Skip to main content

Advertisement

SpringerLink
Log in

Fracture risk associated with glucocorticoid-induced osteoporosis in Japan

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

Abstract

Introduction

Glucocorticoid-induced osteoporosis (GIOP) is associated with elevated fracture risk. Practice guidelines have been published to reduce this risk but are insufficiently followed in everyday practice. The objectives of this study were to estimate fracture incidence in patients exposed to oral glucocorticoids and to analyse the impact of glucocorticoid use on fracture incidence.

Materials and methods

This retrospective cohort study was performed using the Medical Data Vision (MDV) claims database from Japan. All patients aged ≥ 18 years initiating oral glucocorticoids and fulfilling Japanese guideline criteria for starting prophylactic osteoporosis treatment between 2009 and 2019 were identified. These were matched to a cohort of unexposed controls using propensity score matching. Fracture incidence in the two cohorts were compared using a Fine-Gray proportional sub-distribution hazard model.

Results

13,090 glucocorticoid-exposed cases were compared to 13,090 unexposed controls. The 1-year fracture rate (all sites) was 9.3 [95% CI 8.8–9.8] in cases and 5.8 [5.4–6.2] in controls. One-year vertebral fracture rates were 4.3 [4.0–4.7] and 2.3 [2.1–2.6] respectively. In the multivariate analysis, the use of glucocorticoids was associated with an increase in the incidence of osteoporotic fractures (hazard ratio: 1.63 [1.51–1.76]). The glucocorticoid-associated risk tended to be higher in subgroups of patients with rheumatoid arthritis, asthma, COPD and in those aged < 65 years.

Conclusion

Oral glucocorticoid use is associated with an increase in fracture incidence. It is necessary to raise awareness of GIOP and to take public health measures to change the perceptions and behaviour of doctors prescribing glucocorticoids.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. van Staa TP (2006) The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. Calcif Tissue Int 79:129–137

    Article  CAS  PubMed  Google Scholar 

  2. Buckley L, Humphrey MB (2018) Glucocorticoid-induced osteoporosis. N Engl J Med 379:2547–2556

    Article  PubMed  Google Scholar 

  3. Weinstein RS (2011) Clinical practice. Glucocorticoid-induced bone disease (in Eng). N Engl J Med 365:62–70

    Article  CAS  PubMed  Google Scholar 

  4. Weinstein RS (2012) Glucocorticoid-induced osteoporosis and osteonecrosis (in Eng). Endocrinol Metab Clin N Am 41:595–611

    Article  Google Scholar 

  5. Roux C, Thomas T, Paccou J, Bizouard G, Crochard A, Toth E, Lemaitre M, Maurel F, Perrin L, Tubach F (2021) Refracture and mortality following hospitalization for severe osteoporotic fractures: the Fractos study (in Eng). JBMR Plus 5:e10507

    Article  PubMed  PubMed Central  Google Scholar 

  6. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000

    Article  PubMed  Google Scholar 

  7. van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis (in Eng). Osteoporos Int 13:777–787

    Article  PubMed  Google Scholar 

  8. Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton IL, Tenenhouse A, Reeve J, Silman AJ, Pols HA, Eisman JA, McCloskey EV, Mellstrom D (2004) A meta-analysis of prior corticosteroid use and fracture risk (in Eng). J Bone Miner Res 19:893–899

    Article  PubMed  Google Scholar 

  9. Sugiyama T, Tatsuno I, Suzuki S, Yoshida T, Tanaka T, Sueishi M, Saito Y (2009) Incidence of symptomatic vertebral fracture with high-dose glucocorticoid treatment in the Chiba-Shimoshizu Rheumatic Cohort between 1986 and 2006. Endocr J 56:591–599

    Article  CAS  PubMed  Google Scholar 

  10. Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J et al (2017) 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 69:1095–1110

    Article  Google Scholar 

  11. Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, Hope S, Kanis JA, McCloskey EV, Poole KES, Reid DM, Selby P, Thompson F, Thurston A, Vine N, National Osteoporosis Guideline Group (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 12:43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Briot K, Cortet B, Roux C, Fardet L, Abitbol V, Bacchetta J, Buchon D, Debiais F, Guggenbuhl P, Laroche M, Legrand E, Lespessailles E, Marcelli C, Weryha G, Thomas T, Bone Section of the French Society for RO, Research Information Group (2014) 2014 update of recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis. Joint Bone Spine 81:493–501

    Article  PubMed  Google Scholar 

  13. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD, Scientific Advisory Council of Osteoporosis Canada (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–1873

