Nonvertebral Fractures In Women Research Articles

Effects of risedronate on bone marrow adipocytes in postmenopausal women

Aminobisphosphonates promote osteoblastogenesis while inhibiting adipogenesis in vitro. Their effect on adipogenesis in vivo remains unknown. In this study, we demonstrate that risedronate prevents marrow fat infiltration in postmenopausal women after 3 years of treatment. Age-related bone loss is associated with high levels of adipogenesis within the bone marrow at the expense of osteoblast population. Bisphosphonates stimulate osteoblastogenesis while inhibiting adipogenesis in vitro. In the present study, we tested whether the effect of bisphosphonates on marrow adipogenesis in vitro is also seen in vivo. We analyzed transiliac bone biopsies from a randomized, placebo-controlled clinical trial that evaluated the effects of risedronate treatment 5 mg/day on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. Paired bone biopsies were obtained from a subset of patients at baseline and after treatment with placebo or risedronate for 3 years (n = 14 per group). Biopsies were stained with toluidine blue and hematoxylin/eosin. Adipocyte volume/tissue volume (AV/TV), mean adipocyte number (AD(#)), and mean adipocyte diameter (AD(diam)) were quantified. Finally, expression levels of the adipogenesis transcription factor peroxisome proliferator activator gamma 2 (PPARγ2) within the bone marrow were quantified using immunohistochemistry. In the placebo group, AV/TV, AD(#), and AD(diam) significantly increased after 3 years (~15%, p < 0.01). In contrast, AD(diam) remained unchanged and AV/TV and AD(#) were significantly reduced (~20%) in the risedronate group at 3 years (p < 0.01). These changes were associated with a significant reduction in PPARγ2 expression in the bone marrow of risedronate-treated women. Risedronate reduces bone marrow fat in postmenopausal women. These findings are the first demonstration of an effect of bisphosphonates on marrow fat in humans in vivo. By regulating the amount of fat within the bone marrow, this effect may contribute to the beneficial effect of bisphosphonates on bone mass.

Smoking is a strong risk factor for non-vertebral fractures in women with diabetes: the Tromsø Study

In this longitudinal study of 4,160 postmenopausal women (3,947 without and 213 with self-reported diabetes), smoking was strongly related to fracture risk in those with diabetes. Smoking is related to low bone mass and increased risk of fracture risk in postmenopausal women of the general population. The aim of the present longitudinal population-based study was to examine the effect of smoking on the risk of non-vertebral fractures in women ≥ 55 years of age, with specific focus on its relationship with diabetes. A total of 4,160 women (3,947 without and 213 with self-reported diabetes) from the municipality of Tromsø, Norway, were followed for a mean of 7.6 years. Measurements of height and weight and questionnaire information concerning smoking and alcohol consumption habits, physical activity, prevalent diseases, and use of medication were collected before the start of follow-up. Non-vertebral fractures were registered during follow-up. A total of 1,015 without and 66 with diabetes sustained a new non-vertebral fracture. Smoking status (never, past, and current) was significantly associated with an increased risk of fracture both in women with and without diabetes (p values for trend 0.02 and <0.001, respectively, after adjustments for age), but in women without diabetes, the relationship was no longer significant after multiple adjustments. There was a strong interaction between smoking status and diabetes on fracture risk (p= 0.004). Women with diabetes who were current smokers had a 3.47 (95% CI 1.82-6.62) higher risk of non-vertebral fractures than diabetic women who were never smokers (p value for linear trend = 0.001, after multiple adjustments). We conclude that smoking is strongly related to fracture risk in postmenopausal women with self-reported diabetes.

Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: The FLEX Trial

In the Fracture Intervention Trial (FIT) Long Term Extension (FLEX) Trial, 10 years of alendronate (ALN) did not significantly reduce the risk of nonvertebral fractures (NVFs) compared with 5 years of ALN. Continuing ALN reduced the risk of clinical but not morphometric vertebral fractures regardless of baseline vertebral fracture status. In previous studies, ALN efficacy for NVF prevention in women without prevalent vertebral fracture was limited to those with femoral neck (FN) T-scores of -2.5 or less. To determine whether the effect of long-term ALN on fracture differs by vertebral fracture status and femoral neck (FN) T-score, we performed a post hoc analysis using FLEX data, a randomized, double-blind, placebo-controlled trial among 1099 postmenopausal women originally randomized to ALN in the FIT with mean ALN use of 5 years. In the FLEX Trial, women were randomized to placebo (40%) or ALN 5 mg/day (30%) or ALN 10 mg/day (30%) for an additional 5 years. Among women without vertebral fracture at FLEX baseline (n = 720), continuation of ALN reduced NVF in women with FLEX baseline FN T-scores of -2.5 or less [relative risk (RR) = 0.50, 95% confidence interval (CI) 0.26-0.96] but not with T-scores of greater than -2.5 and -2 or less (RR 0.79, 95% CI 0.37-1.66) or with T-scores of greater than -2 (RR 1.41, 95% CI 0.75-2.66; p for interaction = .019). Continuing ALN for 10 years instead of stopping after 5 years reduces NVF risk in women without prevalent vertebral fracture whose FN T-scores, achieved after 5 years of ALN, are -2.5 or less but does not reduce risk of NVF in women whose T-scores are greater than -2.

New and Emerging Therapies for Osteoporosis

New and Emerging Therapies for Osteoporosis

Bone loss and the risk of non-vertebral fractures in women and men: the Tromsø study

We assessed the association between the rate of forearm bone loss and non-vertebral fracture. Bone loss at the distal forearm predicted fractures, independently of baseline BMD, but not independently of follow-up BMD in women. The BMD level where an individual ends up is the significant predictor of fracture risk. Bone loss may predict fracture risk independently of baseline BMD. The influence of follow-up BMD on this prediction is unknown. The aim of this study was to assess the association between bone loss and fracture risk in both sexes in a prospective population-based study. We included 1,208 postmenopausal women (50 to 74 years), and 1,336 men (55 to 74 years) from the Tromsø Study, who had repeated distal and ultra-distal forearm BMD measurements. Non-vertebral fractures were registered from 2001 to 2005. A total of 100 women and 46 men sustained fractures during the follow-up time. Independent of baseline BMD, the RR associated with distal site bone loss of 1 SD %/year was 1.23 (1.01-1.50) for low-trauma fractures (excluding hand, foot, skull & high-trauma) and 1.32 (1.07-1.62) for osteoporotic fractures (hip, wrist and shoulder). However, bone loss did not predict fracture after adjusting for follow-up BMD. The BMD level where an individual ends up became the significant predictor of fracture risk and not the rate of bone loss. Follow-up BMD at ultra-distal site was associated with low-trauma fractures in both sexes. While ultra-distal site BMD changes were not associated with fracture risk in both sexes. Bone loss at the distal forearm predicted non-vertebral fractures, independently of baseline BMD, but not independently of follow-up BMD, in women. The BMD level where an individual ends up is the significant predictor of fracture risk and not the rate of bone loss.

Validación de un algoritmo para el cálculo del riesgo absoluto de fracturas no vertebrales por fragilidad en una cohorte de mujeres posmenopáusicas

Absolute risk estimate for fractures in the individual subject provides meaningful information for interventions. Recently, we have described an algorithm to calculate the absolute risk for non-vertebral fractures in women from Spain, aged 65 years or older, that includes clinical parameters and quantitative bone ultrasound values of the calcaneus (URL: www.ecosap.info). We assessed the performance of the algorithm by means of the statistical analysis of the model calibration. The algorithm was the result of the prospective analysis of 5.201 [corrected] women who were attended for any reason in Primary Care Centres and followed-up for 3 years. Model calibration was evaluated by comparing number of estimated (E) cases predicted with the equation with the number of observed (O) cases, and its accuracy to discriminate women with and without a new fracture. No evidence of statistically significant miscalibration of the model was observed. The E/O ratio was 1,02 (CI 95%: 0,91-1,14). Calibration chi(2) value (difference between the estimated and observed cases) did not reach statistical significance. Area under the curve-ROC was approximately 0.67. These results suggest a good calibration of the proposed algorithm for non-vertebral fracture prediction. It would be desirable to calibrate it with an independent cohort to definitively test its external validity.

