Bone loss and fracture are not infrequent when patients with rheumatic disorders are given glucocorticoid treatment. Glucocorticoids inhibit bone formation and also increase the rate of bone resorption. In addition, they decrease intestinal calcium absorption and promote renal calcium excretion. Alendronate has proved effective in preventing and treating glucocorticoid-induced osteoporosis. Calcitriol reportedly is as effective as alendronate in preventing glucocorticoid-induced osteoporosis in patients having a renal or cardiac transplant. This double-placebo, double-blind trial enrolled 201 patients with rheumatic disease who received glucocorticoids in a daily dose equivalent to at least 7.5 mg of prednisone. They were assigned to receive 10 mg alendronate or 1 μg of alfacalcidol, or respective placebo capsules, once a day, and bone mineral density (BMD) was monitored in the lumbar spine after 18 months of treatment. Patients given glucocorticoid therapy for longer than 12 weeks before the study were excluded.
Mean daily and cumulative doses of glucocorticoid were very similar in the two groups. BMD in the lumbar spine increased 2.1% in patients given alendronate (95% confidence interval [CI], 1.1% to 3.1%) and decreased 1.9% in those given alfacalcidol (95% CI, 3.1 to 0.7%). After 18 months the mean difference in change in BMD was 4.0% (95% CI, 2.4 to 5.5%). A similar BMD pattern was evident in the femoral neck and total hip. Three alendronate-treated patients and eight of those given alfacalcidol had a new vertebral deformity, and three of the latter patients developed symptomatic vertebral fractures. The hazard ratio for new deformity in the alendronate group compared with alfacalcidol recipients was 0.4 (95% CI, 0.1 to 1.4). One patient given alendronate had an esophageal ulcer. Hypercalcemia was less frequent in the alendronate group. None of the participants developed thyroid or renal dysfunction during the study.
The investigators conclude that alendronate is more effective than alfacalcidol for preventing glucocorticoid-induced bone loss in patients with rheumatic disorders.
Department of Rheumatology and Clinical Immunology and the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht; Department of Rheumatology, Free University Medical Center, Amsterdam; Department of Rheumatology, Sint Franciscus Hospital, Rotterdam; Department of Rheumatology Twente, Twenteborg Hospital, Almelo; Department of Rheumatology, University Hospital Maastricht, Maastricht; and Department of Rheumatology, Medical Center Leeuwarden, Leeuwarden, Netherlands; and Department of Epidemiology, Scientific Institute of Public Health, Brussels
N Engl J Med 2006;355:675–684