Xuezhi Jiang

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

ObjectiveThe objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. MethodsThe parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women’s Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. ResultsThere was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46–mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). ConclusionsSupplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis

OBJECTIVE The activated vitamin D receptor (VDR) may have an important role in vascular health. The objective of this study was to determine whether there is an association between the expression of VDRs in coronary arteries and the extent of diet-induced atherosclerosis. METHODS Utilizing a cohort of 39 postmenopausal female cynomolgus monkeys with varying stages of atherosclerosis, histologic sections of the left anterior descending artery (LAD) were analyzed for plaque cross-sectional area, plaque thickness, and VDR quantity using immunohistochemical H-score analysis. The quantities of VDRs were analyzed as a continuous variable and were divided at the median intimal H-score into high vs. low groupings. RESULTS In the LAD, a significant negative correlation was observed between the quantity of VDR and plaque size (both cross-sectional area [p<0.001] and plaque thickness [p<0.001]). Monkeys in the low VDR group had a significantly greater cross-sectional plaque area (1.2mm(2)) and greater plaque thickness (0.3mm) than those in the high VDR group (0.4mm(2), p=0.005; 0.1mm, p=0.003, respectively). CONCLUSIONS Lower concentrations of VDRs in a main coronary artery were associated with greater atherosclerotic plaque size in postmenopausal female monkeys. Given that coronary artery atherosclerosis is a major cause of coronary heart disease in postmenopausal women, further research to ascertain the relationship between VDRs and atherosclerosis is warranted.

The Safety of Direct Trocar Versus Veress Needle for Laparoscopic Entry: A Meta-Analysis of Randomized Clinical Trials

OBJECTIVE This study assessed the safety of direct trocar insertion (DTI) versus Veress needle followed by primary trocar insertion (VN). METHODS Ovid MEDLINE(®), Cochrane Library, Google Scholar, Scopus, and the reference lists of published articles were searched up to September 2011 to identify randomized clinical trials comparing DTI with VN. This meta-analysis was restricted to randomized studies comparing the safety of these two laparoscopic entry techniques. RESULTS Seven randomized studies consisting of 2940 women (VN, n=1525; DTI, n=1415) were identified. The data on the safety of two entry techniques were abstracted, integrated, and analyzed with the meta-analysis method and are presented as pooled relative risk (RR) with 95% confidence intervals (CI). There were 4 cases of a major complication in the VN group in contrast to none in the DTI group. Pooled results failed to show a statistically significant difference in the risk of major complications between the two groups. A significantly higher risk of minor complications was detected in the VN group (RR [95% CI]=10.78 [6.27-18.51]). Among minor complications, preperitoneal injuries (46.73 [11.55-189.10]) and omental injuries (4.51 [2.12-9.62]) were the two most common complications in the VN group. There were significantly increased risks of multiple insertions (more than two attempts) (2.99 [2.11-4.23]) and failed entry (2.21[1.07-4.56]) in the VN group. CONCLUSION This meta-analysis suggests that the commonly used VN entry technique carries a significantly increased risk of minor complications. In addition, the likelihood of multiple insertions and failed entry are significantly higher in the VN group.

Coronary artery vitamin D receptor expression and plasma concentrations of 25-hydroxyvitamin D: their association with atherosclerosis.

Objective The aim of this study was to analyze coronary artery vitamin D receptor (VDR) expression, the plasma concentrations of 25-hydroxyvitamin D3 (25OHD3), and their relationship with coronary artery atherosclerosis. Methods Premenopausal cynomolgus monkeys were fed atherogenic diets containing the equivalent of 1,000 IU/day of vitamin D3. Protein was derived from casein-lactalbumin (C/L, n = 10), soy protein isolate (soy, n = 10), or a combination (n = 19). After 32 months of consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, coronary atherosclerosis was measured in the left circumflex (LCX) artery and left anterior descending (LAD) artery. VDR expression was determined for the LAD, and 25OHD3 concentrations were assessed. Results Both the cross-sectional area of atherosclerotic plaques (in square millimeters) and plaque thickness (in millimeters) in the LCX as well as the LAD arteries were analyzed in these monkeys. Those with higher plasma vitamin D3 concentrations and higher VDR were compared with those with higher plasma 25OHD3 concentrations and lower VDR. Significantly smaller plaque sizes were noted with higher plasma 25OHD3 concentrations and higher VDR. For the LCX artery, there was also a significantly lower plaque size (both plaque thickness and cross-sectional area) in those with higher quantities of VDR and lower 25OHD3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of 25OHD3 (P = 0.009 and P = 0.040, respectively). Conclusions Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than do those with lower quantities of VDR and higher plasma 25OHD3 concentrations. If these findings translate to human beings, it might explain why some individuals with higher plasma concentrations of 25OHD3 have more coronary artery atherosclerosis.

