Fosamax. Anti-Aging-Guide -- Your plan to stay young

J Clin Densitom. 2005 Spring;8(1):7-13.
A systematic review of the effect of alendronate on bone mineral density in men.
Sawka AM, Thabane L, Papaioannou A, Gafni A, Hanley DA, Adachi JD.
McMaster University, Hamilton, Ontario, Canada L8N 1Y2; and St. Joseph's Healthcare, Hamilton, Ontario, Canada L8N1Y2.
Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.

J Periodontol. 2004 Dec;75(12):1579-85.
Effect of alendronate on periodontal disease in postmenopausal women: a randomized placebo-controlled trial.
Rocha ML, Malacara JM, Sanchez-Marin FJ, Vazquez de la Torre CJ, Fajardo ME.
Institute of Medical Research, University of Guanajuato, Leon, Mexico.
BACKGROUND: We investigated the effect of oral alendronate (ALN) treatment on radiological and clinical measurements of periodontal disease in postmenopausal women without hormone replacement therapy. METHODS: We evaluated the effect of 6 months of ALN treatment in 40 postmenopausal women, 55 to 65 years old with established periodontal disease, in a controlled, double-masked, prospective study. Volunteers were paired by age and randomized to receive ALN (10 mg/day) or placebo for the study period. Periodontal mechanical treatment was carried out in both groups. At baseline and after treatment, clinical evaluation, hormone blood levels, distance from the crestal alveolar bone (CAB) to the cemento-enamel junction (CEJ), calcaneus bone mineral density (BMD), hormone levels, serum N-telopeptide (NTx), and bone-specific alkaline phosphatase (BSAP) were assessed. RESULTS: Periodontal disease conditions improved in both groups, but greater improvement in probing depth (-0.8 +/- 0.3 mm versus -0.4 +/- 0.4 mm, P = 0.02) and gingival bleeding (-0.3% +/- 0.13% versus -0.2% +/- 0.06%, P = 0.006) was found in the ALN treated group. Calcaneus BMD increased in the ALN treated group (68 +/- 47 mm3 versus -26 +/- 81 mm3, P = 0.0006). CAB-CEJ distance diminished in the ALN group (-0.4 +/- 0.40 mm versus 0.60 +/- 0.53 mm, P = 0.00008). Marginal reduction in both NTx and BSAP levels was found in the ALN group (-9.4 +/- 6.6 nmol versus -4.3 +/- 4.7 nmol bone collagen equivalents, P = 0.08, and -7.7 +/- 8.4 versus -1.5 +/- 5.0 U/l, P = 0.1, respectively). Hormone levels were unchanged after treatment. Similar improvement of calcaneus BMD and CAB-CEJ distance with ALN treatment was found in obese and non-obese women. CONCLUSION: ALN treatment improved periodontal disease and bone turnover in postmenopausal women.

Obstet Gynecol Surv. 2004 Jun;59(6):446-55; quiz 485.
Hip fracture prevention in postmenopausal women.
Kessel B.
Department of Obstetrics, Gynecology and Women's Health, University of Hawaii, John A. Burns School of Medicine, and The Queen's Medical Center, Honolulu, Hawaii 96813, USA.
Hip fracture is a devastating outcome associated with postmenopausal osteoporosis. This fracture causes considerable pain, disability, diminished quality of life, and mortality. Although bone loss is an important factor associated with hip fracture, there are other demographic and clinical factors such as those that increase the risk of falling (e.g., unsteady gait, medications) that contribute to the likelihood of experiencing a hip fracture. Nonpharmacological interventions to reduce hip fracture risk include regular weight-bearing exercise, fall intervention programs, and external hip protectors. Patients should receive calcium and/or vitamin D supplementation as necessary. Among available pharmacologic options, the bisphosphonates, risedronate (Actonel) and alendronate (Fosamax), have reduced the risk of hip fracture in postmenopausal women with osteoporosis. Raloxifene (Evista), salmon calcitonin nasal spray (Miacalcin), and teriparatide (Forteo) have not demonstrated hip fracture risk reduction in controlled clinical trials. Hormone therapy (HT) reduced hip fracture risk in a recent large placebo-controlled trial; however, the risk/benefit profile of HT has resulted in recommendations to consider alternatives for the management of osteoporosis. Postmenopausal women with osteoporosis should receive adequate calcium/vitamin D supplementation, be encouraged to exercise, and institute risk factor interventions. Treatment with a bisphosphonate should be considered for those who are also at increased risk for hip fracture. TARGET AUDIENCE: Obstetricians & Gynecologyists, Family Physicians LEARNING OBJECTIVES: After completion of this article the reader should be able to list the demographic risk factors for osteoporosis and related fractures, to outline the cost and consequences of hip fractures, and to summarize the various pharmacologic and non-pharmacologic interventions used to reduce the risk of hip fracture.

Endocr Regul. 2003 Dec;37(4):225-38.
Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis.
Stepan JJ, Alenfeld F, Boivin G, Feyen JH, Lakatos P.
3rd Clinic of International Medicine, Charles University School of Medicine, Prague, Czech Republic.
In the treatment of osteoporosis, the aim of the antiresorptive therapy is to restore bone density by decreasing bone remodeling. The process of bone remodeling plays a role in plasma calcium homeostasis and serves to modify bone architecture in order to meet changing mechanical needs, to maintain osteocyte viability, and to repair microdamage in bone matrix. Estrogen deficiency results in a number of detrimental effects on bone, including suppression of osteocyte survival as well as impairment of osteoblast response to mechanical stimuli and repair of ageing bone. In this review, effects of available antiresorptive therapies on endocrine regulations of bone metabolism in postmenopausal osteoporosis are compared. The aim of antiresorptive treatment is to ensure adequate bone remodeling, reparation of microdamage of bone, and increased bone strength. Ideally, this effect should be maintained long-term. Several agents are approved for the treatment of osteoporosis. Calcitonin transiently inhibits osteoclast activity without decreasing osteoblast collagen synthesis. Aminobisphosphonates decrease bone remodeling by decreasing osteoclast activity and by inducing osteoclast apoptosis. This allows more time for secondary mineralization to proceed to completion in the existing bone tissue mass, so increasing the mechanical resistance of bone to loading. Estrogens and raloxifene (a selective estrogen receptor modulator that acts as an estrogen agonist in bone) suppress bone remodeling to the premenopausal range, maintaining the function of osteoblasts and osteocytes. In the placebo-controlled osteoporosis treatment trials, all the above treatments reduced the risk of fractures. Raloxifene therapy was also associated with a favorable or neutral effect in the cardiovascular system, and a reduced incidence of breast cancer. Selection of appropriate drug for treatment of postmenopausal osteoporosis should take into account the long-term effect of the antiresorptive agent on bone. Moreover, the effects on other tissues ++should also be considered, and this encompasses both safety concerns, as well as the potentially beneficial effects on other tissues. Further investigation is needed to evaluate the different modes of action of these agents, and their long-term effects on bone and other tissues.

Bratisl Lek Listy. 2003;104(10):309-13.
The effect of alendronate in the treatment of postmenopausal osteoporosis.
Rozkydal Z, Janicek P.
Ist Orthopaedic Department, St. Anna's Hospital, Masarykiensis University, Brno, Czech Republic.
OBJECTIVES: The aim of the study was the evaluation of the effect of alendronate in the treatment of postmenopausal osteoporosis on subjective criteria and on bone mineral density after two years. MATERIAL AND METHODS: The authors collected data from 44 women by questionaire and analysed the data from DEXA examination. The patients were given Fosamax 10 mg and calcium 500 mg per day in the years 2001-2002. RESULTS: The compliance of alendronate was good in 42 women (95.5%). 15 patients were very satisfied with the treatment, 22 were satisfied and 5 patients claimed no improvement at the end of the study. A positive effect of the treatment was seen in 37 patients (88.1%). 21 patients claimed to have no pain and 15 patients suffered mild intermitent pain at the end of the study. 24 patients used no analgetics and 9 patients used them irregularly. 11 patients claimed to have normal activity and 22 patients had mildly diminished activity in daily life. The authors encountered no symptomatic vertebral or nonvertebral fracture during the study. The mean BMD in the lumbar spine improved in T score by 0.38 SD after one year and 0.35 SD after the second year. The mean BMD has improved in the neck region in T score by 0.21 SD after the first year and 0.21 SD after the second year. The mean BMD in lumbar spine has improved in Z score by 0.31 SD after one year and 0.02 SD after the second year. The mean BMD in the neck region has improved in Z score by 0.31 SD after the first year and 0.16 SD after the second year. The mean change of bone mineral density in lumbar spine was +4.17% after the first years and +4.19% after the second year. The mean change of BMD in the femoral neck region was +4.46% after the first years and + 3.71% after the second year. According to student t-test all the data of increased BMD were statisticaly significant at the 5% level of the significance (p < 0.05). CONCLUSION: Alendronate therapy significantly reduced the pain and the need for analgesics. It improved the daily activity and mobility of the spine in the patients with postmenopausal osteoporosis. It resulted in a positive change of BMD in vertebral region of +8.36% and +8.17% in the femoral neck region after two years. The fracture risk in vertebral region was diminished by 31% and in the femoral neck region by 38% at the end of the study. (Tab. 11, Ref. 14.).

