Abstract
Introduction
This post hoc analysis of the placebo-controlled phase 3 FRAME study assessed the efficacy and safety of romosozumab in a subpopulation of Japanese postmenopausal women with osteoporosis and chronic kidney disease (CKD).
Materials and methods
Data were analyzed by baseline estimated glomerular filtration rate (eGFR), where < 90 mL/min/1.73 m2 denoted CKD and ≥ 90 mL/min/1.73 m2 indicated normal renal function. Efficacy outcomes included percent change in lumbar spine, total hip, and femoral neck bone mineral density (BMD) at 12 months from baseline (primary) and incidence of new vertebral and non-vertebral fractures. Tolerability was also assessed.
Results
Of 489 Japanese patients with available eGFR data, 339 had mild-to-moderate CKD (romosozumab, n = 170; placebo, n = 169) and 150 had normal renal function (romosozumab, n = 75; placebo, n = 75). Compared with placebo, romosozumab increased lumbar spine BMD by 14.8% (95% confidence interval [CI] 13.7–15.9) and 15.2% (95% CI 13.4–16.9) in the eGFR < 90 and ≥ 90 mL/min/1.73 m2 subgroups, total hip BMD by 4.6% (95% CI 3.8–5.4) and 5.5% (95% CI 4.4–6.7), and femoral neck BMD by 4.0% (95% CI 2.9–5.2) and 5.5% (95% CI 3.8–7.1) at 12 months, respectively (all p < 0.001 vs. placebo). New vertebral fracture incidence was numerically lower with romosozumab than placebo at 12 months in both eGFR subgroups, while the incidence of adverse events was similar between subgroups.
Conclusion
Romosozumab for 12 months is an effective and well-tolerated treatment option for Japanese patients with osteoporosis and mild-to-moderate CKD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Qualified researchers may request data from Amgen clinical studies. Complete details are available at the following: https://wwwext.amgen.com/science/clinical-trials/clinical-data-transparency-practices/.
References
Yoshimura N, Nakamura K (2016) Epidemiology of locomotive organ disorders and symptoms: an estimation using the population-based cohorts in japan. Clin Rev Bone Miner Metab 14:68–73
Takeuchi M, Shinkawa K, Yanagita M, Kawakami K (2021) Prevalence, recognition and management of chronic kidney disease in Japan: population-based estimate using a healthcare database with routine health checkup data. Clin Kidney J. https://doi.org/10.1093/ckj/sfab016
Broadwell A, Chines A, Ebeling PR, Franek E, Huang S, Smith S, Kendler D, Messina O, Miller PD (2021) Denosumab safety and efficacy among participants in the FREEDOM extension study with mild to moderate chronic kidney disease. J Clin Endocrinol Metab 106:397–409
Klawansky S, Komaroff E, Cavanaugh PF Jr, Mitchell DY, Gordon MJ, Connelly JE, Ross SD (2003) Relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 14:570–576
Chen H, Lips P, Vervloet MG, van Schoor NM, de Jongh RT (2018) Association of renal function with bone mineral density and fracture risk in the Longitudinal Aging Study Amsterdam. Osteoporos Int 29:2129–2138
Elliott MJ, James MT, Quinn RR, Ravani P, Tonelli M, Palacios-Derflingher L, Tan Z, Manns BJ, Kline GA, Ronksley PE, Hemmelgarn BR (2013) Estimated GFR and fracture risk: a population-based study. Clin J Am Soc Nephrol 8:1367–1376
McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370:412–420
Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26:19–26
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375:1532–1543
Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A (2019) One year of romosozumab followed by two years of denosumab maintains fracture risk reductions: results of the FRAME extension study. J Bone Miner Res 34:419–428
Miyauchi A, Dinavahi RV, Crittenden DB, Yang W, Maddox JC, Hamaya E, Nakamura Y, Libanati C, Grauer A, Shimauchi J (2019) Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos 14:59
Miyauchi A, Hamaya E, Yang W, Nishi K, Libanati C, Tolman C, Shimauchi J (2021) Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial. J Bone Miner Metab 39:278–288
Amgen, Astellas (2021) Evenity® subcutaneous injection 105 mg: package insert in Japan (in Japanese). https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/112922_3999449G1025_1_06. Accessed 8 Sept 2021
Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8:819–823
Drueke TB, Lafage-Proust MH (2011) Sclerostin: just one more player in renal bone disease? Clin J Am Soc Nephrol 6:700–703
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F, Collaboration CKDE (2007) Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53:766–772
Kidney Disease: Improving Global Outcomes, CKD-MBD Update Work Group (2017) KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2011:1–59
Imai E, Yasuda Y, Makino H (2011) Japan Association of Chronic Kidney Disease Initiatives (J-CKDI). Japan Med Assoc J 56:403–405
Ensrud KE, Lui LY, Taylor BC, Ishani A, Shlipak MG, Stone KL, Cauley JA, Jamal SA, Antoniucci DM, Cummings SR, Osteoporotic Fractures Research Group (2007) Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 167:133–139
Nitta K, Yajima A, Tsuchiya K (2017) Management of osteoporosis in chronic kidney disease. Intern Med 56:3271–3276
Cejka D, Marculescu R, Kozakowski N, Plischke M, Reiter T, Gessl A, Haas M (2014) Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 99:248–255
Martin M, Sansalone V, Cooper DML, Forwood MR, Pivonka P (2020) Assessment of romosozumab efficacy in the treatment of postmenopausal osteoporosis: results from a mechanistic PK-PD mechanostat model of bone remodeling. Bone 133:115223
Miller P, Adachi J, Albergaria BH, Cheung AM, Chines A, Gielen E, Langdahl B, Miyauchi A, Oates M, Reid I, Ruiz Santiago N, Vanderkelen M, Yang W, Yu Z (2020) OP0297 efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. Ann Rheum Dis 79:185
Acknowledgements
The authors wish to thank Marion Barnett, who wrote the outline of this manuscript on behalf of inScience Communications, Springer Healthcare, and Sarah Greig, Ph.D., of inScience Communications, Springer Healthcare, who wrote the first draft. This medical writing assistance was funded by Amgen K.K.
Funding
Amgen Inc., Astellas Pharma Inc., and UCB Pharma Inc. sponsored this study (NCT01575834).
Author information
Authors and Affiliations
Contributions
AM enrolled patients. EH provided the concept for the study and contributed to subgroup analysis study design, interpretation, preparation of discussion, and provision of references. CT was involved in conception and interpretation of the manuscript. KN contributed to the confirmation of the contents and interpretation of the safety results. JS performed the statistical analysis and provided interpretation. All authors read and approved drafts of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
A. Miyauchi received consulting fees from Amgen K.K., and Teijin Pharma. E. Hamaya, K. Nishi, and J. Shimauchi are employees of Amgen K.K., and E. Hamaya owns stock in Amgen Inc. C. Tolman is an employee of Amgen K.K. and owns stock in Amgen Inc.
Ethical approval
The trial was conducted according to the Declaration of Helsinki: ethical principles for medical research involving human subjects, and the study protocol was approved by the ethics committee or institutional review board at each study center. Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
About this article
Cite this article
Miyauchi, A., Hamaya, E., Nishi, K. et al. Efficacy and safety of romosozumab among Japanese postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. J Bone Miner Metab 40, 677–687 (2022). https://doi.org/10.1007/s00774-022-01332-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00774-022-01332-8