Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease.
BACKGROUND
Inhaled corticosteroids form the main therapy for asthma, but there is increasing concern about the potential systematic effects of long-term inhaled corticosteroids including their effect on bone metabolism and bone loss.


OBJECTIVE
To determine the effect of inhaled corticosteroids use on biochemical markers of bone turnover, bone mineral density and the development of fractures.


METHODS
We searched the Cochrane Airways Group trials register, electronic reference databases, UK National Research Register, bibliographies of included studies, and contacted pharmaceutical companies.


METHODS
Randomised trials of the effect of inhaled steroid versus placebo on markers of bone function and metabolism, in adults with asthma or mild COPD.


METHODS
Trial quality was assessed and data extracted from the papers included (2 reviewers per paper) and from additional data supplied by the authors.


RESULTS
Of 438 references found, seven met the inclusion criteria. Three studies were in healthy subjects asthma or COPD. The patients were generally less than 60 years old and the male:female ratio was 2:1. There was no evidence of increased risk of loss of bone mineral density (BMD) or fractures. There was no significant change in osteocalcin at conventional doses of inhaled corticosteroids (Standardised Mean Difference [SMD] -0.34 (95% Confidence Interval [CI] -0.72, 0.04), although a statistically significant change was seen in those studies using experimental doses of inhaled steroid in excess of the doses recommended by the British Thoracic Society SMD 0.97 (95% CI -1.61, -0.34). A statistically significant change in parathyroid hormone seen in one small short trial (n=10, 6 weeks) may have been due to the trial design and outcome measurements used.


CONCLUSIONS
In patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroid at conventional doses given for two or three years on BMD or vertebral fracture. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these doses are not available. There is a need for further, even longer term prospective studies of conventional and high doses of inhaled corticosteroids.
Jones
A
A
Department of General Practice, University of Wales College of Medicine, Dept. of General Practice, Llanedeyrn Health Centre, Cardiff, UK, CF23 7PN. research@gors.freeserve.co.uk
Fay
J K
JK
Burr
M
M
Stone
M
M
Hood
K
K
Roberts
G
G
D000280:Administration, Inhalation; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism
D005938:Glucocorticoids