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PubMed2005

Comparison of zinc excretion and biochemical markers of bone remodelling in the assessment of the effects of alendronate and calcitonin on bone in postmenopausal osteoporosis.

OBJECTIVES: The aim of this study was to determinate the clinical usefulness of urinary bone resorption markers, urinary zinc excretion, and other biochemical markers in postmenopausal women with osteoporosis. We also evaluated the effects of alendronate and calcitonin therapies on biochemical markers of bone remodeling and urinary zinc excretion over a 6-month period. SUBJECTS AND METHODS: The study design was a randomized placebo controlled study. The patients were randomly assigned to receive alendronate (10 mg/day; 45 patients) or calcitonin (200 IU/day; 45 patients) or placebo (45 patients) for 6 months. All patients received supplemental calcium (1000 mg/day). To assess bone resorption, we measured excretion of cross-linked N-telopeptides of Type I collagen (uNTx); urinary zinc concentrations and standard chemistry determinations were also measured; and osteocalcin (sOC) was measured as a marker of bone formation. All parameters were measured before therapy and again after 1, 3, and 6 months in all groups. RESULTS: A statistically significant decrease occurred in the levels of sOC, uZn, and uNTx after 3 and 6 months in patients receiving calcitonin therapy (P < 0.05). sOC, uZn, and uNTx levels in the calcitonin group were significantly lower after three and 6 months from both placebo and baseline values of calcitonin group. In the alendronate group, a statistically significant decrease was observed in the levels of uNTx and uZn after 1 month and in the sOC, uZn, and uNTx after 3 and 6 months from both placebo and baseline values of alendronate group (P < 0.05). uNTx, sOC, and uZn decreased about 44%, 36%, and 33%, respectively, in the calcitonin group and about 53%, 51%, and 38%, respectively, in the alendronate group below baseline values 6 months after initiating treatment. In the placebo group, there was no significant decrease in sOC, uZn, and uNTx during the course of the study. CONCLUSION: Our study suggests that in postmenopausal women with osteoporosis, both alendronate and calcitonin reduce the concentrations of uNTx, uZn, and sOC, the effect of the alendronate dose administered being significantly earlier and more pronounced. Measurement of uNTx, uZn, and sOC might be a useful biochemical method of observing the positive clinical effect following alendronate or calcitonin therapy in postmenopausal women.

Alendronate↗
PubMed2006

Histidine decarboxylase-stimulating and inflammatory effects of alendronate in mice: involvement of mevalonate pathway, TNFalpha, macrophages, and T-cells.

Nitrogen-containing bisphosphonates (NBPs) are powerful anti-bone-resorptive drugs, but they frequently induce various inflammatory side effects. Recent clinical applications have disclosed an unexpected new side effect, jaw-bone necrosis and exposure. In vitro studies suggest that the inflammatory effects of NBPs are due to Vgamma2Vdelta2 T-cells, stimulated directly and/or indirectly [the latter via isopentenylpyrophosphate (IPP) in the mevalonate pathway]. Rats and mice, however, lack Vgamma2Vdelta2 T-cells, yet NBPs still induce necrotic and inflammatory reactions. In mice, NBPs induce IL-1-dependent inflammatory reactions, such as inductions of histidine decarboxylase (HDC, the histamine-forming enzyme) in the liver, lung, spleen, and bone marrow, an increase in granulocytic cells in the peritoneal cavity, pleural exudation, and splenomegaly. Here, we examined the involvement of IPP, TNF, macrophages, and T-cells in the inflammatory actions of alendronate (a typical NBP) in mice. Various statins (mevalonate-synthesis inhibitors) suppressed the alendronate-induced HDC inductions, while mevalonate itself augmented such inductions. IPP injection also induced HDC. Like IL-1-deficient mice, TNF-deficient mice were resistant to alendronate-stimulated HDC induction. Alendronate-stimulated HDC inductions were significantly weaker in macrophage-depleted mice and in nude mice than in control mice. Similar, though generally less clear-cut, results were obtained when other alendronate-induced inflammatory reactions were examined. These results suggest that (i) inhibition of the mevalonate pathway causes and/or modifies at least some inflammatory actions of alendronate in mice, (ii) in addition to IL-1, TNF is also involved in the inflammatory actions of alendronate, and (iii) alendronate may act on a variety of cells, including macrophages and T-cells.

