS) achieved a Hidradenitis Suppurativa Clinical Response (HiSCR75), defined as at least a 75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline, results from a randomized clinical trial showed.

Sonelokimab is a novel humanized nanobody that selectively binds to interleukin (IL)-17A and IL-17F, presenting author Brian Kirby, MD, a dermatologist at St. Vincent’s Private Hospital, Dublin, Ireland, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. Sonelokimab is smaller than traditional monoclonal antibodies, he said, “which means it may be able to penetrate tissues better and stay there longer.” It is being developed by MoonLake Immunotherapeutics, based in Zug, Switzerland

Ted Bosworth/MDedge News

According to a press release from the company, nanobodies represent a new generation of targeted therapies derived from antibodies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies.

In a phase 2 study known as the MIRA trial, researchers recruited 234 patients with moderate to severe HS to evaluate two different doses of sonelokimab (120 mg and 240 mg every 2 weeks) with a placebo control arm and adalimumab as an active reference arm. The primary endpoint of was the percentage of participants who achieved a HiSCR75. The study population included adults with Hurley Stage II or III HS who had HS lesions in 2 or more anatomical areas and a total abscess and inflammatory nodule (AN) count of 5 or more lesions; and had been treated with 2 or fewer biologics.

Dr. Kirby reported results from 67 patients in the sonelokimab 120 mg arm, 66 in the sonelokimab 240 mg arm, and 39 in the placebo arm. “It’s worth noting that the baseline AN count ranged between 12 and nearly 15, the mean draining tunnel count ranged between 2.9 and 3.7, and between 7% and 13% of patients were on concomitant antibiotics,” he said.

At 24 weeks, 43.3% of patients in the sonelokimab 120 mg arm achieved a HiSCR 75, compared with 34.8% of those in the sonelokimab 240 mg arm and 14.7% of those in the placebo arm, he reported. Meanwhile, 65.7% of patients in the sonelokimab 120 mg arm achieved an HiSCR 75, compared with 53% of those in the sonelokimab 240 mg arm and 27.9% of those in the placebo arm. Discontinuation rates were low and similar between treatment arms, with fewer than 10% of patients failing to complete week 24 of treatment.

In other findings, 69% of patients in the 120 mg arm achieved a HiSCR 50 at week 24 compared with 60.3% in the 240 mg arm; 56.9% in the 120 mg arm achieved a HiSCR 75 compared with 37.9% in the 240 mg arm; and 37.9% in the 120 mg arm achieved a HiSCR 75 compared with 27.6% in the 240 mg arm.

In addition, complete inflammatory remission as defined by the International HS Severity Score System (IHS4-100) continued to increase to week 24, with 24.1% of patients in the 120 mg arm achieving complete remission, compared with 15.5% of those in the 240 mg arm. Meaningful improvements in quality of life, skin pain, and HS symptoms reported by patients treated with sonelokimab were maintained or increased to week 24. Specifically, more than 60% of patients had a meaningful clinical improvement in their Dermatology Life Quality Index, over 45% had a minimum of a 30% increase in the Numerical Rating Scale **30, and more than 41% of patients reported absent or minimal symptoms on the Patient’s Global Impression of their Disease Severity, “which is a high bar to achieve in HS,” Dr. Kirby said.
 

No Serious Safety Signals Noted

There were no unexpected safety signals to week 24. The incidence of treatment-related adverse events was low, and there were no cases of inflammatory bowel disease. There were no serious infections, no major adverse cardiovascular event (MACE) reports, and no significant abnormalities on liver function tests. “There were also no safety signals on suicidal behavior, attempted suicides, or completed suicides,” he said.

“As you would expect with in IL-17 inhibitor, there was a signal for candidiasis, but all cases were judged to be mild or moderate, and no cases led to discontinuation of treatment from the trial because of candidal infection.”

Based on these data, Dr. Kirby said that larger and longer-term phase 3 trials are planned to further examine the safety and efficacy of sonelokimab at the 120 mg dose for the treatment of moderate-to-severe HS.

One of the session moderators, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, asked Dr. Kirby why he thought the lower dose resulted in generally better outcomes compared with the higher dose.

