Glucocorticoid-Induced Osteoporosis and Osteonecrosis

https://doi.org/10.1016/j.ecl.2012.04.004Get rights and content

Introduction

“A marked osteoporosis of the skeleton was found, it being easily possible to cut the vertebral bodies with a knife, the spongy part of the bone having largely disappeared.” Cushing1 described these adverse effects of long-term endogenous hypercortisolism on bone in his 1932 presentation to the Johns Hopkins Medical Society. Eighteen years later, only 1 year after the introduction of cortisone for the treatment of rheumatoid arthritis, clinicians became aware of the rapidly injurious skeletal effects of glucocorticoid administration.2, 3 At first, it was uncertain whether the hip fractures that had occurred were the result of falls caused by steroid myopathy or merely coincidental with cortisone therapy because vertebral fractures and radiographic osteoporosis had not yet been observed. However, within just a few more years, osteoporosis and fractures were clearly recognized as skeletal complications of treatment with cortisone, prednisolone, and prednisone.4 Collapse of the femoral and humeral heads after high-dose therapy was described shortly thereafter.5, 6 Today, glucocorticoid administration is the most common cause of secondary osteoporosis and the leading cause of nontraumatic osteonecrosis. In patients receiving long-term therapy, glucocorticoids induce fractures in 30% to 50% and osteonecrosis in 9% to 40%.7, 8 Patients are seldom warned about these side effects and, as a result, adverse skeletal events are the most common glucocorticoid-related complications associated with successful litigation.9

Section snippets

Risk Factors

Bone loss in glucocorticoid-induced osteoporosis (GIO) is biphasic, with a rapid reduction in bone mineral density (BMD) of 6% to 12% within the first year, followed by a slower annual loss of about 3% for as long as the glucocorticoids are administered.10 However, the relative risk of fracture escalates by as much as 75% within the first 3 months after initiation of glucocorticoid therapy and this often occurs before a significant decline in BMD.11 There is also a decrease in the risk of

Glucocorticoid-induced osteonecrosis

Aseptic, avascular or ischemic necrosis, and bone infarctions are other terms for osteonecrosis. The most common joint involved is the hip and the most common cause of the disorder is trauma. Glucocorticoids are the second most common cause.8 There are many other causes in adults including alcohol, sickle cell disease, ionizing radiation, Gaucher disease, Caisson disease or decompression sickness, and idiopathic causes. However, before concluding that any case of osteonecrosis is idiopathic, a

Areas of uncertainty

Precise prediction of the risk of fracture is currently not possible in GIO and efforts to alert physicians prescribing glucocorticoids to their responsibilities to prevent bone complications have met with limited success. More data are needed to establish precise clinical thresholds for intervention and develop strategies to convey this information to physicians and patients. In addition, more research is required to ascertain the optimal duration of protective therapy, best treatment of

Summary

  • Glucocorticoid administration is the most common cause of secondary osteoporosis and the leading cause of nontraumatic osteonecrosis.

  • Patients are seldom warned about these side effects and, as a result, adverse skeletal events are the most common glucocorticoid-related complications associated with successful litigation.

  • Disparity between bone quantity and quality in GIO makes ultrasound or BMD measurements inadequate for identifying patients at risk of glucocorticoid-induced fractures.

Acknowledgments

The author thanks Drs Stavros C. Manolagas, Robert L. Jilka, Maria Almeida, and Charles A. O’Brien for their advice and helpful discussions, and Drs Stavros C. Manolagas, Robert L. Jilka, Maria Almeida, Fred H. Faas, and Irina Lendel for reviewing the manuscript.

First page preview

First page preview
Click to open first page preview

References (63)

  • W.G. Heiman et al.

    Avascular necrosis of the femoral and humeral heads after high-dosage corticosteroid therapy

    N Engl J Med

    (1960)
  • V. Pietrogrande et al.

    Osteopathia da prolungato trattmento cortisonico

    Ortop Tramatol

    (1957)
  • R.S. Weinstein

    Clinical practice: glucocorticoid-induced bone disease

    N Engl J Med

    (2011)
  • R.S. Weinstein

    Glucocorticoid-induced osteonecrosis

    Endocrine

    (2012)
  • J.J. Nash et al.

    Medical malpractice and corticosteroid use

    Otolaryngol Head Neck Surg

    (2011)
  • T.P. van Staa et al.

    Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy

    Arthritis Rheum

    (2003)
  • R.S. Weinstein

    Is long-term glucocorticoid therapy associated with a high prevalence of asymptomatic vertebral fractures in postmenopausal women?

    Nat Clin Pract Endocrinol Metab

    (2007)
  • M. Steinbuch et al.

    Oral glucocorticoid use is associated with an increased risk of fracture

    Osteoporos Int

    (2004)
  • F. de Vries et al.

    Fracture risk with intermittent high-dose oral glucocorticoid therapy

    Arthritis Rheum

    (2007)
  • J.R. Curtis et al.

    Longitudinal patterns in the prevention of osteoporosis in glucocorticoid-treated patients

    Arthritis Rheum

    (2005)
  • J.M. Thompson et al.

    Not all postmenopausal women on chronic steroids and estrogen treatment are osteoporotic: predictors of bone mineral density

    Calcif Tissue Int

    (1997)
  • I. Tatsuno et al.

    Age dependence of early symptomatic vertebral fracture with high-dose glucocorticoid treatment for collagen vascular diseases

    J Clin Endocrinol Metab

    (2009)
  • T.P. van Staa et al.

    Use of inhaled glucocorticoids and risk of fractures

    J Bone Miner Res

    (2001)
  • H. Russcher et al.

    Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression

    J Clin Endocrinol Metab

    (2005)
  • M.S. Cooper et al.

    Osteoblastic 11β-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure

    J Bone Miner Res

    (2002)
  • R.S. Weinstein et al.

    Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids: potential mechanisms of the deleterious effects on bone

    J Clin Invest

    (1998)
  • C.A. O’Brien et al.

    Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength

    Endocrinol

    (2004)
  • R.S. Weinstein et al.

    Endogenous glucocorticoids decrease vascularity and increase skeletal fragility in aged mice

    Aging Cell

    (2010)
  • E. Seeman

    Bone quality-the material and structural basis of bone strength and fragility

    N Engl J Med

    (2006)
  • D. Jia et al.

    Glucocorticoids act directly on osteoclasts to increase their lifespan and reduce bone density

    Endocrinol

    (2006)
  • R.S. Weinstein et al.

    The skeletal effects of glucocorticoid excess override those of orchidectomy in mice

    Endocrinol

    (2004)
  • Cited by (303)

    • Regulation of intestinal calcium and phosphate absorption by vitamin D

      2023, Feldman and Pike's Vitamin D: Volume One: Biochemistry, Physiology and Diagnostics
    View all citing articles on Scopus

    Support: This material is based on work supported by a VA Merit Review Grant from the Office of Research and Development, Department of Veterans Affairs and the National Institutes of Health (P01-AG13918). The author has no potential conflicts of interest relevant to this article.

    View full text