Abdulrahim A. Rouzi

Determinants of serum sclerostin in healthy pre- and postmenopausal women

Sclerostin is a secreted Wnt antagonist produced almost exclusively by osteocytes that regulates bone mass. However, there is currently limited information on the determinants of sclerostin in a large population‐based study. The main objectives of the present study were to: (1) establish reference normative interval values for serum sclerostin in randomly selected healthy premenopausal women; (2) study the changes in serum sclerostin in relation to age in premenopausal and postmenopausal women and the factors that may influence bone turnover; and (3) determine the effect of menopausal status on serum sclerostin. A total of 1803 women were studied (including [n = 1235] premenopausal, and [n = 568] postmenopausal women, respectively, aged 20 to 79 years). A total of 443 healthy premenopausal women (aged 35 to 45 years) were used to establish reference normative intervals for serum sclerostin. All women studied were medically examined and had their bone mineral density values obtained for the lumbar spine (L1–L4) and femoral neck according to a detailed inclusion criteria. In all women, values of serum sclerostin increased with increasing age up to the age of 45 years, and remained increased in postmenopausal women. Significant increases were evident in serum sclerostin in postmenopausal women with increasing years since menopause. Using stepwise multiple linear regression analysis, several variables were identified as determinants of serum sclerostin, including age, parathyroid hormone, estradiol (E2), and follicle‐stimulating hormone (FSH) for premenopausal women; age, FSH, and E2 for postmenopausal women; and age, serum osteocalcin, FSH, and E2 in the entire sample studied. Further studies are needed to establish the potential role of this increase in mediating the known age‐related impairment in bone formation.

Sexual function in women with female genital mutilation

OBJECTIVE To compare the sexual function of women with female genital mutilation (FGM) to women without FGM. DESIGN A prospective case-control study. SETTING A tertiary referral university hospital. PATIENT(S) One hundred and thirty sexually active women with FGM and 130 sexually active women without FGM in Jeddah, Saudi Arabia. INTERVENTION(S) Women with and without FGM were asked to answer the Arabic-translated version of the female sexual function index (FSFI) questionnaire. MAIN OUTCOME MEASURE(S) The individual domain scores for pain, arousal, lubrication, orgasm, satisfaction, pain, and overall score of the FSFI were calculated. RESULT(S) The two groups were comparable in demographic characteristics. There were no statistically significant differences between the two groups in mean desire score (+/- standard deviation) or pain score. However, there were statistically significant differences between the two groups in their scores for arousal, lubrication, orgasm, and satisfaction as well as the overall score. CONCLUSION(S) Sexual function in women with FGM is adversely altered. This adds to the well-known health consequences of FGM. Efforts to document and explain these complications should be encouraged so that FGM can be abandoned.

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.

High serum sclerostin predicts the occurrence of osteoporotic fractures in postmenopausal women: The center of excellence for osteoporosis research study

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 ± 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.

Physical Activity in Relation to Serum Sclerostin, Insulin-Like Growth Factor-1, and Bone Turnover Markers in Healthy Premenopausal Women: A Cross-Sectional and a Longitudinal Study

CONTEXT There is limited information on the effects of mechanical loading caused by physical activity (PA) on sclerostin, IGF-I, and bone turnover markers (BTM). OBJECTIVE The objective of the investigation was to study the relationships between serum sclerostin, serum-IGF-I (s-IGF-I), BTM, and the PA level in premenopausal women and to discern how 8 wk of PA training (PAT) affects the serum levels of sclerostin, IGF-I, and BTM. DESIGN This was a cross-sectional study with a subgroup followed up longitudinally. SETTINGS AND SUBJECTS A total of 1235 randomly selected premenopausal women were cross-sectionally studied. We also followed up 58 of these women longitudinally during an 8-wk course of PAT (4 d/wk) and compared them with 62 controls. All women were medically examined, and bone mineral density (BMD) and serum levels of sclerostin, s-IGF-I, and BTM were determined. RESULTS Women with PA of greater than 120 min/wk showed significantly lower serum sclerostin (by 36.8%) but higher s-IGF-I (by 107%) levels than sedentary controls. Bone formation markers were also higher in the PA greater than 120 min/wk group compared with the sedentary controls. In the longitudinal study, the 8-wk PAT program led to a decrease in serum sclerostin (by 33.9%, P<0.0001) but increases in the serum levels of the bone-formation markers and IGF-I (s-IGF-I by 74.2%, P<0.0001). CONCLUSIONS This study demonstrates that even minor changes in PA are associated with effects on serum levels of sclerostin, IGF-I, and BTM and suggests that sclerostin could be a link between mechanical loading and disuse osteoporosis in humans.