“There were no statistically significant differences between the two groups,” Dr. Kirby responded. “The 120 mg dose we know is highly effective in psoriasis, so there may be a ceiling effect. This may also be due to population variability, but the bottom line is that the 120 mg dose performs extremely well.”

Dr. Kirby disclosed that he has received research support from/has been a principal investigator for several pharmaceutical companies, including MoonLake Immunotherapeutics. Dr. Gelfand reported that he has been a consultant to and/or a member of the data safety monitoring board member for several pharmaceutical companies, including MoonLake.

SAN DIEGO — After 24 weeks of treatment with subcutaneously administered sonelokimab 120 mg, about 43% of patients with moderate to severe hidradenitis suppurativa (HS) achieved a Hidradenitis Suppurativa Clinical Response (HiSCR75), defined as at least a 75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline, results from a randomized clinical trial showed.

Sonelokimab is a novel humanized nanobody that selectively binds to interleukin (IL)-17A and IL-17F, presenting author Brian Kirby, MD, a dermatologist at St. Vincent’s Private Hospital, Dublin, Ireland, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. Sonelokimab is smaller than traditional monoclonal antibodies, he said, “which means it may be able to penetrate tissues better and stay there longer.” It is being developed by MoonLake Immunotherapeutics, based in Zug, Switzerland

Ted Bosworth/MDedge News

According to a press release from the company, nanobodies represent a new generation of targeted therapies derived from antibodies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies.

In a phase 2 study known as the MIRA trial, researchers recruited 234 patients with moderate to severe HS to evaluate two different doses of sonelokimab (120 mg and 240 mg every 2 weeks) with a placebo control arm and adalimumab as an active reference arm. The primary endpoint of was the percentage of participants who achieved a HiSCR75. The study population included adults with Hurley Stage II or III HS who had HS lesions in 2 or more anatomical areas and a total abscess and inflammatory nodule (AN) count of 5 or more lesions; and had been treated with 2 or fewer biologics.

Dr. Kirby reported results from 67 patients in the sonelokimab 120 mg arm, 66 in the sonelokimab 240 mg arm, and 39 in the placebo arm. “It’s worth noting that the baseline AN count ranged between 12 and nearly 15, the mean draining tunnel count ranged between 2.9 and 3.7, and between 7% and 13% of patients were on concomitant antibiotics,” he said.

At 24 weeks, 43.3% of patients in the sonelokimab 120 mg arm achieved a HiSCR 75, compared with 34.8% of those in the sonelokimab 240 mg arm and 14.7% of those in the placebo arm, he reported. Meanwhile, 65.7% of patients in the sonelokimab 120 mg arm achieved an HiSCR 75, compared with 53% of those in the sonelokimab 240 mg arm and 27.9% of those in the placebo arm. Discontinuation rates were low and similar between treatment arms, with fewer than 10% of patients failing to complete week 24 of treatment.

In other findings, 69% of patients in the 120 mg arm achieved a HiSCR 50 at week 24 compared with 60.3% in the 240 mg arm; 56.9% in the 120 mg arm achieved a HiSCR 75 compared with 37.9% in the 240 mg arm; and 37.9% in the 120 mg arm achieved a HiSCR 75 compared with 27.6% in the 240 mg arm.

In addition, complete inflammatory remission as defined by the International HS Severity Score System (IHS4-100) continued to increase to week 24, with 24.1% of patients in the 120 mg arm achieving complete remission, compared with 15.5% of those in the 240 mg arm. Meaningful improvements in quality of life, skin pain, and HS symptoms reported by patients treated with sonelokimab were maintained or increased to week 24. Specifically, more than 60% of patients had a meaningful clinical improvement in their Dermatology Life Quality Index, over 45% had a minimum of a 30% increase in the Numerical Rating Scale **30, and more than 41% of patients reported absent or minimal symptoms on the Patient’s Global Impression of their Disease Severity, “which is a high bar to achieve in HS,” Dr. Kirby said.
 

