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Cho: Commentary on “Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials”
Osteoporotic vertebral fractures (OVFs) are a clinically important problem and are becoming more frequent as the aging population continues to increase [1]. Current evidence and new treatment guidelines now recommend initial treatment with anabolic agents for patients at imminent or very high risk of fractures [2].
This meta-analysis [3] conducted to determine whether anabolic agents, including teriparatide and romosozumab, are superior to bisphosphonates (BPs) in preventing new OVFs and promoting fracture healing in patients with OVFs. Six randomized controlled trials (RCTs) involving 3,642 and 3,655 patients with osteoporosis at high risk of fracture, treated with anabolic agents and BPs, respectively, were included in this meta-analysis [4-6].
This study reveals that anabolic agents, specifically teriparatide and romosozumab, significantly reduce the incidence of new OVFs compared to BPs. This is evidenced by highcertainty evidence and low heterogeneity across the included RCTs. The relative risk (RR) of 0.57 for teriparatide and romosozumab versus alendronate and risedronate underscores the superior efficacy of anabolic agents in preventing subsequent fractures. On the contrary, there was no statistically significant difference in the fracture healing of OVF between teriparatide and alendronate (RR, 1.23; 95% confidence interval, 0.95–1.60; p= 0.12; I2= 35%). These results align with current guidelines advocating for the use of anabolic agents in patients at high or very high risk of fractures, highlighting their rapid and significant impact on bone formation and fracture prevention.
Notably, the authors tried to overcome the limitations of meta-analysis including relatively higher heterogeneity and participant duplication across the included studies. Given the increasing prevalence of osteoporosis and its associated complications, this study addresses a critical need for evidence-based treatment strategies, taking into account various factors such as study design, risk of bias, inconsistency, indirectness, imprecision, and other relevant considerations.
The authors emphasize that we should be more careful when interpreting results and obtaining the scientific evidence in meta-analysis using a small number of RCTs. Although this study is inconclusive due to the variations in standards used by physicians to make decisions about fracture healing, the limited number of participants, and the overall low quality of evidence, this article is expected to provide valuable insights into the relative effectiveness of anabolic agents versus BPs in managing OVFs.
The significant reduction in fracture incidence achieved with anabolic agents, particularly teriparatide, supports their use as a first-line treatment in this patient population. While additional research is needed to address the study’s limitations and explore further clinical applications, the current findings represent a crucial step forward in optimizing osteoporosis management and improving patient outcomes. This study is a valuable addition to the literature and provides a strong impetus for the continued advancement of anabolic therapies in osteoporosis treatment.


Conflict of Interest

The author has nothing to disclose.


1. Ballane G, Cauley JA, Luckey MM, et al. Worldwide prevalence and incidence of osteoporotic vertebral fractures. Osteoporos Int 2017;28:1531-42.
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2. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis—2020 Update. Endocr Pract 2020;26:1-46.
3. Jeon I, Park SB, Moon BJ, et al. Comparison of the clinical efficacy of anabolic agents and bisphosphonates in the patients with osteoporotic vertebral fracture: systematic review and meta-analysis of randomized controlled trials. Neurospine 2024;21:416-29.
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4. Geusens P, Feldman R, Oates M, et al. Romosozumab reduces incidence of new vertebral fractures across severity grades among postmenopausal women with osteoporosis. Bone 2022;154:116209.
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5. Ikeda S, Nakamura E, Narusawa K, et al. Comparison of once-weekly teriparatide and alendronate against new osteoporotic vertebral fractures at week 12. J Bone Miner Metab 2020;38:44-53.
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6. Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2018;391:230-40.
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