JAMA. 2003 May 21;289(19):2525-33.
Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial.
Greenspan SL, Resnick NM, Parker RA.
Division of Endocrinology and Metabolism and Division of Geriatric Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pa, USA.
CONTEXT: Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis, but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown. OBJECTIVE: To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe, and how they compare with monotherapy in community-dwelling elderly women. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTING AND PARTICIPANTS: Five hundred seventy-three community-dwelling women age 65 years or older were screened: 485 completed screening and 373 (aged 65 to 90 years) were randomized following a 3-month, open-label, run-in phase with hormone replacement and alendronate placebo. The trial was conducted at a single academic US medical center from January 1996 to May 2001. INTERVENTIONS: Participants were randomly assigned in a 2 x 2 factorial design to receive hormone replacement (conjugated equine estrogen, 0.625 mg/d, with or without medroxyprogesterone, 2.5 mg/d) and alendronate, 10 mg daily, both agents, or neither. All participants received calcium and vitamin D supplements. MAIN OUTCOME MEASURES: Annualized change in bone mineral density of the hip and spine and occurrence of adverse events. RESULTS: Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy, with mean (SD) increases of 5.9% (3.8) at the total hip, 10.4% (5.4) at the posteroanterior lumbar spine, and 11.8% (6.8) at the lateral lumbar spine. Mean (SD) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone (4.2% [3.8] vs 3.0% [4.9]; P<.05, respectively), and alendronate resulted in more responders to therapy. All therapies were well tolerated and participant retention was 90% at 3 years. CONCLUSIONS: Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort. Alendronate was superior to hormone replacement, and combination therapy was superior to either therapy alone. Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy.

Arch Intern Med. 2003 Apr 14;163(7):789-94.
Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial.
Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME.
Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa.
BACKGROUND: Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT. METHODS: The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability. RESULTS: Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo. CONCLUSIONS: A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.

Fertil Steril. 2003 Sep;80(3):541-5.
Effects of hormone therapy and alendronate on C-reactive protein, E-selectin, and sex hormone-binding globulin in osteoporotic women.
Ylikorkala O, Evio S, Valimaki M, Tiitinen A.
Department of Obstetrics and Gynecology, Helsinki, Finland.
C-reactive protein and soluble E-selectin hold promise as surrogate markers for future cardiovascular events. We studied the effects of oral hormone therapy (HT) and alendronate, given alone or together, on these markers and on sex hormone-binding globulin levels in osteoporotic elderly women.Prospective, randomized, double-dummy trial.Outpatient department of a university hospital.Ninety osteoporotic women (T score

