Do Weight-Loss Injections Also Affect Bones? GLP-1 Drugs, Bone Health, and Osteoporosis
In this article
The debate around GLP-1 drugs such as Ozempic and Mounjaro continues to grow. Alongside the discussion of muscle loss, bone health and fracture risk have become the second major question on the scientific agenda. The picture is complex: While animal experiments and some clinical data suggest that GLP-1 drugs may protect bone, new epidemiological findings — particularly the safety data from SELECT — raise questions about fracture risk, especially in older and female patients. So what is actually happening? Three separate sources approach this question from different angles.
The Starting Point: What Does Weight Loss Mean for Bone?
Bone is not merely a skeletal structure; it is metabolically active tissue. Two main cell types govern bone turnover: osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells). Disruption of this balance — with resorption exceeding formation — reduces bone mineral density (BMD) and increases fracture risk. Weight loss affects this balance through several mechanisms.
A reduction in body weight of approximately %7–10 through calorie restriction is accompanied by increased bone turnover markers and reduced bone mineral density. This change is particularly pronounced at the hip and more limited in the lumbar spine. Bariatric surgery presents a much more dramatic picture: Substantial weight loss is associated with disruption of bone microarchitecture and a clear increase in fracture risk — usually becoming evident 3 years after surgery. Roux-en-Y gastric bypass causes more severe bone damage than sleeve gastrectomy.
Data compiled from Karam et al., Osteoporosis International 2025
How Do GLP-1 Drugs Affect Bone Directly? Two Opposing Forces
To understand the effects of GLP-1 drugs on bone, two opposing forces need to be assessed separately: the indirect effect of weight loss and the direct effect of the GLP-1 receptor on bone cells.
Regarding direct effects, in vitro studies show that osteoblasts (bone-forming cells) express the GLP-1 receptor. Binding of GLP-1RAs to this receptor activates the PI3K/AKT, MAPK, and Wnt/β-catenin signaling pathways, thereby increasing osteoblast differentiation and reducing osteoblast apoptosis. At the same time, it suppresses osteoclast activity by regulating the RANKL-OPG axis in favor of osteoprotegerin (OPG). These mechanisms lead to a clear bone-protective effect, particularly in animal models.
However, the indirect effect of weight loss complicates this picture. Mechanical loading is among the strongest stimuli keeping bone tissue healthy. As body weight falls, the mechanical load on the skeleton also decreases; this increases bone turnover and sets the stage for declining bone mineral density. The net effect of GLP-1 drugs on bone arises from the balance between these two forces.
Compiled from Karam et al., Osteoporos Int 2025 · Chen et al., Front Endocrinol 2025
Three Different Sources, Three Different Perspectives
1. Osteoporosis International Review: Are the Preliminary Findings Concerning?
The comprehensive review published by Karam et al. in 2025 summarizes the available human data on GLP-1RAs and bone health. To date, only two randomized controlled trials have assessed bone mineral density at standard measurement sites (the lumbar spine and proximal femur):
Semaglutide RCT (Hansen et al., 2024): In 64 participants without diabetes and at high fracture risk, 52 weeks of semaglutide use produced the following results alongside average weight loss of %9.4: lumbar spine BMD decreased by %2.1 (p=0.01), total hip BMD by %2.6 (p=0.001), and tibial volumetric BMD by %1.5 (p=0.003). The bone resorption marker CTX increased by %54.8 more than with placebo.
Liraglutide + Exercise RCT (Jensen et al., 2024): After an 8-week low-calorie diet of 800 kcal/day, 195 participants were randomized to liraglutide, exercise, combination, and placebo groups. A slight decrease in lumbar spine and hip BMD was observed in all groups. However, the crucial finding was this: Liraglutide alone reduced hip and lumbar spine BMD more than placebo, whereas the liraglutide + exercise combination prevented this loss. These data directly prove the bone-protective role of exercise during GLP-1 therapy.
