J Obes Metab Syndr 2025; 34(1): 1-3
Published online January 30, 2025 https://doi.org/10.7570/jomes25001
Copyright © Korean Society for the Study of Obesity.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Korea
Correspondence to:
Ji Hye Heo
https://orcid.org/0000-0001-5445-8007
Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, 22 Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang 14068, Korea
Tel: +82-31-380-1500
Fax: +82-31-380-4118
E-mail: jihyeheo02@gmail.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
The global prevalence of obesity continues to rise, contributing significantly to adverse health outcomes such as cardiovascular diseases, type 2 diabetes mellitus, and musculoskeletal complications.1 Effective weight management strategies including lifestyle modifications such as diet and exercise, pharmacotherapy, and metabolic surgery are critical in mitigating obesity-related risks. Accordingly, numerous international guidelines recommend pharmacotherapy or metabolic surgery in addition to lifestyle interventions for individuals whose body mass index meets the treatment criteria. While the efficacy of weight management strategies in achieving weight loss has been well documented, their impact on skeletal health, particularly bone mineral density (BMD), remains unclear and often overlooked. Weight loss-associated reductions in mechanical loading, nutrient deficiencies, and hormonal or adipokine alterations may predispose individuals to bone loss, increasing the risk of osteoporosis and fractures.2
To date, studies investigating the effects of specific obesity treatments on bone health have yielded inconsistent findings, largely due to variations in study design and participant characteristics. For instance, Soltani et al.3 reported significant declines in hip and lumbar spine BMD following calorie-restriction-induced weight loss, particularly after 1 year, while exercise-induced weight loss did not adversely affect BMD.4 In contrast, Redman et al.5 found no significant changes in BMD after 6 months of calorie restriction, despite significant weight loss, compared to a control group. Metabolic surgery has been consistently associated with decreased BMD, although the magnitude of bone loss varies by anatomical region (e.g., lumbar spine vs. hip) and type of surgery (restrictive vs. combined restrictive and malabsorptive).4 Conversely, the effects of pharmacological treatments on bone health remain less well-explored.
In a recent issue of Journal of Obesity & Metabolic Syndrome, Kim et al.6 conducted a meta-analysis evaluating changes in BMD across three major obesity treatment strategies: lifestyle interventions, pharmacotherapy, and metabolic surgery. Their analysis of 18 randomized controlled trials comprising 2,510 participants revealed a significant reduction in lumbar spine BMD following metabolic surgery (mean difference=–0.40 g/cm²; 95% confidence interval, –0.73 to –0.07). Pharmacotherapy and lifestyle interventions, however, had neutral effects on BMD. A similar decreasing trend in hip BMD was noted post-metabolic surgery; however, no significant difference was observed compared to other treatment strategies. Although newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide and tirzepatide were not included, Kim et al.6 demonstrated that traditional GLP-1 RAs (e.g., liraglutide, exenatide) induced weight loss without negatively impacting BMD. Recent clinical trials demonstrating that newer GLP-1 RAs can achieve weight loss outcomes comparable to metabolic surgery7,8 suggest that these pharmacological treatments—particularly GLP-1 RAs—provide a unique advantage by preserving bone integrity while effectively promoting weight loss. However, only two randomized controlled trials with a limited number of participants were included in the analysis.
A recent study by Hansen et al.9 reported that weekly semaglutide administration did not enhance bone formation, as indicated by unchanged levels of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), accompanied by increased C-terminal telopeptide (CTx) concentrations and resulted in a cortical bone loss. However, GLP-1 RAs are theoretically considered to have potential benefits for bone health through enhanced osteoblast activity and the inhibition of osteoclast activity.10 These findings underscore the need for further research to clarify the impact of incretin-based therapies on bone health, particularly through well-designed trials that evaluate bone parameters as primary outcomes in individuals undergoing weight management at approved pharmacologic doses.
Interestingly, Kim et al.6 also reported that metabolic surgery had a more pronounced effect on lumbar spine BMD than on hip BMD. While the exact mechanisms remain unclear, it is hypothesized that reduced mechanical loading and impaired calcium and vitamin D absorption following surgery disproportionately affect trabecular bone-rich regions, such as the lumbar spine. These regions are metabolically more active and thus more susceptible to external factors than cortical bone-rich regions, such as the hip.11 However, other studies have also noted significant reductions in hip BMD following metabolic surgery.4 These conflicting findings emphasize the importance of advanced metrics, such as trabecular bone scores, to comprehensively assess bone health in individuals undergoing weight loss treatment.
Kim et al.6 provide valuable insights for clinicians to personalize anti-obesity strategies based on individual skeletal risk profiles. Given the potential negative impact of metabolic surgery on bone health, it is crucial to identify individuals who are most likely to achieve greater benefits than potential risks from this procedure. Furthermore, establishing effective systems for monitoring bone health in individuals who have undergone metabolic surgery is essential to ensure optimal long-term outcomes. Future research should prioritize long-term, large-scale trials that directly compare the effects of various obesity treatments, including newer agents such as semaglutide and tirzepatide, on bone health in the current era of GLP-1-based therapies. Additionally, advanced methodologies for assessing bone quality and microarchitecture beyond BMD are needed to better understand the skeletal implications of weight loss interventions. Finally, mechanistic studies exploring how anti-obesity treatments influence bone metabolism, including their effects on osteoblast and osteoclast activity, will be essential for optimizing obesity management while minimizing skeletal risks.
The author declares no conflict of interest.
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