Effects of parathyroid hormone on bone formation in a rat model for chronic alcohol abuse.
BACKGROUND
Alcoholism is a risk factor for osteoporosis and it is not clear whether the detrimental effects of alcohol on bone are reversible. Parathyroid hormone (PTH) is a potent stimulator of bone matrix synthesis and is being investigated as a therapeutic agent to reverse bone loss. The present investigation was designed to determine the effects of PTH on bone formation in a rat model for chronic alcohol abuse.


RESULTS
Alcohol was administered in the diet of female rats (35% caloric intake) for 2 weeks. Human (1-34) PTH (80 microg/kg/day) was administered subcutaneously during the second week of the study. Alcohol resulted in a transient reduction in steady-state mRNA levels for the bone matrix proteins type 1 collagen, osteocalcin, and osteonectin compared with rats that were fed an alcohol-free (control) diet. As expected, alcohol decreased and PTH increased histologic indices of bone formation. Additionally, two-way ANOVA demonstrated that alcohol antagonized PTH-induced bone formation. Despite antagonism, bone formation and mRNA levels for bone matrix proteins in alcohol-fed rats treated with PTH greatly exceeded the values in rats fed the control diet.


CONCLUSIONS
The results of this study contribute to a growing body of evidence that alcohol-induced bone loss is primarily due to reduced bone formation. We conclude that alcohol does not prevent the stimulatory effects of PTH on bone formation. This is evidence that the effects of alcohol on the skeleton are reversible. Additionally, the positive effects on bone formation in rats that consumed high concentrations of alcohol suggested that PTH may be useful as an intervention to treat alcohol-induced osteoporosis.
Turner
R T
RT
Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA. turner.russell@mayo.edu
Evans
G L
GL
Zhang
M
M
Sibonga
J D
JD
D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D023421:Models, Animal; D015675:Osteocalcin / Q000187:drug effects* / Q000378:metabolism; D015676:Osteonectin / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D015676:Osteonectin; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D015675:Osteocalcin; D000431:Ethanol; D003094:Collagen