No Serious Safety Signals Noted

There were no unexpected safety signals to week 24. The incidence of treatment-related adverse events was low, and there were no cases of inflammatory bowel disease. There were no serious infections, no major adverse cardiovascular event (MACE) reports, and no significant abnormalities on liver function tests. “There were also no safety signals on suicidal behavior, attempted suicides, or completed suicides,” he said.

“As you would expect with in IL-17 inhibitor, there was a signal for candidiasis, but all cases were judged to be mild or moderate, and no cases led to discontinuation of treatment from the trial because of candidal infection.”

Based on these data, Dr. Kirby said that larger and longer-term phase 3 trials are planned to further examine the safety and efficacy of sonelokimab at the 120 mg dose for the treatment of moderate-to-severe HS.

One of the session moderators, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, asked Dr. Kirby why he thought the lower dose resulted in generally better outcomes compared with the higher dose.

“There were no statistically significant differences between the two groups,” Dr. Kirby responded. “The 120 mg dose we know is highly effective in psoriasis, so there may be a ceiling effect. This may also be due to population variability, but the bottom line is that the 120 mg dose performs extremely well.”

Dr. Kirby disclosed that he has received research support from/has been a principal investigator for several pharmaceutical companies, including MoonLake Immunotherapeutics. Dr. Gelfand reported that he has been a consultant to and/or a member of the data safety monitoring board member for several pharmaceutical companies, including MoonLake.

SAN DIEGO — After 24 weeks of treatment with subcutaneously administered sonelokimab 120 mg, about 43% of patients with moderate to severe hidradenitis suppurativa (HS) achieved a Hidradenitis Suppurativa Clinical Response (HiSCR75), defined as at least a 75% reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline, results from a randomized clinical trial showed.

Sonelokimab is a novel humanized nanobody that selectively binds to interleukin (IL)-17A and IL-17F, presenting author Brian Kirby, MD, a dermatologist at St. Vincent’s Private Hospital, Dublin, Ireland, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. Sonelokimab is smaller than traditional monoclonal antibodies, he said, “which means it may be able to penetrate tissues better and stay there longer.” It is being developed by MoonLake Immunotherapeutics, based in Zug, Switzerland

Ted Bosworth/MDedge News

According to a press release from the company, nanobodies represent a new generation of targeted therapies derived from antibodies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies.

In a phase 2 study known as the MIRA trial, researchers recruited 234 patients with moderate to severe HS to evaluate two different doses of sonelokimab (120 mg and 240 mg every 2 weeks) with a placebo control arm and adalimumab as an active reference arm. The primary endpoint of was the percentage of participants who achieved a HiSCR75. The study population included adults with Hurley Stage II or III HS who had HS lesions in 2 or more anatomical areas and a total abscess and inflammatory nodule (AN) count of 5 or more lesions; and had been treated with 2 or fewer biologics.

Dr. Kirby reported results from 67 patients in the sonelokimab 120 mg arm, 66 in the sonelokimab 240 mg arm, and 39 in the placebo arm. “It’s worth noting that the baseline AN count ranged between 12 and nearly 15, the mean draining tunnel count ranged between 2.9 and 3.7, and between 7% and 13% of patients were on concomitant antibiotics,” he said.

At 24 weeks, 43.3% of patients in the sonelokimab 120 mg arm achieved a HiSCR 75, compared with 34.8% of those in the sonelokimab 240 mg arm and 14.7% of those in the placebo arm, he reported. Meanwhile, 65.7% of patients in the sonelokimab 120 mg arm achieved an HiSCR 75, compared with 53% of those in the sonelokimab 240 mg arm and 27.9% of those in the placebo arm. Discontinuation rates were low and similar between treatment arms, with fewer than 10% of patients failing to complete week 24 of treatment.

In other findings, 69% of patients in the 120 mg arm achieved a HiSCR 50 at week 24 compared with 60.3% in the 240 mg arm; 56.9% in the 120 mg arm achieved a HiSCR 75 compared with 37.9% in the 240 mg arm; and 37.9% in the 120 mg arm achieved a HiSCR 75 compared with 27.6% in the 240 mg arm.

