Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): Additional results from the monthly oral therapy with ibandronate for osteoporosis intervention (MOTION) study

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported.Objective: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events.Methods: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, nonin-feriority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed.Results: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were ?75.5% with monthly ibandronate and ?81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in ≤30% of patients per group during this 1-year study.Conclusion: The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.     

Patient preference for once-weekly alendronate 70 mg versus once-daily alendronate 10 mg: a multicenter,randomized, open-label,crossover study

BACKGROUND: Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES: This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the patients believed was more convenient and would be easier to comply with for a long period. METHODS: This was a multicenter, randomized, open-label, preference study in which postmenopausal women with osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion (4 weeks with each study regimen separated by a 1-week washout period). The study regimens included once-weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and secondary end points were assessed with a questionnaire completed by the patient. Adverse events (AEs) were recorded to assess patient tolerability of the study medications. RESULTS: A total of 324 patients met the eligibility requirements; 288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment, 272 completed the questionnaire, and 266 completed the study. Of the patients who completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%; P < 0.001). Most patients also believed that once-weekly dosing was more convenient than once-daily dosing (89.0% vs 7.7%; P < 0.001) and would allow them to achieve better long-term compliance (87.5% vs 8.5%; P < 0.001). Clinical AEs were reported in 30.7% of patients treated with once-weekly alendronate and 30% of patients treated with once-daily alendronate, with no significant differences between treatments. CONCLUSION: When once-weekly alendronate 70 mg was compared with once-daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the preferred dosing regimen.     

A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International

Objectives: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. Methods: This was a 12‐month extension to the Fosamax^® Actonel^® Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12‐month base study continued taking the same double‐blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. Results: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. Conclusions: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.     

Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis

Bisphosphonates are effective agents for postmenopausal osteoporosis, but their efficacy in patients with type 2 diabetes mellitus (DM) is not known. The investigators evaluated bone mineral density (BMD) response to alendronate in women with concurrent late postmenopausal osteoporosis and type 2 DM. In a retrospective, matched case-control study, 26 late postmenopausal osteoporotic women with type 2 DM (age, 67.6±7.3 y; type 2 DM duration, 12.8±6.8 y; duration of menopause, 10.9±7.4 y; time on alendronate: 4.8±2.3 y; body mass index [BMI], 31.4±6.3 kg/m²) were matched with 26 controls according to age, BMI, duration of menopause, and alendronate treatment received. All subjects were given alendronate 10 mg/d or 70 mg/wk, along with sufficient vitamin D (≥400 IU) and calcium (≥1 g/d) intake, for 4.8 y. Response to alendronate therapy was determined by assessment of mean percent change in BMD of total hip, femoral neck, forearm, and lateral spine. The presence of type 2 DM resulted in no difference in spinal BMD response to alendronate therapy. In contrast, BMD in the total hip (mean percent change in BMD, −5.6% vs +1.4%;P=.096), femoral neck (−8.1 % vs +1.1 %;P=.015), and forearm (−3.6% vs +12.7%;P=.013) fell progressively from baseline in subjects with type 2 DM who were taking alendronate for 4.8 y, compared with controls. Elderly, postmenopausal, osteoporotic obese women with type 2 DM are resistant to long-term bisphosphonates, especially in regions of the hip, femoral neck, and forearm compared with the spine. The efficacy of bone resorption inhibitors in patients with type 2 DM, especially in comparison with anabolic agents, should be considered in additional studies.     

COMPARISON OF ALENDRONATE,CALCITONIN AND CALCIUM TREATMENTS IN POSTMENOPAUSAL OSTEOPOROSIS

The present study was planned to assess the safety, tolerability and efficacy on bone mineral density (BMD), pain, quality of life and fracture risk of alendronate, calcitonin and calcium treatments. A total of 151 postmenopausal women with lumbar spine BMD 2 SD or more below the young adult mean were randomly assigned to one of three groups: 51 patients received oral alendronate 10 mg and calcium 1000 mg (alendronate group), 50 patients intranasal salmon calcitonin 100 IU and oral calcium 1000 mg (calcitonin group), and 50 patients oral calcium 1000 mg (calcium group) daily for one year. BMD was assessed by dual energy X-ray absorbtiometry, pain by a visual analogue scale, and quality of life by the Nottingham health profile. Significant increases in BMD at all sites were obtained in the calcitonin and alendronate groups, but not in the calcium group. Pain and quality of life improved significantly in both the calcitonin and alendronate groups, but not in the calcium group. New vertebral fractures were seen in 31.58% of the alendronate, 37.5% of the calcitonin, and 40% of the calcium groups, representing no statistical difference. No serious side-effects were seen in any of the patients during follow-up.     

