Vertebral Fractures In Postmenopausal Women Research Articles

Plasma periostin associates significantly with non-vertebral but not vertebral fractures in postmenopausal women: Clinical evidence for the different effects of periostin depending on the skeletal site

BackgroundPeriostin is preferentially expressed by the periosteum, which mainly covers the long bones. Therefore, the role of periostin in osteoporotic fracture (OF) may differ depending on bone type. We performed a case–control study to investigate whether periostin can serve as a predictor of OF risk, particularly after dividing OFs into non-vertebral and vertebral fractures. MethodsAmong 532 consecutive postmenopausal women not taking any drug or without any disease that could affect bone metabolism, 133 cases with OF (i.e., non-vertebral and/or vertebral fractures) and 133 age- and body mass index-matched controls were enrolled. Non-vertebral (i.e., forearm, humerus, hip, and pelvis; n=81) and morphological vertebral (n=62) fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma periostin levels were also measured. ResultsPlasma periostin was markedly higher in subjects with non-vertebral fracture than their controls even after adjustment for BMD and potential confounders (P=0.006). Each standard deviation increment of plasma periostin was associated with a multivariable-adjusted odds ratio of 1.59 for non-vertebral fracture. The odds for non-vertebral fracture were 2.48-fold higher in subjects in the highest periostin tertile compared with those in the lowest periostin tertile (95% confidence interval=1.10–5.61). However, associations between plasma periostin and vertebral fracture were not observed, regardless of the adjustment model used. Consistently, plasma periostin levels were inversely associated with proximal femur BMD (P=0.007 to 0.030) but not lumbar spine BMD. In subgroup analyses, plasma periostin had no correlation with the levels of classical bone turnover markers. ConclusionsPlasma periostin may be a potential biomarker of the risk of OF, especially in non-spinal skeletal sites, such as the limbs, rather than spine.

Duration of breastfeeding as a risk factor for vertebral fractures

PurposeAmong the risk factors for osteoporosis and fractures, gynecological history (fertile period, parity and breastfeeding) play an important part. Changes in calcium metabolism to enable an adequate mineral transfer to the milk have a prominent role in bone loss during breastfeeding. Data on the influence of breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the present study was to identify any association between duration of breastfeeding and vertebral fractures in postmenopausal women. MethodsAll patients underwent the following tests: bone mineral density measurements of the lumbar spine (L1–L4) and the total and femoral neck using dual-energy X-ray absorptiometry and antero-posterior and lateral radiography of the thoracic and lumbar spine to identify vertebral fractures. ResultsThe study involved 752 women with a mean age of 64.5±9.3; 23% of them reported vertebral osteoporotic fractures. The women with vertebral fractures had breastfed for longer periods (11.8±12.9 vs. 9.3±11.2months, p=0.03) and had more pregnancies (2.6±2.2 vs. 2.2±1.3, p=0.002). Breastfeeding for more than 18months was associated with a two-fold risk of developing vertebral fractures (OR 2.12, 95% CI 1.14–5.38, p=0.04), particularly in those without current or past use of drugs positively affecting bone. ConclusionsOur study showed an association between long periods of breastfeeding and vertebral fractures, supporting a role for lengthy lactation as a risk factor for osteoporotic fractures after menopause. Bearing in mind all the benefits of breastfeeding, this finding suggests the importance of an adequate calcium and vitamin D intake during pregnancy and breastfeeding, with the aid of dietary supplements if necessary.

Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes

Insulin-like growth factor 1 (IGF-1) is a determinant of bone mass and is inversely associated with vertebral fractures (VFs). Sclerostin regulates bone formation by inhibiting Wnt/β-catenin signaling. Currently, there is little information on circulating sclerostin levels among postmenopausal women with type-2 diabetes mellitus (T2DM) with VFs in relation to serum IGF-1 (s-IGF-1). We investigated the relationships between serum sclerostin, s-IGF-1, and VFs in postmenopausal women with T2DM. We assessed cross-sectionally 482 postmenopausal women with T2DM and 482 age-matched postmenopausal women without T2DM who were recruited at diabetic clinics and primary health care centers for inclusion in a bone health survey. The main outcome measures were serum sclerostin, s-IGF-1, bone mineral density (BMD), and bone turnover markers. Lateral X-rays of the thoracic and lumbar spine were taken to diagnose VFs. Serum sclerostin levels were increased, whereas s-IGF-1 levels were decreased when T2DM women were stratified by the number of VFs (P<0.0001). Multiple logistic regression analysis showed that serum sclerostin levels were positively associated with 1 VF (odds ratio [OR]=1.27, (95%CI:1.01–2.03), P=0.016), 2 VFs (OR=1.41, (95%CI:1.03–2.36), P=0.006), and ≥3 VFs (OR=1.54, (95%CI:1.12–2.44) P=0.005). s-IGF-1 levels were inversely associated with 1 VF (OR=0.58, (95%CI:0.39–0.88), P=0.041), 2 VFs (OR=0.42, (95%CI:0.21–0.90), P=0.012), and≥3 VFs (OR=0.19, (95%CI: 0.14–0.27), P<0.001). Increased serum sclerostin and decreased s-IGF-1 were associated with VFs among postmenopausal women with T2DM, suggesting that sclerostin and/or IGF-1 may be involved in increased bone fragility in T2DM and could be potential markers of VF severity.

Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women

The aim of this cross-sectional cohort study was to clarify risk factors for severe vertebral fractures in postmenopausal Japanese women. Subjects were ambulatory volunteers age over 50 years who were recruited from a population of outpatients at a primary care institute. At registration, age, body mass index (BMI), bone mineral density (BMD), and present illness were investigated. Biochemical parameters including urinary levels of type I collagen cross-linked N-telopeptides (NTXs), and pentosidine and plasma levels of homocysteine were measured. Values were compared with different fracture grades (grade 0-3). A total of 1,475 postmenopausal women (66.6 ± 9.0 years) were included in the present study. Distributions of vertebral fracture grades were grade 1, 137 cases (9.3 %); grade 2, 124 cases (8.4 %); and grade 3, 162 cases (11.0 %). Age, BMI, BMD, NTX, pentosidine, and homocysteine were significantly associated with vertebral fracture in unadjusted analysis. In addition, a higher prevalence of hypertension was observed in patients with severe fracture. When comparing vertebral fracture grade 0 versus grade 2-3 by multiple regression analysis, pentosidine and homocysteine levels were a significant risk for moderate/severe vertebral fracture (odds ratio [OR] = 1.17, 95 % confidence interval [CI] 1.00-1.38, p = 0.049; OR = 1.22, 95 % CI 1.03-1.46, p = 0.013). Homocysteine levels were also a significant risk when comparing vertebral fracture grade 0 versus grade 3 (OR = 1.27, 95 % CI 1.04-1.58, p = 0.021). Plasma level of homocysteine was an independent risk for severe vertebral fractures.

Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women

Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant. UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems. This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment. After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40% higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors. These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Genome-wide association identifies a new susceptibility locus at 4q35 associated with clinical vertebral fractures in post-menopausal women: the GEFOS-GENOMOS consortium

Genome-wide association identifies a new susceptibility locus at 4q35 associated with clinical vertebral fractures in post-menopausal women: the GEFOS-GENOMOS consortium

Low Bone Mineral Density, But Not Epidural Steroid Injection, Is Associated with Fracture in Postmenopausal Women with Low Back Pain

