Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Alendronate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1998

Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group.

BACKGROUND: Preventing bone loss associated with menopause and aging and maintaining the normal micro-architecture of bone provide important opportunities for the prevention of osteoporosis and fractures. OBJECTIVE: To determine the safety and efficacy of alendronate, an aminobisphosphonate, for preventing postmenopausal bone loss. DESIGN: 3-year double-blind, randomized, placebo-controlled trial. SETTING: 15 osteoporosis centers throughout the world. PARTICIPANTS: 447 women who had recently experienced menopause (6 to 36 months before study entry). INTERVENTION: Participants were randomly assigned to one of five regimens: oral placebo; oral alendronate, 1, 5, or 10 mg/d; or oral alendronate, 20 mg/d for 2 years followed by placebo during the third year (20/0 mg/d). MEASUREMENTS: Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover and bone quality were assessed with biochemical markers and bone histomorphometry. RESULTS: Alendronate at 5, 10, and 20/0 mg/d increased bone mineral density from baseline at the lumbar spine, femoral neck, and trochanter by 1% to 4% and in the total body by 0.3% to 1.0%; placebo led to losses of 2% to 4% at these sites. Alendronate, 1 mg/d, attenuated losses relative to those seen with placebo. Alendronate decreased markers of bone resorption to a new steady state by 3 months and decreased markers of bone formation by 6 to 12 months. Bone quality remained normal. At all dosages studied, alendronate had a safety and tolerability profile similar to that of placebo. CONCLUSIONS: In early postmenopausal women, alendronate given for 3 years at dosages of 5 mg/d or greater prevented the loss of bone mineral density at the spine and hip and in the total body. Alendronate seems to be a safe and effective nonhormonal option for prevention of postmenopausal bone loss.

Adult↗
PubMed1996

Alendronate stimulation of nocturnal parathyroid hormone secretion: a mechanism to explain the continued improvement in bone mineral density accompanying alendronate therapy.

The major effect of currently available antiresorptive therapy for osteoporosis is to slow or arrest bone loss. Although antiresorptive therapies demonstrate increases in bone mineral density, the effect is usually transient, and a plateau in bone mineral density usually emerges at 1 year. A unique and unexplained feature of treatment with the antiresorptive agent alendronate is continued, and steady improvement in bone mineral density occurs in years 2 and 3. We postulated that a potential mechanism for this unanticipated effect might be an exaggerated nocturnal increase in parathyroid hormone (PTH), which can act as an anabolic agent. We examined day-night levels and diurnal variation of PTH, serum calcium, ionized calcium, and markers of bone formation (osteocalcin) and resorption (N-telopeptide cross-links) over 24 hours in a randomly selected subset of 38 women (placebo: N = 13; mean age +/- SD, 69 +/- 3 years; alendronate: N = 25; mean age +/- SD, 69 +/- 3 years) who had completed 12 to 15 months of a larger (N = 120), randomized, double-blind, placebo-controlled trial with alendronate, 5 mg/day. By month 12, increases in the bone density of the spine (4.6%) and femoral neck (2.7%) were observed in the group treated with alendronate compared with placebo, (spine, 2.2%, p = .05; femoral neck, -0.2%, p < or = .05). Mean nocturnal PTH (10 PM-8 AM) was 21% higher (39 versus 32 pg/ml), and nocturnal serum calcium averaged 3% lower (8.7 versus 9.0 mg/dL) in the alendronate-versus-placebo group (both p < or = .05). Daytime levels (8 AM-10 PM) of PTH did not differ significantly between groups. We observed accompanying decreases in coupled markers of bone formation (osteocalcin, 38% lower, p < or = .01) and resorption (N-telopeptide cross-links, 50% lower, p < or = .01) in the alendronate group. Significant diurnal variations of PTH, serum calcium, and osteocalcin were present in both groups. We conclude that following 1 year of alendronate therapy, women have significant increases in bone mineral density and in nocturnal PTH levels, associated with decreases in nocturnal serum calcium and markers of bone turnover with maintenance of the diurnal variation. The nocturnal increase in PTH may mimic the anabolic effect of low-dose intermittent PTH administration to stimulate bone formation. Therefore, the increase might be a potential mechanism to explain the continued improvement in bone density following more than 1 year of alendronate therapy.

Aged↗
PubMed1998

A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. The Alendronate Research Group.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption. The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored. A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18.2%, respectively. The most common adverse effects were gastrointestinal symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H and P groups, respectively (P < 0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration. Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Adult↗
PubMed1995

Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group.

