Vertebral Fractures In Women Research Articles

High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy

The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy. A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays. Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < -2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4] and with spine BMD (OR 1.4, 95% CI 1.1-1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < -2.5. Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures.

Prevalence of vertebral fractures in women and men in the population-based Tromsø Study

BackgroundOsteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway.MethodsData was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant.ResultsThe prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (p = 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures.ConclusionsThe prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Vertebral fractures in women aged 50 years and older with clinical risk factors for fractures in primary care

BackgroundThe identification of vertebral fractures (VFs) is important for decisions on fracture prevention. Vertebral fracture assessment (VFA) was shown to be a patient-friendly and valid method for detecting undiagnosed VFs in (Dutch) women. However, this has only been investigated in women seeking care at secondary or tertiary institutions. ObjectiveTo investigate the prevalence of previously undiagnosed VFs in women in Dutch primary care using VFA. Study designA total of 566 Dutch women aged 50 years and older (mean age, 69 years; SD=8.4) with clinical risk factors (CRFs) for fractures volunteered for dual-energy X-ray absorptiometry (DXA) measurement and VFA. VFs were defined semi-quantitatively using Genant's method. ResultsOne CRF was present in each of 130 women, 274 had two, and 162 women had more than two CRFs. In 120 (21%) of the women, previously unknown osteoporosis (T-score ≤ −2.5SD) was diagnosed, and in 174 (31%), a previously undiagnosed moderate or severe VF was found. No osteoporosis was found in 130 (75%) of the women with a VF. Based on the outcome of DXA, 21% of the women were eligible for treatment, while the combination of DXA and VFA resulted in a total of 250 (44%) women requiring treatment. ConclusionsThe percentage of previously unknown VFs diagnosed by VFA in women aged 50 years and older with one or more CRFs for fractures in primary care is high. When only using BMD measurements, only half the women eligible for treatment would actually receive this. We recommend performing VFA in all women aged 50 years and older who are referred for DXA based on Dutch case finding criteria.

Association between incident and baseline vertebral fractures in European women: vertebral fracture assessment in the Osteoporosis and Ultrasound Study (OPUS)

Vertebral fracture assessment (VFA) with densitometric devices uses less radiation than spinal radiography. We assessed risk of new vertebral fracture (VF) in women with baseline fracture identified on VFA using algorithm-based qualitative diagnosis. Women with VF had significantly greater risk of VF after 6 years compared to those without baseline fracture. Prevalent VFs predict future fracture and are identifiable on vertebral fracture assessment (VFA) using bone densitometry devices. We have previously performed cross-sectional, but not longitudinal, VFA using the algorithm-based qualitative method (ABQ). We aimed to examine the prevalence and incidence of VF and test the association between prevalent and incident VF identified by ABQ VFA. We used ABQ to assess vertebral images obtained at baseline and 6 years (Hologic devices) in 674 women at ages 39 to 80 years participating in the Osteoporosis and Ultrasound Study. Criteria for prevalent and incident VF were endplate fracture, with/without cortical fracture. We compared proportions (chi-squared test) and characteristics (two-sample t tests and analysis of variance) of women with and without VF and calculated odds ratios for incident VF in women with prevalent VF (logistic regression). Prevalent VF was identified in one premenopausal woman and 41 postmenopausal women. Incident VF was identified in 18 postmenopausal women. Odds ratios (95% CI) for incident VF in postmenopausal women with prevalent VF were 7.8 (2.8, 22.1) (unadjusted) and 4.3 (1.4, 13.7) (adjusted for age and bone mineral density, BMD). Women with prevalent or incident VF were older (P < 0.01), with lower hip BMD (P < 0.001) compared to women without VF. Population-based postmenopausal women had relatively low prevalence and incidence of VF analysed with the ABQ method applied to VFA. Women with prevalent fracture had a significantly greater risk of incident VF than women without prevalent fracture.