Alendronate↗
PubMed2006

Effect of alendronate on endosseous implant integration: an in vivo study in rabbits.

PURPOSE: Alendronate sodium (Fosamax; Merck, Whitehouse Station, NJ) is a second-generation bisphosphonate used widely in osteopenic individuals for decreasing bone resorption and increasing bone density. The ability of alendronate to affect systemic bone remodeling raises natural questions about the drug's influence on dental implant osseointegration. Current knowledge regarding the effect of systemic bisphosphonates, specifically alendronate, on all 3 phrases of osseointegration is incomplete and only a few studies have started to investigate peri-implant bone responses to alendronate-coated implants. The purpose of this study was to determine the effect of systemic alendronate therapy on osseointegration of dental implants based on torque-removal values in rabbits. MATERIALS AND METHODS: Identical titanium dental implants were placed using a standardized surgical protocol in the bilateral distal femur and proximal tibia of 20 New Zealand white rabbits (79 implants total). One week before implant placement, 10 rabbits were given doses of alendronate and continued on weekly dosing for 5 weeks until euthanized. The other 10 rabbits were untreated controls. Torque-removal values were determined using a Tohinichi 15-BTG torque wrench (Tohinichi Mfg Co, Ltd, Tokyo, Japan) for all implants. RESULTS: Analysis of torque data showed no statistical differences between the alendronate and control groups in both femur and tibia sites. A statistically significant difference, however, was noted in torque removal values between femur and tibia sites regardless of drug or non-drug groups. CONCLUSIONS: In summary, orally dosed alendronate administration in rabbits had no significant effect on dental implant torque-removal values 6 weeks after endosseous placement in femur and tibia.

Alendronate↗
PubMed1996

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial.

PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.

Administration, Oral↗
PubMed1995

Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling.

BACKGROUND: The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated. PATIENTS AND METHODS: In a multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate. RESULTS: At each dose, alendronate produced significant reductions in markers of bone resorption and formation, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spine) in subjects receiving placebo. In the 10-mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P < 0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P < 0.05). CONCLUSION: Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.

Adult↗
PubMed2001

A theoretical analysis of the contributions of remodeling space, mineralization, and bone balance to changes in bone mineral density during alendronate treatment.

In patients with osteoporosis, alendronate treatment causes an increase in bone mineral density (BMD) and a decrease in fracture incidence. Alendronate acts by changing the bone remodeling process. Changes in bone remodeling resulting in decreased remodeling space, increased bone balance per remodeling cycle, and increased mineralization (ash mass/bone mass) have all been associated with alendronate treatment. Understanding the relative contributions of these parameters to BMD increases could help predict the utility of long-term (>10 years) or intermittent treatment strategies, as well as treatment strategies in which another pharmaceutical is administered concurrently. We have developed a computer simulation of bone remodeling to compare the contributions of focal bone balance and mineralization on BMD by simulating alendronate treatment using a bone balance method (decreased remodeling space, increased focal bone balance, uniform bone mineralization) and a mineralization method (decreased remodeling space, neutral focal bone balance, varying bone mineralization). Although both methods are able to predict BMD increases caused by alendronate over short periods, our findings suggest that the mineralization method may be more descriptive of long-term alendronate treatment. This implies that mineralization may be a larger contributor to BMD changes caused by alendronate than the focal bone balance. Based on this finding we offer a hypothesis to describe how remodeling space, focal bone balance, and mineralization each contribute to alendronate-induced BMD changes. Future analyses with this method could be used to identify improved dosing regimens and to predict which osteoporosis treatments would best complement each other.

Alendronate↗
PubMed1998

Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group.

BACKGROUND: Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment. METHODS: We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine increased by 2.1+/-0.3 percent and 2.9+/-0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4+/-0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2+/-0.4 percent and 1.0+/-0.4 percent in the respective alendronate groups (P<0.01) and decreased by 1.2+/-0.4 percent in the placebo group (P<0.01). The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate. There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4). Markers of bone turnover decreased significantly in the alendronate groups (P<0.001). There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate. CONCLUSIONS: Alendronate increases bone density in patients receiving glucocorticoid therapy.

Adolescent↗
PubMed2005

Daily and cyclic parathyroid hormone in women receiving alendronate.

