Alendronate (ALN) has had the most extensive clinical use to date in terms of the number of patients, over 4 million, and duration of monitored treatment, over 10 years. Its ability to reduce hip and other fractures is documented in large randomized placebo-controlled clinical trials, and 10 years of follow-up data are available from the extension of phase III ALN clinical trials.8 ALN is widely used for the treatment and prevention of osteoporosis in postmenopausal women and glucocorticoid-treated patients of both genders.9-16 ALN has been proven effective in significantly reducing the incidence of both vertebral and nonvertebral fractures, including those of the hip. The reduced risk of vertebral fracture is also associated with less height loss,17 as well as a significant reduction in the number of days where patients experience disability.18 Because ALN acts via a nonhormonal pathway, it has also been effectively used to increase bone mass associated with a number of different diseases, including Paget's disease of bone, and bone loss associated with hyperparathyroidism, human immunodeficiency virus (HIV) infection (treatment-associated), and cystic fibrosis.19-25 Thus the clinical utility of ALN as an antiosteoporotic, antifracture agent is very broad.
In postmenopausal osteoporosis, bone turnover increases an average of 2-3 standard deviations above mean premenopausal levels.26'27 In high-turnover states such as menopause average mineralization decreases because new bone tissue is remodeled again before it can become fully mineralized.28 Following initiation of ALN treatment, bone turnover is returned to premenopausal levels within a few months.29 By reducing the rate of turnover, there are fewer remodeling sites at any given time and therefore fewer potentially weak areas (stress risers) in trabecular bone. ALN treatment therefore allows secondary mineralization of bone to be completed, which increases inherent bone strength.30,31 At an effective dose, ALN treatment is associated with increases in bone mineral density (BMD) and bone mineral content (BMC), which occur rapidly during the first 6 months to 1 year. This initial, rapid BMD increase has been attributed to 'filling of the remodeling space.' It refers to the continuation of bone formation and subsequent mineralization process, which proceed for months and years, respectively, at existing remodeling sites that were initiated prior to the biphosphate treatment-induced reductions in turnover.
Interestingly, the increase in BMD at some skeletal sites with ALN (10 mg daily) treatment continues for up to 10 years with mean increases (versus baseline) in BMD of 13.7% at the lumbar spine, 10.3% at the trochanter, 5.4% at the femoral neck, and 6.7% at the total proximal femur.8 The ultimate goal for reducing bone turnover and increasing bone BMD is the reduction of fractures, and ALN has proven effective in cutting in half the risk of fractures of the spine, as well as nonvertebral fractures, including those of the hip.9-11'17'29'32'33
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