Alcohol Abuse and Osteoporosis By Daniel Schapira INDEX WORDS:
Alcoholism;
osteoporosis.
0
STEOPOROSIS is a clinical condition characterized by a reduced amount of bone per unit volume and a tendency to fracture bone with only moderate trauma.’ It is the most common skeletal disorder and a major health, social, and economic problem in developed countries.2 A better understanding of its pathophysiology, sophisticated new methods for measuring bone mass, and the successful combination of nutritional measures, physical activity, and drug therapy are factors that have changed the outlook on osteoporosis from pessimism to research interest and therapeutic hope.3 Alcohol abuse is defined as a pattern of pathological use that continues for at least 1 month and that impairs social or occupational functioning.4 This disaster of modern society involves up to 10% of the mature population, its incidence continuously increasing among adolescents of both sexes.536Besides deleterious effects on the gastrointestinal, hepatic, cardiovascular, hematopoietic, genitourinary, and neuromuscular systems, prolonged use of excessive alcohol may affect bone metabolism.’ Chronic alcoholism is associated with aseptic necrosis (osteonecrosis) of the hip and with peripheral neuroarthropathies.8*9 The object of this study is to elucidate the effects of alcohol on bone and to inculpate chronic alcohol abuse as a cumulative, but potentially remediable, risk factor for osteoporosis.
in the production of acetaldehyde, considered to be noxious to various body tissues, which is oxidized to acetate.” NUTRITION AND ALCOHOL
Malnutrition is often present in chronic alcoholics as assessed from dietary histories, anthropometric measures (weight to height ratio, mid arm circumference, skinfold thickness, and lean muscle mass) and biochemical indices. Its etiology is multifactorial. Alcohol provides 29.8 kJ/g. Its abuse may supply a main part of the daily energy requirements of a mature person. However, it does not supply equivalent caloric food value and contains only minimal amounts of nutrients and minerals, inadequate for daily requirements.” Poor dietary intake is common among alcoholics so that alcoholism is considered by some as the major cause of malnutrition in the western world.‘2,‘3 Frequent nonspecific digestive disorders, malabsorption (due to hyperosmolarity and accelerated intestinal transit), direct deleterious effects of alcohol on the intestinal mucosa, inhibition of pancreatic and biliary excretion, and impaired nutrient metabolism (alcohol induced inhibition of albumin synthesis, of gluconeogenesis, of protein release from the liver and of vitamin D use),-all contribute to the malnutrition of chronic alcoholism.14-‘7 These changes may be partially reversed by alcohol abstinence.‘* CHRONIC EFFECTS OF ALCOHOL ON BONE-ETIOLOGICAL
ABSORPTION AND METABOLISM
FACTORS
OF ETHANOL
Ethanol is a molecule that easily moves through cell membranes. It is absorbed (in decreasing amounts) from the proximal portion of the small intestine, the stomach, the large intestine, the buccal and esophageal mucosa and it rapidly equilibrates between blood and tissues. Gastric emptying as well as the absence of nutrients such as fats, carbohydrates, or proteins enhance the absorption of alcohol. Ethanol is predominately metabolized by the liver. It involves two main routes, dehydrogenation of alcohol in the cell cytosol and ethanol oxidation in the microsomes of the smooth endoplasmic reticulum. Both result
Seminars in Arthritis and Rheumatism, Vol 19, No 6 (June), 1990:
Bone and mineral metabolism are disturbed during prolonged alcohol excess. Several factors are responsible for the resulting osteoporosis or osteomalacia:
From the Department of Rheumatology, Rambam Medical Center, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Daniel Schapira, MD: Consultant in Rheumatology. Address reprint requests to: Daniel Schapira, MD. The B Shine Department of Rheumatology. Rambam Medical Center, Haifa 35254, Israel. 0 1990 by W.B. Saunders Company. 0049-0172/90/1906-0006%5.0000/0
pp 37 l-376
371
372
Disturbances of Mineral Metabolism
Calcium is a main constituent of bone and more than 99% of the mineral in the body is concentrated in the skeleton. Adequate calcium intake is important for skeletal health and integrity. The impact of dietary calcium on skeletal mass is maximal in childhood, adolescence and early adulthood. Nevertheless it seems to have a beneficial influence on the prevention of osteoporosis during the second half of life.‘9,20Milk and dairy products are the main dietary source of calcium. In alcoholics, calcium deficient diets are part of the general malnutrition and calcium malabsorption is present along with impaired absorption of other nutrients and minerals. These factors seem to be the main causes of low body calcium. However, calcium deficiency may be potentiated by the following mechanisms: hypomagnesemia, frequently encountered in alcohol abusers through impaired production and release of parathyroid hormone (PTH), decreases intestinal calcium absorption and results in hypocalcemia21’22; low protein diet (which may be responsible for reduced bone formation and enhanced bone loss) diminishes intestinal absorption of calcium23; furthermore, since serum calcium is highly bound to albumin, decreased serum albumin may also contribute to hypocalcemia24; and, phosphate, the other significant component of bone mineral, may be depleted because of inadequate intake, chronic antacid abuse, and malabsorption.25 Excessive use of antacids also enhances hypercalciuria. 26Increased urinary loss of minerals (calcium, phosphate, and magnesium) occurs during chronic or sporadic alcohol ingestion.27*28 In patients with alcohol associated hypertension, a common problem among heavy drinkers, serum phosphate and ionized calcium concentration decrease, while urinary excretion increases.29 The magnitude of hypercalciuria is a valuable marker for estimating the severity of alcohol dependence.”
DANIEL SCHAPIRA
irradiation, diminished dietary intake,33,34chronic liver disease, intestinal malabsorption,35 a low capacity of formation of 250H D, and an accelerated rate of cholecalciferol metabolism.36 The literature is contradictory concerning the impact of hepatic damage and of its extent on vitamin D mediated skeletal metabolism.37v38Total vitamin D metabolite measurements may be misleading in evaluating vitamin D status of patients with liver disease; determination of serum free 250H D levels is recommended.39 Osteoporosis, osteomalacia, or both are the histological manifestations of deficient bone metabolism in chronic alcoholism, in which vitamin D deficiency plays a major ro1e.7S40g41 Osteoporosis is the predominant bone condition in most patients with cirrhosis.42v43 Parathyroid hormone mediated bone resorption is another cause of decreased bone density.44 Parathyroid hormone levels increase during acute alcohol ingestion,45 abnormal secretion being attributed to hypomagnesemia and to deficient 250H D levels.32 Increased serum corticosteroids levels are associated with negative calcium balance.46 With chronic alcohol abuse adrenal hyperplasia and increased levels of plasma cortisol occur. A pseudo Cushing syndrome results, characterized by elevated plasma cortisol levels that normalize following alcohol withdrawal, insufficient suppression by the administration of 1 mg to 2 mg of dexamethasone, and the absence of a diurnal rhythm.47348 Testosterone deficiency is associated with osteopenia.49 During short- and long-term alcohol ingestion reduced levels of serum testosterone are found in linear correlation with trabecular bone volume and with increased urinary hydroxyproline excretion rates. 50~5’A direct effect of alcohol on the testicles results in decreased production of anabolic steroids.52 Clinical and laboratory findings show that these hormones do not act independently but have an added deleterious effect on bone tissue.
