Long-term corticosteroids are prescribed for a number of reasons, including inflammatory bowel disease, chronic obstructive lung disease and rheumatoid arthritis. Steroids cause bone loss by a variety of complex mechanisms. Calcitonin is an anti-resorptive therapy that has been approved for the treatment of established osteoporosis. The purpose of this review was to evaluate calcitonin as a means of preventing bone loss with corticosteroid therapy. Nine randomized controlled trials were included in the review, with 221 patients randomized to calcitonin and 220 to placebo. The results showed that calcitonin prevents bone loss at the spine and forearm by about 3% after the first year of therapy. There was no effect on bone loss at the hip. Calcitonin was not statistically different from placebo at preventing fractures of the spine and long bones, such as hip fractures. Calcitonin was associated with four times the side effects of placebo, and these were mostly nausea and facial flushing.
Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.
Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy.
To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis.
We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts.
Two independent reviewers selected RCTs which met predetermined inclusion criteria.
Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations.
Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for non vertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing.