Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 AE 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women. ß

No abstract

BackgroundHigher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]).MethodsThis study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report.ResultsThe plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P<0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92−7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83−34.44). Results were similar when we compared plasma S1P levels at the 1-year visit.ConclusionsThe associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.

The aim of this prospective study was to assess the efficacy of intra-cervical misoprostol in the management of early pregnancy failure. Twenty women with early pregnancy failure received intra-cervical misoprostol via an endometrial sampling cannula. The first dose was 50 μg of misoprostol dissolved in 5 ml of normal saline. The administration was repeated after 12 h if there was no vaginal bleeding or pain. Nine (45%) women received 1 dose and 11 (55%) women received 2 doses of intra-cervical misoprostol. Abortion within 24 h occurred in 16 (80%) women, and complete abortion was achieved in 14 (70%) cases. Two women with incomplete abortion were managed with 600 μg of misoprostol orally (1 case) and surgical intervention (1 case). The mean time interval between the first dose and the abortion was 10.6 ± 6.3 h. Two women did not respond within 24 h of treatment initiation, 1 woman withdrew consent after the first treatment, and 1 woman developed heavy vaginal bleeding after the first dose and underwent surgical management. Intra-cervical misoprostol is a promising method of medical treatment of early pregnancy failure. Further randomized clinical trials are needed to validate its safety and efficacy.

3.0 (95% CI 1.2-7.2) times higher when the change in hCG levels was <5% between day-7 vs. day of MTX, day-7 vs. day-4, and day-4 vs. day of MTX, respectively. Kaplan-Meier plots demonstrated that EP rupture and EP resolution occurred 7-13 days and 20-36 days after MTX treatment.CONCLUSIONS: Patient with ruptured tubal EPs despite MTX present more frequently with vaginal spotting and have <5% change in hCG levels between the day of MTX and day-4 or day-7 after MTX.