Explore the vast range of titles available.

Abstract Context Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling. Objective We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals. Methods A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and ALP measurement. Fracture data were collected post randomization. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. Phosphate, Ca, and ALP were analyzed in deciles (D1-D10), with deciles 4 to 7 (31%-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations. Results Of the 9915 participants, 907 (9.2%) individuals had incident fractures recorded over 3.9 (SD 1.4) years. In the fully adjusted model, men in the top decile (D10) of phosphate had a 78% higher risk of incident fracture (HR 1.78; 95% CI, 1.25-2.54). No such association was observed for women (HR 1.09; 95% CI, 0.83-1.44). The population attributable fraction in men within the D10 phosphate category is 6.9%. Conclusion This result confirms that high-normal serum phosphate levels are associated with increased fracture risk in older men.

OBJECTIVE: To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS: A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women's Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50-<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors. RESULTS: Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial. CONCLUSIONS: Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.

Aims/hypothesis Serum adiponectin has been reported to impact upon fracture risk in the general population. Although type 2 diabetes is associated with increased fracture risk, it is unclear whether serum adiponectin predicts fractures in individuals with type 2 diabetes. The aim of the study was to prospectively investigate the relationship between serum adiponectin and fracture risk in individuals with type 2 diabetes. Methods In this study, data was obtained from The Fukuoka Diabetes Registry, a multicentre prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. We followed 4869 participants with type 2 diabetes (mean age, 65 years), including 1951 postmenopausal women (defined as self-reported amenorrhea for >1 year) and 2754 men, for a median of 5.3 years. The primary outcomes were fractures at any site and major osteoporotic fractures (MOFs). Results During the follow-up period, fractures at any site occurred in 682 participants, while MOFs occurred in 277 participants. Age-adjusted HRs (95% CIs) of any fracture and MOFs for 1 SD increment in log e -transformed serum adiponectin were 1.27 (1.15, 1.40) and 1.35 (1.17, 1.55) in postmenopausal women and 1.22 (1.08, 1.38) and 1.40 (1.15, 1.71) in men, respectively. HRs (95% CIs) of MOFs for hyperadiponectinaemia (≥ 20 μg/ml) were 1.72 (1.19, 2.50) in postmenopausal women and 2.19 (1.23, 3.90) in men. The per cent attributable risk of hyperadiponectinaemia for MOFs was as high as being age ≥70 years or female sex. Conclusions/interpretation Higher serum adiponectin levels were significantly associated with an increased risk of fractures at any site and with an increased risk of MOFs in individuals with type 2 diabetes, including postmenopausal women.

Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. Over a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 μmol/L; 95% confidence interval [CI], 0.65–1.14) or osteoporotic fracture (HR, 0.97 μmol/L; 95% CI, 0.66–1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 μmol/L; 95% CI, 0.71–1.01). This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation.

BACKGROUND AND OBJECTIVESAlthough intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine. METHODSAltogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group)pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non–protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined. RESULTSResults were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P < 0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P < 0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P < 0.01). CONCLUSIONSLipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia–related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study. CLINICAL TRIAL REGISTRATIONThis study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.

To clarify what kind of risk factors predict incident fractures in patients treated with bisphosphonates, the authors investigated the relationship between baseline characteristics and incident vertebral fracture in Japanese osteoporosis patients undergoing bisphosphonate treatment. This was a multi-center follow-up study conducted at three centers, in which a total of 251 Japanese patients with osteoporosis (mean age 70.5 years) from the three centers were followed for 3.2 ± 2.0 years. Baseline data, including pre-existing fractures, bone mineral density in the lumbar spine (LBMD), bone metabolic markers, urinary pentosidine, and plasma homocysteine, were evaluated. Changes in LBMD, bone turnover markers, and incident fractures after the treatment were followed. Sixty-one patients developed incident vertebral fractures; this group of patients was older and had lower LBMD, a higher prevalent vertebral fracture number, and higher homocysteine and pentosidine levels than patients who did not develop incident vertebral fractures. Changes in LBMD, urinary N-terminal telopeptides of type I collagen (NTX), and bone-derived alkaline phosphatase showed no significant association with the occurrence of vertebral fractures. Cox's proportional hazard model demonstrated that age, prevalent fracture, pentosidine, and homocysteine were independent predictors of the incident vertebral fracture rate under bisphosphonate treatment. Higher baseline levels of pentosidine and homocysteine in osteoporosis patients are potential risk factors for incident vertebral fractures when these patients are treated with bisphosphonates. Further clarification is needed to explain why such patients have higher fracture susceptibility.

