12
In whom and how to prevent glucocorticoid-induced osteoporosis

https://doi.org/10.1016/j.berh.2005.07.002Get rights and content

Glucocorticoid use is widespread in medicine. While it is often life-saving, side-effects are well known. The most common side-effect is osteoporosis. Today we have therapies with proven efficacy for the prevention of vertebral fractures and bone loss. Consequently recognition of glucocorticoid-induced osteoporosis is extremely important given the availability of effective therapy.

Section snippets

Epidemiology

In a large retrospective cohort study evaluating the relationship between oral glucocorticoid use and fracture risk in the UK, it was estimated that approximately 0.9% of the total adult population (around 409 000 people) were using oral glucocorticoids at any one time.5 While the majority were taking doses of 2.5–7.5 mg prednisolone daily, an estimated 93 000 people were taking doses >7.5 mg, and had done so for more than 6 months.5 A significant dose-response was observed for vertebral and hip

Pathophysiology

Bone loss resulting from glucocorticoid therapy is believed to occur through a number of mechanisms. Glucocorticoids decrease intestinal calcium absorption and increase renal calcium elimination through a mechanism that remains unclear.2, 16 This purportedly leads to secondary hyperparathyroidism; however, measurements of parathyroid hormone (PTH) have led to conflicting results, with at least one study reporting reduced levels.17 Others have reported that glucocorticoids enhance the action of

Management

In general, it is recommended that any patient currently prescribed or about to initiate glucocorticoid therapy be assessed for risk factors for osteoporosis and advised on lifestyle modification tactics to reduce the risks. This would include limiting cigarette smoking and alcohol consumption, reducing caffeine intake, participating in weight-bearing activities, and taking precautions to reduce the risk of falls. Particularly in the elderly, in whom the risk of osteoporosis and falls are

Drug therapy

To help understand the terminology, treatment studies are those which assess the efficacy of a medication to stabilize bone mass, and if possible increase bone mass and reduce the risk of fractures in a person already on chronic glucocorticoid therapy and in whom bone loss has already occurred. Prevention studies examine the efficacy of a drug to prevent bone loss in a patient about to initiate treatment with glucocorticoids.

Anabolic therapy (Table 4)

Three randomized controlled trials have used anabolic therapy in the treatment of GIOP (Table 4).64, 65, 66 One study examined human parathyroid hormone, one examined testosterone, and one examined nandrolone decanoate. While the testosterone study examined men, the other two enrolled postmenopausal women. Results of the studies indicated that BMD of the lumbar spine64, 65 and forearm66 increased in the treatment groups, whereas it decreased in the placebo groups following therapy. No effect

Calcium, vitamin D and its analogues (Table 5)

A recent meta-regression analysis demonstrated that vitamin D and its analogues offered a modest benefit in preserving bone density in individuals receiving glucocorticoid treatment, compared to no therapy or calcium-alone therapy.67 Of the prevention studies, Adachi et al8 failed to find any benefit on lumbar spine BMD over a 3-year study period between individuals initiating glucocorticoid therapy of >10 mg/day and treated with 1000 mg/daily of calcium and either placebo or 50 000 IU/week of

Summary of therapeutic options

It appears clear that bisphosphonates offer the greatest protection for the prevention and treatment of GIOP. In addition to maintaining bone density and preventing further losses in individuals who have already sustained complications of glucocorticoids, these medications have also been demonstrated to reduce the risk of fractures. Data are far more compelling for the bisphosphonates than for any other agent. While hormone replacement therapy was extensively used in the past for the treatment

Clinical approach

As always, a patient's individual risk factors should be carefully reviewed when initiating glucocorticoid therapy. Since the evidence indicates that bone loss is most rapid at the onset of glucocorticoid therapy (within the first 3–6 months), preventative measures should be initiated concurrently with the glucocorticoids. Risk factors that should be considered include BMD at the lumbar spine and femoral neck at the onset of glucocorticoid therapy, family history, hormonal status, fracture

References (84)

  • F.H. Wolfhagen et al.

    Cyclical etidronate in the prevention of bone loss in corticosteroid-treated primary biliary cirrhosis. A prospective, controlled pilot study

    Journal of Hepatology

    (1997)
  • B.P. Lukert et al.