Testing an Intervention for Preventing Osteoporosis in Postmenopausal Breast Cancer Survivors

Purpose: To test a 12-month multicomponent intervention for preventing or treating osteoporosis in 21 postmenopausal women who had completed treatment (except Tamoxifen) for breast cancer, and for whom hormone replacement therapy (HRT) was contraindicated.
Design: Pilot intervention study.
Methods: The intervention consisted of home-based strength and weight training exercises, 5 or 10 mg alendronate per day, 1500 mg calcium per day, 400 IU vitamin D per day, education on osteoporosis, and facilitative strategies to promote adherence to the intervention. Outcome measures were: adherence to the intervention, dynamic balance, muscle strength, and bone mineral density (BMD) of the hip, spine, and forearm.
Findings and Conclusions: Adherence to calcium, vitamin D, and alendronate therapy was above 95%, and adherence to strength training exercises was above 85%. Over the 12 months, the 21 participants had significant improvements in dynamic balance, muscle strength for hip flexion, hip extension, and knee flexion, and BMD of the spine and hip. Participants had a significant decrease in BMD of the forearm. Three of the 21 women who had measurable bone loss at baseline had normal BMD after 12 months of the intervention.     

Tolerability of once-weekly alendronate in patients with osteoporosis: a randomized,double-blind,placebo-controlled study

OBJECTIVE: To compare the upper gastrointestinal (GI) tract tolerability of once-weekly oral alendronate, 70 mg, and placebo. PATIENTS AND METHODS: This was a 12-week multicenter, randomized, double-blind, placebo-controlled study. The first patient initiated treatment on June 5, 2000, and the last patient completed treatment on March 1, 2001. The study enrolled 450 postmenopausal women and men with osteoporosis (224 took alendronate, 226 took placebo) who were ambulatory and community dwelling at 48 outpatient study centers in the United States. By design, approximately half of the patients were naive to bisphosphonates. The primary end point was upper GI tract tolerability based on the incidence of any upper GI tract adverse events. Secondary end points included the number of discontinuations due to drug-related upper GI tract adverse events and the change from baseline in bone resorption, assessed by the urinary N-telopeptide-creatinine ratio at 12 weeks. A subgroup analysis of the primary and secondary end points was performed on the patients stratified by prior bisphosphonate use. The safety and tolerability of the weekly alendronate and placebo regimens were captured as clinical and laboratory adverse events. RESULTS: A total of 11% of the alendronate patients and 13% of the placebo patients reported an upper GI tract adverse event. Discontinuations due to drug-related upper GI tract adverse events occurred in 3% of alendronate patients and 1% of placebo patients. The differences between the treatment groups for the primary and secondary end points were not significant. For the primary end point, the upper limit of the 95% confidence interval of the difference was well within the prespecified 14% comparability bound (-2.2%; 95% confidence interval, -8.3% to 3.9%). The overall incidence of upper GI tract adverse events was lower in the subgroup of patients with prior bisphosphonate exposure (8%) than in those who were bisphosphonate naive (16%). However, regardless of prior bisphosphonate exposure, the incidence of upper GI tract adverse events was similar between the alendronate and placebo patients. The urinary N-telopeptide-creatinine ratio showed a significant decrease in the alendronate patients (72% of baseline, P<.001) compared with a slight increase in the placebo patients (106% of baseline) at week 12. CONCLUSION: In this 3-month study, the incidence of upper GI tract adverse events in patients treated with once-weekly alendronate, 70 mg, was comparable to that with placebo.     

