The incremental risk of fragility fractures in aging men.

INTRODUCTION: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population. METHODS: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata. RESULTS: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001). CONCLUSION: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality.

Tobacco Smoke-Induced Hepatic Injury with Steatosis, Inflammation, and Impairments in Insulin and Insulin-Like Growth Factor Signaling.

BACKGROUND: Alcoholic liver disease (ALD) is associated with impairments in hepatic insulin and insulin-like growth factor (IGF) signaling through cell growth, survival, and metabolic pathways. Since not all heavy drinkers develop ALD, co-factors may be important. Epidemiologic data indicate that most heavy drinkers smoke tobacco and experimental data revealed that low-level nitrosamine exposures, including those from tobacco, can cause steatohepatitis with hepatic insulin/IGF resistance and exacerbate ALD. We hypothesize that cigarette smoke (CS) exposures also cause liver injury with impaired hepatic insulin/IGF signaling, and thereby contribute to ALD. METHODS: Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 (CS4) or 8 (CS8) weeks, or CS for 8 weeks with 2 weeks recovery (CS8+R). RESULTS: CS exposures caused progressive liver injury with disruption of the normal hepatic chord architecture, lobular inflammation, apoptosis or necrosis, micro-steatosis, sinusoidal dilatation, and nuclear pleomorphism. Histopathological liver injury scores increased significantly from A8 to CS4 and then further to CS8 (P<0.0001). The mean histological grade was also higher in CS8+R relative to A8 (P<0.0001) but lower than in CS4, reflecting partial resolution of injury by CS withdrawal. CS exposures impaired insulin and IGF-1 signaling through IRS-1, Akt, GSK-3ß, and PRAS40. Livers from CS8+R mice had normalized or elevated levels of insulin receptor, pYpY-Insulin-R, 312S-IRS-1, 473S-Akt, S9-GSK-3ß, and pT246-PRAS40 relative to A8, CS4, or CS8, reflecting partial recovery. CONCLUSION: CS-mediated liver injury and steatohepatitis with impairments in insulin/IGF signalling are reminiscent of the findings in ALD. Therefore, CS exposures (either first or second-hand) may serve as a co-factor in ALD. The persistence of several abnormalities following CS exposure cessation suggests that some aspects of CS-mediated hepatic metabolic dysfunction are not readily reversible.

Effect of weed extracts on seedling growth of some varieties of wheat.

Allelopathic effect ofAvena fatua L., Cyperus rotundus L., Polygonum hydropiper L., and Solanum nigrum L. were examined on seedling growth of certain commonly used varieties of wheat (Triticum aestivum L.) in the Tarai region of U.P. state. The weed extracts inhibited the length of plumule in all the varieties (100%) with Solanum and it was in 12 (92%), 10 (77%) and 06 (46%) varieties with Polygonum, Avena and Cyperus, respectively. In radicle length, it was in 92% with both Polygonum and Solanum; and 85% and 69% of the varieties with Avena and Cyperus, respectively. However, all the four weed extracts reduced the dry weight of plumule, radicle and total seedling in all the varieties (100%) of wheat except in HD--2329 with Cyperus, in which it was positive. The percent reduction (percentage of control) was more than 50% in 92%, 77%, 54% and 39% of the varieties, respectively with Solanum, Polygonum, Avena and Cyperus. Among the weed extracts, the inhibitory effect on seedling growth in different varieties followed the order: Solanum > Polygonum > Avena and > Cyperus. On the basis of the present results, UP--2003 and WH--542 followed by PBW--226, Sangam and HD--248 were more susceptible to all the four weed extracts compared to the rest of the varieties of wheat.

Cell-specific expression of the alpha 1 (I) collagen promoter-CAT transgene in skin and lung: a response to TGF-beta subcutaneous injection and bleomycin endotracheal instillation.

Transgenic mice containing a rat collagen alpha 1 (I) promoter (3.6 kilobases) fused to the reporter gene chloramphenicol acetyl transferase (CAT) express the reporter gene parallel to endogenous gene in most connective tissues other than vascular tissue [Pavlin et al. (1992): J Cell Biol 116:227-236; Bedalov et al. (1994): J Biol Chem 269:4903-4909]. We have challenged transgenic mice with subcutaneous injections of transforming growth factor-beta (TGF-beta) or intratracheal instillation of bleomycin. In situ hybridization studies of skin revealed increased CAT expression in the papillary dermis of TGF-beta treated animals. In contrast, alpha 1 (I) collagen mRNA was expressed throughout the dermis including granulation tissue and reticular dermis. Therefore, the transgenic promoter responds to TGF-beta in a subset of dermal fibroblasts. Endotracheal instillation of bleomycin induces lung fibrosis which is thought to be mediated in part by TGF-beta. CAT gene expression in lungs was increased 6-8-fold at 2 weeks post bleomycin treatment. In situ hybridization studies revealed focal areas of cells expressing both CAT and collagen genes in the interstitium. However, most regions, especially around airways, contained a subset of cells expressing the endogenous gene with little or no CAT expression as judged by in situ hybridization. These cells could be myofibroblasts that require additional cis-acting elements to activate alpha 1 (I) collagen gene expression similar to smooth muscle cells.