    Glucocorticoid-induced osteoporosis: pathogenesis and management

    Annals of Internal Medicine

    (1990)
  • T.P. Van Staa et al.

    Use of oral corticosteroids and risk of fractures

    Journal of Bone and Miner Research

    (2000)
  • T.P. Van Staa et al.

    The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis

    Osteoporosis International

    (2002)
  • T.P. Van Staa et al.

    Use of oral corticosteroids in the United Kingdom

    QJM

    (2000)
  • M. Steinbuch et al.

    Oral glucocorticoid use is associated with an increased risk of fracture

    Osteoporosis International

    (2004)
  • J.A. Kanis et al.

    A meta-analysis of prior corticosteroid use and fracture risk

    Journal of Bone and Miner Research

    (2004)
  • J.D. Adachi et al.

    Vitamin D and calcium in the prevention of corticosteroid induced osteoporosis: a 3 year followup

    Journal of Rheumatology

    (1996)
  • A.D. Adinoff et al.

    Steroid-induced fractures and bone loss in patients with asthma

    New England Journal of Medicine

    (1983)
  • T.J. Hahn et al.

    Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass

    Journal of Clinical Endocrinology and Metabolism

    (1974)
  • T.P. Van Staa et al.

    Use of inhaled corticosteroids and risk of fractures

    Journal of Bone and Miner Research

    (2001)
  • C.E. McEvoy et al.

    Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease

    American Journal of Respiratory and Critical Care Medicine

    (1998)
  • T.P. Van Staa et al.

    Are inhaled corticosteroids associated with an increased risk of fracture in children?

    Osteoporosis International

    (2004)
  • M.B. Leonard et al.

    Long-term, high-dose glucocorticoids and bone and mineral content in childhood glucocorticoid-sensitive nephrotic syndrome

    New England Journal of Medicine

    (2004)
  • H. Kroger et al.

    Decreased axial bone and mineral density in perimenopausal women with rheumatoid arthritis—a population based study

    Annals of the Rheumatic Diseases

    (1994)
  • I.R. Reid

    Steroid-induced osteoporosis

    Osteoporosis International

    (1997)
  • G. Pearce et al.

    Corticosteroid-induced bone loss in men

    Journal of Clinical Endocrinology and Metabolism

    (1998)
  • S.C. Manolagas et al.

    New developments in the pathogenesis and treatment of steroid-induced osteoporosis

    Journal of Bone and Miner Research

    (1999)
  • R.S. Weinstein et al.

    Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone

    Journal of Clinical Investigation

    (1998)
  • M. Sakakura et al.

    Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucocorticoids in human subjects

    Journal of Clinical Endocrinology and Metabolism

    (1975)
  • P. Doerr et al.

    Cortisol-induced suppression of plasma testosterone in normal adult males

    Journal of Clinical Endocrinology and Metabolism

    (1976)
  • R.L. Jilka et al.

    Increased osteoclast development after estrogen loss: mediation by interleukin-6

    Science

    (1992)
  • S.S. Yeap et al.

    Management of corticosteroid-induced osteoporosis

    Rheumatology (Oxford)

    (2002)
  • T.P. Van Staa et al.

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

    Arthritis and Rheumatism

    (2003)
  • L.I. Plotkin et al.

    Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin

    Journal of Clinical Investigation

    (1999)
  • S. Amin et al.

    The comparative efficacy of drug therapies used for the management of corticosteroid-induced osteoporosis: a meta-regression

    Journal of Bone and Miner Research

    (2002)
  • J.D. Adachi et al.

    Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis

    New England Journal of Medicine

    (1997)
  • J.D. Adachi et al.

    Two-year effects of alendronate on bone and mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double- blind, placebo-controlled extension trial

    Arthritis and Rheumatism

    (2001)
  • K.G. Saag et al.

    Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group

    New England Journal of Medicine

    (1998)
  • D.M. Reid et al.

    Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study

    Journal of Bone and Miner Research

    (2000)
  • S. Cohen et al.

    Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

    Arthritis and Rheumatism

    (1999)
  • S. Gonnelli et al.

    Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients

    Calcified Tissue International

    (1997)
  • Cited by (0)

    View full text