Background: Therapy with glucocorticoids often results in bone loss and glucocorticoidinduced osteoporosis. However, the relationship between epidural steroid injection (ESI), bone mineral density (BMD), and vertebral fracture remains to be determined. Objective: To establish a relationship between ESI, BMD, and vertebral fracture in postmenopausal women with low back pain. Study Design: This study was a retrospective, nonblinded, cross-sectional clinical study. Setting: University-based pain management center. Methods: We reviewed the medical records of postmenopausal women with low back pain who were treated with ESI. A total of 352 postmenopausal women were divided into 2 groups. Group 1 consisted of patients without fracture and Group 2 consisted of those with fractures. The results of BMD measurements, as well as any fragility fractures, the anatomical site involved, and the treatment administered, were also recorded. BMD was measured in the lumbar spine, femoral neck, and total femur after the treatment. Results: Of the 352 patients, 218 (62%) had no fractures while 134 (38%) sustained a fracture. The age was significantly higher among patients who sustained fractures, and BMD at the lumbar spine, total femur, and femoral neck regions was significantly lower among patients who sustained fractures. In each region, the prevalence of osteoporosis was significantly higher in patients with fracture than in patients without fracture (all P &lt; 0.05). Age, height, and weight were associated with low BMD. However, our study showed no consistent correlation between BMD and the mean number of ESIs, mean total dose of glucocorticoids, or mean duration of ESIs. Limitations: First, this study is limited by the fact that it was retrospective. Second, the number of cases receiving very frequent, high-dose glucocorticoid injections was very small. Conclusions: Older age and lower BMD were associated with osteoporotic fracture in postmenopausal women treated for low back pain with ESI. The ESIs were not associated with low BMD or fracture. Key words: Bone mineral density, epidural steroid injection, fracture, glucocorticoids, low back pain, postmenopause.

A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on incidence of vertebral fractures, either directly or through non-linear changes in bone mass density

Bone mass density values have been related with risk of vertebral fractures in post-menopausal women. However, bone mass density is not perfectly accurate in predicting risk of fracture, which decreases its usefulness as a surrogate in clinical trials. We propose a modeling framework with three interconnected parts to improve the evaluation of bone mass density accuracy in forecasting fractures after treatment. The modeling framework includes: (1) a piecewise regression to describe non-linear temporal BMD changes more accurately than crude percent changes, (2) a structural equation model to analyze interdependencies among vertebral fractures and their potential risk factors in preference to regression techniques that consider only directional associations, and (3) a counterfactual causal interpretation of the direct and indirect relationships between treatment and occurrence of vertebral fractures. We apply the methods to BMD repeated measurements from a study of the effect of bazedoxifene acetate on incident vertebral fractures in three different geographical regions. We made four observations: (1) bone mass density changes varied largely across participants, (2) baseline age and body mass index influenced baseline bone mass density that, in turn, had an effect on prevalent fractures, (3) direct and/or indirect effects of bazedoxifene acetate on incident fractures were different across regions, and (4) estimates of indirect effects were sensible to the presence of post-treatment unmeasured confounders. In one region, around 40% of the bazedoxifene acetate effect on the occurrence of fracture is explained by its effect on bone mass density. Under the counterfactual approach, these 40% represent the average difference in the occurrence of fracture observed for untreated individuals when their bone mass density values are set at the value under bazedoxifene acetate versus under placebo. Computational methods are available to evaluate and interpret the surrogacytic capability of a biomarker of a primary outcome.

Biochemical markers for bone turnover predict risk of vertebral fractures in postmenopausal women over 10 years: the Japanese Population-based Osteoporosis (JPOS) Cohort Study

We evaluated how bone turnover might predict vertebral fracture risk in postmenopausal women over 10 years. After adjusting for age and femoral neck bone mineral density, high bone-specific alkaline phosphatase and total and free deoxypyridinoline at baseline predicted increased vertebral fracture risk in women with ≥ 5 years since menopause. The aim was to evaluate the ability of bone turnover markers (BTMs) in predicting vertebral fractures. Participants in the 1996 baseline survey of the JPOS Cohort Study included 522 postmenopausal women, with no diseases or medications affecting bone metabolism. Vertebral fractures were ascertained in three follow-up surveys (1999, 2002, and 2006). Initial fracture events were diagnosed morphometrically. The Poisson regression model was applied to estimate the rate ratio (RR) of the following log-transformed BTM values at baseline: osteocalcin and bone-specific alkaline phosphatase (BAP) in serum and C-terminal cross-linked telopeptide of type I collagen, total deoxypyridinoline (tDPD), and free deoxypyridinoline (fDPD) in urine. Eighty-three fracture events were diagnosed over a median follow-up period of 10.0 years. RR per standard deviation (SD) (95 % confidence interval) for BAP was 4.38 (1.45, 13.21) among 65 subjects with years since menopause (YSM) < 5 years. RRs per SD (95 % confidence interval) for BAP, tDPD, and fDPD were 1.39 (1.12, 1.74), 1.32 (1.05, 1.67), and 1.40 (1.12, 1.76), respectively, after adjusting for age and femoral neck bone mineral density (FN BMD) among 457 subjects with YSM ≥ 5 years. Of the 451 women followed at least once until 2002, RRs per SD for BAP, tDPD, and fDPD adjusted for age and FN BMD over 6 years were not significantly different from those over 10 years. BAP was associated with vertebral fracture risk among early postmenopausal women. BTMs can predict vertebral fractures independently of BMD among late postmenopausal women over a 10-year follow-up period.