BACKGROUND: Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed. METHODS: We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements. RESULTS: The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons). The 5-mg dose was less effective than the 10-mg dose, and the regimen of 20 mg followed by 5 mg was similar in efficacy to the 10-mg dose. Overall, treatment with alendronate was associated with a 48 percent reduction in the proportion of women with new vertebral fractures (3.2 percent, vs. 6.2 percent in the placebo group; P = 0.03), a decreased progression of vertebral deformities (33 percent, vs. 41 percent in the placebo group; P = 0.028), and a reduced loss of height (P = 0.005) and was well tolerated. CONCLUSIONS: Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.

Aged↗
PubMed1997

Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups.

OBJECTIVE: To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. DATA SOURCES: Published data and data on file at Merck Research Laboratories. STUDY SELECTION: All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). DATA EXTRACTION: All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. DATA SYNTHESIS: In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. CONCLUSION: In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

Adult↗
PubMed1999

Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group.

Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and deoxypyridinoline (dPyr). The correlation between change from baseline at months 3-12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD ranged from r = -0.45 to r = -0.78 (p < 0.001), and from r = -0.38 to r = 0.10 (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to assess the accuracy of change from baseline at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71% (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive capacities of change from baseline at year 2 in hip BMD in predicting prevention of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone densitometry at the hip measured over 2 years. The sensitive biochemical markers offered a fast and valid alternative to bone densitometry for monitoring of alendronate treatment.

Absorptiometry, Photon↗
PubMed1997

Dose-response relationships for alendronate treatment in osteoporotic elderly women. Alendronate Elderly Osteoporosis Study Centers.

Alendronate (ALN) is an aminobisphosphonate employed as an antiresorptive agent in the treatment of osteoporosis. The present study was carried out to determine dose-response relationships, particularly the effects of relatively low doses of ALN, on bone mineral density (BMD), biochemical indexes of bone and mineral metabolism, and bone histology, with particular attention to effects in elderly women. This prospective, randomized, double blind, 2-yr multicenter study compared the effects of placebo with those of 1.0, 2.5, or 5.0 mg ALN daily. All subjects received supplemental calcium (500 mg daily) as the carbonate. We studied 359 women with lumbar spine BMD at least 2.0 SD below the peak young adult mean. Subjects were stratified by age, with 135 aged 60-69 yr and 224 aged 70-85 yr. Histomorphometry was performed on transiliac bone biopsies obtained from 104 subjects after 1 yr and from 83 subjects after 2 yr. This study elucidated the previously uninvestigated lower region of the dose-response curve for ALN in osteoporosis. Over 2 yr, treatment with 1.0, 2.5, or 5.0 mg/day increased lumbar spine BMD, on the average, by 0.65%, 3.54%, and 5.67%, respectively, compared with that in the placebo group (P < 0.001 vs. placebo for the 2.5 and 5 mg groups). Significant dose-related increases were also seen in BMD at appendicular sites and in total body BMD. Dose-dependent reductions in bone turnover to new steady states were indicated by serum and urine biochemical markers as well as by histomorphometry. There was also a dose-related reduction in the proportion of subjects suffering nonvertebral fractures (P < 0.05). Safety profiles were similar for the ALN and placebo groups and for both age strata. Efficacy was similar for both age strata. There was no evidence of impaired mineralization or other histological abnormalities due to ALN treatment. We conclude that treatment with ALN over a period of 2 yr was well tolerated and produced dose-dependent increases in BMD without evidence of a plateau over the dose range of 1.0-5.0 mg daily. One milligram daily did not result in a significant effect on BMD, and 5.0 mg daily produced favorable effects at all sites measured. Other studies have demonstrated somewhat greater effects on 10 mg daily. ALN, was equally effective and well tolerated in osteoporotic women over 70 yr old as in younger women with the same condition.

Aged↗
PubMed1996

Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and mouse bones.