Prevalence of high-risk cervical human papillomavirus and squamous intraepithelial lesion in Nigeria

Objective The prevalence of cervical cancer and high-risk human papillomavirus (HPV) in Nigerian women remains poorly studied. Our objective was to estimate the prevalence of high-risk HPV and associated squamous intraepithelial lesions (SILs) in Nigeria. Methods After institutional review board approval, data collection was performed by volunteers of FaithCare, Inc, between 2004 and 2008 in 3 regions of Nigeria (Okene, Katari, and Abuja). Demographic data and ThinPrep Pap smears (Cytyc, Marlborough, MA) were collected from 410 women. Pap smears were analyzed for both the presence of SIL and HPV DNA. Results The prevalence of high-risk HPV and SIL was 15.6% and 6.8%, respectively. Of the 28 abnormal Pap tests, 42.9% had atypical squamous cells of undetermined significance, 39.3% had low-grade SIL, 14.3% had high-grade SIL, and 3.6% had atypical glandular cells. There was a strong association between high-risk HPV and SIL in both the combined (p < .001) and individual group data (p < .001, p = .013, and p < .001 for Okene, Abuja, and Katari, respectively). However, there were no statistically significant correlations between either high-risk HPV or presence of SIL and known risk factors including age, history of sexually transmitted disease, and the number of sexual partners. There was also no statistical difference in the prevalence of high-risk HPV and SIL among the 3 locations. Conclusions A strong association exists between high-risk HPV and SIL. The prevalence of cervical high-risk HPV and SIL, however, did not vary in the 3 different locations and is consistent with reports from other regions in Africa.

Denosumab: an antifracture therapy for postmenopausal women with osteoporosis.

O steoporosis is a skeletal disorder characterized by compromised bone strength, leading to bone fragility with increased vulnerability to fracture. Of the 10 million Americans estimated to have osteoporosis, 8 million are women. Women can lose up to 20% of their bone density 5 to 7 years after menopause, making them more susceptible to osteoporosis. Approximately half of all women older than 50 years will have an osteoporosis-related fracture in their remaining lifetime. In 2005, more than 2 million osteoporotic fractures were responsible for an estimated US

Vitamin D deficiency and cardiovascular disease in postmenopausal women: contributions from human and nonhuman primate studies.

19 billion in costs. Of concern, the number of fractures due to osteoporosis is projected to rise to more than 3 million by 2025, which would equate to costs of approximately US

Age as a Predictor of Osteoporotic Fracture Compared with Current Risk-Prediction Models

25.3 billion. To help ensure the most evidence-based and cost-effective approach to bone health, we need to discourage wide variations in screening practices and diagnoses. Although it has been suggested that many women at high risk for fractures are underscreened, underdiagnosed, or undertreated, other women are overscreened, leading to unnecessary, costly, and potentially detrimental treatment. Osteoporotic fractures are most likely to occur in the hip, spine, and wrist, resulting in increased morbidity, healthcare costs, and mortality. Fortunately, medical advances have led to highly efficacious therapies, such as bisphosphonates, selective estrogen receptor modulators, and parathyroid hormone, for the treatment and prevention of osteoporosis. Compliance with therapy, however, is generally poor owing to perceived adverse effects of medication, inconvenient dosing regimens, or both. These reasons, along with inadequate screening and treatment practices, would suggest that an unrecognized potential antifracture benefit of pharmacological therapy exists. Owing to the underdiagnosis and undertreatment of osteoporosis in postmenopausal women at high risk for fractures, the number of fractures rises, women’s health suffers, and, ultimately, healthcare costs increase. It would be desirable, therefore, to develop a drug that not only has a high efficacy in reducing the rate of osteoporotic fractures with an acceptable safety profile but also is associated with better compliance even when used with other complex medication regimens. Denosumab, a Food and Drug AdministrationYapproved antiresorptive agent, is an emerging therapy for osteoporosis in postmenopausal women that may meet many of these goals. Denosumab is a human monoclonal antibody to the receptor activator of nuclear factor J-B ligand (RANKL), an osteoclast-differentiating factor. It inhibits the formation, function, and survival of osteoclasts, resulting in decreased bone resorption and hence increased bone mineral density (BMD). The approved dose is 60 mg administered subcutaneously every 6 months, potentially leading to better compliance with treatment. To date, the results of multiple phase II and phase III trials have shown a higher efficacy of denosumab in improving BMD in postmenopausal women with low BMD, when compared with either placebo or alendronate. In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial, by far the largest of the denosumab clinical trials (phase III), 7,868 postmenopausal women with osteoporosis (T-scores between j4.0 and j2.5 at the lumbar spine or hip) were randomized to receive subcutaneously either denosumab 60 mg or placebo every 6 months for 3 years. Compared with placebo, the BMD of the lumbar spine and hip was significantly improved in the denosumab group (9.2% vs 0 and 4.0% vs j2.0%, respectively). In an extension of the FREEDOM trial, 4,550 participants remained in the trial, and 2,343 received denosumab. After 2 years of extension or 5 years of continuous denosumab, additional gains in BMD were noted at the lumbar spine (3.5%) and hip (1.4%). Denosumab was also effective in improving BMD in postmenopausal women who were previously treated with bisphosphonates. The effects of denosumab on BMD were also observed in men with osteoporosis and were independent of age, baseline testosterone levels, BMD status, and estimated fracture risk. In September 2012, the Food and Drug Administration approved a new indication for denosumabVas treatment to increase bone mass in men with osteoporosis who are at high risk for fractures. Among the above-mentioned clinical trials investigating the efficacy of denosumab in treating postmenopausal osteoporosis, the FREEDOM trial is the only trial that listed new vertebral fractures as primary endpoint. After 36 months, denosumab (60 mg, SC, every 6 mo) was noted to cause a 68% risk reduction for vertebral fractures (2.3% vs 7.2%), a 40% risk reduction for hip fractures (0.7% vs 1.2%), and a 20% risk reduction for nonvertebral fractures (6.5% vs 8.0%), all statistically significant, as compared with placebo. In the extension trial described above, the incidence of new vertebral fractures (2.8%) and new nonvertebral fractures (2.5%) remained low after 5 years of denosumab therapy. Among the estimated 2 million osteoporotic fractures in 2005, 60% were nonvertebral fractures, which result in considerable morbidity