2. SELECT Safety Data: A Warning Signal for Female Patients
⚠ SELECT Study — Hip and Pelvic Fracture Data (Reported in 2025)
In the safety analysis of SELECT, which included 17604 participants, the rate of hip and pelvic fractures in female patients receiving semaglutide was %1.0 (24/2448), while in the placebo group it was %0.2 (5/2424). This difference was even more striking in participants aged 75 and over: in the semaglutide group, %2.4 (17/703), compared with the placebo group, %0.6 (4/663). This difference in rates is statistically significant and makes close monitoring essential, particularly in older and female patients.
3. Real-World Data: Contrasting Findings
The AAOS 2026 presentation (Wajahath et al.) compared 73483 GLP-1RA users with matched controls and reported, over 5 years, a %29 higher risk of osteoporosis (risk ratio 1.29), and an osteomalacia risk 2.55 times that of controls. Gout risk was also increased.
In contrast, the real-world cohort study from China by Chen et al. found the opposite: In 1845 patients with type 2 diabetes, GLP-1RA use showed a markedly protective effect against osteoporosis, with a hazard ratio of 0.69 (%95 CI: 0.45–0.84) in the fully adjusted Cox model. This effect became stronger with longer follow-up and remained consistent across sex, age, BMI, and smoking status.
Why these two real-world datasets produced opposite results needs to be assessed in terms of methodological differences — study population, comorbidity profile, comparator group, and method of adjustment for confounders.
Summary of current studies and the direction of their findings
Are GLP-1 Drugs Safer for Bone than Bariatric Surgery?
Data addressing this question indicate that the bone effects of GLP-1RAs resemble those of weight restriction and are much milder than those of bariatric surgery. Surgery disrupts bone microarchitecture and strength much more markedly; fracture risk clearly increases from year 3, and this effect is much more severe with Roux-en-Y gastric bypass than with sleeve gastrectomy. Calcium and vitamin D deficiency due to malabsorption is one of surgery's most important mechanisms affecting bone. GLP-1RAs do not have this malabsorption component — an important difference.
However, another point must not be overlooked: GLP-1RAs can now produce weight loss approaching that achieved with bariatric surgery. When average weight loss reaches %21 with tirzepatide, the pressure on bone metabolism also increases. Without longer and larger follow-up studies, fracture risk at this degree of weight loss cannot currently be assessed with confidence.
High-Risk Population: Who Needs Special Attention?
🔴 HIGHEST RISK: Postmenopausal Women and People Over 75
The SELECT safety data showed a dramatic increase in fracture risk in this group. Among those over 75, the fracture rate was %2.4 with semaglutide versus %0.6 with placebo. Given the possibility that GLP-1 adds a further burden to existing bone loss from estrogen deficiency in postmenopausal women, assessment of bone mineral density by DXA before treatment is strongly recommended in this population.
🟠 HIGH RISK: Rapid and Substantial Weight Loss (%15+)
Available data indicate that changes in bone metabolism become apparent from approximately %7–10 weight loss. With weight loss above %20 achieved using dual agonists such as tirzepatide, the pressure on bone is expected to increase. Supplements and exercise become even more critical in these patients.
🔵 CAUTION: Sedentary Lifestyle and Low Calcium/Vitamin D Intake
Without mechanical loading, the direct bone-protective effects of GLP-1 may be insufficient. Calcium and vitamin D deficiency already accelerate bone loss processes. Supplementation and a structured exercise plan should be arranged alongside the GLP-1 prescription in these patients.
🟣 LOW RISK: Active, Adequately Nourished Patients with Type 2 Diabetes
The Chinese cohort of Chen et al. and various meta-analyses have shown that GLP-1RA use may reduce osteoporosis and fracture risk in T2DM patients. Since diabetes itself impairs bone caliber, improved blood glucose may be one of the positive effects of GLP-1 on bone.
What Should Be Done? Practical Management Recommendations
🎓 DROZDOGAN Academy — Commentary and Discussion
GLP-1 AGONISTS · BONE HEALTH · OSTEOPOROSIS · FRACTURE RISK · CRITICAL APPRAISAL
Why This Field Matters
While the sarcopenia debate remains unresolved, the effects of GLP-1 drugs on bone health are becoming an increasingly important issue for oncology and general internal medicine. The SELECT safety data, in particular, provide a serious warning: The fact that fracture risk appears so substantially increased among women and those over 75 clearly shows that every clinician prescribing these drugs should incorporate bone assessment into their standard protocol. Integrating bone health into routine GLP-1 follow-up will fill a critical gap for clinicians and patients alike.