Plasma Sphingosine 1-Phosphate Levels and the Risk of Vertebral Fracture in Postmenopausal Women

Although sphingosine 1-phosphate (S1P) plays diverse roles in bone metabolism, the most prominent role seems to be the augmentation of bone resorption. The objective of the study was to investigate the possibility of using S1P as a predictor for osteoporotic vertebral fracture (VF) risk. This was a case-control study conducted in a clinical unit in Korea. Sixty-nine cases having radiological VF and 69 age- and body mass index-matched controls among 460 eligible postmenopausal women participated in the study. Lateral thoracolumbar radiographs, bone mineral density (BMD), bone turnover markers, and plasma S1P levels were obtained from all subjects. S1P levels were markedly higher in subjects with VF (7.49±3.44 μmol/liter) than in those without VF (5.58±2.01 μmol/liter; P=0.001) and increased in a dose-response manner as the number of VF increased (P for the trend<0.001), even after adjustment for lumbar spine BMD and potential confounders. The odds ratio for VF was markedly higher in subjects in the highest S1P quartile category compared with those in the lowest S1P quartile category after adjustment for confounders (odds ratio 9.33, 95% confidence interval 2.68-32.49). S1P levels were inversely correlated with BMD at various sites (P=0.015 to 0.044), whereas they were positively correlated with bone resorption markers (P=0.016 to 0.098). These findings suggest that plasma S1P may be a potential biomarker for the risk of VF, independent of BMD, in postmenopausal women.

Raloxifene for the treatment of postmenopausal osteoporosis

Raloxifene is used to prevent or treat postmenopausal osteoporosis at a dose of 60 mg daily. Compared with calcium plus vitamin D, raloxifene seems more effective in reducing vertebral fractures in postmenopausal women. Compared with calcium plus vitamin D, raloxifene is not more effective in reducing nonvertebral fractures in postmenopausal women. Raloxifene may be associated with venous thromboembolic events and fatal strokes in postmenopausal women, although the association with fatal strokes was only seen in one study of women at high risk of cardiac events. No excess risk of coronary events is seen with raloxifene. Raloxifene may be less effective than certain bisphosphonates in preventing nonvertebral fractures, although no head-to-head comparisons are available.

Decreased PTH Levels Accompanied by Low Bone Formation Are Associated with Vertebral Fractures in Postmenopausal Women with Type 2 Diabetes

Patients with type 2 diabetes (T2DM) have an increased risk of vertebral fractures (VF) compared with non-T2DM controls due to poor bone quality. The aim of this study was to investigate the association between VF and bone turnover. We compared clinical parameters, such as serum PTH and osteocalcin (OC), between hospital-based Japanese T2DM patients (123 postmenopausal women and 132 men over 50 yr old) and medical checkup-based non-T2DM controls (189 women and 51 men). The association between PTH and OC levels was investigated, and the VF risks were compared for four subgroups classified by PTH and OC values. T2DM patients had lower PTH and OC levels than the controls for both sexes (P < 0.01). Multivariate regression analysis showed that PTH levels of T2DM patients were significantly and positively correlated with OC levels (women, r = 0.324, P < 0.01; men, r = 0.343, P < 0.01). When participants were divided into two subgroups based on mean PTH and OC levels, the group of T2DM women with lower PTH and lower OC levels had a significantly higher risk of VF than those with higher PTH and higher OC levels after adjusting for age, body mass index, hemoglobin A(1c), creatinine, 25-hydroxyvitamin D, and lumbar bone mineral density (odds ratio, 4.73; 95% confidence interval, 1.20-18.6; P = 0.026). Patients with T2DM had decreased PTH levels. In T2DM postmenopausal women, lower PTH levels accompanied by low bone formation may elevate VF risk independently of bone mineral density compared with higher bone formation, possibly as a result of reduced bone quality.