Diagnostic imaging of treatment in osteoporosis: SERM

The effectiveness of selective estrogen receptor modulator (SERM) in X-ray, dual X-ray Absorptiometry (DXA), quantitative computed tomography (QCT), and hip structure analysis (HSA) are reviewed. Raloxifene and bazedoxifene increase bone mineral density in the spine and femoral neck, and reduce risk of vertebral fracture in women with osteoporosis, and reduce risk of nonvertebral fractures in women with higher fracture risk. Raloxifene improved bone density and micro architecture in spine and limbs (distal radius and distal tibia) represented by volumetric QCT and high-resolution peripheral QCT. Raloxifene also improved HSA parameters in femoral neck, intertrochanter, and shaft regions. The tendency to change in these parameters is approximately similar in raloxifene and bisphosphonates (alendronate, risedronate, minodronate). These results indicate that raloxifene improved the bone density and bone quality in spine, limbs and hip.

Association of spinal curve deformity and back extensor strength in elderly women with osteoporosis in Japan and the United States

The difference in the shape of sagittal spinal curvature and distribution of vertebral fractures in women of comparable age with osteoporosis from Japan and the United States with different cultures and lifestyles was identified. Back extensor strength was significantly associated with lumbar lordosis in Akita group, indicating the potential importance of strengthening the back extensor. The purpose of the study was to assess the association of osteoporotic spinal deformities with back strength in elderly women in Japan and the United States. Subjects diagnosed with osteoporosis were selected to participate prospectively. In both groups, we measured the angles of thoracic kyphosis and lumbar lordosis with plain lateral radiographs and back extensor strength. The number of vertebral fractures and the ratio of lumbar fractures to thoracic fractures are also evaluated. The level of participants' daily activities was assessed with use of comparable tests in Akita (quality-of-life score) and Minnesota (physical activity score). A total of 102 Japanese women residing in Akita, Japan (Akita group), and 104 white women evaluated in Rochester, MN, USA (Minnesota group), participated in this study. The angle of thoracic kyphosis and lumbar lordosis was higher in the Minnesota group than in the Akita group. The ratio of lumbar fractures to thoracic fractures was higher in the Akita group than in the Minnesota group. In the Akita group, multiple regression analysis revealed that the angle of lumbar lordosis correlated significantly with back extensor strength. We identified the difference in the shape of sagittal spinal curvature and distribution of vertebral fractures in women of comparable age with osteoporosis from two geographic areas of the world with different cultures and lifestyles. Back extensor strength was significantly associated with lumbar lordosis in Akita group, indicating the potential importance of strengthening the back extensor for improving or maintaining lumbar lordosis.

Treatment with Denosumab Reduces the Incidence of New Vertebral and Hip Fractures in Postmenopausal Women at High Risk

The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis. We evaluated the effect of denosumab on the incidence of new vertebral and hip fractures in subgroups of women at higher risk for these fractures. FREEDOM was a 3-yr, randomized, double-blind, placebo-controlled, phase 3 trial. Postmenopausal women (N = 7808) with osteoporosis were enrolled at 213 study sites worldwide. Subjects received s.c. denosumab (60 mg) or placebo every 6 months and daily supplements of calcium (≥1000 mg) and vitamin D (≥400 IU). This post hoc analysis evaluated fracture incidence in women with known risk factors for fractures including multiple and/or moderate or severe prevalent vertebral fractures, aged 75 yr or older, and/or femoral neck bone mineral density T-score of -2.5 or less. Compared with placebo, denosumab significantly reduced the risk of new vertebral fractures in women with multiple and/or severe prevalent vertebral fractures (16.6% placebo vs. 7.5% denosumab; P < 0.001). Similarly, denosumab significantly reduced the risk of hip fractures in subjects aged 75 yr or older (2.3% placebo vs. 0.9% denosumab; P < 0.01) or with a baseline femoral neck bone mineral density T-score of -2.5 or less (2.8% placebo vs. 1.4% denosumab; P = 0.02). These risk reductions in higher-risk individuals were consistent with those seen in patients at lower risk of fracture. Denosumab reduced the incidence of new vertebral and hip fractures in postmenopausal women with osteoporosis at higher risk for fracture. These results highlight the consistent antifracture efficacy of denosumab in patients with varying degrees of fracture risk.

High prevalence of radiological vertebral fractures in women with prolactin-secreting pituitary adenomas

Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.

A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®

The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability. Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX(®) algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk. The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX(®) tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX(®)-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI = 20-39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI = 31-48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability. Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX.