Teriparatide: a review

BACKGROUND: Traditionally, the management of osteoporosis in men and women has included the use of antiresorptive agents in combination with calcium and vitamin D supplementation. The mechanism of action of teriparatide is unique in that it possesses anabolic properties and therefore builds bone. Since the approval of teriparatide in the United States in 2002, a great deal of interest regarding its use in osteoporosis has developed. OBJECTIVES: This article reviews the information available on the new recombinant human parathyroid hormone teriparatide (hPTH [1-34]), including its clinical pharmacology, mechanism of action, pharmacokinetic properties, clinical efficacy, safety profile, potential drug interactions, contraindications and warnings, dosage and administration, and pharmacoeconomics. METHODS: The articles included in this review were identified through searches of PubMed and MEDLINE (1966-December 2003) and International Pharmaceutical Abstracts (1970-December 2003). Search terms included teriparatide, Forteo, recombinant human parathyroid hormone (1-34), and osteoporosis. The references of the identified articles were reviewed for additional publications. Specific product information was also obtained from the manufacturer of teriparatide. RESULTS: Teriparatide has been studied in postmenopausal women with osteoporosis, drug-induced osteoporosis (specifically, corticosteroid-induced osteoporosis), and men with osteoporosis. The data available from various clinical trials have shown an increase in both bone mineral density (BMD) and bone mineral content (BMC) with the use of teriparatide compared with placebo. One study found that women treated with the 20-microg dose and the 40-microg dose were 35% and 40%, respectively, less likely to have one or more new nonvertebral fractures compared with placebo (P = 0.02). Another study compared the use of daily teriparatide 40-microg injections versus oral daily alendronate. Results showed that the incidence of nonvertebral fractures was significantly lower in the teriparatide group than the alendronate group (P < 0.05). A study using 20- and 40-microg daily injections of teriparatide was performed in men with osteoporosis. There was a statistically significant increase in lumbar spine BMD of 5.9% in the 20-microg group and 9.0% in the 40-microg group (both, P < 0.001). In the femoral neck, a 1.5% increase in BMD occurred in the 20-microg group (P = 0.021) and a 0.9% increase in the 40-microg group (P < 0.001). A limited number of studies are available assessing the combination of antiresorptive medications and teriparatide; however, the available data suggest that the effects of teriperatide do not require prior stimulation of bone resorption. CONCLUSIONS: Teriparatide has been shown clinically to improve BMD and BMC in postmenopausal women and in men. Because of its anabolic capabilities, teriparatide can be used as an alternative to the traditional therapies that are currently available for the treatment of osteoporosis, with scheduled monitoring for adverse effects such as hypercalcemia and urinary calcium excretion. In 1 study, mild hypercalcemia was seen most often 4 to 6 hours after SC injection of teriparatide before returning to normal. Urinary calcium was observed to increase by 30 mg/d (0.75 mmol/d) with teriparatide.     

Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen

BACKGROUND: Ibandronate, a nitrogen-containing bisphosphonate, was approved by the US Food and Drug Administration (FDA) in May 2003 as a daily oral regimen for the treatment and prevention of post-menopausal osteoporosis. In March 2005, the FDA approved once-monthly dosing with ibandronate for the same indications. OBJECTIVE: The purpose of this article was to review the efficacy and tolerability of ibandronate 150 mg once monthly in the treatment and prevention of post-menopausal osteoporosis. METHODS: A search of MEDLINE (1966-September 2005) and International Pharmaceutical Abstracts (1971-September 2005) for articles relating to the efficacy and tolerability of once-monthly ibandronate in the treatment of postmenopausal osteoporosis was conducted using the terms ibandronate and ibandronic acid. Additional searches were conducted to identify publications relevant to compliance and pharmacoeconomic considerations using the terms bispbospbonate, compliance, cost, and pharmacoeconomics. The reference lists of identified articles and presentations from recent scientific meetings also were reviewed. Selected safety information from the manufacturer was incorporated. RESULTS: Ibandronate 2.5 mg/d and intermittent ibandronate (20 mg QOD for 12 doses every 3 months) have been shown to effectively reduce the incidence of vertebral fractures; after 3 years of therapy in a placebo-controlled clinical trial, the relative risk reductions for new vertebral fractures with daily and intermittent ibandronate were 62% and 50%, respectively (both, P<0.001 vs placebo). Once-monthly ibandronate has been evaluated in 2 clinical trials: a Phase I dose-ranging trial in 144 healthy postmenopausal women and a Phase III noninferiority trial in 1609 women with postmenopausal osteoporosis who were randomized to receive ibandronate 2.5 mg/d or 1 of 3 monthly ibandronate regimens: 50/50 mg (50 mg given on 2 consecutive days) once monthly; 100 mg once monthly; and 150 mg once monthly. The primary end point of the Phase III trial was the change from baseline in lumbar spine bone mineral density (BMD). After 1 year of therapy, patients who received ibandronate 150 mg once monthly had a significantly greater increase from baseline in lumbar spine BMD compared with those who received ibandronate 2.5 mg/d (4.9% vs 3.9%, respectively; P=0.002). The overall adverse-event profile was similar between the daily and monthly regimens. Drug-related adverse events were reported in 32.4% of patients receiving ibandronate 2.5 mg/d and 36.9% of patients receiving ibandronate 150 mg monthly. Upper gastrointestinal adverse events occurred in a respective 22.8% and 22.5% of the 2 groups. After 1 year of therapy, patients receiving ibandronate 150 mg monthly reported more flulike symptoms (8.3%) compared with those receiving ibandronate 2.5 mg/d (2.8%). In a crossover study comparing preference for and convenience of monthly ibandronate and weekly alendronate in 342 ambulatory women with postmenopausal osteoporosis, significantly more patients preferred the monthly ibandronate regimen to the weekly alendronate regimen (71.4% vs 28.5%, respectively; P<0.001). CONCLUSION: Once-monthly ibandronate is an effective and well-tolerated treatment option for postmenopausal osteoporosis.     