Fertil Steril. 2003 Sep;80(3):536-40.
Effect of daily hormone therapy and alendronate use on bone mineral density in postmenopausal women.
Davas I, Altintas A, Yoldemir T, Varolan A, Yazgan A, Baksu B.
Second Obstetrics and Gynecology Clinic, Sisli Etfal Training and Research Hospital, Istanbul, Turkey.
To evaluate the effect of daily oral and transdermal hormone therapy alone or in combination with alendronate on bone mineral density in postmenopausal women.Comparative prospective clinical study.Outpatient clinic of a training and research hospital.One hundred seventy-three consecutive postmenopausal women with no previous hormone therapy and a bone mineral density T score <-1 SD were randomly enrolled.Oral conjugated estrogen, alone or with alendronate, or transdermal estrogen, alone or with alendronate, given for 1 year. All patients also received medroxyprogesterone acetate and calcium.Bone density measurement at L2 to 4 region by dual-energy X-ray absorptiometry.At the end of 1 year, significant increase in bone density measurements were seen in all groups. Oral conjugated estrogen and transdermal estrogen have the same effect on bone mineral density loss. Hormone therapy alone stabilized the bone mineral density loss. Hormone therapy together with alendronate resulted in better values in all groups.Hormone therapy is adequate in osteopenic women. However, hormone therapy plus alendronate is advantageous in women with considerable bone mineral density loss.

Am J Med. 2003 Aug 15;115(3):209-16.
Early discontinuation of treatment for osteoporosis.
Tosteson AN, Grove MR, Hammond CS, Moncur MM, Ray GT, Hebert GM, Pressman AR, Ettinger B.
Department of Medicine, Dartmouth Medical School, Hannover, New Hampshire 03756, USA.
PURPOSE: To identify factors associated with early treatment discontinuation of three agents commonly prescribed for women with low bone density. METHODS: A telephone survey was conducted in 2000 to 2001 in a random sample of women aged 45 years or older who had bone density T-scores -1.0 or lower and who had initiated treatment with hormone replacement therapy, raloxifene, oral endronate. Logistic regression was used to estimate adjusted odds ratios for early treatment discontinuation. RESULTS: Among 956 women who were interviewed an average of 7 months after treatment initiation, 334 were taking hormone therapy, and 88 (26%) had discontinued; 256 were taking raloxifene, and 48 (19%) had discontinued (P = 0.03 vs. hormone therapy); and 366 were taking alendronate, and 70(19%) had discontinued (P = 0.02 vs. hormone therapy).Women with bothersome side effects (somewhat bothered: odds ratio [OR] = 4.0; 95% confidence interval [CI]: 2.5 to 6.5; very or extremely bothered: OR = 25; 95% CI: 16 to 39) or who thought that their bone density test results did not show osteoporosis (OR = 1.6; 95% CI: 1.0 to 2.5) were more likely to discontinue therapy, as compared with women reporting regular exercise (OR = 0.7; 95% CI: 0.4 to 1.0) or a willingness to take prescribed medications (OR = 0.6; 95% CI: 0.4 to 0.9).After adjustment for side effects and patient characteristics, the odds of early treatment discontinuation did not differ significantly among treatments. CONCLUSION: Improved adherence to osteoporosis treatment requires that treatment side effects be minimized and women be educated regarding their bone density test results.

Bone. 2003 Jul;33(1):132-43.
Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial.
Uusi-Rasi K, Kannus P, Cheng S, Sievanen H, Pasanen M, Heinonen A, Nenonen A, Halleen J, Fuerst T, Genant H, Vuori I.
UKK Institute for Health Promotion Research, 33501 Tampere, Finland.
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.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Jun;24(3):306-9.
The efficacy of alendronate in the prevention and treatment of postmenopausal osteoporosis.
Cheng ZQ, Yin W, Fan JY, Ma TJ.
Department of Endocrinology, General Hospital, Tianjin Medical University, Tianjin 300075, China.
OBJECTIVE: To investigate the effectiveness of alendronate Chinese national product in the prevention and treatment of postmenopausal osteoporosis. METHODS: The 56 postmenopausal women with osteopenia or osteoporosis were randomly divided into two groups: treated with alendronate 10 mg/d (28 cases) orally and placebo (28 cases), for 6 months. All subjects received 600 mg/d of calcium carbonate and vitamin D 1,000 U/d. Bone mineral density (BMD) of the lumbar spine, femoral neck, trochanter and Ward's triangle were measured by dual energy X-ray absorptiometry as well as the markers of bone turnover were analysed at the beginning and the end of the study. RESULTS: The results showed that lumbar spine BMD increased by 5% in the alendronate group (P < 0.01), but decreased in BMD of the lumbar spine and femur in the placebo group (P < 0.05) after 6 months of treatment. In the alendronate group the marker of bone resorption and bone formation were significantly decreased after alendronate therapy. There were no change in placebo group. CONCLUSIONS: Alendronate (Chinese national product) is effective in reducing bone turnover and promoting bone mass of postmenopausal osteoporosis.