BACKGROUND: We evaluated whether patients with osteoporosis treated with long-term alendronate have a response to parathyroid hormone treatment and whether short, three-month cycles of parathyroid hormone therapy could be as effective as daily administration. METHODS: We randomly assigned 126 women with osteoporosis who had been taking alendronate for at least 1 year to continued alendronate plus parathyroid hormone (1-34) subcutaneously daily, continued alendronate plus parathyroid hormone (1-34) subcutaneously daily for three 3-month cycles alternating with 3-month periods without parathyroid hormone, or alendronate alone for 15 months. RESULTS: In both parathyroid hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic parathyroid hormone, bone formation declined during cycles without parathyroid hormone and increased again during cycles with parathyroid hormone. Bone resorption increased in both parathyroid hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P<0.001 for each parathyroid hormone group as compared with the alendronate group and no significant difference between parathyroid hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities. CONCLUSIONS: This study suggests that a regimen of three-month cycles of parathyroid hormone alternating with three-month cycles without parathyroid hormone causes the early phase of action of parathyroid hormone (characterized by pure stimulation of bone formation) to be dissociated from the later phase (activation of bone remodeling). The early phase may be more important to the increase in spinal bone mineral density. In patients with persistent osteoporosis after prior alendronate treatment, both daily treatment and cyclic treatment with parathyroid hormone increase spinal bone mineral density.

Aged↗
PubMed2005

One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis.

BACKGROUND: Since the use of parathyroid hormone as a treatment for osteoporosis is limited to two years or less, the question of whether antiresorptive therapy should follow parathyroid hormone therapy is important. We previously reported results after the first year of this randomized trial comparing the use of full-length parathyroid hormone (1-84) alone, alendronate alone, or both combined. In the continuation of this trial, we asked whether antiresorptive therapy is required to maintain gains in bone mineral density after one year of therapy with parathyroid hormone (1-84). METHODS: In the data reported here, women who had received parathyroid hormone (1-84) monotherapy (100 microg daily) in year 1 were randomly reassigned to one additional year with either placebo (60 subjects) or alendronate (59 subjects). Subjects who had received combination therapy in year 1 received alendronate in year 2; those who had received alendronate monotherapy in year 1 continued with alendronate in year 2. Bone mineral density at the spine and hip was assessed with the use of dual-energy x-ray absorptiometry and quantitative computed tomography (CT). RESULTS: Over two years, alendronate therapy after parathyroid hormone therapy led to significant increases in bone mineral density in comparison with the results for placebo after parathyroid hormone therapy, a difference particularly evident for bone mineral density in trabecular bone at the spine on quantitative CT (an increase of 31 percent in the parathyroid hormone-alendronate group as compared with 14 percent in the parathyroid hormone-placebo group). During year 2, subjects receiving placebo lost substantial bone mineral density. CONCLUSIONS: After one year of parathyroid hormone (1-84), densitometric gains appear to be maintained or increased with alendronate but lost if parathyroid hormone is not followed by an antiresorptive agent. These results have clinical implications for therapeutic choices after the discontinuation of parathyroid hormone.

Aged↗
PubMed1999

Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.

Nitrogen-containing bisphosphonates were shown to cause macrophage apoptosis by inhibiting enzymes in the biosynthetic pathway leading from mevalonate to cholesterol. This study suggests that, in osteoclasts, geranylgeranyl diphosphate, the substrate for prenylation of most GTP binding proteins, is likely to be the crucial intermediate affected by these bisphosphonates. We report that murine osteoclast formation in culture is inhibited by both lovastatin, an inhibitor of hydroxymethylglutaryl CoA reductase, and alendronate. Lovastatin effects are blocked fully by mevalonate and less effectively by geranylgeraniol whereas alendronate effects are blocked partially by mevalonate and more effectively by geranylgeraniol. Alendronate inhibition of bone resorption in mouse calvaria also is blocked by mevalonate whereas clodronate inhibition is not. Furthermore, rabbit osteoclast formation and activity also are inhibited by lovastatin and alendronate. The lovastatin effects are prevented by mevalonate or geranylgeraniol, and alendronate effects are prevented by geranylgeraniol. Farnesol and squalene are without effect. Signaling studies show that lovastatin and alendronate activate in purified osteoclasts a 34-kDa kinase. Lovastatin-mediated activation is blocked by mevalonate and geranylgeraniol whereas alendronate activation is blocked by geranylgeraniol. Together, these findings support the hypothesis that alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function. This inhibition is prevented by exogenous geranylgeraniol, probably required for prenylation of GTP binding proteins that control cytoskeletal reorganization, vesicular fusion, and apoptosis, processes involved in osteoclast activation and survival.

