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Archives of Osteoporosis

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01-12-2023 | Stroke | Review Article

Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis

Authors: Rongjin Chen, Changshun Chen, Bin Geng, Chenhui Yang, Hefang Xiao, Fei Yang, Hao Wang, Yayi Xia

Published in: Archives of Osteoporosis | Issue 1/2023

Abstract

Purpose

Osteoporosis is a metabolic bone disease that commonly results in middle-aged and elderly people following fractures. Odanacatib (ODN), a potential osteoporosis medication, was stopped in the Long-term Odanacatib Fracture Trial (LOFT) phase III study because it increased the risk of stroke. Herein, we conducted a systematic review and meta-analysis to further assess the efficacy and safety of ODN in osteoporosis treatment.

Methods

We searched the PubMed, EMBASE, Cochrane Library, and Web of Science, using the core search terms “osteoporosis” and “odanacatib.” The primary outcomes were the percentage change in markers of bone turnover and bone formation as well as that in the bone mineral density (BMD) of the lumbar spine, hip, femoral neck, and greater trochanter. The secondary outcome was the risk of adverse events (AEs), used to explore the safety of ODN.

Results

Ten articles—all double-blinded, randomized, placebo-controlled trials—were included. All trials were considered to be of high quality if they met the inclusion and exclusion criteria. We found that ODN increases BMD in the lumbar spine, total hip, and femoral neck, whereas it decreases the concentration of serum C-telopeptides of type I collagen (sCTx) and urinary N-telopeptide/creatinine ratio (uNTx/Cr). We found no significant differences in total, drug-related, serious, or skin AEs between the ODN and control groups. However, significant differences in fracture and stroke AEs were found between the ODN and control groups.

Conclusion

ODN is an appealing long-term osteoporosis treatment method; however, further research should focus on the potential increased risk of fracture and stroke.

Amin S, Achenbach SJ, Atkinson EJ, Khosla S, Melton LJ 3rd (2014) Trends in fracture incidence: a population-based study over 20 years. J Bone Miner Res 29:581–589. https://doi.org/10.1002/jbmr.2072CrossRefPubMed

Petermann-Rocha F, Ferguson LD, Gray SR, Rodríguez-Gómez I, Sattar N, Siebert S, Ho FK, Pell JP, Celis-Morales C (2021) Association of sarcopenia with incident osteoporosis: a prospective study of 168,682 UK Biobank participants. J Cachexia Sarcopenia Muscle 12:1179–1188. https://doi.org/10.1002/jcsm.12757CrossRefPubMedPubMedCentral

Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C (2020) The epidemiology of osteoporosis. Br Med Bull 133:105–117. https://doi.org/10.1093/bmb/ldaa005CrossRefPubMed

Statham LA, Aspray TJ (2019) Odanacatib: the best osteoporosis treatment we never had? Lancet Diabetes Endocrinol 7:888–889. https://doi.org/10.1016/S2213-8587(19)30348-1CrossRefPubMed

Mullard A (2016) Merck & Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov 15:669. https://doi.org/10.1038/nrd.2016.207CrossRefPubMedPubMedCentral

Binkley N, Orwoll E, Chapurlat R, Langdahl BL, Scott BB, Giezek H, Santora AC (2021) Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis. Osteoporos Int 32:173–184. https://doi.org/10.1007/s00198-020-05701-9CrossRefPubMed

Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, Recker R, Dardzinski B, Verbruggen N, Ather S, Rosenberg E, de Papp AE (2013) Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial. J Clin Endocrinol Metab 98:571–580. https://doi.org/10.1210/jc.2012-2972CrossRefPubMed

Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, DaSilva C, Santora AC, Ince BA (2010) Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 25:937–947. https://doi.org/10.1359/jbmr.091035CrossRefPubMed

Bonnick S, De Villiers T, Odio A, Palacios S, Chapurlat R, DaSilva C, Scott BB, De Le BaillyTilleghem C, Leung AT, Gurner D (2013) Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial. J Clin Endocrinol Metab 98:4727–4735. https://doi.org/10.1210/jc.2013-2020CrossRefPubMed

10.

Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, Verbruggen N, Hustad CM, DaSilva C, Petrovic R, Santora AC, Ince BA, Lombardi A (2011) Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res 26:242–251. https://doi.org/10.1002/jbmr.212CrossRefPubMed

11.