Alendronate and etidronate are bisphosphonates used clinically to treat diseases associated with increased bone resorption. Etidronate is less potent and was reported to cause osteomalacia. This study examines if differences in distribution of alendronate and etidronate in the skeleton can explain differences in efficacy and in effects on mineralization between the two drugs. Eight-day old rat pups were injected s.c. with 3H-alendronate or 3H-etidronate both at either 1.3 mumol/kg or at their respective pharmacological effective doses in the growing rat of 0.12 mumol/kg for alendronate and 72.8 mumol/kg for etidronate. Twelve hours after administration at 1.3 mumol/kg both drugs showed a three- to fourfold higher localization on osteoclast vs. osteoblast surface. At the pharmacologically effective doses, 3H-alendronate labeled eightfold more osteoclast surface than osteoblast surface. In contrast, 3H-etidronate labeled approximately equal fractions of osteoclast and osteoblast surface. When similar doses of 3H-etidronate and 3H-alendronate (0.24 mumol/kg 3H-etidronate vs. 0.20 mumol/kg 3H-alendronate; 1.5 mumol/kg 3H-etidronate vs. 1.2 mumol/kg 3H-alendronate; and 14.6 mumol/kg 3H-etidronate vs. 12.0 mumol/kg 3 H-alendronate) were injected intravenously into adult mice at similar specific activities, 3H-etidronate labeled 1.5-2.5 times more osteoclast surface than 3-H-alendronate, but 3 to 15 times more osteoblast surface. Consequently, the ratio between the fraction of labeled osteoclast surface and the fraction of labeled osteoblast surface ranged for 3H-alendronate from 9 to 24, whereas for 3H-etidronate the range was from 4 to 7, due to more extensive labeling of osteoblast surface by 3H-etidronate. In a third experiment, we confirmed in adult mice the previous observation made in rat pups that normal bone formation occurs over alendronate-covered bone surfaces, and found that it occurred over etidronate-covered surfaces as well. Forty nine days after s.c. administration of alendronate at 0.12 mumol/kg or etidronate at 1.3 mumol/kg or 55.3 mumol/kg into adult mice bone formed over drug label. The distance from incorporated label to bone surface for both drugs (12.7 microns for alendronate and 8.7 and 9.2 microns for etidronate) was similar to wall width (defined by cement line) in controls (10.6 microns). In conclusion, alendronate, especially at pharmacologically active doses, shows higher uptake on resorption vs. formation surfaces than etidronate. The extent of bone formation on surfaces containing alendronate or etidronate is similar and is comparable to the "wall width" in controls.

Alendronate↗
PubMed1998

Alendronate/interleukin-1beta cotreatment increases interleukin-6 in bone and UMR-106 cells: dose dependence and relationship to the antiresorptive effect of alendronate.

Aminobisphosphonates inhibit bone resorption but have been shown to elicit acute-phase-like elevations in interleukin-6 (IL-6) in bone in vitro. The current studies were carried out to determine the relationship between the antiresorptive effects of the aminobisphosphonate alendronate and its effects on IL-6. Resorption was elicited in cultured 19-day fetal rat limb bones by 72 h treatment with interleukin-1beta (IL-1beta). Bone mass was quantitated at the end of the culture period to assess resorption. IL-6 was determined by bioassay (7TD1 cell proliferation). IL-1beta (18 and 180 pM) stimulated bone resorption and increased IL-6. Alendronate (70 microM) inhibited the IL-1beta-stimulated resorption. Alendronate alone did not affect IL-6 production by the bones. The IL-6 production from bones stimulated with 18 pM IL-1beta was not significantly affected by alendronate, but the IL-6 production from bones stimulated with 180 pM IL-1beta plus alendronate (21 and 70 microM) was higher than with IL-1beta alone. Indomethacin (1 mM) inhibited the IL-6 increase elicited by 180 pM IL-1beta and the enhanced IL-6 production elicited by cotreatment with IL-1beta and alendronate. Since bone cultures contain multiple cell types, further experiments were carried out to determine whether alendronate could increase IL-1beta-stimulated IL-6 production in an osteoblast cell line, UMR-106. Alendronate alone did not affect IL-6 in UMR-106 cells. Alendronate (70 microM) in combination with IL-1beta (180, 1.8, or 8 nM), or 7 microM alendronate, in combination with 8 nM IL-1beta, significantly increased IL-6 in 48 h cell cultures. The results from the bone organ cultures show that alendronate can enhance IL-6 production elicited by higher concentrations of the cytokine IL-1beta in bone, but that this effect on IL-6 does not prevent the inhibitory actions of alendronate on bone resorption. The results with the UMR106 cells indicate that one cellular site at which this enhancement of IL-6 production can occur is the osteoblast.

Alendronate↗
PubMed1995

Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.