Skeletal dysplasia and lethality in mice lacking the mid-region, nuclear localization signal and C-terminus of parathyroid hormone-related protein

Introduction: Age-related bone loss is associated with high levels of adipogenesis within the bone marrow. Since osteoblasts and adipocytes share a common marrow stromal cell precursor, it is possible that with aging, there is a preferential “switch” in commitment of this precursor to the adipocyte over the osteoblast lineage. Previously, we have reported a potential anabolic effect of bisphosphonates through the stimulation of osteoblastogenesis and inhibition of adipogenesis in vitro (Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. Duque G, Rivas D. J Bone Miner Res. 2007, 22:1603–11). In the current study, we tested the hypothesis that the effect of bisphosphonates on marrow adipogenesis in vitro is also present in vivo. Methods: We analyzed transiliac bone biopsies from a randomized, placebo-controlled clinical trial that evaluated the effects of risedronate treatment 5 mg/day on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. Paired bone biopsies were obtained from a subset of patients at baseline and after treatment with placebo or risedronate for 3 years (placebo, n=18, risedronate, n=14). Biopsies were stained with toluidine blue and hematoxylin/eosin. Adipocyte volume/tissue volume (AV/TV) adipocyte number (Ad#) and mean adipocyte size were quantified. Results: In the placebo group AV/TV and Ad# significantly increased (<15%). In contrast, there were significant decreases in these parameters (<28%) in the risedronate group (p<0.01). In addition, mean adipocyte size was significantly reduced (<25%) in the risedronate group (p<0.01) at 3 years. Conclusion: Risedronate reduces marrow adipogenesis in postmenopausal women, independently of its effect on bone mass. These findings are the first demonstration of an effect of bisphosphonates on marrow fat in humans in vivo. This effect may contribute to the beneficial effect of bisphosphonates on bone mass. (1) Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. Duque G, Rivas D. J Bone Miner Res. 2007, 22:1603–11.

Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a population-based cohort of women

Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma nonvertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors. Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older. The design was a retrospective nested case-control study (density-based sampling) within the Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with 453 cases and 1,304 matched controls. The current use of antiresorptives was associated with a decreased risk of fracture with OR = 0.68, 95% CI: 0.52-0.91; where OR is the adjusted odds ratio and CI is the confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42-0.89 for ages 50-74; OR = 0.76, 95% CI: 0.50-1.17 for ages 75+; OR = 0.58, 95% CI: 0.40-0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59-1.42 for those without a major risk factor. Major risk factors were prevalent low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score < or = -2.5. Antiresorptive therapy is associated with a clinically important reduction in low-trauma nonvertebral fracture risk among community-dwelling women aged 50 and older. Antiresorptive therapy may be less effective for women 75 and older and women without major risk factors.

Albuminuria and Risk of Nonvertebral Fractures

Individuals with end-stage renal disease are at higher risk of fractures compared with subjects in the general population. We examined whether elevated albumin-creatinine ratios (ACRs) were associated with nonvertebral fractures in subjects without diabetes or macroalbuminuria. A total of 4497 subjects (2267 men and 2230 women) 55 to 74 years old at baseline were followed for a mean of 8.4 years. Measurements of ACR, height, weight, blood pressure, lipids, serum creatinine, and bone mineral density were performed, and information about smoking and drinking habits, physical activity, prevalent diseases, and use of medication was collected before the start of follow-up. Nonvertebral fractures were registered during follow-up. A total of 135 men and 382 women sustained a new nonvertebral fracture. For a 1-SD higher value for the log-transformed ACR, the relative risk for a fracture was 1.01 in men (P = .94, after multiple adjustments) and 1.15 in women (P = .005). Women with ACRs in the highest quartile had a 71% higher risk of nonvertebral fractures compared with women with ACRs in the lowest quartile (P value for linear trend over the quartiles, .001). Bone mineral density tended to be lower with higher ACRs in both sexes, but this did not explain the increased fracture risk in women. Albumin-creatinine ratio was associated with nonvertebral fractures in women without diabetes or macroalbuminuria but not in men.