J Biomed Mater Res. 2001;58(6):645-50.
The effect of alendronate (Fosamax) and implant surface on bone integration and remodeling in a canine model.
Frenkel SR, Jaffe WL, Valle CD, Jazrawi L, Maurer S, Baitner A, Wright K, Sala D, Hawkins M, Di Cesare PE.
Musculoskeletal Research Center and Department of Orthopaedic Surgery, New York University Hospital for Joint Diseases, New York, New York 10003, USA.
Patients at high risk for osteoporosis and its associated morbidity, including postmenopausal women, are being pharmacologically managed to stabilize and improve bone mass. Alendronate sodium (Fosamax) is a commonly used antiresorptive agent effective in osteopenic women for reducing bone resorption, increasing bone density, and decreasing fracture incidence. With the increased incidence of alendronate-treated women who are undergoing hip replacement or fracture repair by prosthesis placement, data are needed to predict how alendronate affects host bone integration with uncemented surfaces. The aim of this study was to determine the effect of alendronate on new bone formation and attachment to implant surfaces in a normal and simulated estrogen-deficient, calcium-deficient canine model, using an implantable bone growth chamber. Alendronate did not affect host bone integration to surfaces commonly used in uncemented total joint arthroplasty, but there were significant differences dependent solely on the type of surface.

Int J Clin Pract Suppl. 1999 Apr;101:40-5.
The antifracture efficacy of alendronate.
Seeman E.
Department of Endocrinology, Austin & Repatriation Medical Center, Heidelberg, Melbourne, Australia. Alendronate Phase III Treatment Study Group.
Two multicentre, double-blind, randomised trials were performed involving 994 postmenopausal women (mean age 64 yr, range 45-80 yr) with osteoporosis and using identical protocols at centres in the USA and internationally. Patients were included if bone density was +/- 2.5 standard deviations below the young-normal mean. The presence of fracture was not an inclusion criterion. Patients received placebo or alendronate (ALN) (5 or 10 mg/day for 3 yr, or 20 mg/day for 2 yr, then 5 mg/day for 1 yr). All received 500 mg elemental calcium. Analysis of vertebral fracture rates was based on preplanned pooling of all treatment groups. Analysis of nonvertebral fracture rates was based on preplanned pooling of this protocol and 3 similar studies in postmenopausal women with osteoporosis. Bone density decreased in the patients receiving placebo and increased in the patients receiving ALN. The optimum dose to increase bone density was 10 mg daily. After 3 years, bone density was 8.8 +/- 0.4% (lumbar spine), 5.9 +/- 0.5% (femoral neck) and 7.8 +/- 0.6 (trochanter) higher in the patients treated with 10 mg/day ALN than in patients receiving placebo. One or more new vertebral fractures occurred in 17 of 526 patients receiving ALN (3.2%) and 22 of 355 patients receiving placebo (6.2%) (a 48% reduction, (P = 0.034). Of the patients having new vertebral fractures, > or = 2 fractures occurred in 3 of 17 (18%) ALN-treated patients and 15 of 22 (68%) receiving placebo (P < 0.001). Fewer patients receiving ALN had vertebral fractures whether stratified by age or by the presence or absence of vertebral fractures at entry. Among patients sustaining vertebral fractures, height loss was 23.3 mm in patients receiving placebo and 5.9 mm in patients receiving ALN. Clinical adverse events, mainly upper gastrointestinal irritation, resulted in discontinuations in 6% (placebo), 5.4% (5 mg), 4.1% (10 mg), 8% (20 mg/5 mg). In the pooled analysis across all 5 osteoporosis treatment clinical trials, nonvertebral fractures occurred in 73 of 1012 ALN-treated women (76 fractures in 2240 patient-years) and in 60 of 590 women receiving placebo (70 fractures in 1347 patient-years). After 3 years, the cumulative incidences (ALN vs placebo) were 9% and 12.6%, a 29% reduction in absolute risk compared with placebo (P = 0.048). Alendronate is a well-tolerated new treatment that reduces the risk and severity of new vertebral fractures, reduces height loss and may reduce the risk of nonvertebral fractures.

