osteoprotegerin and Alcoholism

The aim of this study was to investigate possible changes in immunohistochemical expression of proteins regulating the bone resorption process in the periodontium of rats subjected to alcoholism and/or estrogen deficiency. The investigated proteins were receptor activator of nuclear factor-kappa β ligand (RANKL), a protein that stimulates bone resorption, and osteoprotegerin (OPG), a protein that inhibits bone resorption. At the molecular level, decreased OPG expression and/or increased RANKL expression are consistent with a greater predisposition to bone resorption.. Wistar female rats were divided into ovariectomized (ovx) and non-ovariectomized (sham) groups, and subdivided into ad libitum diet (free diet), alcoholic diet (20% solution), and isocaloric diet (diet with a similar amount of calories as compared with groups ingesting an alcoholic diet). The alveolar bone crest and adjacent tissues were evaluated by immunohistochemical analyses for detection of OPG and RANKL.. A significant decrease in OPG expression and a significant increase in RANKL expression were observed in ovariectomized animals which received alcohol as compared with non-ovariectomized animals which received isocaloric diet (experimental control). When estrogen deficiency was evaluated independently of the diet type, a significant decrease in OPG expression and a significant increase in RANKL expression were observed in ovariectomized animals as compared with non-ovariectomized animals.. Estrogen deficiency associated with alcoholic diet, as well as estrogen deficiency (analyzed independently of diet type), decreased the immunostaining for OPG and increased the immunostaining for RANKL in the periodontium of rats.

Topics: Alcoholism; Animals; Bone Resorption; Female; Immunoenzyme Techniques; Osteoprotegerin; Ovariectomy; Periodontal Ligament; RANK Ligand; Rats; Rats, Wistar

Osteoprotegerin (OPG) is a parameter of increasing interest in the search for pathophysiological mechanisms of reduced bone mineral density (BMD). It has been shown to be increased in alcohol-dependent subjects. In our study, we wanted to examine whether changes in OPG and receptor activator of the nuclear factor-κB ligand (RANKL) levels during an 8-week abstinence period in alcohol-dependent patients treated in an alcohol rehabilitation clinic would occur and whether alcohol-related variables, smoking, status, or physical activity prior to the study served as an influence on BMD and on OPG/RANKL levels.. Forty-three patients, who were abstinent not longer than a week, were included in the study. OPG and RANKL as well as other markers of bone metabolism were measured at baseline, and after 8 weeks of treatment, BMD was measured once.. OPG levels decreased significantly, while osteocalcin, a marker of bone formation, increased significantly. RANKL as well as RANKL/OPG ratio, Serum CrossLaps, and all examined hormones showed no significant changes over time. Inflammatory parameters showed a significant reduction after 8 weeks. We detected no influence of potentially confounding variables of alcohol dependency on the course of OPG or other laboratory values.. Our results could point to the well-known risk for reduced BMD in these patients being reversible with abstinence through an excess of bone formation. We also confirmed earlier findings that inflammatory processes play a role in the pathogenesis of alcohol-induced disturbances in bone metabolism.

Topics: Adult; Alcohol Abstinence; Alcoholism; Biomarkers; Bone Density; Female; Humans; Longitudinal Studies; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Prospective Studies; RANK Ligand

Binge alcohol-related bone damage is prevented by concurrent administration of bisphosphonates, suggesting an activation of bone resorption with patterned alcohol exposure. Although chronic alcohol abuse is known to cause osteopenia, little is known about the effects of binge drinking on bone metabolism. We examined the effects of binge alcohol exposure on the relationship between bone damage and modulation of bone remodeling-specific gene expression profiles. Our hypothesis was that bone damage observed in young adult rats after binge alcohol exposure is associated with differential expression of bone remodeling-related gene expression. We further hypothesized that this differential gene expression specific to bone remodeling (bone resorption or formation related) would be influenced by the duration of binge alcohol exposure. Binge alcohol (3 g/kg, i.p.) was administered on 3 consecutive days each week, for 1 or 4 weeks, to adult male rats. Matched control animals were injected with an equal volume of isotonic saline. Lumbar vertebrae, L4-5, were analyzed for the presence of bone damage by quantitative computed tomography and compressive strength analysis. Total RNA was isolated from an adjacent vertebrae (L3), and whole transcriptome gene expression data were obtained for each sample. The expression levels of a subset of bone formation and resorption-associated differentially expressed genes were validated by quantitative reverse transcriptase-polymerase chain reaction. Bone loss was not observed after 1 week of treatment but was observed after four binge alcohol cycles with a 23% decrease in cancellous bone mineral density and 17% decrease in vertebral compressive strength compared with control values (P < 0.05). We observed that the duration of binge alcohol treatment influenced the modulation of expression profiles for genes that regulate the bone formation process. The expression of key bone formation-related marker genes such as osteocalcin and alkaline phosphatase were significantly reduced (P < 0.05) after acute binge alcohol exposure, and expression of regulators of osteoblast activity such as bone morphogenetic proteins and parathyroid hormone receptor displayed significantly (P < 0.05) decreased differential expression. The expression of sclerostin, a key canonical Wnt inhibitory protein, was significantly increased after acute binge alcohol treatment. The expression of important regulators of osteoclast maturation and activity such as NF-kapp

Topics: Acute Disease; Alcoholism; Alcohols; Alkaline Phosphatase; Animals; Bone and Bones; Bone Remodeling; Bone Resorption; Chronic Disease; Gene Expression; Interleukin-6; Lumbar Vertebrae; Male; NF-kappa B; Osteocalcin; Osteoprotegerin; RANK Ligand; Rats; Rats, Sprague-Dawley