Potential Mechanisms of Alcohol-Induced Bone Disease

2011

The normal growth of bone cells depends upon a variety of orchestrated factors, including adequate nutrition and the function and interaction of various hormones and intercellular regulating factors. Research in this area suggests that while the exact mechanism through which alcohol affects the integrity of the skeleton is not known, much has been learned. Even so, likely candidates have not been clearly identified.

Chronic consumption of relatively low amounts of alcohol (one to two drinks per day for women; three to four drinks per day for men) can interfere with the normal metabolism of nutrients. As a result of poor diets, impaired nutrient absorption, or increased renal excretion, alcoholics often have deficiencies in minerals such as calcium, phosphate, and magnesium, as well as low levels of vitamin D, which is necessary for the absorption of calcium from the intestinal system. However, there is little histomorphometric evidence that nutritional deficiencies related to alcohol use are a major cause of alcohol-induced bone disease.

Another candidate that may contribute to alcohol-induced bone disease is calcitonin, a peptide produced by the thyroid gland. Calcitonin inhibits bone resorption, in effect protecting bone. Some evidence suggests that the acute administration of alcohol (equal to about four drinks in a 150-pound male) increases calcitonin levels by about 38 percent three hours after consumption by nonalcoholic males. Such hypercalcitoninemia might explain why moderate intake of alcohol is associated with higher bone density. However, little is known about repeated alcohol use or how chronic alcohol affects calcitonin.

Blood calcium levels are regulated primarily through parathyroid hormone (PTH). When blood calcium levels drop, parathyroid hormone induces the release of calcium from bone and reduces renal excretion of calcium. In nonalcoholic subjects, acute alcohol consumption decreased parathyroid hormone levels three hours after drinking, but prolonged drinking for three weeks increased parathyroid hormone levels as well as serum calcium. It is still unclear how alcohol might affect parathyroid hormone and calcium in a clinical population where decreases in bone density are typically observed.

Gonadal hormones may also play a role in alcohol-induced bone disease since impaired gonadal function is a well-known risk factor for osteoporosis. Moreover, alcohol abuse has long been associated with impotence, sterility, testicular atrophy, and low testosterone in men, and menstrual disturbances, spontaneous abortions and miscarriages, impaired fertility, sexual function, and premature menopause in women. Studies in women have yielded inconsistent results. Alcohol increases estradiol, a potent form of estrogen, but this effect has only been reported in postmenopausal women who are undergoing hormone replacement therapy. Nonetheless, if moderate alcohol consumption increases estrogen, it could explain the positive relationship between alcohol use and increased bone density in women.

Chronic heavy drinking alters the growth and proliferation of many different cell types. In alcoholics, biochemical and histomorphometric studies reveal a significant impairment in osteoblastic, but not osteoclastic activity, suggesting that alcohol’s primary adverse effects on bones is through osteoblasts. Since bone remodeling and mineralization both are dependent on osteoblasts, chronic heavy alcohol consumption will ultimately reduce bone mass and consequently lead to fractures.

Alcohol may decrease osteoblast proliferation through a direct toxic mechanism or by the inhibition of intracellular signaling processes that regulate cell replication. Preprogrammed cell death (apoptosis) of some cells is enhanced by alcohol.

Alcohol reduces cell protein and deoxyribonucleic acid (DNA) synthesis in normal osteoblasts and impairs the induction of compounds called polyamines which regulate the synthesis of DNA. By disrupting the intra-cellular process that normally stimulates polyamine biosynthesis vital to osteoblast proliferation, alcohol even at low blood alcohol levels (.04 percent range) may inhibit cell division. Exogenous polyamines antagonize the inhibitory effect of alcohol on cell proliferation. Osteocalcin is a small peptide synthesized by osteoblasts. When released into the circulation, osteocalcin levels are positively correlated with histomorpho-metric parameters of bone formation in healthy individuals and patients with metabolic bone disease. Alcohol produces a dose-dependent decrease in osteocalcin levels and chronic alcoholic patients have significantly lower osteocalcin levels than controls.