Homocysteine, Folate, and Vitamin B12 Levels and Vertebral Fracture Risk in Postmenopausal Women

The objective of this study was to examine the influence of homocysteine, vitamin B12, and folate on the prevalence of asymptomatic osteoporotic vertebral fractures (VFs) using vertebral fracture assessment (VFA) in postmenopausal women. The study cohort consisted of 188 consecutive postmenopausal women (mean age, weight, and body mass index of 57.9±8.5 [41–91]yr, 74.4±13.5 [38–150]kg, and 30.4±5.2 [17.1–50.7]kg/m2, respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a Lunar Prodigy Vision densitometer (GE Healthcare Inc., Waukesha, WI). VFs were defined using a combination of Genant's semiquantitative approach and morphometry. Fifty-eight (30.9%) patients had densitometric osteoporosis. VFs were identified using VFA in 76 (40.4%) patients: 61 women had grade 1 VFs and 15 had grade 2 or 3 VFs. No statistical difference was shown between the 3 groups (absence of VFs, VFs grade 1, and VFs grade 2/3) concerning the biological parameters. Comparison of patients according to quartiles of homocysteine levels showed that women in the highest quartile were older and had a lower bone mineral density (BMD); however, the prevalence of VFs was not statistically different from that of women in the other quartile groups. Stepwise regression analysis showed that homocysteine was not independently associated with the presence of VFs, which was mainly related to the osteoporotic status. Although a weak association was observed between hyperhomocysteinemia and low BMD and a trend to higher prevalence of grade 2/3 VFs was observed, our study did not confirm that homocysteine, vitamin B12, and folate status are important determinants of prevalent asymptomatic VFs in postmenopausal women.

Frequency, distribution and severity of prevalent osteoporotic vertebral fractures in postmenopausal women

Assessment of previous vertebral fractures provides useful information to predict future fracture risk. This study aimed to determine the frequency, distribution and severity of prevalent osteoporotic vertebral fractures in postmenopausal women. Data on patient characteristics, bone densitometry values, and spine radiographs (T2-L5) were reviewed in 232 postmenopausal women admitted to our osteoporosis clinic. Prevalent vertebral fractures were detected in 28 (12.1%) women (95%CI: 7.8 16.3). Fifteen women (6.5%) had mild fractures and 13 (5.6%) had moderate or severe fractures according to Genant's semi-quantitative technique. The T-score was associated with the presence of prevalent vertebral fractures (OR= 0.61; 95%CI: 0.38-0.96, P= 0.034). The most frequently fractured vertebrae were T11 and T12, followed by T7 and T9. Sixty percent of fractures were wedge-type while 40% were biconcave. The frequency of wedge-type fractures at the T11-T12 levels (93.8%) was higher compared to that at all other levels (44.1%) (P= 0.001). We determined the frequency, distribution, and severity of prevalent fractures and identified certain distribution patterns of fracture locations and types. To verify our results and detect possible predictive factors for fracture risk, population-based larger trials are needed.