Engelke K, Fuerst T, Dardzinski B, Kornak J, Ather S, Genant HK, de Papp A (2015) Odanacatib treatment affects trabecular and cortical bone in the femur of postmenopausal women: results of a two-year placebo-controlled trial. J Bone Miner Res 30:30–38. https://doi.org/10.1002/jbmr.2292CrossRefPubMed

12.

Langdahl B, Binkley N, Bone H, Gilchrist N, Resch H, Rodriguez Portales J, Denker A, Lombardi A, De Le BaillyTilleghem C, Dasilva C, Rosenberg E, Leung A (2012) Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res 27:2251–2258. https://doi.org/10.1002/jbmr.1695CrossRefPubMed

13.

McClung MR, O’Donoghue ML, Papapoulos SE, Bone H, Langdahl B, Saag KG, Reid IR, Kiel DP, Cavallari I, Bonaca MP, Wiviott SD, de Villiers T, Ling X, Lippuner K, Nakamura T, Reginster JY, Rodriguez-Portales JA, Roux C, Zanchetta J, Zerbini CAF, Park JG, Im K, Cange A, Grip LT, Heyden N, DaSilva C, Cohn D, Massaad R, Scott BB, Verbruggen N, Gurner D, Miller DL, Blair ML, Polis AB, Stoch SA, Santora A, Lombardi A, Leung AT, Kaufman KD, Sabatine MS, investigators L (2019) Odanacatib for the treatment of postmenopausal osteoporosis: results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT extension study. Lancet Diabetes Endocrinol 7:899–911. https://doi.org/10.1016/S2213-8587(19)30346-8CrossRefPubMed

14.

Nakamura T, Shiraki M, Fukunaga M, Tomomitsu T, Santora AC, Tsai R, Fujimoto G, Nakagomi M, Tsubouchi H, Rosenberg E, Uchida S (2014) Effect of the cathepsin K inhibitor odanacatib administered once weekly on bone mineral density in Japanese patients with osteoporosis—a double-blind, randomized, dose-finding study. Osteoporos Int 25:367–376. https://doi.org/10.1007/s00198-013-2398-2CrossRefPubMed

15.

Recker R, Dempster D, Langdahl B, Giezek H, Clark S, Ellis G, de Villiers T, Valter I, Zerbini CA, Cohn D, Santora A, Duong LT (2020) Effects of odanacatib on bone structure and quality in postmenopausal women with osteoporosis: 5-year data from the phase 3 long-term odanacatib fracture trial (LOFT) and its extension. J Bone Miner Res 35:1289–1299. https://doi.org/10.1002/jbmr.3994CrossRefPubMed

16.

Feng S, Luo Z, Liu D (2015) Efficacy and safety of odanacatib treatment for patients with osteoporosis: a meta-analysis. J Bone Miner Metab 33:448–454. https://doi.org/10.1007/s00774-014-0609-3CrossRefPubMed

17.

Gajic-Veljanoski O, Tomlinson G, Srighanthan J, Adachi JD, Josse R, Brown JP, Cheung AM (2014) Effect of odanacatib on BMD and fractures: estimates from Bayesian univariate and bivariate meta-analyses. J Clin Endocrinol Metab 99:3070–3079. https://doi.org/10.1210/jc.2014-1162CrossRefPubMed

18.

Drake MT, Clarke BL, Oursler MJ, Khosla S (2017) Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev 38:325–350. https://doi.org/10.1210/er.2015-1114CrossRefPubMedPubMedCentral

19.

Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK (2006) Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 52:499–509PubMed

20.

Peroni A, Zini A, Braga V, Colato C, Adami S, Girolomoni G (2008) Drug-induced morphea: report of a case induced by Balicatib and review of the literature. J Am Acad Dermatol 59:125–129. https://doi.org/10.1016/j.jaad.2008.03.009CrossRefPubMed

Title: Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis
Authors: Rongjin Chen
Changshun Chen
Bin Geng
Chenhui Yang
Hefang Xiao
Fei Yang
Hao Wang
Yayi Xia
Publication date: 01-12-2023
Publisher: Springer London
Keywords: Stroke
Osteoporosis
Osteoporosis
Published in: Archives of Osteoporosis / Issue 1/2023
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI: https://doi.org/10.1007/s11657-023-01261-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and safety of odanacatib for osteoporosis treatment: a systematic review and meta-analysis

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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