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PubMed1998

A risk-benefit assessment of alendronate in the treatment of involutional osteoporosis.

Osteoporosis is the most frequent metabolic condition experienced by elderly individuals. It is characterised by a low bone mass and microarchitectural deterioration of bone tissue leading to an increase in bone fragility and susceptibility to fracture. Osteoporosis constitutes a significant financial burden for health services as well as a source of pain and disability and a cause of a decrease in the quality of life for patients with the condition. Effective therapy for osteoporosis is, therefore, urgently needed. Currently, a number of different therapeutic approaches exist that have more or less proven positive effects on the incidence of fractures, for example estrogen replacement therapy, calcitonin, fluoride salts, calcium plus vitamin D supplementation and the first-generation bisphosphonate etidronate (etidronic acid). Alendronate (alendronic acid) is an alkylaminobisphosphonate with a very potent antiresorptive capability. In contrast to etidronate, alendronate possesses an excellent ratio between its potency for inhibiting bone resorption and its potency for impairing bone formation. In addition, no case of focal or generalised osteomalacia has so far been observed with alendronate. The bioavailability of oral alendronate is poor and the agent has to be taken in a fasting state, at least 30 minutes before breakfast, with a full glass of water. Alendronate has demonstrated its ability to increase bone mass significantly above the placebo values at any studied skeletal site in a wide variety of patient subgroups regardless of age, race, baseline rate of bone turnover or baseline bone mineral density. Alendronate is the only medication with a demonstrated positive effect on symptomatic and asymptomatic vertebral fracture rate, as well as on nonvertebral fracture rate. In clinical trials, alendronate was generally well tolerated and no significant clinical or biological adverse experiences were observed. However, postmarketing data have included reports of oesophageal lesions compatible with the diagnosis of alendronate-induced chemical oesophagitis, in around 1% of patients taking the agent. However, in the vast majority of cases alendronate tablets had been taken incorrectly. Therefore, with proper use, that is, use complying with the manufacturers administration recommendations, this potentially dangerous complication should be minimised and should not outweigh the overall positive benefit of alendronate in the prevention of fractures.

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PubMed2006

Alendronic acid produces greater effects than risedronic acid on bone density and turnover in postmenopausal women with osteoporosis : results of FACTS -international.

BACKGROUND: The objective of the study was to evaluate the effects of alendronic acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. METHODS: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score < or = -2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70 mg weekly (Fosamax) and placebo identical to risedronic acid weekly or active risedronic acid 35 mg weekly (Actonel) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phosphatase [BSAP] and urinary type I collagen N-telopeptides [NTx]); and safety and tolerability as assessed by reporting of adverse experiences. RESULTS: Alendronic acid produced greater increases in BMD than did risedronic acid at 12 months at all sites measured. Mean percentage increases from baseline in hip trochanter BMD at month 12 were 3.56% and 2.71% in the alendronic acid and risedronic acid groups, respectively (treatment difference [95% CI]: 0.83% [0.22, 1.45; p = 0.008]). Mean percentage increases from baseline were greater with alendronic acid than risedronic acid at the lumbar spine, total hip and femoral neck BMD at month 12 (p = 0.002, p < 0.001, p = 0.039, respectively). Increases in BMD with alendronic acid compared with risedronic acid were also significantly greater at 6 months at the trochanter and total hip. There was a greater reduction in bone turnover with alendronic acid compared with risedronic acid: NTx decreased 58% with alendronic acid compared with 47% with risedronic acid at 12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. CONCLUSIONS: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Aged↗
PubMed1999

[A study of the safety of rapid infusion of alendronate].

To investigate the safety of rapid infusion of alendronate, we used alendronate therapy for 11 breast cancer patients with bone metastasis. Of the 11 patients, only 1 had hypercalcemia and the remaining 10 normocalcemia. Rapid infusion of alendronate consisted of an administration of alendronate 10 mg diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 1 to 9 alendronate treatments. During alendronate therapy, only one patient complained of general fatigue, and the remaining 10 showed no alendronate-induced clinical symptoms. Rapid infusion of alendronate caused an increase in BUN level in two patients receiving intravenous hyperalimentation (IVH), a mild increase of GOT level in one, and a decrease of serum phosphorus level in two receiving IVH. However, no increase was found in serum creatinine and GOT levels. In addition, no patients showed alendronate-induced hypocalcemia. In conclusion, rapid infusion of alendronate brings about no major adverse effects, and makes it easier for many patients with bone metastasis to receive alendronate therapy on an outpatient basis.

Alendronate↗
PubMedDate not supplied

Effect of concurrent administration of alendronate sodium and retinol on development of changes in histomorphometric parameters of bones induced by ovariectomy in rats.

