Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial K. Uusi-Rasi, a, * P. Kannus, a,b S. Cheng, c H. Sieva ¨nen, a M. Pasanen, a A. Heinonen, a A. Nenonen, a,d J. Halleen, e T. Fuerst, f H. Genant, f and I. Vuori a a UKK Institute for Health Promotion Research, 33501 Tampere, Finland b Department of Surgery, Tampere University Medical School and University Hospital, 33014 Tampere, Finland c Department of Health Sciences, University of Jyva ¨skyla ¨, 40014 Jyva ¨skyla ¨, Finland d Department of Clinical Chemistry, Tampere University Hospital, 33014 Tampere, Finland e Department of Anatomy, University of Turku, 20520 Turku, Finland f University of California, Osteoporosis and Arthritis Research Group, Department of Radiology, San Francisco, CA 94105, USA Received 17 December 2002; revised 10 February 2003; accepted 26 February 2003 Abstract In this randomized, double-blind, placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate, alone or in combination, on the mass and structure of bone, risk factors for falling (muscle strength and power, postural sway, and dynamic balance), and cardiorespiratory fitness in postmenopausal women. A total of 164 healthy, sedentary, early postmenopausal women were randomly assigned to one of four experimental groups: (1) 5 mg of alendronate daily plus progressive jumping exercise, (2) 5 mg alendronate, (3) placebo plus progressive jumping exercise, or (4) placebo. The primary endpoint was 12-month change in bone mass and geometry (measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites) and physical performance; the secondary endpoint was change in biochemical markers of bone turnover. The jumping exercise was conducted an average 1.6  0.9 (mean  SD) times a week. Alendronate daily was effective in increasing bone mass at the lumbar spine (alendronate vs placebo 3.5%; 95% CI, 2.2– 4.9%) and femoral neck (1.3%; 95% CI, 0.2–2.4%) but did not affect other bone sites. Exercise alone had no effect on bone mass at the lumbar spine or femoral neck; it had neither an additive nor an interactive effect with alendronate at these bone sites. However, at the distal tibia the mean increase of 3.6% (0.3–7.1%) in the section modulus (that is, bone strength) and 3.7% (0.1–7.3%) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group, indicating exercise-induced thickening of the bone cortex. Bone turnover was reduced in alendronate groups only. Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power, dynamic balance, and cardiorespiratory fitness. As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck, while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites, as well as improving the participants’ muscular performance and dynamic balance. Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures. © 2003 Elsevier Science (USA). All rights reserved. Keywords: Alendronate; Exercise; Bone mass; Bone structure; Physical performance; Balance Introduction Osteoporosis and related fractures among elderly people are a significant public health problem, and the number of fractures is expected to rise dramatically as populations age [1,2]. Therefore, effective methods for prevention and treat- ment are needed. Currently, alendronate is one of the most widely used and studied drug therapies for osteoporosis. Clinical studies have confirmed that alendronate is able to inhibit bone loss [3]. Four to 6% increase in bone mass of the spine and hip with simultaneous 20 to 50% reduction in the risk of vertebral, hip, and other fractures have been reported after 2 to 3 years of alendronate treatment in elderly women with established osteoporosis [3,4]. Also, recent studies have shown that alendronate is effective in  In addition to the authors, the following investigators were members of the study group: Pekka Oja, Ph.D., the UKK Institute; Kalervo Va ¨a ¨na ¨nen, M.D., University of Turku; and Harri Suominen, Ph.D., University of Jyva ¨skyla ¨, Finland. * Corresponding author. Fax: +358-3-282-9200. E-mail address: kirsti.uusi-rasi@uta.fi (K. Uusi-Rasi). Bone 33 (2003) 132–143 www.elsevier.com/locate/bone 8756-3282/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S8756-3282(03)00082-6