In addition, complete inflammatory remission as defined by the International HS Severity Score System (IHS4-100) continued to increase to week 24, with 24.1% of patients in the 120 mg arm achieving complete remission, compared with 15.5% of those in the 240 mg arm. Meaningful improvements in quality of life, skin pain, and HS symptoms reported by patients treated with sonelokimab were maintained or increased to week 24. Specifically, more than 60% of patients had a meaningful clinical improvement in their Dermatology Life Quality Index, over 45% had a minimum of a 30% increase in the Numerical Rating Scale **30, and more than 41% of patients reported absent or minimal symptoms on the Patient’s Global Impression of their Disease Severity, “which is a high bar to achieve in HS,” Dr. Kirby said.
 

No Serious Safety Signals Noted

There were no unexpected safety signals to week 24. The incidence of treatment-related adverse events was low, and there were no cases of inflammatory bowel disease. There were no serious infections, no major adverse cardiovascular event (MACE) reports, and no significant abnormalities on liver function tests. “There were also no safety signals on suicidal behavior, attempted suicides, or completed suicides,” he said.

“As you would expect with in IL-17 inhibitor, there was a signal for candidiasis, but all cases were judged to be mild or moderate, and no cases led to discontinuation of treatment from the trial because of candidal infection.”

Based on these data, Dr. Kirby said that larger and longer-term phase 3 trials are planned to further examine the safety and efficacy of sonelokimab at the 120 mg dose for the treatment of moderate-to-severe HS.

One of the session moderators, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, asked Dr. Kirby why he thought the lower dose resulted in generally better outcomes compared with the higher dose.

“There were no statistically significant differences between the two groups,” Dr. Kirby responded. “The 120 mg dose we know is highly effective in psoriasis, so there may be a ceiling effect. This may also be due to population variability, but the bottom line is that the 120 mg dose performs extremely well.”

Dr. Kirby disclosed that he has received research support from/has been a principal investigator for several pharmaceutical companies, including MoonLake Immunotherapeutics. Dr. Gelfand reported that he has been a consultant to and/or a member of the data safety monitoring board member for several pharmaceutical companies, including MoonLake.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.

Fractures, particularly hip and spine fractures, are a major cause of mortality and morbidity among older individuals. The term “osteoporosis” indicates increased porosity of bones resulting in low bone density; increased bone fragility; and an increased risk for fracture, often with minimal trauma.

During the adolescent years, bone accrues at a rapid rate, and optimal bone accrual during this time is essential to attain optimal peak bone mass, typically achieved in the third decade of life. Bone mass then stays stable until the 40s-50s, after which it starts to decline. One’s peak bone mass sets the stage for both immediate and future bone health. Individuals with lower peak bone mass tend to have less optimal bone health throughout their lives, and this becomes particularly problematic in older men and in the postmenopausal years for women.

The best strategy to optimize bone health is to prevent osteoporosis from occurring in the first place. This requires attention to factors that contribute to optimal bone health. One’s genes have a major impact on bone density and are currently not modifiable.

Modifiable factors include mechanical loading of bones through exercise activity, maintaining a normal body weight, and ensuring adequate intake of micronutrients (including calcium and vitamin D) and macronutrients. Medications such as glucocorticoids that have deleterious effects on bones should be limited as far as possible. Endocrine, gastrointestinal, renal, and rheumatologic conditions and others, such as cancer, which are known to be associated with reduced bone density and increased fracture risk, should be managed appropriately.

A deficiency of the gonadal hormones (estrogen and testosterone) and high blood concentrations of cortisol are particularly deleterious to bone. Hormone replacement therapy in those with gonadal hormone deficiency and strategies to reduce cortisol levels in those with hypercortisolemia are essential to prevent osteoporosis and also improve bone density over time. The same applies to management of conditions such as anorexia nervosa, relative energy deficiency in sports, inflammatory bowel disease, celiac disease, cystic fibrosis, chronic kidney disease, and chronic arthritis.

Once osteoporosis has developed, depending on the cause, these strategies may not be sufficient to completely reverse the condition, and pharmacologic therapy may be necessary to improve bone density and reduce fracture risk. This is particularly an issue with postmenopausal women and older men. In these individuals, medications that increase bone formation or reduce bone loss may be necessary.

