Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial 1 John A. Kanis, a, * Olof Johnell, b Dennis M. Black, c Robert W. Downs, Jr., d Somnath Sarkar, e Thomas Fuerst, f Roberta J. Secrest, e and Imre Pavo e a WHO Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK b Department of Orthopaedics, Malmo General Hospital, Malmo, Sweden c Division of Clinical Epidemiology, University of California, San Francisco, CA 94143, USA d Division of Endocrinology and Metabolism, Virginia Commonwealth University, Richmond, VA 23298, USA e Eli Lilly and Company, Indianapolis, IN 46285, USA f Synarc, Inc., San Francisco, CA 94105 USA Received 17 December 2002; revised 26 March 2003; accepted 23 May 2003 Abstract Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32– 0.88) for those with osteopenia and 0.31 (0.06 – 0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04 – 0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis. © 2003 Elsevier Inc. All rights reserved. Keywords: Raloxifene; Osteopenia; Osteoporosis; Vertebral fracture; Postmenopausal women; Postmenopausal osteoporosis Introduction Vertebral fractures are among the most common osteo- porotic fractures [1,2] and typically occur in postmeno- pausal women in their mid 60s, as a result of rapid peri- menopausal bone loss [3]. They are associated with significant morbidity including back pain, disability, limited physical activity, increased number of days of bed rest, kyphosis, and loss of height [4,5]. Women with vertebral fracture have a four-fold increased risk of a second vertebral fracture within the following year [6] and for fractures resulting in hospitalization a marked increase in subsequent osteoporotic fractures is observed [7], particularly within the first year of fracture [8]. New vertebral fractures are also * Corresponding author. WHO Collaborating Centre for Metabolic Bone Disease, University of Sheffield, Beech Road, Sheffield S10 2RX, United Kingdom. Fax: +44-114-285-1813. E-mail address: w.j.pontefract@sheffield.ac.uk (J.A. Kanis). 1 Eli Lilly and Company (Indianapolis, IN) sponsored the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Bone 33 (2003) 293–300 www.elsevier.com/locate/bone 8756-3282/03/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/S8756-3282(03)00200-X