Alendronate is an aminobisphosphonate that acts as a potent inhibitor of osteoclastic bone resorption. To understand the mechanism of action of alendronate in vivo, in this study we investigated the relationship between distribution of [14C]-alendronate in rat bone and its effects on bone resorption in vitro or in rat hypercalcemic models. A single IV dose of 0.05 approximately 1.25 mg/kg inhibited the increase in plasma calcium level induced by bovine PTH or 1 alpha(OH)D3. The minimal effective dose of pamidronate (1.25 mg/kg) and etidronate (over 31.25 mg/kg) were at least 5 times and 25 times, respectively, higher than the dose of alendronate in the rat hypercalcemic model prepared by 1 alpha(OH)D3. The relative potencies of compounds in the hypercalcemic rat models reflected those of inhibitory effects on bone resorption in vitro. We conducted the ivory-slice assay under two conditions: (a) addition of a given bisphosphonate after adherence of the osteoclasts; and (b) preincubation of the ivory slices with a given bisphosphonate. The inhibitory IC50 values of alendronate under condition (b) were similar to those under condition (a). To evaluate the interaction between osteoclasts and alendronate in bone, we investigated the localization of [14C]-alendronate in the tibia of growing rats (4-day-old rats). Alendronate did not distribute uniformly in the tibia. At 1 day after injection (0.05 mg SC), dense labeling was seen primarily under osteoclasts. We injected 0.05 mg/kg of [14C]-alendronate (single i.v.) into rats [14C]-alendronate was rapidly eliminated from plasma, and mainly distributed to the bone in rats. These data suggest that alendronate which distributed on bone surface mainly contributed to the antihypercalcemic action in vivo.

Alendronate↗
PubMed1997

Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women.

PURPOSE: Previously we have reported a significant increase in bone mineral density (BMD) of the spine and the hip and reductions in biochemical indices of bone turnover in postmenopausal women with osteoporosis treated with alendronate at various doses over 1 to 2 years. We have followed BMD and biochemical parameters in these patients for 1 or 2 years after discontinuation of alendronate to determine resolution of alendronate effects. PATIENTS AND METHODS: Participants received daily oral doses of placebo, 5 or 10 mg of alendronate for 2 years, or 20 or 40 mg of alendronate for 1 year followed by 1 year of placebo. No treatment was given in the third year of study. RESULTS: Lumbar spine BMD changes in the 5- and 10-mg groups (-1.4 and -0.4%) were similar to those in the placebo group (-1.2%) 1 year after discontinuation of drug and lumbar spine BMD changes in the 20- and 40-mg groups (-1.2% and 0.8%) were similar to those in the placebo group (-0.9%) 2 years after discontinuation of drug. BMD of the total hip followed the same pattern of resolution. The difference in BMD between alendronate and placebo groups at the end of alendronate treatment was maintained up to 2 years. Residual reductions in the bone resorption markers urinary deoxypyridinoline (D-Pyr) and collagen type 1 cross-linked N telopeptides and the bone formation markers serum bone-specific alkaline phosphatase and osteocalcin remained for 1 year after discontinuation of 5 and 10 mg of alendronate and for 2 years after discontinuation of 20 and 40 mg of alendronate, other than return of D-Pyr to baseline 1 year after cessation of treatment with the 5- and 10-mg doses. CONCLUSIONS: A residual decrease in bone turnover may be found up to 2 years after discontinuation of alendronate. Accelerated bone loss is not observed when treatment is discontinued. However, continuous therapy with alendronate is required to achieve a continuous gain in BMD.

Adult↗
PubMed1997

Alendronate inhibition of protein-tyrosine-phosphatase-meg1.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent bisphosphonate that inhibits osteoclastic bone resorption and has proven effective for the treatment of osteoporosis. Its molecular mechanism of action, however, has not been defined precisely. Here we report that alendronate is a potent inhibitor of the protein-tyrosine-phosphatase-meg1 (PTPmeg1). Two substrates were employed in this study: fluorescein diphosphate and the phosphotyrosyl peptide src-pY527. With either substrate, alendronate was a slow binding inhibitor of PTPmeg1. Among the other bisphosphonates studied, alendronate was more potent and selective for PTPmeg1. The hydrolysis of fluorescein diphosphate by PTP epsilon and PTPmeg1 was sensitive to alendronate, with IC50 values of less than 1 microM; PTPsigma, however, under the same conditions, was inhibited by only 50% with 141 microM alendronate. Similarly, with the src-pY527 substrate, alendronate inhibition was also PTP dependent. Alendronate inhibited PTPmeg1 with an IC50 value of 23 microM, PTPsigma with an IC50 value of 2 microM, and did not inhibit PTP epsilon at concentrations up to 1 mM. The alendronate inhibition of these three PTPs and two substrates is consistent with the formation of a ternary complex comprised of enzyme, substrate, and inhibitor. PTP inhibition by hisphosphonates or vanadate was diminished by the metal chelating agent EDTA, or by the reducing agent dithiothreitol, suggesting that a metal ion and the oxidation of a cysteine residue are required for full inhibition. These observations show substrate- and enzyme-specific PTP inhibition by alendronate and support the possibility that a certain PTP(s) may be the molecular target for alendronate action.

Alendronate↗
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.

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 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↗
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↗
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↗