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.     

Serum ionic fluoride concentrations are significantly decreased after treatment with alendronate in patients with osteoporosis

BackgroundWe determined serum ionic fluoride (SIF) concentrations before and after treatment of osteoporosis with alendronate to clarify whether SIF concentrations directly reflect a change in bone metabolism.MethodsA total of 45 postmenopausal women with primary osteoporosis who were treated with alendronate over a 6-month period were enrolled (mean age, 64.2 years). SIF concentrations were measured by the flow injection method with an ion-selective electrode. Concentrations of bone turnover markers (serum bone alkaline phosphatase, serum osteocalcin, serum type I collagen cross-linked N-telopeptide and urinary deoxypryridinoline) and lumbar spine BMD (LsBMD) were also measured. SIF, bone turnover markers and LsBMD before and after treatment were compared.ResultsConcentrations of SIF as well as concentrations of all bone turnover markers were significantly decreased after treatment: means (standard deviations) before and after treatment were 0.62 (0.13) and 0.32 (0.09) μmol/l, respectively (P < 0.001) and the percent change was ? 46.3%. LsBMD was also significantly increased by 6.7% after treatment.ConclusionsThe reduction of SIF concentrations is probably caused by inhibition of bone resorption due to the action of alendronate. The findings suggest that SIF concentrations directly reflect a change in bone metabolism.     

Prevention and treatment of osteoporosis in women with breast cancer

Women who have had breast cancer may be at higher risk for osteoporosis than other women. First, they are more likely to undergo early menopause, due to chemotherapy-induced ovarian failure or oopherectomy. In addition, chemotherapy may have a direct adverse effect on bone mineral density (BMD), and osteoclastic activity may increase from the breast cancer itself. While estrogen therapy is considered standard for the prevention and treatment of osteoporosis, use of estrogen in women with a history of breast cancer is usually contraindicated. The approach to osteoporosis in women with breast cancer is also affected by the use of tamoxifen in many, as this drug appears to have opposite effects on BMD in premenopausal and postmenopausal women. We have reviewed therapeutic alternatives for the prevention and treatment of osteoporosis, focusing on patients with a history of breast cancer. Alendronate and raloxifene are currently approved in the United States for the prevention of osteoporosis; alendronate, raloxifene, and calcitonin are approved for treatment. Alendronate has the greatest positive effect on BMD and reduces the incidence of vertebral and nonvertebral fractures. Raloxifene and calcitonin appear to reduce the incidence of vertebral fractures; their effects on the incidence of nonvertebral fractures are not yet proven. Although no published studies specifically address the use of these approved agents for osteoporosis in women with breast cancer, understanding their relative effects on BMD in postmenopausal women in general will facilitate therapy selection in this population. Postmenopausal women with a history of breast cancer should undergo bone mineral analysis. Normal results and absence of other risk factors ensure that calcium and vitamin D intake are adequate. If osteopenia or other risk factors are present, preventive therapy with alendronate or raloxifene should be considered. For osteoporosis, treatment with alendronate should be strongly considered. Raloxifene and calcitonin are alternatives when alendronate is contraindicated. Further studies are needed to evaluate the optimal timing of initial bone mineral analysis in premenopausal women after breast cancer diagnosis and to determine the value of preventive treatment in women scheduled to undergo chemotherapy.     