Impaired Hormonal Metabolism
Vitamin D affects the homeostasis of calcium through intestinal absorption, bone resorption, and renal reabsorption. 31 In chronic alcoholics serum levels of vitamin D metabolites are reduced.32*33This deficiency is attributed to several factors including: reduced exposure to solar
Toxic Effect of Alcohol on Bone Tissue
A direct toxic effect of alcohol on bone tissue has been reported in human and animal studies. This results in reduced bone formations (represented by lesser osseous matrix, osteoblast perimeters, and reduced serum levels of bone
ALCOHOL ABUSE AND DSTEDF’CMOSIS
glaprotein-the vitamin K dependent protein synthesized by osteoblasts), uncoupling of the normal association between resorption and formation, increased bone resorption, diminished trabecular bone volume (TBV), and defective mineralization.7*40~s’~53~s6 Reduced bone formation and mineralization rate seem to be the main causes of osteopenia in alcoholism.57 Other investigators report severe inhibition of bone remodeling independent of the calciotropic hormones’s Other Factors
The correlation between the body muscle and bone mass is well known and physical activity is generally accepted as efficient prevention and treatment of osteoporosis.59 Reduced body weight and muscle mass, as well as physical inactivity, are considered risk factors for osteoporosis. Some studies found that alcoholic patients are leaner than controls.60 Also, the medical consequences of alcoholism may prevent regular physical activity in part of this population. In cases of chronic alcoholic myopathy, muscle weakness and atrophy may contribute to reduced bone mass.6’ Increased bone loss in the appendicular skeleton occurs in chronic smokers, attributable to depressed plasma estrogen or testosterone levels. Heavy smoking is commonly associated with chronic alcohol abuse.* Both addictions have a negative influence on bone formation, probably a result of defective osteoblastosis6* As mentioned, aluminum containing antacid may induce osteoporosis by inducing calcium loss. The deleterious effect of this metal on osteoblast function may further inhibit bone formation.63 Excessive use of antacids by alcoholics enhances bone loss in this population.M ALCOHOL ABUSE-A “IDIOPATHIC”
RISK FACTOR FOR
373
degree of osteoporosis, the cumulative dietary and social risk factors for alcoholism, and the severity of liver disease correlate positively.‘.(” The classification of involutional osteoporosis into senile and postmenopausal types has camouflaged the existence of osteopenia in relatively young men. Idiopathic osteoporosis has been reported in young men but alcohol was not incriminated as a precipitating factor.68.69Other studies have shown reduced bone mass and skeletal demineralization in male alcoholics. In nearly half of chronic alcohol abusers, one third of whom were younger than 50 years, extensive radiological bone loss was demonstrated; and in some cases osteoporosis was histologically confirmed.” Vice versa, alcohol use was more prevalent and individual consumption greater in a large cohort of male patients with vertebral fractures than in the control group. Alcohol related bone loss adds to that induced by aging. Fracture risk is increased by the other cumulative risk factors for osteoporosis.” CLINICAL REFLECTIONS
Fractures are the ominous hallmark of advanced osteoporosis, and an increased fracture frequency is found with chronic alcoholism.7’~73 Usually fractures are attributed to trauma due to confusional states, neurological and musculoskeleta1 disturbances, hypoglycemia, or seizures following alcohol withdrawal.24 Alcohol inducedosteopenia increases the frequency of spontaneous fractures or that associated with minimal trauma.67’7676 Alcohol consumption augments the risk of fracture in patients with disturbances of calcium and bone metabolism. Alcohol-related traumatic and spontaneous fractures constitute an important health problem and a significant economic burden to society.”