Bazedoxifene acetate for the management of postmenopausal osteoporosis

Osteoporosis is a gender-related disease that is especially prevalent in postmenopausal women. New drugs have been developed led by issues of interest and concerns about this disease, each one striving to be more effective and safer than the previous one. Bazedoxifene acetate is a new, third-generation, selective estrogen receptor modulator. This drug is used to treat postmenopausal osteoporosis in women with a high risk of fracture. Bazedoxifene acetate significantly prevents bone mass loss at 20 mg/day in healthy postmenopausal women with normal or low bone mineral density. The risk of vertebral fractures in women with osteoporosis was reduced by 42% (P < 0.05) after 3 years in a pivotal study. Five years later, the reduction was still 35% (P = 0.014). Post hoc analysis in women with a high risk of fractures showed a 50% reduced risk of nonvertebral fractures (P = 0.02) after 3 years and a 37% reduction (P = 0.06) after 5 years. Bazedoxifene acetate shows anti-fracture potential in the first few years after menopause and a greater antiestrogen effect at the level of the uterus. This has made this compound an appropriate option in young postmenopausal women with osteoporosis and a risk of fractures.

Incidence of symptomatic vertebral fractures in women of childbearing age newly treated with high-dose glucocorticoid

The treatment and prevention of glucocorticoid (GC)-induced osteoporosis have been controversial in premenopausal women during their childbearing years. This study assessed the incidence and risk factors for symptomatic vertebral fracture in women of childbearing age newly treated with high-dose GC. An observational cohort study was conducted at the rheumatic center of Shimoshizu National Hospital in Chiba, Japan, from 1986 to 2006. The prevalence of symptomatic vertebral fractures, as determined by x-rays, was assessed in premenopausal (aged <50 years) women with collagen vascular disease newly treated with high-dose GC (> or =20 mg/d prednisolone equivalent) compared with their counterparts who did not receive GC. Differences in the incidences of vertebral fractures were compared between groups by the Kaplan-Meier method and evaluated by the log-rank test. Hazard ratios (HRs) with 95% CIs were estimated using the Cox proportional hazards regression model. A total of 373 women were assessed: 292 patients in the high-dose GC treatment group (mean [SD] initial age, 32.4 [8.2] years; initial dose, 43.8 [14.9] mg/d; follow-up time, 124.2 [75.4] months) and 81 patients in the non-GC control group (initial age, 39.3 [7.8] years; follow-up time, 106.5 [79.7] months). Symptomatic vertebral fractures occurred more frequently in the high-dose GC group (11.3%) than in the non-GC group (1.2%). Using the Cox model, the adjusted HR for the high-dose GC group was 13.96 (95% CI, 1.87-104.22) relative to the non-GC group. In the high-dose GC group, Kaplan-Meier analyses revealed that the incidence of fractures in women in their forties was significantly higher in comparison with those in their twenties (P < 0.001) and thirties (P < 0.05), and that the incidence of fractures in those who consumed alcohol (>80 g/wk of pure alcohol) was significantly higher than in those who did not (P < 0.05). The Cox model also revealed that the risk was independently higher with every 10-year increment of initial age (HR = 2.27; 95% CI, 1.46-3.53), with every GC dose increase (HR = 2.28; 95% CI, 1.58-3.31), and with each 1-gram decrease of cumulative GC dose (HR = 0.95; 95% CI, 0.93-0.98). In this study, high-dose GC use was associated with a significantly high prevalence of symptomatic vertebral fractures in premenopausal women with collagen vascular disease during their childbearing years. However, the fracture risk was relatively low in women of childbearing age, especially those in their twenties and thirties during the early years of treatment.

Genotypes and Haplotypes of the Estrogen Receptor Genes, but Not the Retinoblastoma-interacting Zinc Finger Protein 1 Gene, Are Associated with Osteoporosis