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y, Subcommittee to Study Diagnostic Criteria for Glucocorticoid-Induced Osteoporosis (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109

    Article  PubMed  Google Scholar 

  15. Park SY, Gong HS, Kim KM, Kim D, Kim HY, Jeon CH, Ju JH, Lee SS, Park DA, Sung YK, Kim SW (2018) Korean guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. J Bone Metab 25:195–211

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kirigaya D, Nakayama T, Ishizaki T, Ikeda S, Satoh T (2011) Management and treatment of osteoporosis in patients receiving long-term glucocorticoid treatment: current status of adherence to clinical guidelines and related factors. Intern Med 50:2793–2800

    Article  CAS  PubMed  Google Scholar 

  17. Suzuki Y, Nawata H, Soen S, Fujiwara S, Nakayama H, Tanaka I, Ozono K, Sagawa A, Takayanagi R, Tanaka H, Miki T, Masunari N, Tanaka Y (2014) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research: 2014 update. J Bone Miner Metab 32:337–350

    Article  PubMed  Google Scholar 

  18. Soen S, Kaku M, Okubo N, Touzeni S, Saito K, Kobayashi M (2021) Epidemiology of glucocorticoid-induced osteoporosis and management of associated fracture risk in Japan (in Eng). J Bone Miner Metab 39:1019–1030

    Article  CAS  PubMed  Google Scholar 

  19. Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55

    Article  Google Scholar 

  20. Austin PC (2014) A comparison of 12 algorithms for matching on the propensity score (in Eng). Stat Med 33:1057–1069

    Article  PubMed  Google Scholar 

  21. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, Oden A, Zethraeus N, Pfleger B, Khaltaev N (2005) Assessment of fracture risk (in Eng). Osteoporos Int 16:581–589

    Article  PubMed  Google Scholar 

  22. Okazaki R, Watanabe R, Inoue D (2016) Osteoporosis associated with chronic obstructive pulmonary disease (in Eng). J Bone Metab 23:111–120

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kazama JJ (2017) Chronic kidney disease and fragility fracture (in Eng). Clin Exp Nephrol 21:46–52

    Article  CAS  PubMed  Google Scholar 

  24. Kumarathas I, Harsløf T, Andersen CU, Langdahl B, Hilberg O, Bjermer L, Løkke A (2020) The risk of osteoporosis in patients with asthma (in eng). European clinical respiratory journal 7:1763612

    Article  PubMed  PubMed Central  Google Scholar 

  25. Schacter GI, Leslie WD (2021) Diabetes and Osteoporosis: Part I, Epidemiology and Pathophysiology (in eng). Endocrinol Metab Clin North Am 50:275–285

    Article  PubMed  Google Scholar 

  26. Cauley JA, Hovey KM, Stone KL, Andrews CA, Barbour KE, Hale L, Jackson RD, Johnson KC, LeBlanc ES, Li W, Zaslavsky O, Ochs-Balcom H, Wactawski-Wende J, Crandall CJ (2019) Characteristics of self-reported sleep and the risk of falls and fractures: the women’s health initiative (WHI) (in Eng). J Bone Miner Res Off J Am Soc Bone Miner Res 34:464–474

    Article  CAS  Google Scholar 

  27. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  28. Kim D, Cho SK, Park B, Jang EJ, Bae SC, Sung YK (2018) Glucocorticoids are associated with an increased risk for vertebral fracture in patients with rheumatoid arthritis (in Eng). J Rheumatol 45:612–620

    Article  CAS  PubMed  Google Scholar 

  29. van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis (in Eng). Arthritis Rheum 54:3104–3112

    Article  PubMed  Google Scholar 

  30. Chalitsios CV, Shaw DE, McKeever TM (2021) Corticosteroids and bone health in people with asthma: a systematic review and meta-analysis (in Eng). Respir Med 181:106374

    Article  PubMed  Google Scholar 

  31. Chalitsios CV, Shaw DE, McKeever TM (2021) Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies (in Eng). Thorax 76:21–28

    Article  PubMed  Google Scholar 

  32. Weare-Regales N, Hudey SN, Lockey RF (2021) Practical guidance for prevention and management of glucocorticoid-induced osteoporosis for the allergist/immunologist (in Eng). J Allergy Clin Immunol Pract 9:1841–1850

