The effects of binge alcohol exposure on bone resorption and biomechanical and structural properties are offset by concurrent bisphosphonate treatment

Abstract

Background: Chronic alcohol consumption reduces bone mass and strength, increasing fracture risk for alcohol abusers. Mechanisms underlying this vulnerability involve modulation of bone remodeling. Direct effects of alcohol on bone formation have been documented; those on bone resorption are less well studied. Skeletal effects of exposure to high blood alcohol concentrations (BAC's) attained during binge drinking have not been studied. We examined the effects of repeated binge-like alcohol treatment on bone resorption, bone mineral density and vertebral compressive strength in adult male rats treated with the aminobisphosphonate, risedronate.

Methods: A binge alcohol exposure model was developed using intraperitoneal (IP) injection to administer a 20% (vol/vol) alcohol/saline solution (3 g/kg, 1X/day) on four consecutive days for 1, 2 or 3 weeks in 400 g rats, with and without weekly risedronate treatment (0.5 mg/kg, 1X/week). Total serum deoxypyridinoline (Dpd) a crosslink of bone type collagen released during resorption was measured by ELISA. Bone mineral density (BMD) was measured using peripheral quantitative computed tomography (pQCT). Vertebral compressive strength was determined using an Instron materials testing machine. Trabecular integrity was analyzed by computer-aided trabecular analysis system (TAS).

Results: Peak BAC's averaged 308.5 +/- 12 mg/dL; average BAC was 258.6 +/- 28.7 mg/dL at time of euthanasia. No significant effects of treatment were observed after 1 or 2 weeks of binge alcohol exposure. At 3 weeks of alcohol treatment serum Dpd was significantly increased (205%, p < 0.05) over controls. Bone mineral density (BMD) in cancellous bone of distal femur and lumbar spine were significantly decreased (34% and 21% respectively, p < 0.01) after 3 weeks of binge treatment. Vertebral (L4) compressive strength (maximum load sustained before failure) also decreased (27%, p < 0.05) after 3 binge alcohol cycles. Risedronate maintained the Dpd level (p < 0.01), BMD (p < 0.001) and vertebral structural biomechanical properties (p < 0.01) of binge-treated rats at control levels (E vs ER). Indices of trabecular architectural integrity [Trabecular bone volume/tissue volume (BV/TV), bone area (BAR) and trabecular separation (Tb.Sp)] analyzed at week 3 showed (BV/TV) and (BAR) were significantly reduced in alcohol-binged rats (p < 0.01), while (Tb.Sp) was significantly increased (p < 0.01). Risedronate also maintained the trabecular architectural indices of binge-treated rats at control levels (E versus ER, p < 0.01).

Conclusions: In adult male rats, BAC's reflective of those attained during alcoholic binge drinking may affect the skeleton in part by stimulating bone resorption, an effect mitigated by risedronate.

Fig. 1

Body Weights of Alcohol Binge Treated Rats: Rats were weighed twice weekly throughout the study period, weights of animals after each week of alcohol treatment is shown above. Weights were not significantly affected by alcohol or risedronate treatment. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group, (E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group.

Fig. 2

Serum Dpd Levels of Alcohol Binge-Treated Rats: Serum Dpd levels assayed as described in the methods section. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group,(E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group. * p < 0.05. ** p < 0.01.

Fig. 3

Bone Mineral Density of Distal Femur Cortical Bone in Alcohol-Binge-Treated Rats: BMD was measured as described in Method Section. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group,(E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group.

Fig. 4

Bone Mineral Density of Distal Femur Cancellous Bone in Alcohol Binge-Treated Rats: BMD was measured as described in Method Section. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group,(E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group. * p < 0.01. ** p < 0.001.

Fig. 5

Bone Mineral Density of Vertebral Cancellous Bone in Alcohol Binge-Treated Rats. BMD was measured as described in Method Section. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group,(E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group. * p < 0.05. ** p < 0.01.

Fig. 6

Lumbar Spine L4 Compression Strength in Alcohol Binge-Treated Rats. L4 Vertebral Compressive Strength was measured as described in Method Section. Significance determined using one-way ANOVA and Tukey’s multiple comparisons procedure. (C) Control Group,(E), Ethanol Group, (CR) Control Risedronate Group, (ER) Ethanol-Risedronate Group. * p < 0.05. ** p < 0.01.