Reduction In Vertebral Fractures Research Articles

Calcium supplementation on bone loss in postmenopausal women.

Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. To assess the effects of calcium on bone density and fractures in postmenopausal women. We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio. Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Preventing osteoporotic fractures with antiresorptive therapy: implications of microarchitectural changes.

Prospective studies have demonstrated that low bone mass correlates well with increased risk of osteoporotic fractures at various skeletal sites. Trials have likewise confirmed that enhancing bone mass with antiresorptive therapy reduces fracture incidence in individuals at risk. However, correlation of bone mineral density (BMD) increases with therapeutic risk reduction has proved less consistent than correlation of BMD decreases with greater fracture risk in the untreated. Indeed, various analyses have indicated that - even during treatment with potent bisphosphonates like alendronate and risedronate - BMD changes from baseline account for <30% of the reduction in vertebral fractures in treated women. It is clearly, therefore, that factors other than BMD are involved in the reduction of fracture risk achieved by antiresorptive therapies. According to recent micro-computed tomography imaging and other studies, antiresorptive therapy can help rebuild the microarchitecture of bone as well as strengthen the materials that go into it. When treating individuals with osteoporosis, these microarchitectural changes contribute to the reduction of fracture risk achieved by antiresorptive therapies.

Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study

Despite its well-known benefits, chronic corticosteroid therapy causes osteoporotic fractures in approximately 30-50% of patients treated. To prevent the occurrence of these fractures, treatment with oral bisphosphonates is recommended. However, current oral bisphosphonates, which are given either daily or weekly, are associated with stringent, inconvenient dosing guidelines. Less frequent dosing may provide greater acceptability. The objective of this study was to investigate the efficacy and safety of ibandronate, a highly potent nitrogen-containing bisphosphonate, when given by intravenous (i.v.) injection every 3 months in men and women with established corticosteroid-induced osteoporosis (CIO; lumbar spine [L2-L4] bone mineral density [BMD] T-score < or =-2.5). A total of 115 participants were assigned to receive daily calcium supplements (500 mg) plus either ibandronate (2 mg) injections every 3 months or daily oral alfacalcidol (1 microg), for 3 years. Intermittent i.v. ibandronate injections produced significantly greater increases in mean BMD at the lumbar spine (13.3% versus 2.6%, respectively; p<0.001), and femoral neck (5.2% versus 1.9%, respectively; p<0.001) versus daily oral alfacalcidol, after 3 years, relative to baseline. This study was not statistically powered to show a difference between the groups with respect to fracture incidence. Nevertheless, after 36 months, the frequency of patients with new vertebral fractures was significantly lower in the patients receiving ibandronate relative to those taking alfacalcidol (8.6% versus 22.8%, respectively; p=0.043). This is the first time that significant vertebral fracture reduction has been demonstrated with an i.v. bisphosphonate in CIO. Patients treated with i.v. ibandronate injections also experienced less back pain (p<0.001) and less height loss (p=0.001) than those receiving oral alfacalcidol. Both regimens were well tolerated. In conclusion, intermittent i.v. ibandronate injections are efficacious, well-tolerated, and convenient, and promise to offer physicians an important therapeutic advance in the management of osteoporosis.

Surrogates for fracture endpoints in clinical trials.

Surrogates for fracture endpoints in clinical trials.

American Society of Clinical Oncology Clinical Practice Guidelines: The Role of Bisphosphonates in Multiple Myeloma

