title: Vitamin D and ibandronate prevent cancellous bone loss associated with binge alcohol treatment in male rats.
abstract: Decreased bone mass and bone strength can result from excess alcohol consumption in humans and alcohol treatment in the rat. Although the specific mechanism is unknown, the damaging effects of alcohol abuse modulate the bone remodeling cycle and increase bone turnover. Chronic alcohol consumption models have shown an inhibition of bone formation. We previously reported that binge alcohol treatment increases bone resorption and that alcohol-induced damage can be prevented by treatments with intermittent parathyroid hormone and bisphosphonates. In this study, we hypothesized that an effective dose of vitamin D (cholecalciferol) or a single dose of ibandronate would prevent bone loss caused by binge alcohol treatment in male rats. Forty-eight adult (450 gram) male Sprague-Dawley rats were randomly assigned to 6 treatment groups (n=8): (a) saline i.p., 3 days/week (C); (b) binge alcohol, 3 g/kg i.p., 3 days/week (A); (c) vitamin D, 5,000 IU/kg daily s.c. (D); (d) binge alcohol and vitamin D (AD); (e) ibandronate (120 microg, given as a single i.p. injection (I)); and (f) alcohol and ibandronate (AI) . After 4 weeks of treatment, proximal tibia and L3 and L4 vertebrae were analyzed for bone mineral density (BMD) by quantitative computerized tomography and compressive strength-to-failure using an Instron materials testing machine. Type I collagen cross-linked c-telopeptide, calcium, and 25-OH vitamin D levels were measured in serum collected at the time of sacrifice. Binge alcohol significantly decreased cancellous BMD by 58% in tibia and 23% in lumbar spine (p<0.05). Binge alcohol treatment decreased L3 and L4 compressive strength-to-failure by 21% (p<.05). Treatment with vitamin D at 5,000 IU/kg/day prevented alcohol-induced bone loss, significantly increasing both tibial and vertebral cancellous BMD values (161% increase in tibia and 40% increase in vertebra, respectively, p<0.05) compared to alcohol alone groups. Pre-treatment with the single dose of 120 microg ibandronate prevented alcohol-induced bone loss, increasing cancellous BMD by 186% in tibiae and by 46% in vertebrae compared to the alcohol alone group (p<0.05). In summary, binge alcohol-induced tibial and vertebral bone loss can be prevented using an effective dose of vitamin D or a single dose of ibandronate even during high blood alcohol concentrations that have been shown to impair osteoblast functions and increase bone resorption.
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation, and the Alcohol Research Program, Loyola University Stritch School of Medicine, 2160 So. First Ave., Maywood, Illinois 60153, USA. fwezema@lumc.edu
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Wezeman
authors.forename: Dainius
authors.initials: D
authors.lastname: Juknelis
authors.forename: Ryan
authors.initials: R
authors.lastname: Himes
authors.forename: John J
authors.initials: JJ
authors.lastname: Callaci
mesh_terms: D000438:Alcohols / Q000009:adverse effects*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D000077557:Ibandronic Acid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects; D013314:Stress, Mechanical; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology*
chemical_list: D000438:Alcohols; D024042:Collagen Type I; D004164:Diphosphonates; D014807:Vitamin D; D002118:Calcium; D000077557:Ibandronic Acid