Agreement between semi-automatic radiographic morphometry and Genant semi-quantitative method in the assessment of vertebral fractures

Semi-automatic morphometry is highly reproducible and not time intensive; however, no study has evaluated agreement between semi-automated morphometric methods and the Genant semi-quantitative method performed as a rule by radiologists. Our study shows substantial agreement between both methods; however, semi-automatic morphometry upgrades mild deformities and overestimates the prevalence of fractures. The aim of this study was to evaluate the agreement between radiologists using the Genant semi-quantitative (SQ) method and semi-automated morphometry in the diagnosis of vertebral fractures in post-menopausal women. Cross-sectional study was conducted in 2006-2007 in an age-stratified population-based sample of 824 post-menopausal women over the age of 50. From this population two sets of 95 and 50 X-ray were randomly extracted to test inter-rater agreement and agreement between SQ and semi-automated morphometry, and vertebral fractures were classified according to both methods. The Genant method was used to homogenise the diagnosis of fractures. Agreement was evaluated with weighted kappa. We evaluated each vertebral body independently and also the whole vertebral column (T4-L4) classifying women into the worst grade of fracture. For the qualitative interpretation of the agreement, we used the criteria described by Landis and Koch (Biometrics 33:159-174, 1977). The radiologists' agreement was 98.4% (Kappa, 0.75; 95% CI, 0.42-0.89). Agreement between semi-automated morphometry and SQ reached 97.6% and Kappa was 0.86 (95% CI, 0.66-0.94). In the whole evaluation of the spine semi-automated morphometry overestimates, the prevalence of fractures compared with the radiologists were 15.8% of women with fractures and 7.4% of women with moderate-severe fractures by semi-automated morphometry vs. 8.4% and 3.2% by the SQ method. The negative predictive value for MorphoXpress was 99% while the positive was 40%. Semi-automated morphometry shows high reliability and a substantial agreement with the SQ approach but overestimates the prevalence of fractures. Its role in routine clinical practice is limited because positive results should be reassessed by qualitative or semi-quantitative methods.

Parathyroid hormone for osteoporosis treatment

Abstract Osteoporosis may cause disastrous fractures and is a great threat to old people. Different medicines, including calcitonin, selective estrogen receptor modulators (SERM) and bisphosphonates, have been developed to treat the condition. In contrast to these bone resorption antagonists, parathyroid hormone (teriparatide) which works through the regulation of calcium and phosphate metabolism can increase bone deposition. Patients given teriparatide (20 μg) daily for 2 years experienced a significant increase in hip bone bone mineral density (BMD) of 3.5% and 3.9% after 1 and 2 years, respectively, as well as a significant increase in vertebra BMD of 7.2% and 10.9% after 1 and 2 years, respectively. Teriparatide treatment also reduced the risk of one or more new vertebral fractures in postmenopausal women with osteoporosis by 65% and the risk of multiple new vertebral fractures by 77%. Furthermore, teriparatide resulted in a 53% decrease in the risk for nonvertebral osteoporotic fractures and a 90% decrease in moderate or severe new nonvertebral fractures. Compared to alendronate, 12-month treatment with teriparatide resulted in greater increases in femoral neck and total hip BMD. Also, patients treated with teriparatide tended to be at lower risk of nonvertebral fractures, 4.1% in the teriparatide group versus 13.7% in the alendronate group. If there is a need to switch from bisphosponates to teriparatide, a 6-month interval is recommended to prevent interference with the osteogenic effects of teriparatide. Other effects of teriparatide, including stimulation of bone healing and osteoconduction in porous joint replacement materials that may be extensively applied to orthopedic clinical practice, warrant further studies and confirmation.

Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study

In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated. This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years. A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (N = 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers. At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%; P < 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (n = 1,324; femoral neck T-score ≤-3.0 and/or ≥ 1 moderate or severe or ≥ 2 mild vertebral fracture[s]), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%; P = 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction; P < 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (P < 0.05) and was generally safe and well tolerated. The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.

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.

Effect of teriparatide compared with risedronate on reduction of back pain and new vertebral fractures in postmenopausal women with osteoporotic vertebral fractures

Effect of teriparatide compared with risedronate on reduction of back pain and new vertebral fractures in postmenopausal women with osteoporotic vertebral fractures

Effect of teriparatide compared with risedronate on back pain and incident vertebral fractures in postmenopausal women with osteoporotic vertebral fractures

Effect of teriparatide compared with risedronate on back pain and incident vertebral fractures in postmenopausal women with osteoporotic vertebral fractures