Clinical Investigations Effects of Risedronate Treatment on Bone Density and Vertebral Fracture in Patients on Corticosteroid Therapy S. Wallach, 1 S. Cohen, 2 D. M. Reid, 3 R. A. Hughes, 4 D. J. Hosking, 5 R. F. Laan, 6 S. M. Doherty, 7 M. Maricic, 8 C. Rosen, 9 J. Brown, 10 I. Barton, 11 A. A. Chines 11 * 1 Hospital for Joint Diseases, New York, New York, USA 2 Metroplex Clinical Research Center, Dallas, Texas, USA 3 Aberdeen Royal Infirmary, Aberdeen, UK 4 St Peters Hospital, Chertsey, UK 5 Nottingham City Hospital, Nottingham, U.K. 6 Department of Rheumatology, University Hospital Nijmegen Netherlands 7 Hull Royal Infirmary, Hull, UK 8 University of Arizona, Tucson, Arizona, USA 9 St. Joseph Hospital, Bangor, Maine, USA 10 CHUL, Ste-Foy, Quebec, Canada 11 Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, USA Received: 11 October 1999 / Accepted: 1 May 2000 / Online publication: 27 July 2000 Abstract. Men and women (n  518) receiving moderate- to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500–1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall popu- lation, the mean (SE) lumbar spine BMD increased 1.9 ± 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 ± 0.4% in the placebo group (P  0.005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A signifi- cant reduction of 70% in vertebral fracture risk was ob- served in the risedronate 5 mg group compared with the placebo group (P  0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastroin- testinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in pa- tients receiving moderate-to-high doses of corticosteroid therapy. Key words: Corticosteroid — Risedronate — Calcium — Vitamin D — BMD Exposure to supraphysiological doses of corticosteroids can cause symptomatic osteoporosis, with fractures after mini- mal trauma [1–4]. Although the pathogenesis is still unclear, the problem is of clinical concern because of the extensive use of corticosteroids in the treatment of a wide range of disorders. It is estimated that bone loss induced by long- term corticosteroid therapy (equivalent to 7.5 mg predni- sone daily or greater) leads to fractures in 30–50% of pa- tients [1–4]. Corticosteroid-induced bone loss is dependent on the average corticosteroid dose and the duration of treat- ment, and affects primarily trabecular bone [1–3]. It occurs most rapidly in the first year of treatment, but continues at a slower rate during subsequent therapy [2–8]. The magnitude of the problem has generated great in- terest in potential preventive and therapeutic strategies to maintain or increase bone mass, both during the initiation of corticosteroid therapy and later, when corticosteroid- induced osteoporosis (CIO) has already developed. Numer- ous therapies, including calcium and vitamin D supplemen- tation [9–14], hormone-replacement therapy (HRT) in women [5], fluoride [6], and calcitonin [7], have been suc- cessful to some extent in preventing bone loss. Bisphospho- nates have also been shown to be efficacious in the treat- ment of CIO [8, 9, 15–19], and a recent meta-analysis * Other investigators of the study are listed in the Appendix. Correspondence to: S. Wallach Calcif Tissue Int (2000) 67:277–285 DOI: 10.1007/s002230001146 © 2000 Springer-Verlag New York Inc.