Journal of Obesity & Metabolic Syndrome

Search

Article

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.

The Impact of Obesity Treatments on Bone Health: Insights from Recent Research

Ji Hye Heo *

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

Received: January 10, 2025; Reviewed : January 13, 2025; Accepted: January 13, 2025

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.

  1. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011;378:804-14.
    Pubmed CrossRef
  2. Stefanakis K, Kokkorakis M, Mantzoros CS. The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. Metabolism 2024;161:156057.
    Pubmed CrossRef
  3. Soltani S, Hunter GR, Kazemi A, Shab-Bidar S. The effects of weight loss approaches on bone mineral density in adults: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int 2016;27:2655-71.
    Pubmed CrossRef
  4. Chen X, Zhang J, Zhou Z. Changes in bone mineral density after weight loss due to metabolic surgery or lifestyle intervention in obese patients. Obes Surg 2021;31:1147-57.
    Pubmed CrossRef
  5. Redman LM, Rood J, Anton SD, Champagne C, Smith SR, Ravussin E, et al. Calorie restriction and bone health in young, overweight individuals. Arch Intern Med 2008;168:1859-66.
    Pubmed KoreaMed CrossRef
  6. Kim MJ, Kim S, Jung HN, Jung CH, Lee WJ, Cho YK. Effects of anti-obesity strategies on bone mineral density: a comprehensive meta-analysis of randomized controlled trials. J Obes Metab Syndr 2025;34:41-53.
    Pubmed CrossRef
  7. Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002.
    Pubmed CrossRef
  8. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205-16.
    Pubmed CrossRef
  9. Hansen MS, Wölfel EM, Jeromdesella S, Møller JK, Ejersted C, Jørgensen NR, 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.
    Pubmed KoreaMed CrossRef
  10. Xie B, Chen S, Xu Y, Han W, Hu R, Chen M, et al. The impact of glucagon-like peptide 1 receptor agonists on bone metabolism and its possible mechanisms in osteoporosis treatment. Front Pharmacol 2021;12:697442.
    Pubmed KoreaMed CrossRef
  11. Rolvien T, Amling M. Disuse osteoporosis: clinical and mechanistic insights. Calcif Tissue Int 2022;110:592-604.
    Pubmed KoreaMed CrossRef