A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromsø Study

As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50-84 years at baseline in the Tromsø Study (1994-1995). Non-vertebral fractures were documented between 1994 and 2005. During 8.4 years (range 0.01-10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (s.d.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03-1.33) and men (HR 1.26; 95% CI 1.03-1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95-1.24) or men (HR 1.22; 95% CI 0.99-1.49). Each s.d. decrease in BMD increased fracture risk in women (HR 1.36; 95% CI 1.19-1.56) and men (HR 1.41; 95% CI 1.15-1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

Erratum: Is risedronate or alendronate more effective at preventing nonvertebral fractures in women with osteoporosis?

Erratum: Is risedronate or alendronate more effective at preventing nonvertebral fractures in women with osteoporosis?

Is risedronate or alendronate more effective at preventing nonvertebral fractures in women with osteoporosis?

Is risedronate or alendronate more effective at preventing nonvertebral fractures in women with osteoporosis?

Carotid Plaque Echogenicity and Risk of Nonvertebral Fractures in Women: A Longitudinal Population-Based Study

Atherosclerosis and osteoporosis appear to be related, but prospective studies on the relationship are sparse. In order to examine whether carotid artery plaques with different morphology predict nonvertebral fractures, we followed 2,733 women, aged 55-74 years (75% of the eligible population in Tromsø, Norway), for 6 years. At baseline, plaque morphology in terms of ultrasound echogenicity was categorized into three groups, ranging from low echogenicity (echolucent plaques with a high content of soft tissue) to strong echogenicity (echogenic plaques with a high content of dense fibrous tissue and calcified material). We found that the age-adjusted relative risk (RR) of fracture was significantly higher among women with echogenic plaques than among women without plaques: 1.7 (95% confidence interval [CI] 1.0-2.7). After adjustment for bone mineral density at baseline in addition to age, the RR was 1.6 (95% CI 1.0-2.6), and further adjustments for body mass index, body height, high-density lipoprotein cholesterol, smoking status, and muscle strength did not influence the association. Subjects with other plaque types were not at an increased risk compared to subjects without plaques: RR < or = 1.1, after multiple adjustments. We conclude that in the general population elderly women with echogenic carotid plaques are at higher risk of nonvertebral fractures than women without plaques.

Strontium Ranelate Reduces the Risk of Vertebral and Nonvertebral Fractures in Women Eighty Years of Age and Older

Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients > or = 80 years of age. About 25-30% of the population burden of all fragility fractures in the community arise from women > or = 80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly. An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis > or = 80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.

Disc space narrowing as a new risk factor for vertebral fracture: The OFELY study

In a previous cross-sectional analysis, we found a positive association between disc space narrowing (DSN) and vertebral fracture. The aim of the present study was to analyze prospectively the risk of vertebral and nonvertebral fractures in women with spine osteoarthritis (OA). Using radiographs, spine OA was evaluated in 634 postmenopausal women from the OFELY (Os des Femmes de Lyon) cohort (mean+/-SD age 61.2+/-9 years). Prevalence and severity of spine OA were assessed by scoring osteophytes and DSN. Incidental clinical fractures were prospectively registered during annual followup, and vertebral fractures were evaluated by radiography every 4 years. During an 11-year followup, fractures occurred in 121 women, including 42 with vertebral fractures. No association was found between osteophytes and the risk of fracture. In contrast, DSN was associated with an increased risk of vertebral fractures but not of nonvertebral fractures. After adjusting for confounding variables, the presence of DSN was associated with a marked increased risk of vertebral fractures, with an odds ratio of 6.59 (95% confidence interval 1.36-31.9). In addition, 95% of incident vertebral fractures were located above the disc with the most severe narrowing. This longitudinal study shows that, despite a higher bone mineral density (BMD), women with spine OA do not have a reduced risk of fracture and that DSN is significantly associated with vertebral fracture risk. The location of DSN and of incident vertebral fractures suggests that disc degeneration impairs the biomechanics of the above spine, which leads to the increased risk of vertebral fractures, independent of BMD. We suggest that DSN is a newly identified risk factor for vertebral fracture that should be taken into consideration when assessing vertebral fracture risk in postmenopausal women.