Alendronate↗
PubMed2000

Effects of alendronate and hormone replacement therapy, alone or in combination, on bone mass in postmenopausal women with osteoporosis: a prospective, randomized study.

The effectiveness of hormone replacement therapy (HRT) and alendronate, alone and in combination, was evaluated in 120 postmenopausal patients with osteoporosis with bone mineral density (BMD) measurements at least 2 SD below the mean value for young premenopausal subjects. They had no contra-indications to HRT or alendronate use and were randomized to three different treatment groups. Group I was treated with micronized 17 beta-oestradiol 2 mg and norethisterone acetate 1 mg/day per os, group II received alendronate 10 mg/day per os and group III received micronized 17 beta-oestradiol 2 mg, norethisterone acetate 1 mg/day per os and alendronate 10 mg/day per os for 1 year. Elementary calcium 1500 mg/day was supplied to patients in all three groups. Spinal and femoral neck BMD and markers of bone mineral metabolism were measured on each patient before treatment and 6 and 12 months after treatment in 95 patients. At the end of the 12th month, significant increases in spinal and femoral neck BMD were found in all groups. Increases in spinal BMD were significantly higher in patients treated with alendronate and alendronate with HRT when compared with patients treated with HRT only. No significant difference was found in femoral neck BMD changes between the groups. Significant decreases in bone resorption and markers of bone formation were observed in all groups. Alendronate was found to be more effective than HRT and could have a very beneficial effect when added to the HRT regimen in patients with postmenopausal osteoporosis. Alendronate might also be used in postmenopausal patients with osteoporosis when HRT is contra-indicated or when there is reluctance to use hormonal treatment.

Alendronate↗
PubMed2006

Does alendronate prevent collapse in osteonecrosis of the femoral head?

UNLABELLED: Progression of collapse in osteonecrosis of the femoral head is related to the repair response, especially bone resorption around the necrotic region. A preliminary clinical study was done to determine whether systemic alendronate would prevent collapse and lead to pain relief in patients with osteonecrosis of the femoral head. Fourteen patients (20 hips) with osteonecrosis of the femoral head received daily administration of 5 mg alendronate (alendronate group) for 1 year. Eight patients (13 hips) with osteonecrosis of the femoral head did not receive alendronate (control group). All patients had measurements of biochemical markers of bone turnover at entry into the study, and the patients in the alendronate group repeated the measurements at 3 months, 6 months, and 12 months. All patients had clinical and plain radiographic examinations at entry into the study and at 3 months, 6 months, and 12 months. The alendronate group showed a greater decrease of biochemical marker of bone resorption than biochemical marker of bone formation. The alendronate group showed a lower frequency of collapse of the femoral head and reported less hip pain than the control group. Our results suggest alendronate has the potential to prevent collapse of the femoral head, even with extensive necrosis, presumably by inhibiting bone resorption in the necrotic region. LEVEL OF EVIDENCE: Therapeutic study, level II (prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

Adolescent↗
PubMed1999

Pharmacokinetics of intravenous alendronate.

Alendronate is a potent bisphosphonate that has been studied for the treatment of osteoporosis and Paget's disease of the bone. To examine the pharmacokinetics of this drug, several groups of postmenopausal women were dosed intravenously in several studies. Twelve patients with metastatic bone disease were administered an intravenous dose of 10 mg of 14C-labeled alendronate (approximately 26 muCi), and plasma, feces, and urine samples were collected for 72 hours. Radioactivity was excreted almost exclusively in urine, and all of it was accounted for by alendronate. Overall recovery accounted for 47% of dose, with the remainder presumed to be retained in bone. Metabolism of alendronate was not observed. Renal clearance of alendronate was 71 mL/min. An additional 10 subjects were given repeated i.v. administrations of alendronate to demonstrate that previous exposure does not alter the pharmacokinetic behavior of the drug. Examination of the findings from these and other studies in which alendronate was administered intravenously revealed that disposition of single doses is linear in the range of 0.125 to 10 mg. With the possible exception of a somewhat greater skeletal retention of a systemically administered dose, the pharmacokinetics of i.v. alendronate were found to be similar to those of other bisphosphonates.

