Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Romosozumab reportedly increases bone mineral density (BMD) potently but might adversely affect cardiovascular disease (CVD). We evaluated the efficacy of romosozumab in osteoporotic HD patients with a high risk of fracture.

Materials and methods

This was a single-center 1-year study in Japanese HD patients. Among 96 HD romosozumab-treated HD patients with high risk of fracture, 76 HD patients completed 1 year of subcutaneous administration of romosozumab (210 mg/4 weeks) for 1 year. Romosozumab-untreated HD patients (n = 55) were also included. Changes in BMD and serum markers, together with fracture occurrence, and CVD events, were monitored.

Results

During romosozumab treatment of 76 HD patients, BMD time-dependently increased significantly by 15.3% ± 12.9% at the lumbar spine (L1–4), and 7.2% ± 8.3% at the femoral neck at 1 year. Serum BAP and total P1NP increased significantly and serum TRACP-5b decreased at 4 weeks. Fragility fractures occurred in three (3.8%) patients. Hypocalcemia occurred at 4–48 weeks despite the increased dosing of active vitamin-D derivatives, but without any symptom. New CVD events occurred in 5.2% of romosozumab-treated HD patients and10.9% in romosozumab-untreated HD patients.

Conclusions

BMD was increased significantly during romosozumab treatment at the lumbar spine, and the femoral neck, respectively, at 1 year in HD patients. Hypocalcemia occurred but without any intolerable event. There was no apparent increase in CVD events during 1 year of study, suggesting romosozumab as a promising agent for HD patients with severe osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Nitta K, Goto S, Masakane I, Hanafusa N, Taniguchi M, Hasegawa T, Nakai S, Wada A, Hamano T, Hoshino J, Joki N (2020) Annual dialysis data report for 2018, JSDT Renal Data Registry: survey methods, facility data, incidence, prevalence, and mortality. Ren Replace Ther 6:41

    Article  Google Scholar 

  2. Vilaca T, Salam S, Schini M, Harnan S, Sutton A, Poku E, Allen IE, Cummings SR, Eastell R (2020) Risks of hip and nonvertebral fractures in patients with CKD G3a–G5D: a systematic review and meta-analysis. Am J Kidney Dis 76:521–532

    Article  Google Scholar 

  3. Maeno Y, Inaba M, Okuno S, Kohno K, Maekawa K, Yamakawa T, Ishimura E, Nishizawa Y (2009) Significant association of fracture of the lumbar spine with mortality in female hemodialysis patients: a prospective observational study. Calcif Tissue Int 85:310–316

    Article  CAS  Google Scholar 

  4. Kanazawa I, Inaba M, Inoue D, Uenishi K, Saito M, Shiraki M, Suzuki A, Takeuchi Y, Hagino H, Fujiwara S, Sugimoto T (2020) Executive summary of clinical practice guide on fracture risk in lifestyle diseases. J Bone Miner Metab 38:746–758

    Article  Google Scholar 

  5. Kidney Disease (2009) Improving global outcomes (KDIGO) CKD–MBD Work Group: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD–MBD). Kidney Int Suppl 113:S1–S130

    Google Scholar 

  6. Wakasugi M, Kazama JJ, Wada A, Hamano T, Masakane I, Narita I (2020) Long-term excess mortality after hip fracture in hemodialysis patients: a nationwide cohort study in Japan. J Bone Miner Metab 38:718–729

    Article  Google Scholar 

  7. Tentori F, McCullough K, Kilpatrick RD, Bradbury BD, Robinson BM, Kerr PG, Pisoni RL (2014) High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int 85:166–173

    Article  Google Scholar 

  8. Hickson LJ, Farah WH, Johnson RL, Thorsteinsdottir B, Ubl DS, Yuan BJ, Albright R, Rule AD, Habermann EB (2018) Death and postoperative complications after hip fracture repair: dialysis effect. Kidney Int Rep. 3:1294–1303

    Article  Google Scholar 

  9. Pharmaceuticals and Medical Devices Agency (2019) Evenity subcutaneous injection 105 mg. Prescribing information https://www.pmda.go.jp/PmdaSearch/iyakuDetail/112922_3999449G1025_1_03#WARNINGS (in Japanese)

  10. Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA (2016) Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 375:1532–1543

    Article  CAS  Google Scholar 

  11. Fabre S, Funck-Brentano T, Cohen-Solal M (2020) Anti-sclerostin antibodies in osteoporosis and other bone diseases. J Clin Med 9:3439

    Article  CAS  Google Scholar 

  12. Fixen C, Tunoa J (2021) Romosozumab: a review of efficacy, safety, and cardiovascular risk. Curr Osteoporos Rep 19(1):15–22. https://doi.org/10.1007/s11914-020-00652-w