Retinol is a commonly used vitamin, especially by elderly people. Alendronate sodium, an aminobisphosphonate, is a potent antiresorptive drug used in the treatment of osteoporosis in postmenopausal women. Frequently, alendronate sodium and retinol are used concurrently. There are no reports on the interaction between alendronate sodium and retinol. The aim of the present study was to investigate the effect of concurrent administration of alendronate sodium and retinol on bone remodeling in ovariectomized rats. The histomorphometric parameters of long bones were studied. The experiments were carried out on 3-month-old Wistar rats, divided into 7 groups: I (C) - sham operated control rats, II (OVX) - ovariectomized control rats, III (OVX + ALN) - ovariectomized rats + alendronate sodium (3 mg/kg po), IV (OVX + R-1) - ovariectomized rats + retinol (700 IU/kg po), V (OVX + R-2) - ovariectomized rats + retinol (3500 IU/kg po), VI (OVX + ALN + R-1) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (700 IU/kg po), VII (OVX + ALN + R-2) - ovariectomized rats + alendronate sodium (3 mg/kg po) + retinol (3500 IU/kg po). The drugs were administered to the rats daily by oral gavage (alendronate sodium in the morning, retinol in the afternoon) for 28 days. Body mass gain, bone mass, mineral content in the tibia, femur and L-4 vertebra, histomorphometric parameters of the right tibia (width of osteoid, periosteal and endosteal transverse growth, area of the transverse cross section of the bone marrow cavity and the cortical bone) and the right femur (width of epiphyseal and metaphyseal trabeculae, width of epiphyseal cartilage) were studied. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. Alendronate sodium administered at a dose of 3 mg/kg po daily inhibited the development of changes induced by ovariectomy in the skeletal system of rats. Retinol, especially administered at the dose of 3500 IU/kg daily, intensified the changes in the osseous system caused by estrogen deficiency in rats. Retinol administered concurrently with alendronate sodium attenuated the antiresorptive effect of alendronate sodium on the skeletal system in ovariectomized rats.

Alendronate↗
PubMed2004

Ten years' experience with alendronate for osteoporosis in postmenopausal women.

BACKGROUND: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. METHODS: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. RESULTS: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. CONCLUSIONS: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

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PubMed2000

Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial.

OBJECTIVES: To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)-particularly those of the stomach, duodenum, or esophagus-in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes. DESIGN: Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d. PARTICIPANTS: A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded. MEASUREMENTS: Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups-gastroduodenal and esophageal-to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes. RESULTS: The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs. 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged > or =75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs). CONCLUSION: In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.

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PubMed2002

Gastric and duodenal safety of daily alendronate.

BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. RESULTS: Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS: Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

Adult↗
PubMedDate not supplied

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

Absorptiometry, Photon↗
PubMed2004

Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden.

BACKGROUND: One third of all the hip fractures occur in men. The risk for mortality following hip fracture is higher for men compared to women. The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures and increases bone mineral density (BMD) in osteoporotic women. Similar effects of alendronate were observed in men in some other trials. There are also results demonstrating alendronate to be cost-effective in the treatment of osteoporosis in women. OBJECTIVE: To investigate the cost effectiveness of alendronate for male osteoporosis in Sweden by assuming the same relative risk reduction of fractures in men as for women, based on the FIT trial. DESIGN: A Markov model earlier used to analyze cost effectiveness of alendronate in treatment of postmenopausal osteoporosis in Sweden was adapted to fit a cohort of Swedish men. Cost effectiveness of alendronate vs. no treatment was assessed by transitioning men in the model over time between different health states. TIME HORIZON: The patients were followed from start of intervention until 100 years of age or death. In the base-case alendronate was assumed to have a fracture-risk-reducing effect for 10 years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. RESULTS: Taking a societal perspective treating a 71-year-old man (mean age in the FIT) with low BMD and prior vertebral fracture (VFA) with alendronate was found to be associated with a cost of 14,843 per quality adjusted life year (QALY) gained. CONCLUSIONS: The results in this study indicate that treating osteoporotic men with alendronate was projected to be cost-effective, under the assumption of the same fracture-risk-reducing effect of alendronate for men as for women.

Aged↗
PubMed1998

Alendronate induces gastric injury and delays ulcer healing in rodents.

