Current Osteoporosis Reports

, Volume 17, Issue 1, pp 1–7 | Cite as

Glucocorticoid-Induced Osteoporosis: New Insights into the Pathophysiology and Treatments

  • Nancy E. LaneEmail author
Therapeutics and Medical Management (S Jan de Beur and B Clarke, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Therapeutics and Medical Management


Purpose of this Review

The goal of the review is to provide an updated understanding of the pathophysiology of glucocorticoid-induced osteoporosis and treatment recommendations.

Recent Findings

Glucocorticoids reduce osteoblast and osteocyte lifespan and activity and reduce the vascularity of the bone that together may explain the greater reductions in bone strength than those of bone mass. Treatments with parathyroid hormone fragments appear to reverse glucocorticoid-induced bone loss and fracture risk partially through maintaining bone vascularity and bone strength.


This review identifies how glucocorticoid anti-osteogenic and vascular effects together may reduce bone strength. It also provides guidance to clinicians on rationale treatment for glucocorticoid-induced osteoporosis.


Glucocorticoids Bone cells Bone vascularity Osteonecrosis Parathyroid hormone 


Compliance with Ethical Standards

Conflict of Interest

Nancy Lane reports having a patent (LLP2A-ale) issued.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Weinstein RS. Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin N Am. 2012;41:595–611. Scholar
  2. 2.
    Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int. 2004;15:323–8. Scholar
  3. 3.
    Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. 2003;48(11):3224–9. Scholar
  4. 4.
    Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum. 2008;58:1674–86. Scholar
  5. 5.
    Yao W, Dai W, Jiang JX, Lane NE. Glucocorticoids and osteocyte autophagy. Bone. 2013;54(2):279–84. Scholar
  6. 6.
    Xia X, Kar R, Gluhak-Heinrich J, Yao W, Lane NE, Bonewald LF, et al. Glucocorticoid-induced autophagy in osteocytes. J Bone Miner Res. 2010;25(11):2479–88. Scholar
  7. 7.
    Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, et al. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res. 2006;21(3):466–76. Scholar
  8. 8.
    Jia J, Yao W, Guan M, Dai W, Shahnazari M, Kar R, et al. Glucocorticoid dose determines osteocyte cell fate. FASEB J. 2011;25(10):3366–76. Scholar
  9. 9.
    Uda Y, Azab E, Sun N, Shi C, Pajevic PD. Osteocyte Mechanobiology. Curr Osteoporos Rep. 2017;15(4):318–25. Scholar
  10. 10.
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102(2):274–82. Scholar
  11. 11.
    Nyman JS, Roy A, Shen X, Acuna RL, Tyler JH, Wang X. The influence of water removal on the strength and toughness of cortical bone. J Biomech. 2006;39(5):931–8. Scholar
  12. 12.
    Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O'Brien CA, et al. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell. 2010;9(2):147–61. Scholar
  13. 13.
    Weinstein RS. Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity. Bone. 2010;46(3):564–70. Scholar
  14. 14.
    Mohan G, Lay EY, Berka H, Ringwood L, Kot A, Chen H, et al. A novel hybrid compound LLP2A-Ale both prevented and rescued the osteoporotic phenotype in a mouse model of glucocorticoid-induced osteoporosis. Calcif Tissue Int. 2017;100(1):67–79. Scholar
  15. 15.
    Yang L, Boyd K, Kaste SC, Kamdem L, Rahija RJ, Relling MVA. Mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday. J Orthop Res. 2009;27(2):169–75. Scholar
  16. 16.
    Lane NE, Mohan G, Yao W, Shidara K, Lay YE, Junjing J, et al. Prevalence of glucocorticoid induced osteonecrosis in the mouse is not affected by treatments that maintain bone vascularity. Bone Reports. 2018;9:181–9.Google Scholar
  17. 17.
    Jiang L, Zhang W, Wei L, Zhou Q, Yang G, Qian N, et al. Early effects of parathyroid hormone on vascularized bone regeneration and implant osseointegration in aged rats. Biomaterials. 2018;179:15–28. Scholar
  18. 18.
    Ding Q, Sun P, Zhou H, Wan B, Yin J, Huang Y, et al. Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor-mediated angiogenesis. Int J Mol Med. 2018;42(1):171–81. Scholar
  19. 19.
    Güler-Yüksel M, Hoes JN, Bultink IEM, Lems WF. Glucocorticoids, Inflammation and bone. Calcif Tissue Int. 2018;102(5):592–606. Scholar
  20. 20.
    Kanis JA, Johansson H, Oden A, McCloskey EV. Guidance for adjustment of FRAX according to the dose of glucocorticoids. Osteoporos Int. 2011;22(3):809–16. Scholar
  21. 21.
    • Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res. 2017;69(8):1095–110. Guidelines for the treatment of glucocorticoid-induced osteoporosis were revised. The methodology utilized was case based and recommendations are made for young, middle age, and older men and women. CrossRefGoogle Scholar
  22. 22.
    Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998;339(5):292–9. Scholar
  23. 23.
    Wallach S, Cohen S, Reid DM, Hughes RA, Hosking DJ, Laan RF, et al. Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int. 2000;67(4):277–85. Scholar
  24. 24.
    Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, et al. HORIZON investigators. Zoledronic acid and risedronate in the prevention and treatment of GIOP (HORIZON): a multicenter, double-blind, double-dummy, randomized controlled trial. Lancet. 2009;373(9671):1253–63. Scholar
  25. 25.
    Yao W, Cheng Z, Pham A, Busse C, Zimmermann EA, Ritchie RO, et al. Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis Rheum. 2008;58(11):3485–97. Scholar
  26. 26.
    Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest. 1998;102(8):1627–33. Scholar
  27. 27.
    Saag KG, Shane E, Boonen S, Marín F, Donley DW, Taylor KA, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357(20):2028–39. Scholar
  28. 28.
    • Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018;6(6):445–54. This randomized, double blind, active control study demonstrated that in glucocorticoid-treated subjects, denosumab increased bone mass at the lumbar spine after 12 months significantly more than subjects treated with risedronate. This result was observed in both subjects initiating glucocorticoid treatment or chronic glucocorticoid therapy. CrossRefGoogle Scholar
  29. 29.
    • Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, et al. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018;33(2):190–8. This post hoc analysis of the extension of the phase 3 FREEDOM trial determined that subjects that discontinued denosumab had an increase risk of vertebral fractures that was similar to the untreated subjects. Also, many of the subjects that had an incident vertebral fracture after discontinuation of denosumab had multiple vertebral fractures, and subjects with a prior fracture had a greater risk. These results led to the recommendation that subjects discontinuing denosumab should transition to another anti-resorptive agent for a period of time.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Musculoskeletal HealthUniversity of California at Davis Health SystemSacramentoUSA

Personalised recommendations