Chronic alcohol abuse is a major risk factor for osteoporosis but the effects of moderate drinking on bone metabolism are largely uninvestigated. Here, we studied the long-term dose-response (0, 3, 6, 13, and 35% caloric intake) effects of alcohol on cancellous bone in the proximal tibia of 8-month-old female rats. After 4 months of treatment, all alcohol-consuming groups of rats had decreased bone turnover. The inhibitory effects of alcohol on bone formation were dose dependent. A reduction in osteoclast number occurred at the lowest level of consumption but there were no further reductions with higher levels of consumption. An imbalance between bone formation and bone resorption at higher levels of consumption of alcohol resulted in trabecular thinning. Our observations in rats raise the concern that moderate consumption of alcoholic beverages in humans may reduce bone turnover and potentially have detrimental effects on the skeleton.

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Depositional models that use heterogeneity in mud‐dominated successions to distinguish and diagnose environments within the offshore realm are still in their infancy, despite significant recent advances in understanding the complex and dynamic processes of mud deposition. Six cored intervals of the main body of the Mancos Shale, the lower Blue Gate Member, Uinta Basin, were examined sedimentologically, stratigraphically and geochemically in order to evaluate facies heterogeneity and depositional mechanisms. Unique sedimentological and geochemical features are used to identify three offshore environments of deposition: the prodelta, the mudbelt and the sediment‐starved shelf. Prodelta deposits consist of interlaminated siltstone and sandstone and exhibit variable and stressed trace fossil assemblages, and indicators of high sedimentation rates. The prodelta was dominated by river‐fed hyperpycnal flow. Mudbelt deposits consist of interlaminated siltstone and sandstone and are characterized by higher bioturbation indices and more diverse trace fossil assemblages. Ripples, scours, truncations and normally graded laminations are abundant in prodelta and mudbelt deposits indicating dynamic current conditions. Mudbelt sediment dispersal was achieved by both combined flow above storm wave base and current‐enhanced and wave‐enhanced sediment gravity flows below storm wave base. Sediment‐starved shelf deposits are dominantly siltstone to claystone with the highest calcite and organic content. Bioturbation is limited to absent. Sediment‐starved shelf deposits were the result of a combination of shelfal currents and hypopycnal settling of sediment. Despite representing the smallest volume, sediment‐starved shelf deposits are the most prospective for shale hydrocarbon resource development, due to elevated organic and carbonate content. Sediment‐starved shelf deposits are found in either retrogradational to aggradational parasequence sets or early distal aggradational to progradational parasequence sets, bounding the maximum flooding surface. An improved framework classification of offshore mudstone depositional processes based on diagnostic sedimentary criteria advances our predictive ability in complex and dynamic mud‐dominated environments and informs resource prospectivity.

Estrogen is essential for normal growth and remodeling of bone. Although the mechanism of estrogen action on bone cells has been widely investigated, the full spectrum of signal transduction pathways activated by estrogen is unknown. In this report, we investigate the effects of the gonadal hormone 17beta-estradiol on the regulation of signal transducer and activator of transcription-1 (Stat1) protein in cultured human fetal osteoblast cells, devoid of the classical estrogen receptors (ERs). 17beta-estradiol (10 nM) led to rapid (within 15 min) activation of Stat1 protein as indicated by increases in tyrosine phosphorylation and DNA binding activity. Also, 17beta-estradiol increased gamma-activated sequence-dependent transcription in transient transfection assays, suggesting an increase in Stat protein-dependent transcription. Estrogen-dependent Stat1 activation was blocked in cells that transiently express dominant-negative Stat1 mutant protein. Activation of Stat1 by 17beta-estradiol was not inhibited by ER antagonist ICI 182,780, providing further evidence that it is not dependent on classical ERs. 17beta-Estradiol induced rapid (within 15 min) Stat1 phosphorylation and stimulated gamma-activated sequence-dependent transcription in ER-negative breast cancer cells, indicating that these results are not unique to bone cells. The rapid estrogenic effect involving the phosphorylation and activation of Stat1 was blocked in the presence of Src family kinase inhibitor PP2; activated Stat1 was associated with Src protein in estrogen-treated cells. These findings indicate the requirement for Src kinase pathways in estrogen-mediated Stat1 activation. Thus, the ER-independent activation of Stat1 in 17beta-estradiol-treated osteoblast and breast cancer cells may partially mediate the actions of estrogen on target cells.

Reduced weight bearing accentuates the detrimental effects of alcohol on cortical bone in adult male rats by further inhibiting bone formation. This finding suggests that reduced physical activity may be a comorbidity factor for osteoporosis in alcohol abusers.