Gastric ulceration associated with the use of NSAIDs is most frequently observed in elderly women, the same sector of society most likely to be receiving therapy for osteoporosis. As some anti-osteoporosis medications have been suggested to irritate the upper gastrointestinal mucosa, we evaluated the ability of one such drug, alendronate, to damage the gastric mucosa and to influence the severity and healing of gastric ulcers in rodents. The effects of alendronate on indomethacin-induced antral ulceration was evaluated in the rabbit, while effects on ulcer healing and on the formation of gastric erosions was evaluated in the rat. Effects of alendronate on gastric acid secretion, blood flow and prostaglandin synthesis were also evaluated. Alendronate caused erosions in the rabbit stomach, but not antral ulceration. However, at the highest doses tested (80 mg) alendronate increased the incidence and size of indomethacin-induced antral ulcers. Alendronate also enhanced indomethacin-induced gastric damage in the rat, and delayed gastric ulcer healing. These effects of alendronate were not attributable to changes in gastric acid secretion, blood flow, prostaglandin synthesis or the pharmacokinetics of indomethacin. The damaging effects of alendronate on the stomach were due to topical irritant effects and could be observed at concentrations as low as 4 mg/ml within 30 min of oral administration or topical superfusion. These results support preliminary clinical evidence that alendronate can damage the gastric mucosa. While gastric injury may be a rare occurrence in patients taking this drug, concomitant use of alendronate and NSAIDs may increase the incidence or severity of ulceration.

Alendronate↗
PubMed2000

Weekly administration of alendronate: rationale and plan for clinical assessment.

OBJECTIVE: This paper describes the rationale and supporting data for once-weekly dosing of alendronate. BACKGROUND: Alendronate sodium, a bisphosphonate that potently inhibits bone resorption, has been shown to increase bone mass and substantially reduce the incidence of osteoporotic fractures, including fractures of the hip. The standard regimen of daily administration has generally been well tolerated. However, weekly administration may provide greater convenience to patients without compromising efficacy or tolerability. The pharmacokinetics of alendronate and bone remodeling theory predict similar efficacy for weekly and daily administration if the cumulative dose is the same. Bone resorption in individual remodeling units normally proceeds for approximately 2 weeks; alendronate inhibits the rate and extent of resorption. Because the half-life of residence on bone surfaces is several weeks, weekly administration of alendronate should inhibit bone resorption to an overall extent similar to that of daily dosing, thereby producing similar effects on bone mass and strength. Animal studies demonstrate that both weekly and daily parenteral administration of alendronate effectively increase bone mass and strength, but confirmation of efficacy is needed for weekly oral dosing in humans. Although daily bisphosphonates (alendronate and risedronate) elicited esophageal irritation in a canine model of gastroesophageal reflux, weekly dosing with alendronate at a higher unit dose did not. Thus, the lower frequency of weekly dosing with a higher unit dose may actually reduce the risk of upper gastrointestinal irritation compared with daily administration of a lower dose. CONCLUSIONS: Current safety and efficacy data justify further investigation of once-weekly dosing of alendronate. Two positive-control, double-blind, randomized trials of osteoporosis treatment and prevention are currently being performed to assess the comparability of weekly, biweekly, and daily dosing of alendronate with regard to effects on bone density, safety, and tolerability.

Alendronate↗
PubMed2003

Effect of alendronate and exercise on bone and physical performance of postmenopausal women: a randomized controlled trial.

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.

Alendronate↗
PubMed2004

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International.

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.

Alendronate↗
PubMed2002

Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women.

OBJECTIVE: To review the effect of alendronate on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Controlled trials registry from 1980 to 1999, and we examined citations of relevant articles and proceedings of international meetings. STUDY SELECTION: We included 11 trials that randomized women to alendronate or placebo and measured bone density for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: The pooled relative risk (RR) for vertebral fractures in patients given 5 mg or more of alendronate was 0.52 [95% confidence interval (CI), 0.43-0.65]. The RR of nonvertebral fractures in patients given 10 mg or more of alendronate was 0.51 (95% CI 0.38-0.69), an appreciably greater effect than for the 5 mg dose. We found a similar reduction in RR across nonvertebral fracture types; in particular, RR reductions for fractures traditionally thought to be "osteoporotic," such as hip and forearm, were very similar to RR reductions for "nonosteoporotic" fractures. Individual studies showed similar results, reflected in the P values of the test of heterogeneity (P = 0.99 for vertebral and 0.88 for nonvertebral fractures). Alendronate produced positive effects on the percentage change in bone density, which increased with both dose and time. After 3 yr of treatment with 10 mg of alendronate or more, the pooled estimate of the difference in percentage change between alendronate and placebo was 7.48% (95% CI 6.12-8.85) for the lumbar spine (2-3 yr), 5.60% (95% CI 4.80-6.39) for the hip (3-4 yr), 2.08% (95% CI 1.53-2.63) for the forearm (2-4 yr), and 2.73% (95% CI 2.27-3.20) for the total body (3 yr). Heterogeneity of the treatment effect of alendronate was not consistently explained by any of our a priori hypotheses; in particular, the effect was very similar in prevention and treatment studies. The pooled RR for discontinuing medication due to adverse effects for 5 mg or greater of alendronate was 1.15 (95% CI 0.93-1.42). The pooled RR for discontinuing medication due to gastro-intestinal (GI) side effects for 5 mg or greater was 1.03 (0.81-1.30, P = 0.83), and the pooled RR for GI adverse effects with continuation of medication was 1.03 (0.98 to 1.07) P = 0.23. CONCLUSIONS: Alendronate increases bone density in both early postmenopausal women and those with established osteoporosis while reducing the rate of vertebral fracture over 2-3 yr of treatment. Reductions in nonvertebral fractures are evident among postmenopausal women without prevalent fractures and have bone mineral density (BMD) levels below the World Health Organization threshold for osteoporosis. The impact on fractures appears consistent across all fracture types, casting doubt on traditional distinctions between osteoporotic and nonosteoporotic fractures.