Nutritional approach to the deterioration of bone integrity and increased fracture risk appears to be particularly appropriate in elderly women living in nursing homes. To investigate the beneficial effect of the consumption of soft plain cheese on bone resorption markers in institutionalized elderly women. Prospective, randomized crossover controlled study. Six French nursing homes or other institutions for elderly. Institutionalized women ≥ 65 years old with low vitamin D status and calcium intake below 700 mg/day. Consumption of soft plain cheese made of semi-skimmed milk which was fortified by both vitamin D3 (+ 1.25µg/100g) and milk extracted Ca, thus achieving a total Ca content of 151 mg/100g as compared to about 118 mg/100g for standard fresh cheese. Two servings were taken every day during the 6 weeks that preceded or followed a period of 6 weeks without soft plain cheese consumption. The primary end point was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX) selected as a marker of bone resorption. 29 women aged 73–94 yr were selected, 21 of them with mean age 87.2±6.1 years remained compliant The intervention increased calcium and protein intakes by 51% (904±228 vs. 599±122 mg/d) and 33 % (74.2±17.1 vs. 55.6±12.7 g/d, mean±SD), respectively. The dietary intervention was associated with a statistically significant increase in serum levels of both 25OHD and IGF-I, while those of PTH, CTX and TRAP5b were significantly reduced. Compliance was 93,4 %. The daily consumption of two servings of soft plain cheese was well accepted in terms of tastiness and appetite suited portion size. This randomized crossover controlled trial demonstrates that in elderly women living in nursing homes, the consumption of soft plain cheese increasing the supply of vitamin D, calcium and proteins, could reduce bone resorption and thereby reduce the risk of incidental fragility fractures in the long term.

The clinical relevance of D-dimer levels when screening for venous thromboembolism (VTE) in elderly patients with a hip fracture has been reported but has not been fully investigated in patients with fractures caused by high-energy injuries. The purpose of this study was to evaluate the usefulness and limitations of D-dimer in such patients. We enrolled 80 consecutive patients who underwent surgical treatment for fracture of the pelvis or lower extremity caused by high-energy injuries. None had received pharmacological prophylaxis for VTE. All patients underwent routine ultrasonography preoperatively and postoperatively (average 6.1 days after injury and 7.8 days after surgery). Contrast-enhanced computed tomography was performed routinely at the same time points for patients with a pelvic fracture or multiple fractures. D-dimer levels were compared in patients with and without VTE. Receiver operating characteristic (ROC) curve analysis was done and the appropriate D-dimer cutoff level determined for VTE screening. VTE was diagnosed in 34 of the 80 patients. D-dimer levels were significantly higher in patients with VTE than without it at almost all time points preoperatively and postoperatively except in patients with an isolated lower extremity fracture. ROC curve analysis suggested moderate to high accuracy for predicting VTE in patients with a pelvic fracture or multiple fractures preoperatively and postoperatively. Cutoff levels with high sensitivity and specificity for patients with a pelvic fracture or multiple fractures were set at around 7 days after the injury and surgery. D-dimer can be used as a VTE screening tool in patients with fractures caused by high-energy injuries. Our results suggested that D-dimer analysis to predict VTE was useful in patients with a pelvic fracture or multiple fractures. Our results also suggested that it was less useful for predicting VTE in patients with an isolated lower extremity fracture.

Summary Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70–85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. Introduction Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70–85 years. Methods Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. Results The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (−2.8%) compared to the middle (−1.6%) and lowest tertiles (−1.2%) ( P  < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. Conclusion In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.

Abstract Context The associations of circulating insulin-like growth factor-1 (IGF-1) levels with bone mineral density and fracture risk are inconclusive in observational studies. Objective We conducted a mendelian randomization study to assess the associations of serum IGF-1 levels with estimated bone mineral density (eBMD) and fracture. Methods Genetic instruments for IGF-1 were selected at the genome-wide significance level (P < 5 × 10–8) from a genome-wide association study including 358 072 individuals of European ancestry. Summary-level data for eBMD (426 824 individuals) and fracture (53 184 fracture cases and 373 611 noncases) were obtained from the UK Biobank study. Univariable and multivariable mendelian randomization analyses methods were used to estimate the associations of IGF-1 with eBMD and fracture. The main outcome measure included the change of eBMD and odds ratio of fracture per genetically predicted 1-SD increase of serum IGF-1 levels. Results For 1-SD increase in IGF-1, the change of eBMD levels was 0.04 g/cm2 (95% CI, 0.01-0.07; P = .011) and the odds ratio of fracture was 0.94 (95% CI, 0.91-0.98; P = .003). The associations persisted with similar magnitude after adjustment for height. The association was consistent for fracture but not for eBMD after excluding genetic instruments that might directly influence these outcomes. The association between IGF-1 and fracture was somewhat attenuated after adjustment for eBMD (odds ratio 0.96; 95% CI, 0.92-0.99; P = .012). Conclusion The present study supports a role for IGF-1 in preventing fracture, possibly and partly mediated by greater bone mineral density.