    Article  PubMed  Google Scholar 

  13. Sakura M, Inaba M, Yoda K, Ichii M, Yamada S, Yamakawa T, Ishimura E, Okuno S, Shoji S (2016) High coronary heart disease risk in hemodialysis patients with central sleep apnea: a pilot study. Am J Nephrol 44:388–395

    Article  Google Scholar 

  14. Inaba M, Okuno S, Nagayama H, Yamada S, Ishimura E, Imanishi Y, Shoji S (2015) Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone. J Ren Nutr 25:242–246

    Article  CAS  Google Scholar 

  15. Japan Osteoporosis Society (2015) Guideline for prevention and treatment of osteoporosis 2015. Life Science Publishing (in Japanese)

  16. Shidara K, Inaba M, Okuno S, Yamada S, Kumeda Y, Imanishi Y, Yamakawa T, Ishimura E, Nishizawa Y (2008) Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients. Calcif Tissue Int 82:278–287

    Article  CAS  Google Scholar 

  17. Yamada S, Inaba M, Kurajoh M, Shidara K, Imanishi Y, Ishimura E, Nishizawa Y (2008) Utility of serum tartrate-resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction. Clin Endocrinol 69:189–196

    Article  CAS  Google Scholar 

  18. Ueda M, Inaba M, Okuno S, Maeno Y, Ishimura E, Yamakawa T, Nishizawa Y (2005) Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH. Life Sci 77:1130–1139

    Article  CAS  Google Scholar 

  19. Ueda M, Inaba M, Okuno S, Nagasue K, Kitatani K, Ishimura E, Shimizu M, Miki T, Kim M, Nishizawa Y (2002) Clinical usefulness of the serum N-terminal propeptide of type I collagen as a marker of bone formation in hemodialysis patients. Am J Kidney Dis 40:802–809

    Article  CAS  Google Scholar 

  20. Nishizawa Y, Miura M, Ichimura S, Inaba M, Imanishi Y, Shiraki M, Takada J, Chaki O, Hagino H, Fukunaga M, Fujiwara S (2019) Executive summary of the Japan Osteoporosis Society Guide for the use of bone turnover markers in the diagnosis and treatment of osteoporosis. Clin Chim Acta 498:101–107

    Article  CAS  Google Scholar 

  21. Kohno K, Inaba M, Okuno S, Maeno Y, Maekawa K, Yamakawa T, Ishimura E, Nishizawa Y (2009) Association of reduction in bone mineral density with mortality in male hemodialysis patients. Calcif Tissue Int 84:180–185

    Article  CAS  Google Scholar 

  22. Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M (2013) Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial 17:247–288

    Article  Google Scholar 

  23. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A (2017) Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 377:1417–1427

    Article  CAS  Google Scholar 

  24. Genant HK, Engelke K, Bolognese MA, Mautalen C, Brown JP, Recknor C, Goemaere S, Fuerst T, Yang YC, Grauer A, Libanati C (2017) Effects of Romosozumab compared with teriparatide on bone density and mass at the spine and hip in postmenopausal women with low bone mass. J Bone Miner Res 32:181–187

    Article  CAS  Google Scholar 

  25. Lin ZZ, Wang JJ, Chung CR, Huang PC, Su BA, Cheng KC, Chio CC, Chien CC (2014) Epidemiology and mortality of hip fracture among patients on dialysis: Taiwan national cohort study. Bone 64:235–239

    Article  Google Scholar 

  26. Kunizawa K, Kunizawa K, Hiramatsu R, Hoshino J, Mizuno H, Ozawa Y, Sekine A, Kawada M, Sumida K, Hasegawa E, Yamanouchi M, Hayami N, Suwabe T, Sawa N, Ubara Y, Takaichi K (2020) Denosumab for dialysis patients with osteoporosis: a cohort study. Sci Rep 10:2496

    Article  CAS  Google Scholar 

  27. Malluche HH, Mawad H, Monier-Faugere MC (2008) Effects of treatment of renal osteodystrophy on bone histology. Clin J Am Soc Nephrol 3:S157–S163

    Article  Google Scholar 

  28. London GM, Marchais SJ, Guérin AP, Boutouyrie P, Métivier F, de Vernejoul MC (2008) Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol 19:1827–1835

    Article  CAS  Google Scholar 

  29. D’Haese PC, Spasovski GB, Sikole A, Hutchison A, Freemont TJ, Sulkova S, Swanepoel C, Pejanovic S, Djukanovic L, Balducci A, Coen G (2003) A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int Suppl 85:S73–S78

    Article  CAS  Google Scholar 

  30. Musci I, Hercz G (1997) Adynamic bone disease: pathogenesis, diagnosis and clinical relevance. Curr Opin Nephrol Hypertens 7:356–361

