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Comparative Effectiveness of Drug Treatments to Prevent Fragility Fractures: A Systematic Review and Network Meta-Analysis
Abstract
CONTEXT: Osteoporosis and osteopenia are associated with increased fracture incidence. OBJECTIVE: The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures. DATA SOURCES: We searched multiple databases through 12/9/2011. STUDY SELECTION: Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D. DATA EXTRACTION: Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data. DATA SYNTHESIS: This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral fractures, respectively) and the highest probability of being ranked first for efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral fractures, respectively). However, differences to denosumab, zoledronate, risedronate, ibandronate, and alendronate were not statistically significant. Raloxifene and bazedoxifene were likely less effective, although these data were limited. Calcium and vitamin D were ineffective given separately but reduced the risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence interval, 0.68–0.96). CONCLUSIONS: Teriparatide, bisphosphonates, and denosumab are most effective in reducing the risk of fragility fractures. Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.
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“1) in community-dwelling individuals.[9,10] Therefore, the rationale for continuing to use calcium supplements for osteoporosis management is under question, and this questioning becomes even more acute when the possible side-effects of calcium supplements are considered.”
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“These general measures can be effective [13], especially in elderly subjects confined to nursing homes, and the vitamin D deficient; however, medical therapy is needed when a previous fracture has already occurred.”
BackgroundAdvances in Controlled Drug Delivery for Treatment of Osteoporosis
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“The Endocrine Society commissioned a network meta-analysis to inform recommendations of treatment for its 2012 clinical practice guideline for osteoporosis in men (47, 48).”
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Bell, K., Strand, H., & Inder, W. J. (2014) · Archives of Osteoporosis · doi:10.1007/s11657-013-0167-7 · Cited by 39
“Pharmacological treatment of osteoporosis has been shown to reduce the likelihood of fracture by between 50 and 67 % [40].”
BackgroundCost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan
Mori, T., Crandall, C. J., & Ganz, D. A. (2017) · Osteoporosis International · doi:10.1007/s00198-017-3940-4 · Cited by 39
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“systematic reviews compared denosumab with bisphosphonates; two meta-analyses used vertebral fracture as the endpoint,((9,10)) while two other reviews used differences in BMD changes((11)) and fragility fractures((12)) as endpoints in indirect head-to-head comparisons.”
Women’s Values and Preferences Regarding Osteoporosis Treatments: A Systematic Review
Barrionuevo, P., Gionfriddo, M. R., Castañeda-Guarderas, A., Zeballos-Palacios, C. L., Bora, P. R., Mohammed, K. S., Benkhadra, K., Sarigianni, M., & Murad, M. H. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00193 · Cited by 36
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Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis
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“Physical activity [5], supplementing with calcium and vitamin D, [6, 7] and pharmacological therapies [8] (including estrogen [9], bisphosphonates [10], denosumab [11], or teriparatide [12]) are the most commonly used clinical approaches for the prevention or treatment of osteoporosis.”
BackgroundKhatib, R., Santesso, N. A., Pickard, L. E., Osman, O., Giangregorio, L., Skidmore, C. J., & Παπαϊωάννου, Α. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-130 · Cited by 34
“Treatments to reduce the risk of fractures are available [12].”
BackgroundBone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial
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New and developing pharmacotherapy for osteoporosis in men
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“The relative efficacy of denosumab, alendronate, and ibandronate in preventing fractures remain controversial [6, 21, 26, 29].”
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“Currently there are several drug classes for the treatment of osteoporosis: estrogen , selective estrogen receptor modulators (SERMs) (such as raloxifene and bazedoxifene), antiresorptive drugs [such as bisphosphonates (BPs)], anabolic drugs [such as recombinant human parathormon (rh-PTH)], dual action drug (such as s…”
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Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures
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Osteoporosis therapy: a novel insight from natural homeostatic system in the skeleton
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Metadata
- Authors
- Murad, M. H., Drake, M. T., Mullan, R. J., Mauck, K. F., Stuart, L. M., Lane, M. A., Abu Elnour, N. O., Erwin, P. J., Hazem, A., Puhan, M. A., Li, T., & Montori, V. M.
- Affiliations
- Knowledge and Evaluation Research Unit (M.H.M., R.J.M., L.M.S., M.A.L., N.O.A.E., V.M.M.), Rochester, Minnesota 55905
- Division of Endocrinology, Diabetes, Metabolism, Nutrition (M.T.D., V.M.M.), Rochester, Minnesota 55905
- University of Minnesota Rochester (US)
- Mayo Clinic (US)
- University of North Dakota (US)
- Johns Hopkins University (US)
- Corresponding author
- Murad, Mohammad Hassan
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-06-01
- Volume
- 97
- Issue
- 6
- Pages
- 1871-1880
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2103599857
- Cited by
- 277
- References
- 48
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 12 · 2021: 18 · 2020: 33 · 2019: 36 · 2018: 23 · 2017: 15 · 2016: 27 · 2015: 23 · 2014: 35 · 2013: 23 · 2012: 7
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- fragility fractures, osteoporosis, osteopenia, fracture prevention, teriparatide, bisphosphonates, denosumab, selective estrogen receptor modulators, raloxifene, bazedoxifene, calcium and vitamin D, hip fracture, vertebral fractures, comparative effectiveness
- MeSH terms
- Denosumab, Antibodies, Monoclonal, Calcium, Humans, Osteoporosis, Vitamin D, Selective Estrogen Receptor Modulators, Bone Density Conservation Agents, Fractures, Bone, Antibodies, Monoclonal, Humanized
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