Osteoporosis is a common age-related disease with a strong genetic influence. Polymorphisms of ESR1 have consistently been shown to be associated with bone mineral density (BMD) and fracture; however, in regulating bone metabolism, ESR1 interacts with both ESR2 and RIZ1. We therefore examined the effects of polymorphisms in the ESR1, ESR2, and RIZ1 genes and their haplotypes on vertebral fractures and BMD in a case-control study comprising 462 osteoporotic patients and 336 controls. In ESR1, we found the variant C allele of the XbaI polymorphism to be associated with decreased risk of vertebral fractures in women (P < 0.01), whereas in men, the T allele seemed protective (P = 0.05). The variant G allele of the PvuII polymorphism decreased the risk of vertebral fractures independently of lumbar spine BMD in women (P = 0.04) but had no effect in men. Haplotype X-P-H (XbaI:C, PvuII:G, and a high number of TA repeats) was associated with decreased risk of vertebral fractures in women (P = 0.04) but not men. In ESR2, the G allele of the AluI polymorphism was associated with increased fracture risk (P = 0.04), and the haplotype that comprises rs1256031:T and AluI:A increased lumbar spine BMD by 0.04 +/- 0.02 g/cm(2) (P < 0.05) and decreased the risk of vertebral fractures (P = 0.04). There was no effect of the RIZ1 polymorphism on BMD or fracture risk and no evidence of interaction between the polymorphisms and haplotypes thereof. We confirm that genetic variants in ESR1 and ESR2, but not RIZ1, are important in osteoporosis. We found no evidence of interaction between polymorphisms, but we found that the effects of genetic variants in ESR1 might be sex dependent.

Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly

The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders. The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly. This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in São Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant's semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present. The prevalence of vertebral fracture was 27.5% (95% CI 23.8-31.1) in women and 31.8% in men (95% CI 27.1-36.5) (P = 0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio = 1.03, 95% CI 1.01-1.06; p = 0.019) and total femur BMD (PR = 0.27, 95% CI 0.08-0.98; p = 0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR = 0.26, 95% CI 0.07-0.98; p = 0.046) was an independent parameter in predicting vertebral fractures. Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.

Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis using vertebral fracture assessment

To study the prevalence and risk factors of vertebral fractures (VFs) in a large cohort of patients with RA using VF assessment (VFA). We enrolled 172 women with RA, none of whom were taking osteoporosis medications. Patients underwent dual X-ray absorptiometry at the hip and spine and VFA, and completed a questionnaire. Radiological status was assessed by the modified Sharp erosion and narrowing score. VFA was classified using a combination of Genant semi-quantitative approach and morphometry. Patients had a mean (s.d.) disease duration of 8.4 (5.2) years. VFs were detected in 36% (62/172). This group of women had a statistically significant lower weight, height and lumbar spine and total hip BMD and T-scores than those without a VFA-identified VF. They also had more long-standing and severe disease and a greater consumption of corticosteroids. Stepwise regression analysis showed that the presence of VFs was independently associated with low weight and total hip T-score and long disease duration, CRP and Sharp erosion score. RA is a risk factor on its own for the development of osteoporosis and VFs and this risk increases more with low weight, disease duration and severe course of disease. These findings may suggest that to prevent the development of VFs, precautions should be taken immediately to suppress the disease activity and correct the weight loss in patients with RA.

Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density

IntroductionThere is evidence that variations of thyrotropin (TSH) even in its reference range may influence bone mineral density (BMD). In fact, low-normal TSH values have been associated with high prevalence of osteoporosis in post-menopausal women. However, data associating TSH and risk of fractures are scanty and limited to subjects with subclinical thyrotoxicosis. Materials and methodsIn this observational study, we investigated the correlation between serum TSH and prevalence of radiological vertebral fractures in a cohort of 130 post-menopausal women with normal thyroid function. ResultsOsteoporosis was observed in 80 women (61.5%), whereas 49 women (37.7%) had osteopenia. Vertebral fractures were found in 49 women (37.7%), who were significantly older, with higher prevalence of osteoporosis and with lower serum TSH values as compared with women who did not fracture. Stratifying the patients according to serum TSH values, vertebral fractures were found to be significantly (p=0.004) more prevalent in first tertile (56.8%) of TSH values as compared with the second (23.3%) and third tertiles (32.6%). Multivariate logistic regression analysis demonstrated that low serum TSH maintained a significant correlation with vertebral fractures (odds ratio 2.8, C.I. 95% 1.20–6.79) even after correction for age, BMD, BMI and serum free-thyroxine values. DiscussionLow-normal TSH values are associated with high prevalence of vertebral fractures in women with post-menopausal osteoporosis or osteopenia, independently of thyroid hormones, age and BMD.