To determine clinical practice guidelines for the use of bisphosphonates in the prevention and treatment of lytic bone disease in multiple myeloma and to determine their respective role relative to other conventional therapies for this condition. An expert multidisciplinary Panel reviewed pertinent information from the published literature through January 2002. Values for levels of evidence and grade of recommendation were assigned by expert reviewers and approved by the Panel. Expert consensus was used if there were insufficient published data. The Panel addressed which patients to treat and when to treat them in the course of their disease. Additionally, specific drug delivery issues, duration of therapy, initiation of treatment and management of treatment of lytic bone disease was reviewed and compared with other forms of therapy for lytic bone lesions. Finally, the Panel discussed patient and physician expectations associated with this therapy for bony metastases, as well as public policy implications related to the use of bisphosphonates. The guidelines underwent external review by selected physicians, by the Health Services Research Committee members, and by the ASCO Board of Directors. The available evidence involving randomized controlled trials is modest but supports that oral clodronate, intravenous pamidronate, and intravenous zoledronic acid are superior to placebo in reducing skeletal complications. A reduction in vertebral fractures has consistently been seen across all studies. No agent has shown a definitive survival benefit. Intravenous zoledronic acid has recently been shown to be as effective as intravenous pamidronate. Because there are no direct comparisons between clodronate and pamidronate or zoledronic acid, the superiority of one agent cannot be definitively established. However, the panel recommends only intravenous pamidronate or zoledronic acid in light of the use of the time to first skeletal event as the primary end point and more complete assessment of bony complications in studies evaluating it. Additionally, clodronate is not available in the United States. The choice between pamidronate and zoledronic acid will depend on choosing between the higher drug cost of zoledronic acid, with its shorter, more convenient infusion time (15 minutes), versus the less expensive drug, pamidronate, with its longer infusion time (2 hours). Bisphosphonates provide a meaningful supportive benefit to multiple myeloma patients with lytic bone disease. However, further research on bisphosphonates is warranted, including the following: (1) when to start and stop therapy, (2) how to integrate their use with other treatments for lytic bone disease, (3) how to evaluate their role in myeloma patients without lytic bone involvement, (4) how to distinguish between symptomatic and asymptomatic bony events, and (5) how to better determine their cost-benefit consequence.

Meta-analyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis.

To review the effect of raloxifene on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 2000 and examined citations of relevant articles and the proceedings of international osteoporosis meetings. We included seven trials that randomized women to raloxifene or placebo, with both groups receiving similar calcium and vitamin D supplementation, and measured bone density for at least one year. For each trial, three independent reviewers abstracted the data and assessed the methodological quality using a validated tool. Data from one large dominating trial suggest a reduction in vertebral fractures with a relative risk (RR) of 0.60 [95% confidence interval (CI) 0.50-0.70, P < 0.01]. The RR of nonvertebral fractures in patients given 60 mg or more of raloxifene in the larger study was 0.92 (95% CI 0.79-1.07, P = 0.27). Raloxifene resulted in positive effects on the percentage change in bone density, which increased over time and was independent of dose. At the final year, point estimates and 95% CIs for the differences in percent change in bone density (95% CI) between raloxifene and placebo groups were 1.33 (95% CI 0.37-2.30) for total body, 2.51 (95% CI 2.21-2.82) for lumbar spine, 2.05 (95% CI 0.71-3.39) for combined forearm, and 2.11 (95% CI 1.68-2.53) for combined hip (P < 0.01 at all four sites). Results were similar across studies, and formal tests of heterogeneity did not approach conventional statistical significance. Raloxifene slightly increased rates of withdrawal from therapy as a result of adverse effects (RR 1.15, 95% CI 1.00-1.33, P = 0.05). The pooled RR was significant for hot flashes 1.46 (95% CI 1.23-1.74, P < 0.01) and nonsignificant for leg cramps 1.64 (95% CI 0.84-3.20, P = 0.15). Raloxifene increases bone density, and the effect increases over 2 yr. The data suggest a positive impact of raloxifene on vertebral fractures. There was little effect of raloxifene on nonvertebral fractures.

VII. Meta-Analysis of Calcium Supplementation for the Prevention of Postmenopausal Osteoporosis

To summarize controlled trials examining the effect of calcium on bone density and fractures in postmenopausal women. We searched MEDLINE and EMBASE up to 1998 and the Cochrane Controlled Register up to 2000, and we examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. We included 15 trials (1806 patients) that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm, or recorded the number of fractures, and followed patients for at least 1 yr. For each trial, three independent reviewers assessed the methodological quality and extracted data. We found calcium to be more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% [95% confidence interval (CI) 0.24-3.86] for total body bone density, 1.66% (95% CI 0.92-2.39) for the lumbar spine, 1.64% (95% CI 0.70-2.57) for the hip, and 1.91% (95% CI 0.33-3.50) for the distal radius. The relative risk (RR) of fractures of the vertebrae was 0.77, with a wide CI (95% CI 0.54-1.09); the RR for nonvertebral fractures was 0.86 (95% CI 0.43-1.72). Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but do not meaningfully address the possible effect of calcium on reducing the incidence of nonvertebral fractures.

Raloxifene: recent information on skeletal and non-skeletal effects.

