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      Seven years’ experience with alendronate in postmenopausal Japanese women with osteoporosis

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          Abstract

          A retrospective study was performed to evaluate the outcome of alendronate (ALN) treatment for seven years in postmenopausal Japanese women with osteoporosis. Forty-seven postmenopausal women with osteoporosis (mean age at baseline 65.7 years) treated with ALN for over seven years in our outpatient clinic were analyzed. Lumbar spine bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, and urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) were monitored during the seven-year treatment period. Urinary NTX and serum ALP levels decreased (−48.2% at three months and −15.7% at seven years, respectively) and lumbar spine BMD increased (+12.8% at seven years) compared with baseline values. No serious adverse events were observed, including osteonecrosis of jaw, atypical femoral diaphysis fractures, or atrial fibrillation. To our knowledge, this is the first report of the outcome of ALN treatment for seven years in Japanese patients with osteoporosis. ALN successfully suppressed bone turnover and increased lumbar spine BMD from the baseline value over the course of the seven-year treatment period without causing any severe adverse events.

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          Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.

          The optimal duration of treatment of women with postmenopausal osteoporosis is uncertain. To compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years. Randomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT). One thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment. Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003). The primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence. Compared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (-2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95% CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens. Women who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years. clinicaltrials.gov Identifier: NCT 00398931.
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            Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.

            A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001). A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.) Copyright 2007 Massachusetts Medical Society.
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              Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2010
                2010
                26 April 2010
                : 6
                : 201-206
                Affiliations
                [1 ] Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan
                [2 ] Department of Neurology, Mitate Hospital, Fukuoka, Japan
                [3 ] Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, Japan
                Author notes
                Correspondence: Jun Iwamoto, Institute for Integrated Sports Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, Tel +81 3 3353 1211, Fax +81 3 3352 9467, Email jiwamoto@ 123456sc.itc.keio.ac.jp
                Article
                tcrm-6-201
                2861441
                20463781
                0a82ece2-31b6-43f8-bd75-33b90f28cad3
                © 2010 Iwamoto et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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                Original Research

                Medicine
                alendronate,bone turnover,long-term treatment,bone mineral density,osteoporosis
                Medicine
                alendronate, bone turnover, long-term treatment, bone mineral density, osteoporosis

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