Association of breast arterial calcification with stroke and angiographically proven coronary artery disease: a meta-analysis.

ObjectiveCardiovascular disease (CVD) is the leading cause of death among American postmenopausal women and all adult Americans. The medical community and the lay community have recently become intrigued with vitamin D and its potential role in reducing the risk of CVD. Research findings from multiple retrospective studies, few prospective studies, and recent nonhuman primate studies have been inconsistent and conflicting. The objective of this study is to review what is known about the topic, what questions remain unanswered, and where the research community should be focusing. MethodsA literature search was conducted through PubMed and Google Scholar up to August 1, 2014. One hundred six articles, including 18 double-blind, placebo-controlled, randomized clinical trials, relevant to the study topic were identified. All studies were stratified based on study design and primary outcome. The effects of vitamin D on CVD were reviewed and summarized. ResultsAlthough there is an abundance of observational studies suggesting an association with CVD protection, the most well-controlled randomized human trial data available show no benefit of vitamin D on CVD. However, highly controlled nonhuman primate studies indicate a beneficial relationship. ConclusionsWell-designed research, with CVD as primary outcome, is needed to help bridge the gap in our knowledge on this topic. In the meantime, caution should be applied to avoid overdiagnosis and overtreatment of vitamin D deficiency.

Menopausal medicine clinic: an innovative approach to enhancing the effectiveness of medical education.

OBJECTIVE: To compare several fracture risk-prediction models and their predictive values. METHODS: Women older than age 49 years were sent for dual-energy X-ray absorptiometry screening between January 2007 and March 2009. Data collection included multiple osteoporosis risk factors. The ability to identify fractures was analyzed and compared using the North American Menopause Society 2006 and 2010 Position Statements, The Fracture Risk Assessment Tool, along with age alone. The area under the curve (AUC) comparison with chance (AUC 0.50) and paired AUC comparisons between models were used to investigate the efficacy of each model in predicting osteoporotic fractures. RESULTS: Among the 615 women studied, with mean (standard deviation) age of 61.4 (8.3) years and 94.5% being white, 15 have experienced a fracture. All screening approaches were significantly better than chance at predicting fractures. Paired comparisons of the detection ability of fracture prediction models showed no significant differences. Age alone was a significant predictor for fracture (AUC 0.79, 95% confidence interval [CI] 0.67–0.91, P<.001) with the optimal cutoff age of 65 years, which was associated with a sensitivity (95% CI) of 80% (77–83%) and specificity (95% CI) of 73% (70–77%). Compared with young postmenopausal women (younger than 65 years), the odds ratio (95% CI) of fractures in older women (65 years or older) is 10.2 (2.32–44.97). In addition, when age was added, it significantly increased the AUC of each model. CONCLUSION: These data suggest that all current screening modalities are effective in predicting fracture but not significantly better than age alone. Age should be considered carefully while evaluating patients for osteoporosis screening and treatment. LEVEL OF EVIDENCE: II