Alendronate↗
PubMed2004

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial.

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

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PubMedDate not supplied

Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis.

PURPOSE: To evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone metabolism and bone mineral density (BMD) in both HIV-infected men and women treated with highly active antiretroviral therapy (HAART). METHOD: We performed a 52-week prospective, multicenter, randomized, open-label clinical trial. Eligible participants were on stable HAART and had BMD values at the femoral neck or lumbar spine that corresponded to a t score less than -1. Patients were randomized to receive alendronate 70 mg weekly or no alendronate; calcium 1000 mg daily and vitamin D 500 IU daily were provided to all study recipients. Primary endpoint of the study was the change in bone metabolism evaluated by N-telopeptide of type 1 collagen and bone-specific alkaline phosphatase; the secondary endpoint was BMD variation. RESULTS: 18 patients were randomized to the alendronate and 23 to the no-alendronate group (controls). The alendronate-treatment group compared to controls had a significant decrease in serum N-telopeptides, 1914 +/- 1433.4 vs. 3967 +/- 1650.5 pM/L (p = .005) after 1 year. Lumbar spine BMD increased by 4% in the alendronate group (p = .004) vs. 3.7% (p = .062) in controls, compared to baseline values. Femoral neck BMD decreased by 0.5% in the alendronate group (p = .05) and by 3.5% in the control group (p = .04). No between-groups differences for BMD were found (Delta lumbar-BMD 0.0351 +/- 0.0406 in cases and 0.0356 +/- 0.073 in controls [p = .977], Delta femoral-BMD -0.085 +/- 0.160 in cases and -0.100 +/- 0.165 in controls [p = .795]). CONCLUSION: Alendronate plus vitamin D and calcium was effective in reducing bone resorption. Alendronate improved lumbar BMD and minimized femoral BMD decrease after 52 weeks compared to treatment with vitamin D and calcium alone in patients on HAART with osteopenia/osteoporosis.

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PubMed1999

Etidronate and alendronate in the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis. DATA SOURCE: A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized. DATA SYNTHESIS: Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate. CONCLUSIONS: No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.

Aging↗
PubMed1998

Alendronate does not block the anabolic effect of PTH in postmenopausal osteoporotic women.

In rodent osteoporosis models, anabolic activity of parathyroid hormone (PTH) is preserved in the presence of antiresorptive agents. Anabolic activity is also preserved when PTH is administered to estrogenized postmenopausal women. In contrast, in the ewe treated with tiludronate, PTH-induced stimulation of bone turnover did not occur. To determine whether PTH in combination with alendronate could be a viable treatment for osteoporosis, we performed a short-term study of postmenopausal women with osteoporosis (n = 10) already on alendronate 10 mg/day to determine whether PTH could increase bone formation assessed biochemically. Patients continued alendronate alone (n = 5) or continued alendronate with 400 IU/day subcutaneous human PTH (1-34) added for 6 weeks. Subjects receiving PTH had serum and urine sampling weekly during PTH treatment and for 5 weeks thereafter. Sampling was performed approximately biweekly for subjects who had been on alendronate alone for 11 weeks. Samples were analyzed for osteocalcin (OC), propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), cross-linked urinary N-telopeptide (NTX), and free urinary pyridinoline (PYD). Markers of bone formation increased within 3 weeks in the PTH plus alendronate group, with mean peak levels at 5-7 weeks: OC 49%, p < 0.01; PICP 61%, p < 0.01; and BSAP 24%, p = 0.12. Levels returned to baseline after discontinuing PTH, with PICP declining the most rapidly. There were no significant changes at any time in the alendronate alone group. There were no increments in either urinary NTX or PYD in either treatment group throughout the observation period. The bone turnover marker changes seen with PTH plus alendronate were similar to those seen with PTH plus hormone replacement. These data suggest that: PTH can stimulate bone formation, evidenced by elevations of bone formation markers, even in the presence of a potent bisphosphonate; in the presence of alendronate, PTH-stimulated bone formation precedes stimulation of bone resorption, suggesting that PTH stimulates bone formation de novo; and the combination of PTH and alendronate may be a viable treatment option for postmenopausal women with osteoporosis.

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