    Google Scholar 

  31. Kumar M, Shelke D, Shah S (2019) Prognostic potential of markers of bone turnover in delayed-healing tibial diaphyseal fractures. Eur J Trauma Emerg Surg 45:31–38

    Article  Google Scholar 

  32. Iwata K, Mashiba T, Hitora T, Yamagami Y, Yamamoto T (2014) A large amount of microdamages in the cortical bone around fracture site in a patient of atypical femoral fracture after long-term bisphosphonate therapy. Bone 64:183–186

    Article  Google Scholar 

  33. Yamashita J, McCauley LK (2019) Effects of intermittent administration of parathyroid hormone and parathyroid hormone-related protein on fracture healing: a narrative review of animal and human studies. JBMR Plus 3:e10250

    Article  CAS  Google Scholar 

  34. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370:412–420

    Article  CAS  Google Scholar 

  35. Miyaoka D, Inaba M, Imanishi Y, Hayashi N, Ohara M, Nagata Y, Kurajoh M, Yamada S, Mori K, Emoto M (2019) Denosumab improves glomerular filtration rate in osteoporotic patients with normal kidney function by lowering serum phosphorus. J Bone Miner Res 34:2028–2035

    Article  CAS  Google Scholar 

  36. Kang JH, Keller JJ, Lin HC (2013) Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos Int 24:271–277

    Article  CAS  Google Scholar 

  37. Burger D, Levin A (2013) “Shedding” light on mechanisms of hyperphosphatemic vascular dysfunction. Kidney Int 83:187–189

    Article  CAS  Google Scholar 

  38. Ma L, Zhao S (2017) Risk factors for mortality in patients undergoing hemodialysis: a systematic review and meta-analysis. Int J Cardiol 238:151–158

    Article  Google Scholar 

  39. Miyaoka D, Imanishi Y, Ohara M, Hayashi N, Nagata Y, Yamada S, Mori K, Emoto M, Inaba M (2019) Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency. Osteoporos Int 30:241–249

    Article  CAS  Google Scholar 

  40. Yamamoto M, Kawanobe Y, Takahashi H, Shimazawa E, Kimura S, Ogata E (1984) Vitamin D deficiency and renal calcium transport in the rat. J Clin Invest 74:507–513

    Article  CAS  Google Scholar 

  41. Cavalier E, Souberbielle JC, Delanaye P (2019) PTH determination in hemodialyzed patients—a laboratory perspective. Semin Dial 32:490–492

    Article  Google Scholar 

  42. Yajima A, Inaba M, Tominaga Y, Ito A (2007) Minimodeling reduces the rate of cortical bone loss in patients with secondary hyperparathyroidism. Am J Kidney Dis 49:440–451

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, Inoue Hospital, Osaka, Japan

    Motohiko Sato

  2. Renal Center, Inoue Hospital, Osaka, Japan

    Yoshihiro Tsujimoto

  3. Renal Center, Ohno Memorial Hospital, 1-26-10, Minami-Horie, Nishi-ku, Osaka, Osaka, 550-0015, Japan

    Masaaki Inaba & Yoshiteru Ohno

  4. Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Medical School, Osaka, Japan

    Shinsuke Yamada & Masanori Emoto

Authors
  1. Motohiko Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masaaki Inaba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinsuke Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masanori Emoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshiteru Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshihiro Tsujimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MS: contributed to the study design, performed study, data analysis, drafted the main manuscript, and provided final approval for submission; MI: contributed to the study design, performed study, data analysis, reviewed the manuscript critically for important intellectual content, and provided final approval for submission; SY: contributed to performed data analysis, and provided final approval for submission; ME: reviewed the manuscript critically for important intellectual content and provided final approval for submission; YO: reviewed the manuscript critically for important intellectual content, and provided final approval for submission; and YT: reviewed the manuscript critically for important intellectual content, and provided final approval.

Corresponding author

Correspondence to Masaaki Inaba.

Ethics declarations

Conflict of interest

M. S. has received personal fees from Amgen. M. I. has received lecture fee from Daiichi Sankyo. S. Y., Y. O., M. E., and Y. T. have nothing to disclose.

Ethical approval

The protocol was approved by the Ethics Review Committee of Inoue Hospital (Approval #250) and conducted in accordance with the principles of the Declaration of Helsinki. All patients provided consent to participate in this study.

Informed consent

All patients provided consent to participate in this study and written informed consent was obtained from each participant prior to participation.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, M., Inaba, M., Yamada, S. et al. Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study. J Bone Miner Metab 39, 1082–1090 (2021). https://doi.org/10.1007/s00774-021-01253-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-021-01253-y

Keywords

Search

Navigation