Adult↗
PubMed2004

Response to therapy with once-weekly alendronate 70 mg compared to once-weekly risedronate 35 mg in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The FACT study (Fosamax Actonel Comparison Trial) was a 1-year-head-to-head trial comparing the efficacy and tolerability of once weekly (DW) alendronate 70 mg and OW risedronate 35 mg for the treatment of postmenopausal osteoporosis. The present analysis was performed to determine the percentage of patients who had changes during the study in BMD and biochemical markers (BCMs) of bone turnover above or below specific cut-off points. A subgroup analysis of upper gastrointestinal (UGI) tolerability was also performed. RESEARCH DESIGN AND METHODS: 1053 postmenopausal women with low BMD were randomized to alendronate 70 mg OW (N = 520) or risedronate 35 mg OW (N = 533). The percentage of patients who had measured BMD gains > or = 3%, and > or = 5% after 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS) was analyzed. The percentage of patients who experienced any bone loss, and those with measured losses of 3% or more at these sites after 12 months, was determined. The percentage of patients achieving reductions in urinary N-telopeptide of type 1 human collagen (NTX) > or = 40%, and serum C-telopeptide of type 1 collagen (CTx) > or = 60%, bone-specific phosphatase (BSAP) > or = 30%, and N terminal propeptide of type 1 procollagen (P1NP) > or = 50% at 3 months and 12 months was also determined. Tolerability, based on adverse experience reporting, was evaluated in a subgroup of patients with history of UGI disorders at baseline. RESULTS: A greater percentage of alendronate- than risedronate-treated patients had measured BMD gains (> or = 0%) (p < 0.05) at all sites at 12 months. Significantly more (p < 0.01) alendronate- than risedronate-treated patients had measured gains in BMD > or = 3% and > or = 5% at the hip trochanter, total hip, and LS spine. Significantly more (p < 0.05) risedronate- than alendronate-treated patients had an apparent loss of BMD (> 0% and > or = 3% loss) at the same sites. After 3 months, significantly (p < 0.001) more alendronate- than risedronate- treated patients achieved predefined reductions in all BCMs. Similar tolerability was demonstrated in both treatment groups, regardless of whether or not patients had a history of UGI disorders at baseline. CONCLUSIONS: Significantly more alendronate- than risedronate-treated patients achieved predefined increases in BMD at 12 months and reductions in BCMs at 3 months. Significantly more risedronate- than alendronate-treated patients were classified as apparent 'non-responders' (i.e. experienced any bone loss) after 12 months of therapy. The tolerability profiles of the two medications were similar.

Administration, Oral↗
PubMed1996

Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone.

Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.

Administration, Oral↗
PubMed2005

Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures.

UNLABELLED: Analyses of data from 3658 postmenopausal women with osteoporosis enrolled in the Fracture Intervention Trial showed that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. INTRODUCTION: Most osteoporosis studies examine the relative risk of fracture based on the entire duration of treatment. Because older patients tend to be at higher risk for osteoporosis-related fractures, this analysis examined the effect of alendronate treatment on the relative risk of fracture in terms of the age that patients attained during the study. MATERIALS AND METHODS: We studied 3658 postmenopausal women with osteoporosis 55-80 years of age at baseline enrolled in the Fracture Intervention Trial, a large randomized, double-blind, placebo-controlled study. Patients were treated with placebo or with alendronate at a daily dose of 5 mg for 2 years followed by 10 mg for an additional 1-2.5 years, and monitored for clinical fractures. Age, rather than study time, was the dynamic variable in our analysis. RESULTS: The relative risk reductions for hip, clinical spine, and wrist fractures were constant across age groups, without evidence of a decline at older ages. Specifically, alendronate reduced the risk of clinical fracture by 53% at the hip (relative risk [RR] = 0.47; 95% CI = 0.27-0.81; p < 0.01), 45% at the spine (RR = 0.55; 95% CI = 0.37-0.83; p < 0.01), and 31% at the wrist (RR = 0.69; 95% CI = 0.50-0.98; p = 0.038). In addition, alendronate produced a significant risk reduction of 40% (RR = 0.60; 95% CI = 0.47-0.77; p < 0.01) for the composite event of clinical hip, spine, and wrist fractures. As a consequence of the constant relative risk model, the absolute risk reduction with alendronate treatment increased with age because of the age-related increase in fracture risk in the placebo group. The absolute risk reduction for the composite event (hip, spine, and wrist fractures together) for alendronate treatment versus placebo was 65, 80, 111, and 161 women with fractures per 10,000 PYR for the 55 to <65, 65 to <70, 70 to <75, and 75-85 year age groups, respectively. CONCLUSIONS: These data show that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. The effectiveness is somewhat greater in patients with femoral neck T score < or = -2.5 than in those with a T score < or = -2.0.

