REVIEW: Sensitivity of bone to glucocorticoids (steroids)

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Clinical Science (2004) 107, (111-123) (Printed in Great Britain)

Review article

Sensitivity of bone to glucocorticoids

Mark S. COOPER

Division of Medical Sciences, University of Birmingham, Queen

Hospital, Edgbaston, Birmingham B15 2TH, U.K.

Glucocorticoids are used widely in a range of medical specialities, but

their main limitation is an adverse impact on bone. Although physicians are

increasingly aware of these deleterious effects, the marked variation in

susceptibility between individuals makes it difficult to predict who will

develop skeletal complications with these drugs. Although the mechanisms

underlying the adverse effects on bone remain unclear, the most important

effect appears to be a rapid and substantial decrease in bone formation.

This review will examine recent studies that quantify the risk of fracture

with glucocorticoids, the mechanisms that underlie this increase in risk and

the potential basis for differences in individual sensitivity. An important

determinant of glucocorticoid sensitivity appears to be the presence of

glucocorticoid-metabolizing enzymes within osteoblasts and this may enable

improved estimates of risk and generate new approaches to the development of

bone-sparing anti-inflammatory drugs.

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INTRODUCTION

The adverse effects of glucocorticoids on the skeleton were first recognized

by Harvey Cushing [1] 70 years ago in the context of the disease that bears

his name. However, the problem of GIOP (glucocorticoid-induced osteoporosis)

has increased dramatically in recent decades with the introduction of

synthetic glucocorticoids to treat a range of inflammatory diseases [2,3].

Physicians in most medical specialities are increasingly aware of the

effects of therapeutic glucocorticoids on the skeleton, but the marked

variation in susceptibility between individuals has made it difficult to

predict individuals who are likely to have adverse effects with these drugs.

The mechanisms underlying the effects of glucocorticoids on bone have been

sought for many years, but no single effect has emerged as being of prime

importance. In the last few years, key advances have been made in several

areas, including the epidemiology of GIOP, the impact of glucocorticoids on

bone cells in vitro and in vivo and the basis for variation in sensitivity

between individuals. Additionally, the recent identification of

glucocorticoid-modifying enzymes in bone cells suggests that endogenous

glucocorticoids may make a greater contribution to bone metabolism than

previously thought. This article will critically review these recent

advances and will highlight areas where considerable uncertainty still

exists.

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For the entire article, please see:

http://www.clinsci.org/cs/107/0111/cs1070111.htm

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