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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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“Osteoanabolics seem to have an advantage over antiresorptives, in terms of bone mass accrual [2], bone architecture and strength improvement [3] and fracture risk reduction [4].”
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“…with meta-analyses have shown zoledronic and alendronate to have similar efficiency on the reductions in the risks of different types of fractures (Murad et al., 2012; Zhou et al., 2016), there may exist a trade-off under investigation— zoledronic has a greater annual cost than alendronate but…”
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Kobza, A. O., Παπαϊωάννου, Α., Lau, A. N., & Adachi, J. D. (2020) · Immunotherapy · doi:10.2217/imt-2020-0158 · Cited by 20
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“We extracted data on the basis of the efficacy of these strategies from a recent network meta-analysis, including the risk of fracture after treatment in the target population.(10)”
MethodNasal salmon calcitonin blunts bone microstructure alterations in healthy postmenopausal women
Rizzoli, R., Sigaud, A., Azria, M., & Herrmann, F. R. (2014) · Osteoporosis International · doi:10.1007/s00198-014-2937-5 · Cited by 19
Alendronate alters osteoblast activities
Krüger, T. B., Herlofson, B. B., Landin, M. A., & Reseland, J. E. (2016) · Acta Odontologica Scandinavica · doi:10.1080/00016357.2016.1217041 · Cited by 19
“[3,4] ALN administration has shown significant, progressive increase in bone mineral density, and is known to reduce the incidence of hip, vertebral and non-vertebral fractures.[5] The structure of bone in the human skeleton varies, depending on site and developmental lineage.”
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“In our study, we estimated the comparative effectiveness among multiple osteoporotic treatments by using a recently published networkmeta-analysis, whichwe considered to be the best source of available data [28].”
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López-Delgado, L., Riancho‐Zarrabeitia, L., & Riancho, J. A. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2016.1154533 · Cited by 19
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“BMD t-score in BPs/control group less than −2.5 (20)/ less than −1.5 (9), −1.5 to −2.5 (13),no less than −2.5 (19) 0.709 (SD 0.003)g/cm2/ 0.698 (SD 0.004)g/cm2 Preoperative mean ODI scores in BPs/control group 20.3/21.6 - 36 (SD 10)/40 (SD 10) - 63.5 (SD 6.3)/64 (SD 5.67) 20.8 (SD 2.6)/21.9 (SD 2.6) 39.2 (SD 2.27)/38.…”
BackgroundInfluentialEffects of teriparatide retreatment in a patient with β‐thalassemia major
Tournis, S., Dede, A. D., Savvidis, C., Triantafyllopoulos, I. Κ., Kattamis, A., & Παπαϊωάννου, Ν. (2015) · Transfusion · doi:10.1111/trf.13237 · Cited by 17
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Isolated Compounds from Turpinia formosana Nakai Induce Ossification
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“Although these drugs were found to be effective at controlling osteoporosis, their long-term use is associated with adverse effects particularly in patients with lower risk of fractures [5,6].”
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Self-citationPHARMACOLOGICAL MANAGEMENT OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN: THE CURRENT STATE OF THE ART
Gatti, D., & Fassio, A. (2019) · Journal of Population Therapeutics and Clinical Pharmacology · doi:10.15586/jptcp.v26i4.646 · Cited by 31
Osteoporosis in older persons: current pharmacotherapy and future directions
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“The four most commonly used bisphosphonates include three oral (alendronate, risedronate and ibandronate) and one intravenous (zoledronate) [28].”
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“Notwithstanding, a meta-analysis showed that calcium and vitamin D supplementation was ineffective in preventing vertebral fractures (24).”
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“to vertebral fractures increases with number and severity [8, 9], and treatments that can reduce the risk are available [10].”