Predictors of success of reversal of sterilization

OBJECTIVE To determine the prognostic variables effecting the successful pregnancy outcome of reversal of sterilization. DESIGN Demographic and clinical history data were collected prospectively. SETTING Division of Infertility and Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada. PATIENTS AND INTERVENTION Between 1981 and 1992, 217 consecutively referred patients underwent reversal of sterilization by a single surgeon using microsurgical techniques. MAIN OUTCOME MEASURES Prognostic variables associated with success were examined using logistic regression and expressed as odds ratios with corresponding 95% confidence intervals. RESULTS Age at reversal was a significant factor with the odds of a successful outcome for those < or = 35 years compared with those > 35 years being 2.3 with a 95% confidence interval of 1.3 to 4.1. There was some evidence that average tubal length as categorized in 2-cm intervals was a significant prognostic factor with the odds of a successful outcome for those with an average length of > 4 cm to those < or = 4 cm being 5.3 with a 95% confidence interval of 1.4 to 20.0. CONCLUSIONS Nonsubjective analysis of the prognostic variables of reversal of sterilization associates only age and tubal length of > 4 cm with intrauterine pregnancy.

The use of intrapartum defibulation in women with female genital mutilation

Objective To assess the use of intrapartum defibulation for women who have had female genital mutilation.

Second-trimester pregnancy termination with misoprostol in women with previous cesarean sections.

Misoprostol is a synthetic prostaglandin E ana1 log widely used for the prevention and treatment of gastroduodenal ulcers. It is inexpensive, requires no refrigeration, and is widely available in many countries. It can be given orally, intravaginally, rectally, or sublingually w1x. Termination of pregnancy in the second trimester with misoprostol is safe and effective, with a success rate of more than 90% w2x. However, the ideal regimen of misoprostol still remains to be determined. There is very limited published experience on the use of misoprostol for termination of pregnancy in the second trimester in women with one or two previous cesarean sections, and conflicting case reports have been reported w3,4x. The objective of this study was to report a case series of 10 women with one or two previous cesarean sections who underwent pregnancy termination with misoprostol in the second trimester because of intrauterine fetal death. Between September 1998 and March 2002, 59 consecutive pregnant women underwent second-

Independent predictors of all osteoporosis-related fractures among healthy Saudi postmenopausal women: The CEOR Study

This study was designed to identify independent predictors of all osteoporosis-related fractures (ORFs) among healthy Saudi postmenopausal women. We prospectively followed a cohort of 707 healthy postmenopausal women (mean age, 61.3±7.2 years) for 5.2±1.3 years. Data were collected on demographic characteristics, medical history, personal and family history of fractures, lifestyle factors, daily calcium intake, vitamin D supplementation, and physical activity score. Anthropometric parameters, total fractures (30.01 per 1000 women/year), special physical performance tests, bone turnover markers, hormone levels, and bone mineral density (BMD) measurements were performed. The final model consisted of seven independent predictors of ORFs: [lowest quartile (Q(1)) vs highest quartile (Q(4))] physical activity score (Q(1) vs Q(4): ≤12.61 vs ≥15.38); relative risk estimate [RR], 2.87; (95% confidence interval [CI]: 1.88-4.38); age≥60 years vs age<60 years (RR=2.43; 95% CI: 1.49-3.95); hand grip strength (Q(1) vs Q(4): ≤13.88 vs ≥17.28 kg) (RR=1.88; 95% CI: 1.15-3.05); BMD total hip (Q(1) vs Q(4): ≤0.784 vs 0.973 g/cm(2)) (RR=1.86; 95% CI: 1.26-2.75); dietary calcium intake (Q(1) vs Q(4): ≤391 vs ≥648 mg/day) (RR=1.66; 95% CI: 1.08-2.53); serum 25(OH)D (Q(1) vs Q(4): ≤17.9 vs ≥45.1 nmol/L) (RR=1.63; 95% CI: 1.06-2.51); and past year history of falls (RR=1.61; 95% CI: 1.06-2.48). Compared with having none (41.9% of women), having three or more clinical risk factors (4.8% of women) increased fracture risk by more than 4-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of T-score of [total hip/lumbar spine (L1-L4)] was associated with a 14.2-fold greater risk than having no risk factors and being in the highest T-score tertile. Several clinical risk factors were independently associated with all ORFs in healthy Saudi postmenopausal women. The combination of multiple clinical risk factors and low BMD is a very powerful indicator of fracture risk.

The routine use of cefazolin in cesarean section

Objective: To determine the effectiveness and safety of the routine use of antibiotic prophylaxis in women undergoing cesarean section. Method: Four hundred and forty‐one women undergoing cesarean sections were randomly assigned either to a single dose of 1 g intravenous cefazolin or placebo after clamping of the umbilical cord. The primary outcome was the development of post‐operative febrile morbidity and the secondary outcomes were infection‐related complications. Result: There were 211 emergency and 230 elective cesarean sections. In the emergency cesarean sections, 34 (30.6%) women developed post‐operative febrile morbidity in the placebo group compared to 11 (11%) women in the cefazolin group. This was a statistically significant difference (P=0.001). Similarly, there were statistically significant differences between the two groups in the development of wound infection (P<0.001), use of therapeutic antibiotics (P=0.001), and post‐operative days in hospital (P=0.003). No statistically significant differences were detected in the development of other infection‐related complications. In the elective cesarean sections, no statistically significant differences were found in post‐operative febrile morbidity and infection‐related complications. There were no serious side effects related to the use of cefazolin. Conclusion: The routine use of a single dose of cefazolin is safe and effective in emergency but not elective cesarean section.