A small but carefully monitored 20-week study reveals that semaglutide produces weight loss in older adults without immediate damage to bone density, raising new questions about what long-term use of GLP-1 drugs may mean for aging bones.
Study: Bone mineral density and turnover response to GLP-1 receptor agonists in overweight/obese older adults with prediabetes/type 2 diabetes: a post hoc analysis of a 20-week pilot trial. 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 about 40% of older Americans. Excess adiposity is associated with an increased risk of various comorbidities throughout life, with older people being particularly susceptible to obesity-related functional decline. Although weight loss can improve chronic diseases, 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 increased risk of fractures in older people. Recent years have seen substantial advances in the management of obesity, including the development of GLP-1RA. The health benefits of GLP-1RA extend beyond diabetes management: older adults are increasingly turning to GLP-1RA for disease management and weight management.
Preclinical studies have suggested that these drugs may promote bone formation, while clinical findings have been largely neutral, underscoring the current uncertainty about their net skeletal effects.
Researchers test bone effects of semaglutide in elderly
In the present study, researchers explored the impact of using semaglutide for 20 weeks on bone health in older people. 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 ≥ 65 years of age and had a body mass index (BMI) of 27 to 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, history of cardiovascular events, impaired renal function, contraindications to medication, or uncontrolled hypertension were excluded. Participants were randomly assigned to receive lifestyle counseling plus semaglutide therapy or lifestyle counseling alone. The lifestyle advisory group met only with dietitians to discuss exercise, diet, and behavior modification as recommended by the Diabetes Prevention Program.
The semaglutide plus lifestyle counseling group was also instructed to prepare and self-administer a semaglutide injection once a week. Semaglutide dosing 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 were encouraged for at least 150 minutes per week.
Dual-energy Fasting blood samples were collected at baseline and after week 20, and bone turnover markers, C-telopeptide of collagen type 1 (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. Additionally, partial Pearson correlations were estimated to evaluate whether changes in body weight were associated with changes in BMD, CTX, and P1NP.
Participants lost weight but not bone mass
There were 20 participants in the study, with a mean age of 72.7 years and a BMI of 32.9 kg/m2. About 50% of participants were women, 90% identified as white, and 45% identified as Hispanic. Six people 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 total body composition between the 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 observed a consistent directional trend toward lower BMD in the semaglutide group during follow-up.
Furthermore, P1NP and CTX showed no significant differences between the groups. Changes in body weight were not 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 pelvic BMD. Changes in body weight were inversely but weakly correlated with changes in P1NP and CTX.
Early findings show no measurable bone damage
The group that received semaglutide plus lifestyle counseling achieved significantly greater weight loss than the group that received lifestyle counseling alone. 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, although non-significant, trend toward lower BMD and greater marker turnover in the semaglutide group warrants further investigation.
Limitations of the study include small sample size, short duration, lack of evaluator blinding, and lack 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 therapy with higher doses or longer duration of GLP-1RA may have different skeletal implications.
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