Int J Clin Pract Suppl. 1999 Apr;101:62-6.
Alendronate in the treatment of Paget's disease of bone.
Reid IR, Siris E.
University of Auckland, Auckland, New Zealand.
This review reports the results of 2 recently completed long-term, randomised, double-blind, multicentre, controlled studies in which men and women with moderate to severe Paget's disease received oral alendronate 40 mg daily for 6 months One study conducted in the United States, compared the effects of alendronate 60 mg/day (n=41) with those of oral etidronate 400 mg/day (n=47); the other, conducted in the United Kingdom, Australia, and New Zealand, compared the effects of alendronate (n=27) with those of placebo (n=28). In both studies alendronate significantly reduced serum concentrations of alkaline phosphatase by more than 70%, which was significant in comparison with baseline (P < 0.001) and the comparator regimens (P < 0.001). Response to treatment (i.e. a > 60% decrease in or normalisation of serum alkaline phosphatase) was seen in more than three-quarters of patients treated with alendronate in both trials, compared with less than one-third of patients treated with etidronate and no patients treated with placebo. Radiologic scores, reflecting the status of osteolytic lesions, improved in a greater proportion of patients receiving alendronate than in those receiving etidronate or placebo. Histomorphometric analysis performed at 6 months showed that bone formed during alendronate treatment was of normal quality, without evidence of impaired mineralisation or other abnormalities. Alendronate was well tolerated, with an adverse event profile comparable with those of etidronate and placebo. These studies therefore showed that 6 months of treatment with oral alendronate suppresses disease activity in patients with Paget's disease of bone, with beneficial effects on biochemical, radiologic, and histomorphometric indices superior to those of etidronate and placebo.

Int J Clin Pract Suppl. 1999 Apr;101:14-7.
The effects of alendronate on bone turnover and bone quality.
Meunier PJ, Arlot M, Chavassieux P, Yates AJ.
Hopital Edouard Herriot, Lyon, France.
During Phase III clinical trials with alendronate, biochemical and histological studies assessed bone turnover and bone quality in patients treated for 3 years. Patients were randomised in double-blind fashion to receive placebo, alendronate 5 or 10 mg/day for 3 years or 20 mg/day for 2 years followed by 5 mg/day for 1 year. All patients also received 500 mg/day of calcium carbonate. Decreases in bone resorption with alendronate preceded decreases in bone formation. After approximately 6 months of continuous treatment, a new steady state of bone turnover was attained, leading to the increase in bone density. No subsequent decrease in the rate of bone turnover or of frozen bone was noted. Alendronate treatment did not impair bone mineralisation, induce the formation of woven bone or have any other adverse effects on bone quality.

Rev Med Liege. 1998 Apr;53(4):220-2.
Drug clinics. The drug of the month. Alendronate (Fosamax).
Scheen AJ.
Service de Diabetologie, Universite de Liege.
Alendronate (Fosamax, Merck Sharp & Dohme) is an aminobisphosphonate which inhibits bone turnover by suppressing the activity of osteoclasts without increasing the risk of osteomalacia. Alendronate is highly effective at preventing bone loss associated to absence of endogenous estrogen and induces a sustained increase in bone mass. Fosamax is indicated and reimbursed in the treatment of osteoporosis in postmenopausal women, with either an history of bone fracture confirmed by X-ray exam or obvious osteoporosis assessed by bone mineral density measurement. The recommended dosage is 10 mg once daily, continuously. The drug should be absorbed after an overnight fast to improve its bioavailability and with a big glass of plain water to reduce the risk of oesophageal ulcerations. Large randomized controlled trials for up to 3 years have demonstrated that alendronate is able to reduce the risk and rate of occurrence of vertebral and nonvertebral fractures in postmenopausal women.