Ranélate de strontium : une nouvelle approche de l'ostéoporose post-ménopausique

Strontium ranelate is a novel antiosteoporotic agent that decreases bone resorption while stimulating bone formation. Two large phase III randomized, placebo-controlled studies have been performed to document its effects on the risks of vertebral and non vertebral fractures in postmenopausal women. In 1649 osteoporotic women with prevalent vertebral fracture enrolled in the SOTI study, strontium ranelate was proven efficient in reducing the risk of incident vertebral fractures and improving quality of life. In 5091 osteoporotic women enrolled in the TROPOS study, a significant reduction was observed in the risk of experiencing a new non-vertebral fracture and major osteoporotic fractures over 3 years. The incidence of hip fracture was significantly decreased in a subgroup of 1977 osteoporotic patients aged 74 years or over. In the TROPOS study, a significant reduction over 3 years of the relative risk of first vertebral fracture was demonstrated in women without prevalent vertebral fracture. Furthermore, strontium ranelate was proven able to decrease the relative risk of vertebral and non vertebral fractures in women aged 80 years and over. In osteopenic patients without prevalent fracture, strontium ranelate was shown to reduce the relative risk of vertebral fracture. Strontium ranelate demonstrated in these studies a very good safety profile.

Cost-effectiveness of risedronate for the treatment of osteoporosis and prevention of fractures in postmenopausal women.

Randomized, double-blind, controlled studies have shown that treatment with risedronate reduces the risk of vertebral fracture in postmenopausal women with established vertebral osteoporosis. They also show that the drug decreases the risk of non-vertebral fractures in women with osteoporosis. The aim of this study was to investigate the cost-effectiveness of risedronate in postmenopausal women with osteoporosis. A Markov model was applied to a UK setting. Treatment effects were computed by meta-analysis of randomized, controlled trials and given over 5 years to subjects aged between 60 and 80 years. Quality-adjusted life years (QALYs) and life years gained were used as outcome measures. Intervention with risedronate was cost-effective in women aged 60 years and older. Cost savings were also found for postmenopausal women aged 70 years and older with established vertebral osteoporosis (a prior spine fracture and BMD T-score < or =-2.5 SD). This treatment was cost-effective for women aged 65 years and older who had a prior vertebral fracture and a BMD T-score at the threshold of osteoporosis ( T-score=-2.5 SD), and in women with a T-score < or =-2.5 SD, but without a prior vertebral fracture. In women aged 60-80 years and at the threshold of osteoporosis ( T-score=-2.5 SD) but without a prior vertebral fracture, treatment exceeded the threshold for cost-effectiveness. However, if an additional, independent risk factor was assumed (e.g., corticosteroid use) treatment became cost-effective.

The association between iliocostal distance and the number of vertebral and non-vertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO).

BackgroundThe identification of new methods of evaluating patients with osteoporotic fracture should focus on their usefulness in clinical situations such that they are easily measured and applicable to all patients. Thus, the purpose of this study was to examine the association between iliocostal distance and vertebral and non-vertebral fractures in patients seen in a clinical setting.MethodsPatient data were obtained from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). A total of 549 patients including 508 women and 41 men participated in this cross-sectional study. There were 142 women and 18 men with prevalent vertebral fractures, and 185 women and 21 men with prevalent non-vertebral fractures.ResultsIn women multivariable regression analysis showed that iliocostal distance was negatively associated with the number of vertebral fractures (-0.18, CI: -0.27, -0.09; adjusted for bone mineral density at the Ward's triangle, epilepsy, cerebrovascular disease, inflammatory bowel disease, etidronate use, and calcium supplement use) and for the number of non-vertebral fractures (-0.09, CI: -0.15, -0.03; adjusted for bone mineral density at the trochanter, cerebrovascular disease, inflammatory bowel disease, and etidronate use). However, in men, multivariable regression analysis did not demonstrate a significant association between iliocostal distance and the number of vertebral and non-vertebral fractures.ConclusionsThe examination of iliocostal distance may be a useful clinical tool for assessment of the possibility of vertebral fractures. The identification of high-risk patients is important to effectively use the growing number of available osteoporosis therapies.

Risedronate for the prevention of fractures in postmenopausal osteoporosis.

To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.

The effect of alendronate on rates of vertebral and non-vertebral fractures in women with vertebral fractures: Preliminary results of the fracture intervention trial

The effect of alendronate on rates of vertebral and non-vertebral fractures in women with vertebral fractures: Preliminary results of the fracture intervention trial