A small but carefully monitored 20-week study reveals that semaglutide delivers weight loss in older adults without immediate harm to bone density, raising new questions about what longer-term use of GLP-1 drugs may mean for aging bones.
Study: Bone mineral density and turnover response to GLP-1 receptor agonists in older adults with overweight/obesity and prediabetes/type 2 diabetes: a 20-week pilot trial post hoc analysis. Image credit: SERASOOT/Shutterstock.com
In a recent study published in Frontiers in Aging, researchers investigated the effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), on bone health in older adults.
Obesity affects around 40 % of older individuals in the United States. Excess adiposity is associated with a higher risk of various comorbidities throughout life, with older people being particularly susceptible to functional decline related to obesity. Although weight loss can ameliorate chronic conditions, it presents challenges for older people due to its potential negative effects on bone health.
Weight loss has been linked to lower bone mineral density (BMD) and an increased risk of fractures in older individuals. Recent years have witnessed substantial advances in obesity management, including the development of GLP-1RAs. The health benefits of GLP-1RAs extend beyond diabetes management, with older adults increasingly turning to GLP-1RAs for disease and weight management.
Preclinical studies have suggested that these medications may support bone formation, whereas clinical findings have been largely neutral, underscoring the ongoing uncertainty about their net skeletal effects.
Researchers test semaglutide’s bone effects in elders
In the present study, researchers explored the impact of 20-week use of semaglutide on bone health in older individuals. This study was a post hoc analysis of a pilot trial conducted between April 2023 and May 2024. Community-dwelling adults were recruited if they were aged ≥ 65 years and had a body mass index (BMI) of 27–40 kg/m², fasting blood glucose levels > 100 mg/dL, or glycated hemoglobin levels between 5.7 % and 7.5 %.
Individuals with type 1 diabetes, a history of cardiovascular events, impaired renal function, contraindications to medication, or uncontrolled hypertension were excluded. Participants were randomized to lifestyle counseling plus semaglutide therapy or lifestyle counseling alone. The lifestyle counseling-only group met with dieticians to discuss exercise, diet, and behavior modification based on the Diabetes Prevention Program recommendations.
The semaglutide plus lifestyle counseling group additionally received instructions to prepare and self-administer a semaglutide injection once weekly. The semaglutide dose was initiated at 0.25 mg/week for four weeks, followed by 0.5 mg/week for four weeks, and then 1 mg/week for 12 weeks. Moderate-intensity physical activity and resistance training for at least 150 minutes/week were encouraged.
Dual-energy x-ray absorptiometry scans were performed to determine body composition at baseline and after week 20. A regions-of-interest analysis was performed to derive the regional BMD values of the leg, lumbar spine, and pelvis from the whole-body scans. Fasting blood samples were collected at baseline and after week 20, and bone turnover markers, collagen type 1 C-telopeptide (CTX) and procollagen type 1 intact N-terminal propeptide (P1NP), were measured.
Medical history and demographic information were self-reported at baseline. The researchers performed an analysis of covariance to determine changes over time in body weight, bone turnover markers, and BMD, adjusting for sex, age, and baseline values. Furthermore, partial Pearson correlations were estimated to assess whether changes in body weight were associated with changes in BMD, CTX, and P1NP.
Participants shed weight but not bone mass
The study enrolled 20 participants, with an average age of 72.7 years and a BMI of 32.9 kg/m2. About 50 % of participants were female, and 90 % identified as White, with 45 % identifying as Hispanic. Six individuals had diabetes, 11 had hypertension, four had osteoporosis, and 14 had prediabetes. Participants were equally assigned to the two groups.
The semaglutide plus lifestyle counseling group experienced significantly greater weight loss (-4.9 kg) compared to the lifestyle counseling-only group (-0.8 kg). There were no significant differences in whole-body composition between groups. Likewise, regional BMD values of the leg, lumbar spine, and pelvis were not significantly different between the two groups. However, despite the lack of statistical significance, the authors noted a consistent directional trend toward lower BMD in the semaglutide group at follow-up.
Further, P1NP and CTX showed no significant differences between groups. Body weight changes were non-significantly and weakly correlated with changes in whole-body BMD, leg BMD, and lumbar spine BMD. Still, they were significantly and strongly associated with changes in pelvis BMD. Body weight changes were inversely but weakly correlated with changes in P1NP and CTX.
Early findings show no measurable bone harm
The semaglutide plus lifestyle counseling group achieved significantly greater weight loss than the lifestyle counseling-only group. However, there were no significant changes in BMD, CTX, and P1NP between the two groups.
The modest level of weight loss, approximately 5 %, may fall below thresholds typically associated with measurable bone loss, which could partly explain the neutral findings. A consistent, though nonsignificant, trend toward lower BMD and higher turnover markers in the semaglutide group warrants further investigation.
The study’s limitations include the small sample size, short duration, lack of assessor blinding, and absence of detailed monitoring of diet and physical activity, all of which may affect interpretation. Given the widespread adoption of GLP-1RAs, larger and longer trials are needed to define the risk-benefit profile for bone health in older adults. This is particularly important as greater weight loss induced by higher-dose or longer-duration GLP-1RA therapy may have different skeletal implications.
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