Alendronato

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Alendronate or Alfacalcidol in Glucocorticoid-Induced Osteoporosis
Ron N.J. de Nijs, M.D., Ph.D., Johannes W.G. Jacobs, M.D., Ph.D., Willem F. Lems, M.D., Ph.D., Roland F.J. Laan, M.D., Ph.D., Ale Algra, M.D., Ph.D., Anne-Margriet Huisman, M.D., Ph.D., Erik Buskens, M.D., Ph.D., Chris E.D. de Laet, M.D., Ph.D.,Ans C.M. Oostveen, M.D., Ph.D., Piet P.M.M. Geusens, M.D., Ph.D., George A.W. Bruyn, M.D., Ph.D., Ben A.C. Dijkmans, M.D., Ph.D., and Johannes W.J. Bijlsma, M.D., Ph.D., for the STOP Investigators*

A BS T R AC T
Background

Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture.
Methods

We performed arandomized, double-placebo, double-blind clinical trial of 18 months’ duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 μg) and a placebo tablet of alendronatedaily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities.
Results

A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, –3.1 to –0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as comparedwith eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4).
Conclusions

From the Department of Rheumatology and Clinical Immunology (R.N.J.N., J.W.G.J., J.W.J.B.) and the Julius Center for Health Sciences and Primary Care (A.A., E.B.), University Medical Center Utrecht, Utrecht; theDepartment of Rheumatology, Free University Medical Center, Amsterdam (W.F.L., B.A.C.D.); the Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen (R.F.J.L.); the Department of Rheumatology, Sint Franciscus Hospital, Rotterdam (A.-M.H.); the Department of Rheumatology Twente, Twenteborg Hospital, Almelo (A.C.M.O.); the Department of Rheumatology, University Hospital Maastricht,Maastricht (P.P.M.M.G.); and the Department of Rheumatology, Medical Center Leeuwarden, Leeuwarden (G.A.W.B.) — all in the Netherlands; and the Department of Epidemiology, Scientific Institute of Public Health, Brussels (C.E.D.L.). Address reprint requests to Dr. de Nijs at the Department of Rheumatology and Clinical Immunology, F02 127, University Medical Center Utrecht, P.O. Box 85500, 3508 GAUtrecht, the Netherlands, or at r.denijs@mmc.nl. *Additional investigators who participated in the Steroid Osteoporosis Prevention (STOP) study are listed in the Appendix. N Engl J Med 2006;355:675-84.
Copyright © 2006 Massachusetts Medical Society.

During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced boneloss than was alfacalcidol. (ClinicalTrials.gov number, NCT00138983.)

n engl j med 355;7

www.nejm.org

august 17, 2006

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lucocorticoids are frequently used in...