Raloxifene, a selective estrogen receptor modulator, is currently used for both prevention and treatment of postmenopausal osteoporosis. Recent data from the MORE (Multiple Outcomes of Raloxifene Evaluation) trial have evaluated health-related quality of life, 1-year clinical vertebral fracture reduction, and the correlation of bone mineral density and biochemical markers of bone turnover with vertebral fracture reduction. In addition, new information on the effects of raloxifene in breast cancer prevention, cardiovascular disease in high-risk women, and uterine disorders is reviewed.

Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women, including the effect of hormone replacement therapy.

To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. Prospective, observational study. One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long-term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.

Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women

The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58–75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up ( p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up ( p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials.

BackgroundHormone replacement therapy (HRT) is often seen as the treatment of choice for preventing fractures in women. We undertook a recent meta-analysis of randomised trials which suggested that HRT reduced non-vertebral fractures by 30%. In this analysis we extend that analysis to vertebral fractures.MethodsWe searched the main electronic databases until the end of August 2001. We sought all randomised controlled trials (RCTs) of HRT where women had been randomised to at least 12 months of HRT or to no HRT.ResultsWe found 13 RCTs. Overall there was a 33% reduction in vertebral factures (95% confidence interval (CI) 45% to 98%).ConclusionsThis review and meta-analysis showed a significant reduction in vertebral fractures associated with HRT use.

Etidronate for treating and preventing postmenopausal osteoporosis.

To systematically review the efficacy of etidronate on bone density, fractures and toxicity in postmenopausal women. We searched MEDLINE from 1966 to December 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included thirteen trials (with 1010 participants) that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least one year. For each trial, three independent reviewers assessed the methodological quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.60% (95% CI 0.41 to 0.88). There was no effect on non-vertebral fractures (pooled relative risk 1.00, (95% CI 0.68 to 1.42)). Etidronate, relative to control, increased bone density after three years of treatment in the lumbar spine by 4.27% (95% CI 2.66 to 5.88), in the femoral neck by 2.19% (95% CI 0.43, 3.95) and in the total body by 0.97% (95% CI 0.39, 1.55). Effects were larger at 4 years, though the number of patients followed was much smaller. Etidronate increases bone density in the lumbar spine and femoral neck. The pooled estimates of fracture reduction with etidronate are consistent with a reduction in vertebral fractures, but no effect on non-vertebral fractures.

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1-3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

Quality indicators for the management of osteoporosis in vulnerable elders.

Osteoporosis is a major cause of morbidity and death in older persons. For women who are 50 years of age, the estimated lifetime risk for osteoporotic fracture is 54%, and studies suggest that the ...

Fluoride for treating postmenopausal osteoporosis.

To assess the efficacy of fluoride therapy on bone loss, vertebral and non-vertebral fractures and side effects in postmenopausal women. We searched Medline, Current Contents and the Cochrane Controlled Trial Registry up to December 1998. Two independent reviewers selected RCTs which met predetermined inclusion criteria. Two reviewers independently extracted data using predetermined forms and assessed the methodological quality of the trials using a validated scale. For dichotomous outcomes, relative risks (RR) were calculated and for continuous outcomes, weighted mean differences (WMD) of percentage change from baseline were calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95%CI: 7.15,9.09) after two years of treatment and 16.1%(95%CI: 14.65,17.5) after four years. The RR for new vertebral fractures was not significant at two years [0.87 (95%CI: 0.51,1.46)] or at four years [0.9(95%CI: 0.71,1.14)]. The RR for new non-vertebral fractures was not significant at two years 1.2(95%CI: 0.68,2.1) but was increased at four years in the treated group 1.85(95%CI: 1.36,2.5), especially if used at high doses and in a non slow release form. The RR for gastrointestinal side effects was not significant at two years 2.18(95%CI: 0.86,1.21) but was increased at four years in the treated group 2.18(95%CI: 1.69,4.57) especially if fluoride was used at high doses and in a non slow release form. The number of withdrawals and dropouts was not different between treated and control groups at two and four years. Although fluoride has an ability to increase BMD at lumbar spine, it does not result in a reduction of vertebral fractures. In increasing the dose of fluoride, one increases the risk of non-vertebral fracture and gastrointestinal side effects without any effect on the vertebral fracture rate.