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.     

Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials

To determine the efficacy of teriparatide supplementation for improving bone mineral density (BMD) and fracture risk in postmenopausal osteoporosis and if effects vary with factors. We identified eight randomised controlled trials (n = 2388) using electronic databases, supplemented by a hand-search of the reference lists. All trials aimed to evaluate the efficacy of daily subcutaneous teriparatide injection in postmenopausal osteoporosis. The main outcomes were fracture risk and percentage change of BMD from baseline. Data were pooled by employing a random-effect model. In trials that reported BMD as an outcome, treatment was associated with an increase of bone mass of 8.14% [95% confidence interval (CI): 6.72-9.55%; eight trials, n = 2206] in spine and 2.48% (95% CI: 1.67-3.29%; seven trials, n = 1303) at the hip. In trials that reported fracture as an outcome, treatment was associated with a 70% risk reduction in vertebral fractures (risk ratio 0.30, 95% CI: 0.21-0.44; three trials, n = 1452) and 38% risk reduction in non-vertebral fractures (risk ratio 0.62, 95% CI: 0.44-0.87; three trials, n = 1842). The PTH treatment with total calcium intake more than 1500 mg was related to a significant increase in BMD gains at total hip (1.40% vs. 3.72%; p = 0.004). However, long-term duration did not appear to contribute to differences in responsiveness to teriparatide. Evidence supports the use of teriparatide in treatment of women with postmenopausal osteoporosis who are at risk for fracture. Further studies directly comparing concurrent therapy and calcium supplement with long-term duration are warranted.     

渐进抗阻训练结合阿仑膦酸钠提高绝经后骨质疏松症患者腰椎骨密度的初步研究

目的观察渐进抗阻训练结合阿仑膦酸钠疗法对提高绝经后骨质疏松症患者腰椎骨密度的效果。方法20例绝经后骨质疏松症患者随机分为A、B两组,各10例,A组接受渐进抗阻训练结合阿仑膦酸钠治疗,B组仅接受阿仑膦酸钠治疗,疗程均为3个月。治疗前后用双能X线吸收仪分别测量腰椎骨密度。结果治疗前,两组患者的骨密度差异无显著性意义;治疗3个月后,A组患者的腰椎骨密度提高(4.520±0.68)%,B组提高(0.100±0.01)%,两组间的差异有非常显著性意义(P<0.01)。结论渐进抗阻训练结合阿仑膦酸钠疗法可提高绝经后骨质疏松症患者腰椎的骨密度,效果明显优于单纯服用阿仑膦酸钠。     

Comparing therapies for postmenopausal osteoporosis prevention and treatment

OBJECTIVE: To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis. DATA SOURCES: Articles were identified through searches of the MEDLINE (1966-July 2002), EMBASE (1980-July 2002), and International Pharmaceutical Abstracts (1970-July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials. CONCLUSIONS: Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.     