Medications that reduce bone loss include bisphosphonates and denosumab; these are also called “antiresorptive medications” because they reduce bone resorption by cells called osteoclasts. Bisphosphonates include alendronate, risedronate, ibandronate, pamidronate, and zoledronic acid, and these medications have direct effects on osteoclasts, reducing their activity. Some bisphosphonates, such as alendronate and risedronate, are taken orally (daily, weekly, or monthly, depending on the medication and its strength), whereas others, such as pamidronate and zoledronic acid, are administered intravenously: every 3-4 months for pamidronate and every 6-12 months for zoledronic acid. Ibandronate is available both orally and intravenously.

Denosumab is a medication that inhibits the action of receptor activator of nuclear factor-kappa ligand 1 (RANKL), which otherwise increases osteoclast activity. It is administered as a subcutaneous injection every 6 months to treat osteoporosis. One concern with denosumab is a rapid increase in bone loss after its discontinuation.

Medications that increase bone formation are called bone anabolics and include teriparatide, abaloparatide, and romosozumab. Teriparatide is a synthetic form of parathyroid hormone (recombinant PTH1-34) administered daily for up to 2 years. Abaloparatide is a synthetic analog of parathyroid hormone–related peptide (PTHrP), which is also administered daily as a subcutaneous injection. Romosozumab inhibits sclerostin (a substance that otherwise reduces bone formation and increases bone resorption) and is administered as a subcutaneous injection once a month. Effects of these medications tend to be lost after they are discontinued.

In 2019, the Endocrine Society published guidelines for managing postmenopausal osteoporosis. The guidelines recommend lifestyle modifications, including attention to diet, calcium and vitamin D supplements, and weight-bearing exercise for all postmenopausal women. They also recommend assessing fracture risk using country-specific existing models.

Guidelines vary depending on whether fracture risk is low, moderate, or high. Patients at low risk are followed and reassessed every 2-4 years for fracture risk. Those at moderate risk may be followed similarly or prescribed bisphosphonates. Those at high risk are prescribed an antiresorptive, such as a bisphosphonate or denosumab, or a bone anabolic, such as teriparatide or abaloparatide (for up to 2 years) or romosozumab (for a year), with calcium and vitamin D and are reassessed at defined intervals for fracture risk; subsequent management then depends on the assessed fracture risk.

People who are on a bone anabolic should typically follow this with an antiresorptive medication to maintain the gains achieved with the former after that medication is discontinued. Patients who discontinue denosumab should be switched to bisphosphonates to prevent the increase in bone loss that typically occurs.

In postmenopausal women who are intolerant to or inappropriate for use of these medications, guidelines vary depending on age (younger or older than 60 years) and presence or absence of vasomotor symptoms (such as hot flashes). Options could include the use of calcium and vitamin D supplements; hormone replacement therapy with estrogen with or without a progestin; or selective estrogen receptor modulators (such as raloxifene or bazedoxifene), tibolone, or calcitonin.

It’s important to recognize that all pharmacologic therapy carries the risk for adverse events, and it’s essential to take the necessary steps to prevent, monitor for, and manage any adverse effects that may develop.

Managing osteoporosis in older men could include the use of bone anabolics and/or antiresorptives. In younger individuals, use of pharmacologic therapy is less common but sometimes necessary, particularly when bone density is very low and associated with a problematic fracture history — for example, in those with genetic conditions such as osteogenesis imperfecta. Furthermore, the occurrence of vertebral compression fractures often requires bisphosphonate treatment regardless of bone density, particularly in patients on chronic glucocorticoid therapy.

Preventing osteoporosis is best managed by paying attention to lifestyle; optimizing nutrition and calcium and vitamin D intake; and managing conditions and limiting the use of medications that reduce bone density.

However, in certain patients, these measures are not enough, and pharmacologic therapy with bone anabolics or antiresorptives may be necessary to improve bone density and reduce fracture risk.

Dr. Misra, of the University of Virginia and UVA Health Children’s Hospital, Charlottesville, disclosed ties with AbbVie, Sanofi, and Ipsen.
 

A version of this article appeared on Medscape.com.