Strengths
Three separate sources offer different perspectives, from animal models to real-world data. The review by Karam et al. systematically documents the direct bone-protective mechanisms of GLP-1 — PI3K/AKT, Wnt/β-catenin, and the RANKL-OPG axis. The strong evidence from the liraglutide + exercise RCT for preserving BMD gives clinicians a directly applicable roadmap. The real-world study by Chen et al. documents the possible protective effect of GLP-1 in diabetic bone damage with extended follow-up.
Limitations and Contradictions
The biggest problem in this field is that the available human data are both limited and conflicting. Although SELECT's fracture findings raise a major alarm, the study does not assess this as a primary endpoint, and adjusted risk estimates have not been fully disclosed publicly. The AAOS presentation has not yet been published in a peer-reviewed journal, leaving methodological details incomplete. Chen et al.'s single-center Chinese cohort has a substantial risk of selection bias. The most critical gap is this: None of the large GLP-1 clinical trials assessed fracture risk as a primary endpoint. The data available to us were not designed to answer this question.
Implications for Clinical Practice
The practical message is clear: GLP-1 drugs should not be treated as "neutral" for bone health. Before starting GLP-1 therapy, FRAX assessment and DXA measurement when necessary should be performed, particularly in postmenopausal women, people over 75, and patients already at risk of bone loss. Adequate calcium and vitamin D should be ensured during treatment, and structured resistance exercise should be planned as an essential component. In patients with osteoporosis, combining antiosteoporosis treatment with GLP-1 should be considered. Given the inadequate monitoring of bone in Turkey, this practical approach could make a substantial difference.
Future Questions
The most urgent need in this field is long-term randomized trials with fracture risk as the primary endpoint. Comparative bone safety data for semaglutide and tirzepatide are particularly critical in postmenopausal women and people over 75. The bone effects of dual agonists such as tirzepatide at levels of weight loss approaching bariatric surgery also need assessment. The potential effects of triple agonists that also target the glucagon receptor on bone metabolism remain largely unknown. How tools such as FRAX and the trabecular bone score (TBS) should be used for risk stratification specific to patients taking GLP-1 is another important issue that needs inclusion in clinical guidelines.
Scientific References
- Karam L, Mabilleau G, Paccou J. Effects of glucagon-like peptide-1 receptor agonists on bone health in people living with obesity. Osteoporos Int 2025;36(11):2115–2126. doi: 10.1007/s00198-025-07664-1
- Chen M, Lyu Y, Zhao J et al. Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study. Front Endocrinol 2025;16:1586589. doi: 10.3389/fendo.2025.1586589
- Wajahath M et al. GLP-1 Receptor Agonist Use Increases Five-Year Risk for Osteoporosis. Presented at: AAOS Annual Meeting; March 2–6, 2026; New Orleans.
- Hansen MS et al. Once-weekly semaglutide versus placebo in adults with increased fracture risk: a randomised, double-blinded, two-centre, phase 2 trial. EClinicalMedicine 2024;72:102624.
- Jensen SBK et al. Bone health after exercise alone, GLP-1 receptor agonist treatment, or combination treatment: a secondary analysis of a randomized clinical trial. JAMA Netw Open 2024;7(6):e2416775.
- Kushner RF et al. Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial. Obesity 2025;33(3):452–462.
- Lincoff AM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med 2023;389(24):2221–2232.
- Cheng L et al. Glucagon-like peptide-1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Metab Res Rev 2019;35(7):e3168.
- Paccou J, Caiazzo R, Lespessailles E, Cortet B. Bariatric surgery and osteoporosis. Calcif Tissue Int 2022;110:576–591.
This article was created using various editorial tools, including artificial intelligence, as part of the process. It was reviewed by human editors before publication.
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