Hypovitaminosis D and prevalence of vertebral fractures in women with GIO

Hypovitaminosis D and prevalence of vertebral fractures in women with GIO

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis

Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen receptor modulator (SERM) being developed for the prevention and treatment of osteoporosis. Preclinical studies on bazedoxifene have demonstrated estrogen agonist effects on the skeleton and lipid metabolism but not on breast and uterine endometrium. In combination with estrogen, bazedoxifene antagonizes the stimulatory action of estrogens on proliferation of breast cancer cells and endometrium. Phase III clinical studies have shown favorable effects on the skeleton without stimulation of endometrium and breast. Bazedoxifene prevents bone loss in postmenopausal women without osteoporosis and reduces vertebral fractures in women with postmenopausal osteoporosis. In women at high risk of fracture with multiple risk factors, bazedoxifene reduces nonvertebral fracture risk in post-hoc analysis. Bazedoxifene in combination with conjugated estrogens represents a new form of therapeutic agents for the treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis. Clinical trials with bazedoxifene/conjugated estrogens have shown beneficial effects on bone mineral density and bone turnover markers with improvement in vasomotor symptoms and little or no stimulation of breast and endometrium.

Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome

Chronic mild endogenous glucocorticoid excess has been shown to cause bone loss and to increase fracture risk in both post-menopausal and premenopausal women. Currently, it is unclear if patients with subclinical Cushing's syndrome (SCS) with osteoporosis or osteopenia may benefit from antiresorptive treatment and the type of therapy to be given. This pilot randomized study was aimed at evaluating the effects of 12-month im administration of clodronate (100 mg every week) on vertebral and femoral bone mineral density (BMD), bone turnover markers and on subjective pain in premenopausal women with SCS due to adrenal incidentalomas. Forty-six women (age, 43.1+/-7.7 yr) with SCS due to adrenal incidentaloma and osteoporosis/osteopenia were randomized to receive clodronate plus supplement of Calcium (500 mg daily) and Vitamin D3 (800 mg daily) (group 1, no.=23) or supplements only (group 2, no.=23). Both groups were similar in terms of age, body mass index, cortisol levels, BMD values, and bone turnover markers. All of the women were re-evaluated after 12 months. After 12 months of treatment, in group 1, a significant increase in lumbar BMD occurred (p=0.04), while bone turnover markers decreased by about one third (p<0.05). In group 2, bone turnover markers did not change and BMD values slightly decreased (p=ns). The differences in bone turnover markers and in lumbar BMD between the two groups were significant (p<0.05, all). No new vertebral fracture occurred in group 1, while in group 2 the spine radiographies revealed 2 new fractures and a worsening of two pre-existent fractures. An improvement in subjective back pain, assessed by visual analogue scale pain score was observed in group 1 (from 4.3+/-2.7 to 2.9+/-2.0; p<0.05) but not in group 2 (from 4.4+/-3.1 to 4.2+/-3.4; p=ns). No significant changes occurred in cortisol secretion or clinical picture of the SCS during the study. Intramuscular administration of clodronate effectively increased lumbar BMD values, preserved bone mass at the femoral neck, stabilized vertebral fracture index, and decreased subjective back pain in pre-menopausal women with SCS. Since the untreated group continued to lose bone, antiresorptive treatment should be considered in patients with SCS, according to the prevision of surgical treatment, prevalent fractures, BMD values, age, concomitant morbidities, and desire for pregnancy.

Diabetic Patients Have an Increased Risk of Vertebral Fractures Independent of BMD or Diabetic Complications

Although patients with type 2 diabetes (T2DM) have an increased risk of hip fracture, risk of vertebral fracture (VF) and its association with BMD are still unclear. We examined Japanese T2DM patients (161 men >50 yr and 137 postmenopausal women) and non-DM controls (76 and 622, respectively) by lateral spine radiography and DXA at the lumbar spine (L), femoral neck (FN), and radius (R). Logistic regression analysis adjusted for age, body mass index, and L-BMD showed that the presence of T2DM was an independent risk factor for prevalent VFs in women (OR = 1.86, p = 0.019) and men (OR = 4.73, p < 0.001). BMD at any site, however, was not significantly associated with the presence of prevalent VFs in T2DM patients, in contrast to the significant association in controls (at least p = 0.010). Comparison of T2DM patients with and without VFs showed no significant differences in BMD values, bone markers, or diabetes status. Receiver operating characteristic analysis showed that the absolute L-, FN-, and R-BMD values for detecting prevalent VFs were higher in T2DM patients than controls, whereas their sensitivity and specificity were lower. T2DM patients may have an increased risk of VFs independent of BMD or diabetic complication status, suggesting that bone quality may define bone fragility in T2DM.