    Article  PubMed  Google Scholar 

  33. Watanabe R, Tanaka T, Aita K, Hagiya M, Homma T, Yokosuka K, Yamakawa H, Yarita T, Tai N, Hirano J, Inoue D, Okazaki R (2015) Osteoporosis is highly prevalent in Japanese males with chronic obstructive pulmonary disease and is associated with deteriorated pulmonary function (in Eng). J Bone Miner Metab 33:392–400

    Article  PubMed  Google Scholar 

  34. Graat-Verboom L, Wouters EF, Smeenk FW, van den Borne BE, Lunde R, Spruit MA (2009) Current status of research on osteoporosis in COPD: a systematic review (in Eng). Eur Respir J 34:209–218

    Article  CAS  PubMed  Google Scholar 

  35. Lehouck A, Boonen S, Decramer M, Janssens W (2011) COPD, bone metabolism, and osteoporosis (in Eng). Chest 139:648–657

    Article  CAS  PubMed  Google Scholar 

  36. Mäkitie O, Zillikens MC (2021) Early-onset osteoporosis (in Eng). Calcif Tissue Int. https://doi.org/10.1007/s00223-021-00885-6

    Article  PubMed  PubMed Central  Google Scholar 

  37. Briot K (2018) Bone and glucocorticoids. Ann Endocrinol (Paris) 79:115–118

    Article  Google Scholar 

  38. Bhalla AK (2010) Management of osteoporosis in a pre-menopausal woman (in Eng). Best Pract Res Clin Rheumatol 24:313–327

    Article  PubMed  Google Scholar 

  39. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739

    Article  CAS  PubMed  Google Scholar 

  40. LaFleur J, McAdam-Marx C, Kirkness C, Brixner DI (2008) Clinical risk factors for fracture in postmenopausal osteoporotic women: a review of the recent literature (in Eng). Ann Pharmacother 42:375–386

    Article  PubMed  Google Scholar 

  41. Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jonsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Smoking and fracture risk: a meta-analysis (in Eng). Osteoporos Int 16:155–162

    Article  CAS  PubMed  Google Scholar 

  43. Austin PC, Latouche A, Fine JP (2020) A review of the use of time-varying covariates in the Fine-Gray subdistribution hazard competing risk regression model (in Eng). Stat Med 39:103–113

    Article  PubMed  Google Scholar 

  44. Bergh C, Wennergren D, Möller M, Brisby H (2020) Fracture incidence in adults in relation to age and gender: a study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area (in Eng). PLoS ONE 15:e0244291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was sponsored and funded by Daiichi Sankyo Co. Ltd. The authors thank Creativ-Ceutical for data acquisition and analysis for preparing this manuscript. The medical writing was provided by Dr. Adam Doble of Foxymed.

Author information

Authors and Affiliations

  1. Soen Orthopaedics, Osteoporosis and Rheumatology Clinic, Kobe, Japan

    Satoshi Soen

  2. Primary Medical Science Department, Medical Affairs Division, Japan Business Unit, Daiichi Sankyo Co. Ltd, 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426, Japan

    Miki Kaku, Kengo Saito & Makiko Kobayashi

  3. Data Intelligence Department, Digital Transformation Management Division, Daiichi Sankyo Co. Ltd, Tokyo, Japan

    Naoki Okubo

  4. Creativ-Ceutical, K.K., Tokyo, Japan

    Yoshie Onishi

Authors
  1. Satoshi Soen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miki Kaku
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoki Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshie Onishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kengo Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Makiko Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors are responsible for the work described in this paper. SS, MKaku, NO, KS, and MKobayashi were involved in the conception, design or planning of the study. NO and YO were involved in the analysis of data. SS, MKaku, NO, KS, and MKobayashi interpreted the study results. All authors contributed to development and critical review of the manuscript.

Corresponding author

Correspondence to Miki Kaku.

Ethics declarations

Conflict of interest

SS has received consulting fees, speaking fees or honoraria from Asahi Kasei Pharma, Astellas, Amgen, Daiichi Sankyo, Eli Lilly Japan, and UCB Japan. MKaku, NO and KS are employees of Daiichi Sankyo, a pharmaceutical company which markets medications for the treatment of osteoporosis. MKobayashi is a former employee of Daiichi Sankyo Co., Ltd. YO is an employee of Creativ-Ceutical, a consultancy company who received funding from Daiichi Sankyo for the implementation of this 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.

Supplementary file1 (DOCX 77 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soen, S., Kaku, M., Okubo, N. et al. Fracture risk associated with glucocorticoid-induced osteoporosis in Japan. J Bone Miner Metab 40, 636–647 (2022). https://doi.org/10.1007/s00774-022-01325-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-022-01325-7

Keywords

Search

Navigation