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Eastell, R. (2012) · Medicine · doi:10.1016/j.mpmed.2012.10.007 · Cited by 13
Effect of Clodronate Treatment on Risk of Fracture: A Systematic Review and Meta-analysis
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“The results of recent meta-analyses that have evaluated the efficacy of available therapies (bisphosphonates, teriparatide, selective oestrogen receptor modulators, denosumab, or calcium and vitamin D) in reducing the risk of fragility fractures in post-menopausal osteoporosis have concluded that differences in effica…”
ResultIdentification and management of osteoporosis in older adults
Eastell, R. (2016) · Medicine · doi:10.1016/j.mpmed.2016.10.011 · Cited by 12
Albert, S. G., & Wood, E. M. (2021) · Endocrine Practice · doi:10.1016/j.eprac.2021.06.015 · Cited by 11
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“In comparison to previous studies evaluating the effectiveness of other anti-osteoporotic agents for fragility fractures, BPs have shown better efficacy than other anti-osteoporotic agents such as raloxifene, and bazedoxifene [43].”
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Keppler, A. M., Kraus, M., Blaschke, M., Thomasser, N., Kammerlander, C., Böcker, W., Neuerburg, C., & Stumpf, U. C. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10040848 · Cited by 9
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“Although these drugs effectively reduce the incidence of fragility fractures in patients with postmenopausal osteoporosis, the reduction in risk is no greater than 70 % [2].”
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“Compared with placebo, bisphosphonates, parathyroid hormone analog (PTH1-34, teriparatide), denosumab, selective estrogen receptor modulators, and the combination of calcium and vitamin D have all been shown to reduce fracture risk and are supported by at least moderate quality evidence (MacLean et al., 2008; Murad et…”
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Menopause-related osteoporosis
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Hsu, Y., Xu, X., & Jeong, S. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-319-69287-6_25 · Cited by 8
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“Bisphosphonates inhibit bone resorption and are a common and important therapeutic agent for low bone density as they prevent fractures in osteoporosis and osteopenia [42,53,54].”
BackgroundLeslie, W. D., Edwards, B. J.-A., Al‐Azazi, S., Yan, L., Lix, L. M., Czaykowski, P. M., & Singh, H. (2020) · Osteoporosis International · doi:10.1007/s00198-020-05596-6 · Cited by 7
Iwamoto, J., & Seki, A. (2015) · Calcified Tissue International · doi:10.1007/s00223-015-0006-5 · Cited by 7
“Although these drugs effectively reduce the incidence of fragility fractures in patients with postmenopausal osteoporosis, the reduction in risk is no greater than 70 % [2].”
Wiedemann, A., Renard, É., Molin, A., Weryha, G., Oussalah, A., Guéant, J., & Feillet, F. (2020) · Calcified Tissue International · doi:10.1007/s00223-020-00704-4 · Cited by 7
Peng, Y., Langermann, S., Kothari, P., Liu, L. L., Zhao, W., Hu, Y., Chen, Z., Perini, M. M. D. L., Li, J., Cao, J., et al. (2023) · JBMR Plus · doi:10.1002/jbm4.10825 · Cited by 7
“[78,79] However, two recent studies did not observe signi fi cant changes in BMD of the lower extremities of individuals with SCI after 6 months of teri-paratide coupled with mechanical loading or vibration, [80,81] suggesting an uncertain role of teriparatide in the treatment of bone loss after SCI.”
ResultUpper gastrointestinal safety and tolerability of oral alendronate: A meta-analysis
Zhou, M., Zheng, Y., Li, J., Wu, J., XU, W., Cui, L., Yao, W., & LIU, Y. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2848 · Cited by 7
Wiznia, D. H., Ndon, S. U., Kim, C.-Y., Zaki, T. D., & Leslie, M. P. (2016) · Geriatric Orthopaedic Surgery & Rehabilitation · doi:10.1177/2151458516681635 · Cited by 7
Reynolds, A. W., Liu, G., Kocis, P. T., Skowronski, J. N., LESLIE, D. L., & Fox, E. (2018) · Intern J Endocrinol Metab · doi:10.5812/ijem.12104 · Cited by 7
“Pharmacologic treatments for osteoporosis have been shown in randomized controlled trials to reduce the incidence of vertebrae fractures by approximately 50% and non - vertebral fractures by about 30% (3-5).”