Risedronate Reverses Bone Loss in Postmenopausal Women With Low Bone Mass: Results From a Multinational, Double-Blind, Placebo-Controlled Trial

This study evaluated risedronate, a bisphosphonate used to treat Paget’s disease of bone, for effectiveness and safety when used to prevent or reverse loss of bone mineral density (BMD) in postmenopausal women with low bone mass. A total of 543 women up to age 80 years who were at least 1 year postmenopausal were entered into a randomized, double-blind, placebo-controlled study in which patients received risedronate in a dose of 2.5 or 5 mg. BMD was measured in the lumbar spine, femoral neck, and trochanter. The two treatment groups and placebo recipients had comparable BMD in the lumbar spine at baseline. At least 2 years of treatment were completed by 355 participants. BMD at the lumbar spine increased by 4 percent after 2 years in patients given 5 mg of risedronate, and a lesser increase was noted in those given 2.5 mg. Patients receiving placebo had no change. Benefit was not a function of time since menopause (Fig. 1). Changes in BMD at the femoral neck and trochanter were less impressive than in the spine except for a nearly 3 percent increase at the trochanter after 2 years of 5 mg of risedronate. Serum levels of bone-specific alkaline phosphatase decreased by nearly one-fourth after 2 years of treatment with 5 mg of risedronate and increased by 8 percent on average in patients taking the placebo (Fig. 2). The reduction in the N-telopeptide/creatinine ratio after 2 years on 5 mg of risedronate was substantially greater than in the placebo group. There were positive trends toward a reduction in vertebral fractures, mostly with the higher dose of risedronate. Adverse events, including gastrointestinal erosion and ulceration, were comparably frequent in all groups. Risedronate was a rapidly effective and well-tolerated treatment for postmenopausal osteoporosis in this trial, regardless of time since menopause.Fig. 1: Change in BMD at the lumbar spine during treatment with 5 mg of risedronate (▪), 2.5 mg of risedronate (▴), or placebo (○), stratified into: A) ≤5 years postmenopausal or B) >5 years postmenopausal. ***, P < .001 versus placebo. Values are means ± SEM.Fig. 2: Changes in A) serum concentrations of bone-specific alkaline phosphatase and B) NTx/creatinine during treatment with 5 mg of risedronate (▪) or placebo (○). ***, P < .001 versus placebo. Values are means ± SEM.J Clin Endocrinol Metab 2000;85:1895–1900

A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study

PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47– to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43– to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60– to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59– to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1.5%, P <0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group ( P <0.01) and by 14% in the 400-IU group ( P <0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

Fluoride for the Treatment of Postmenopausal Osteoporotic Fractures: A Meta-Analysis

We conducted an effectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women. A literature search was conducted on MEDLINE, Current Contents and the Cochrane Controlled Trial Registry. Two independent reviewers selected randomized controlled trials which met predetermined inclusion criteria. They independently extracted data using predetermined forms and assessed the methodologic quality of the trials using a validated scale. For dichotomous outcomes, the relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) of percentage change from baseline was calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95% CI: 7.15, 9.09) after 2 years of treatment and 16.1% (95% CI: 14.65, 17.5) after 4 years. The RR for new vertebral fractures was not significant at 2 years [0.87 (95% CI: 0.51, 1.46)] or at 4 years [0.9 (95% CI: 0.71, 1.14)]. The RR for new nonvertebral fractures was not significant at 2 years [1.2 (95% CI: 0.68, 2.10)] but was increased at 4 years in the treated group [1.85 (95% CI: 1.36, 2.50)], especially if used at high doses and in a non-slow-release form. The RR for gastrointestinal side effects was not significant at 2 years [2.18 (95% CI: 0.86, 1.21)] but was increased at 4 years in the treated group [2.18 (95% CI: 1.69, 4.57)], especially if fluoride was used at high doses and in a non-slow-release form. The number of withdrawals and dropouts was not different between treated and control groups at 2 and 4 years. Thus, although fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate.

Postmenopausal osteoporosis management.

Osteoporosis is perhaps the widest-ranging social, physical, and economic impact of estrogen deficiency. Postmenopausal bone loss is the major determinant of osteoporosis. Osteoporotic risk can be determined by measuring bone mineral density using dual X-ray absorptiometry. The radiation free quantitative bone ultrasound is emerging in the assessment of bone structure giving reliable estimates of fracture risk. Diet and exercise are important in determining a woman's risks for osteoporosis. Hormone replacement therapy clearly decreases bone turnover and prevents postmenopausal bone loss and reduces fractures. Tibolone as well as raloxifene prevent bone loss and solid data demonstrate a reduction of vertebral fractures after raloxifene administration.

Calcium supplementation on bone loss in postmenopausal women.

Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. To assess the effects of calcium on bone density and fractures in postmenopausal women. We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio. Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.