阿仑膦酸钠对中老年骨质疏松症患者骨密度的影响

背景阿仑膦酸钠是近来所采用的一种试图通过抑制破骨细胞来治疗骨质疏松症的药物,其效果与单纯补钙有何差异,尚待进一步观察.目的观察口服阿仑膦酸钠片对中老年骨质疏松症症状及骨密度的影响,并与葡萄糖酸钙口服液的干预效果比较.设计随机分组,采用自身对照及同期实验对照.单位北京大学深圳医院骨科.对象病例来源于1999-07/2001-07在北京大学深圳医院骨科门诊就诊的中老年骨质疏松症患者68例,选择年龄45岁以上,并排除继发性骨质疏松症患者,有62例患者纳入本次实验,用随机数字法随机分为治疗组(口服阿仑膦酸钠片)32例和对照组(口服葡萄糖酸钙口服液)30例.干预在综合治疗的基础上,治疗组每天给予阿仑膦酸钠片10 mg,对照组给予葡萄糖酸钙口服液,2支/次(每支约含葡萄糖酸钙100 mg,相当于钙9 mg),3次/d,两组疗程均为3个月.根据躯体疼痛改善情况、有无新的骨折发生及骨密度改善情况,分3级进行判定.主要观察指标①两组治疗前后骨密度值比较.②两组疗效比较.③两组不良反应和副作用比较.结果治疗组30例和对照组26例的观察结果纳入分析.①两组治疗前后骨密度值比较治疗组用药3个月,患者的骨密度明显上升,治疗前后比较,差异有显著性意义[(0.667±0.083)和(0.716±0.082)g/cm2;t=2.473,P＜0.01];对照组骨密度治疗前后比较,差异无显著性意义[(0.671±0.081)和(0.680±0.073)g/cm2;t=1.812,P＞0.05];两组治疗后比较,差异有显著性意义(t=2.384,P＜0.01).②两组疗效比较治疗组有效率高于对照组,差异有显著性意义(X2=14.9,P=0.005).③两组不良反应和副作用比较治疗组服药期间有7例患者轻度腹部不适,对照组无任何不良反应.结论阿仑膦酸钠片不仅能抑制骨的吸收,还能促进骨质恢复,增加骨量,可协助治疗中老年骨质疏松症,其疗效较单纯的葡萄糖酸钙口服液好.     

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

BACKGROUND: Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. METHODS: Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. RESULTS: Bone ALP decreased significantly from baseline at 3 months (P 相似文献   

Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial.

Corticosteroid-induced osteoporosis is the most common secondary cause of osteoporosis. We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy x-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SE) changes in BMD of the lumbar spine by QCT and DXA in the PTH group were 35+/-5.5% and 11+/-1.4%, respectively, compared with a relatively small change of 1.7+/-1.8% and 0+/-0.9% in the estrogen-only group. The differences in mean percentage between the groups at 1 yr were 33.5% for the lumbar spine by QCT (P < 0.001) and 9.8% for the lumbar spine by DXA (P < 0.001). The changes in the hip and forearm were not significantly different between or within the groups. During the first 3 mo of PTH treatment, markers of bone formation increased to nearly 150%, whereas markers of bone resorption increased only 100%, suggesting an early uncoupling of bone turnover in favor of formation. These results suggest that parathyroid hormone dramatically increases bone mass in the central skeleton of postmenopausal women with corticosteroid- induced osteoporosis who are taking hormone replacement.     

Risedronate: a new oral bisphosphonate

BACKGROUND: Bisphosphonates have been effective in the treatment of osteoporosis and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is approved by the US Food and Drug Administration for the prevention and treatment of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the treatment of Paget's disease of bone. OBJECTIVE: This article reviews current studies of risedronate in osteoporosis and Paget's disease of bone and, to the extent possible, compares risedronate with other bisphosphonates and other therapies. Information on the pharmacokinetics and adverse effects of risedronate, and the drug's use in other disorders, is also reviewed. METHODS: Clinical studies and review articles concerning the use of risedronate published in the English-language literature from 1966 through October 2000 were identified through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical Abstracts using the search terms risedronate and NE 58095. Recent clinical studies, review articles, and consensus statements regarding the use of other bisphosphonates were identified through searches of the same databases for this period using the search terms bisphosphonates, alendronate, osteoporosis, and Paget's disease of bone. RESULTS: The use of risedronate therapy in patients with postmenopausal osteoporosis has been shown to increase bone mineral density (BMD) and decrease the incidence of fractures compared with placebo. In glucocorticoid-induced osteoporosis, risedronate has been shown to increase BMD without having a consistently significant effect on the risk of fractures. Although there are no direct comparisons between bisphosphonates in glucocorticoid-induced osteoporosis, risedronate appears to be less effective than alendronate and more effective than etidronate in terms of effects on BMD and/or fracture risk. In Paget's disease of bone, risedronate has been reported to be more effective than etidronate in decreasing serum alkaline phosphatase levels and bone pain. Finally, risedronate has been associated with a lower incidence of gastric ulcers than alendronate. CONCLUSIONS: In terms of efficacy in the prevention and treatment of osteoporosis and the treatment of Paget's disease of bone, risedronate is comparable to alendronate, the other orally available bisphosphonate. It appears to have better gastrointestinal tolerability than alendronate and may be preferred for patients in whom this is a concern. However, direct comparative and pharmacoeconomic studies are necessary to determine risedronate's relative place in the therapy of osteoporosis and Paget's disease of bone.