BackgroundResultYou, R., & Liu, Z. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.575893 · Cited by 7
“…Beta Murad et al. (2012) Relative risk of wrist fracture 0.50 0.34–0.73 Beta Wells et al. (2008) Relative risk of other fractures 0.78 0.66–0.92 Beta Murad et al. (2012) Persistence rate 0.57 (year 1) N/A N/A Cheng et al. (2013) Compliance rate 0.71 (year 1) N/A N/A Cheng et al. (2013),…”
BackgroundInfluentialCazzaniga, M. E., Giordano, M., Bandera, M., Cassani, C., Bounous, V. E., Lania, A. G., Biasi, G., Destro, M., Ricci, S., Lucini, D., et al. (2021) · Clinical Breast Cancer · doi:10.1016/j.clbc.2021.01.010 · Cited by 7
Controversies in osteoporosis management
Reid, I. R. (2016) · Internal Medicine Journal · doi:10.1111/imj.13131 · Cited by 6
Aktuelle Osteoporoseprophylaxe und -therapie
Bartl, R., & Bärtl, C. (2015) · Der Internist · doi:10.1007/s00108-015-3791-z · Cited by 6
Takeuchi, Y., Hamaya, E., Taketsuna, M., & Sowa, H. (2015) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000441 · Cited by 6
Chiu, W., Lin, C., Yang, W., Tsai, K., & Reginster, J. (2019) · Osteoporosis International · doi:10.1007/s00198-019-05127-y · Cited by 6
Zhao, S., Zhao, W., Du, D., Zhang, C., Zhao, T., Zheng, L., Jin, L., Gu, M., Xu, J., & Yang, Z. (2021) · Journal of Investigative Medicine · doi:10.1136/jim-2021-001961 · Cited by 6
Kraus, M., Neuerburg, C., Thomasser, N., Stumpf, U. C., Blaschke, M., Plötz, W., Saller, M. M., Böcker, W., & Keppler, A. M. (2022) · Medicina · doi:10.3390/medicina58111564 · Cited by 6
Trichilo, S., & Pivonka, P. (2017) · Courses and lectures · doi:10.1007/978-3-319-58845-2_2 · Cited by 6
Should Vitamin D Supplementation Be a Regular Part of Asthma Care?
Gordon, B. R. (2013) · Otolaryngologic Clinics of North America · doi:10.1016/j.otc.2013.08.013 · Cited by 6
Executive Summary- Lebanese FRAX-Based Osteoporosis Guidelines 2013
Chakhtoura, M., Baddoura, R., Fuleihan, G. E., Arabi, A., Halaby, G., Uthman, I. W., Okais, J., Salti, I., Seoud, M., Taha, A., et al. (2013) · Cited by 5
Agarwal, A. R., Kinnard, M. J., Murdock, C. J., Zhao, A. Y., Ahiarakwe, U., Cohen, J. S., Moseley, K. F., Golladay, G. J., & Thakkar, S. C. (2024) · Osteoporosis International · doi:10.1007/s00198-024-07085-6 · Cited by 5
“Osteoporosis pharmacotherapy is effective in preventing fragility fractures [4].”
Actualización en el tratamiento de la osteoporosis: manejo desde una unidad del dolor (1.ª parte)
Alvarez, R. M., Garcés, F. M., Mollinedo, F. T., Orcasitas, A. C., & Maguregui, A. A. (2014) · Revista de la Sociedad Española del Dolor · doi:10.4321/s1134-80462014000600006 · Cited by 5
“La asociación de alendronato y hormona paratiroidea (1-84) produce un efecto similar sobre la DMO lumbar que los fármacos por separado, no existen sinergias entre ellos (58).”
BackgroundInfluentialDenosumab for glucocorticoid-induced osteoporosis
Reid, I. R. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0035-z · Cited by 5
Løbo, R. A. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4557-2758-2.00015-9 · Cited by 5
Kao, F., Hsu, Y., Chen, T., Tu, Y., & Liu, P. (2020) · Clinical Therapeutics · doi:10.1016/j.clinthera.2020.04.011 · Cited by 5
Obo, T., Fujishiro, T., Mizutani, M., Yano, T., Hayama, S., Nakaya, Y., Nakano, A., & Neo, M. (2021) · World Neurosurgery · doi:10.1016/j.wneu.2021.02.096 · Cited by 5
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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