Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study)

Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans.     

Male osteoporosis: deadly, but ignored

Male osteoporosis is a relatively unknown condition for many physicians. Yet about 500,000 fractures happen in men every year. For comparison, prostate cancer is diagnosed in 200,000 men annually. Mortality rate during the first year of hip fracture is higher than 30%, and 50% of patients do not regain their previous mobility and independence. This review focuses on epidemiology, underling causes, diagnostic tools, and treatment of male osteoporosis and prevention of fractures.     

Comparison of testosterone, alendronate, and a combination of both therapies in men with low bone mineral density.

BACKGROUND: Both bisphosphonates and testosterone are known to improve bone mineral density (BMD) in men with low bone mass, but whether combination therapy is superior to these agents used alone is not clear. We compared the changes in lumbar spine BMD when men with low bone mass were treated with each agent alone or as combination therapy. METHODS: In a retrospective study, we analyzed serum and BMD data from 149 men who had been evaluated in the Endocrinology Clinic at the Dallas Veterans Affairs Medical Center, Dallas, Texas. The subjects were divided into three cohorts: 59 men receiving testosterone therapy alone, 68 men receiving alendronate therapy alone, and 22 receiving combination therapy. RESULTS: Compared with the baseline values, the lumbar spine and BMD increased significantly in each of the testosterone, alendronate, and combination therapy cohorts (median annualized rate of change: 2.1% [p < .001], 2.6% [p < .001], and 2.5% [p = .04], respectively). The combination therapy group did not demonstrate any additional increase in BMD at the lumbar spine or total hip compared with either agent alone. The results did not change after adjusting for differences in baseline weight, age, BMD, or baseline testosterone level. CONCLUSION: The results suggest that the combination of testosterone and alendronate does not appear to be superior to single-drug therapy in our patient population.     

Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds

In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a K(i) value of 6 micro M. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.     

Scale-Up and Testing of Polyurethane Bio-Foams as Potential Cryogenic Insulation Materials

This article compares the properties of closed-cell PUR bio-foams produced on a laboratory scale and on an industrial scale. In the formulation used, the polyol premix contained 40 wt.% of a bio-polyol based on rapeseed oil. Selected useful properties of the foams obtained on the two scales and the use of one-step and spraying methods were compared. In the case of the spraying method, the experimental system was compared to a commercial one. Given the possibility of applying the bio-foams in insulation systems for cryogenic and liquefied natural gas (LNG) applications, a compressive strength analysis of the foams was carried out at room temperature as well as at −196 °C. It was found that the foams modified with the bio-polyol were characterized by a higher compressive strength at low temperatures than commercial foams based on a petrochemical polyol.     

A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.     

The Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Increases Bone Resorption in Women with Type 2 Diabetes: A Randomized, Controlled Trial

In previous studies, with up to 16 weeks of exposure to rosiglitazone or pioglitazone, circulating markers of bone formation [procollagen I N-terminal propeptide (P1NP), osteocalcin, and bone-specific alkaline phosphatase] decreased but no change in bone resorption markers was found. We examined the effect of rosiglitazone on bone resorption and formation markers when used for 24 weeks. This post-hoc analysis of a double-blind, placebo-controlled, randomized trial evaluated the effects of 6 months of rosiglitazone use versus placebo on circulating markers of bone turnover in 111 patients with type 2 diabetes and cardiovascular disease or additional cardiac risk factors. The principal end points for analysis were changes in bone formation and resorption markers, measured by P1NP and carboxy-terminal cross-links (CTX), respectively. There were 111 subjects who completed the study and had baseline and 6-month data; mean age was 56, including 41% women and 67% nonwhite (50 black, 18 Hispanic, and six other), and subjects were evenly distributed between placebo and rosiglitazone groups. Women treated with rosiglitazone had higher CTX levels (0.43 ng/mL) than those who received placebo (0.23 ng/mL) (P = 0.007), with no significant differences in P1NP or OPG. Overall, in stratified analyses of men and in stratified analyses among different ethnicities, there were no statistically significant differences observed in CTX, P1NP, OPG, PTH, or 25-OHD between the treatment groups. Women taking rosiglitazone had higher circulating markers of bone resorption, which is contrary to prior studies of shorter duration, where the principal observation was a decrease in markers of bone formation.