Age Factors↗
PubMed2006

Three-year changes in bone mineral density around the knee after a six-month course of oral alendronate following total knee arthroplasty. A prospective, randomized study.

BACKGROUND: Bone mineral density decreases after total knee arthroplasty and is believed to affect prosthetic fixation. Treatment with alendronate has been shown to improve short-term bone mineral density after total knee arthroplasty; however, the long-term effects of this therapy are unknown. The purpose of this study was to evaluate the long-term effects of a six-month course of alendronate on bone mineral density after total knee arthroplasty. METHODS: Sixty patients were randomly assigned to receive either oral alendronate at a dosage of 10 mg/day for six months or no alendronate. The bone mineral density in the distal aspect of the femur and the proximal aspect of the tibia was measured preoperatively and at six, twelve, and thirty-six months after total knee arthroplasty. RESULTS: Fifty-four patients (twenty-nine in the alendronate group and twenty-five in the control group) completed the study. The alendronate group showed significant increases in bone mineral density in the distal aspect of the femur compared with the controls at six months (+4.8% and -14.2%, respectively; p < 0.01) and twelve months (+1.6% and -11.5%, respectively; p < 0.01). No significant difference in bone mineral density was detected between the groups at thirty-six months (-3.9% and -12.2%, respectively; p = 0.08). Similar trends in bone mineral density changes were also observed in the proximal aspect of the tibia. CONCLUSIONS: A six-month course of alendronate initially increased bone mineral density at six and twelve months after total knee arthroplasty, but no difference was noted after thirty-six months. The effect of alendronate on bone mineral density after total knee arthroplasty may be limited after discontinuation of therapy.

Administration, Oral↗
PubMedDate not supplied

[Effects of alendronate on the markers of bone metabolic activity in postmenopausal women with osteoporosis].

INTRODUCTION: Bisphosphonates are synthetic compounds used in treatment of osteoporosis and inhibition of bone resorption. MATERIAL AND METHODS: The research included a group of 30 postmenopausal women with osteoporosis, treated with alendronate (70 mg per week--Fosamax tablets in combination with calcium and active vitamin D--Alpha D3 0.25mcg). The control group included 20 women with osteoporosis treated with hormone substitution therapy (HST), calcitonin and deca duraboline. Bone metabolic activity, was evaluated using osteocalcin for bone formation and cross-laps for bone resorption. Blood samples were taken before therapy and 6-8 weeks after. RESULTS: The serum levels of osteocalcin and cross-laps during application of alendronate were statistically significantly lower comparing to those in pre-therapy. The serum levels of osteocalcin and cross-laps during the therapy applied in the control group were statistically insignificantly lower than values in pre-therapy. Osteocalcin has a tendency of decreasing in both groups, and it was slightly more evident in alendronate group. Cross-laps demontrated the same tendency of decreasing in both groups, and it was more evident in alendronate group. DISCUSSION: Our results have shown the efficacy of alendronate in preventing bone loss, which was highly statistically significant. They have also shown its suppressive effect on bone formation and resorption, but the effects were statistically less significant. CONCLUSION: Alendronate significantly reduces the level of bone resorption in postmenopausal women with osteoporosis. Its effects on bone formation are less expressed Alendronate's effects on bone metabolism become evident not later than 6-8 weeks after therapy application. Parameters of bone metabolic activity are very useful diagnostic means in evaluation of alendronate effect on bone metabolic activity and in the prognosis of bone mass loss.

Alendronate↗