Binge alcohol treatment increases vertebral bone loss following ovariectomy: compensation by intermittent parathyroid hormone

Abstract

Background: Postmenopausal estrogen deficiency and alcohol abuse are known risk factors for osteoporosis. Previous studies of the combined effect of alcohol and ovariectomy on bone loss using chronic alcohol-feeding models have not demonstrated additional alcohol-induced bone loss in ovariectomized (OVX) animals. Binge alcohol treatment causes rapid bone loss in male rats. We hypothesized that binge alcohol would cause additional bone loss in OVX rats.

Methods: Ninety-six adult (400 g) female Sprague-Dawley rats (48 sham-operated and 48 OVX, pair fed) were randomly divided into 4 treatment groups: (a) saline-treated, (b) binge alcohol-treated (3 g/kg alcohol as a 20% weight to volume alcohol/saline solution, intraperitoneal (IP), 3 times per week), (c) parathyroid hormone (PTH)-treated (80 microg/kg, SC, 5 d/wk), and (d) binge alcohol plus PTH. Rats were treated for either 2 or 4 weeks. Following treatment periods, blood was collected for alcohol concentration (BAC) measurements; lumbar vertebrae were removed for bone mineral density (BMD) levels, trabecular microarchitecture assessment, and vertebral compressive strength analysis.

Results: Peak binge BACs averaged 300 mg/dL. Alcohol and OVX decreased cancellous BMD: alcohol and OVX treatment in combination caused additional cancellous BMD loss and significant cortical BMD reductions. Compressive strength was also decreased by OVX and alcohol. Combination treatment resulted in further declines in bone strength. Micro-CT analysis revealed a significant effect of combined OVX and alcohol treatment resulting in decreased trabecular bone volume/total volume (BV/TV). Intermittent PTH administration compensated for losses of BMD, compressive strength, and restored BV/TV deficits caused by OVX, alcohol, or their combination.

Conclusions: Bone loss following OVX can be significantly increased by concurrent binge alcohol treatment. The effects of alcohol and OVX are compensated by concurrent intermittent treatment with PTH. These results suggest that postmenopausal women who abuse alcohol may place their skeleton at additional risk for osteoporotic fracture.

Fig. 1

Rat vertebral trabecular bone mineral density analysis. (A) Two weeks of treatment. (B) Four weeks of treatment: ^ap<0.05 compared with sham–saline group; ^bp<0.05 compared with sham alcohol group; ^cp<0.05 compared with ovriectomized–saline group, 1-way ANOVA and Tukey’s multiple comparison procedure; ^dp<0.05; ^ep<0.01; ^fp<0.001 compared with its respective non-PTH group, Student’s t test.

Fig. 2

Rat vertebral cortical bone mineral density analysis. (A) Two weeks of treatment. (B) Four weeks of treatment: ^ap<0.05 compared with sham–saline group, 1-way ANOVA and Tukey’s multiple comparison procedure; ^dp<0.05; ^ep<0.01; ^fp<0.001 compared with its respective non-PTH group; Student’s t-test.

Fig. 3

Rat vertebral compressive strength analysis. (A) Two weeks of treatment. (B) Four weeks of treatment: ^ap<0.05 compared with sham–saline group, 1-way ANOVA and Tukey’s multiple comparison procedure; ^dp<0.05; ^ep<0.01; ^fp<0.001 compared with its respective non-parathyroid hormone group, Student’s t test.

Fig. 4

Visualization of rat vertebral trabecular architecture using 3-dimensional micro-computed tomography. All specimens depicted after 4 weeks of treatment. (A–D) No parathyroid hormone (PTH) treatment. (E–H) With PTH treatment.

Fig. 5

Rat vertebral BV/TV analysis. (A) Two weeks of treatment. (B) Four weeks of treatment: ^ap<0.05 compared with sham–saline group, 1-way ANOVA and Tukey’s multiple comparison procedure; ^ep<0.01; ^fp<0.001 compared with its respective non-parathyroid hormone group, Student’s t test.