OSTEOPOROSIS
Unlike some systemic medical disorders caused by chronic alcoholism, osteoporosis may advance for many years without clinical manifestations; therefore, this condition may be overlooked or forgotten.6s The incidence and the severity of osteoporosis among alcoholics is increased. Chronic alcohol abusers of both sexes have reduced axial and appendicular bone mass as compared with the normal population.60*M*67 Alcohol-associated osteopenia may appear at a relatively young age and progress with time. The
PREVENTION AND TREATMENT
The prevention and treatment of osteoporosis in alcoholics are similar to idiopathic osteoporosis. Nevertheless, several points deserve emphasis. Osteoporosis should be suspected in every chronic alcohol abuser, regardless of the other medical consequences of alcoholism. Sporadic alcohol ingestion should arouse suspicion. Osteoporosis should be diagnosed by techniques for precise bone mass and bone mineral measure-
374
DANIEL SCHAPIRA
ment. Patients with “idiopathic” osteoporosis should be routinely and thoroughly questioned about drinking habits. Once a connection between alcohol overuse and osteoporosis has been established the following measures are recommended: medical and psychiatric treatment may interrupt the cycle of chronic alcohol ingestion and diminish the risk of further skeletal deterioration; the patient should be given adequate social and economic support. A careful dietary history should be followed by an adequate, wellbalanced diet, rich in milk and calcium containing products. Exposure to sunlight and physical exercise should be encouraged. Excessive antacid and tobacco use should be avoided. Other risk factors for osteoporosis should be identified and minimized. If senile or postmenopausal osteoporosis is present concomittantly specific treatments (calcium supplements, estrogen, fluoride, calcitonin, etc) are prescribed. The personality disturbances and low compliance of some alcohol abusers reduces the therapeutic success ratio.78*79 Nervous system and liver function improve-
ment are possible beneficial effects of alcohol abstinence.24’80 However, the effects of ethanol withdrawal on bone tissue are uncertain. Elevated serum bone glaprotein levels and histological parameters of increased bone formation were found in alcoholic abstainers as compared with active drinkers. Bone mineral content, bone density, and the histological parameters of bone resorption did not change; however, the relatively short period of abstinence makes these results unconclusive.51v33 CONCLUSIONS
The relation between chronic alcoholism and osteoporosis is not fortuitous. The link between these two widespread conditions is supported by biochemical, histological, and clinical evidence. Osteoporosis should be suspected in alcohol abusers and alcohol dependence should be considered in osteoporotic patients. Alcohol is detrimental to skeletal integrity and its abuse is an important risk factor for the development of osteoporosis. The influence of alcohol withdrawal on bone tissue is uncertain.
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12. Hillman RW: Social aspects of alcoholism, in Kissin B Begleitedt (eds): The Biology of Alcoholism (vol 4). New York, NY, Plenum Press, 1976, pp 515-586 13. Lieber S: Medical Disorders of Alcoholism: Pathogenesis and Treatment. Philadelphia, PA, Saunders, 1982 14. Mott CB, Sarles M, Tiscornia 0, et al: Inhibitory action of alcohol on human exocrine pancreatic secretion. Am J Dig Dis 17:902-910, 1972 15. Morgan M, Sherlock S: Sex related differences among 100 patients with alcoholic liver disease. Br Med J 1:939-941, 1977 16. Lieber CS: The influence of alcohol on nutritional status. Nutr Rev 46:241-254, 1988 17. Rothshild MA, Oratz M, Schreiber SS: Alcohol, aminoacids and albumin synthesis. Gastroenterology 67: 12001213,1974 18. Halstead CH, Robles EA, Mezey E: Decreased jejunal uptake of labeled folic acid (3H-PGA) in alcoholic patients: role of alcohol and nutrition. N Engl J Med 285:701-706, 1971 19. Sandler RB, Slemenda CW, LaPorte RE, et al: Postmenopausal bone density and milk consumption in childhood and adolescence. Am J Clin Nutr 42:270-274,1985 20. Marcus R: Calcium intake and skeletal integrity. Is there a critical relationship? J Nutr 117:631-635, 1986 21. Rude RK, Oldham SB, Singer FR: Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency. Clin Endocrinol5:209-224, 1976
ALCOHOL ABUSE AND OSTEOPOROSIS
22. Wolfe SM, Victor M: The relationship of hypomagnesemia and alkalosis to alcohol withdrawal symptoms. Ann NY Acad Sci 162:973-984,1969 23. McChance RA, Widdowson EM, Lehmann H: The effect of protein intake on the absorption of calcium and magnesium. Biochem J 36:686-691,1942 24. Hodges DL, Nanda Kumar V, Redford JB: Effects of alcohol on bone, muscle and nerve. Am Fam Physician 34:149-156, 1986 25. Stein JH, Smith WO, Ginn HE: Hypophosphatemia in acute alcoholism. Am J Bed Sci 252:78-83, 1966 26. Spencer H, Kremer L: Antacid induced calcium loss. Arch Intern Med 143:657-659,1983 (edit) 27. Kalbfleish JB, Lindenman RD, Ginn HE et al: Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subjects. J Clin Invest 42:1471-1475.1963 28. McDonald JT, Margen S: Wine versus ethanol in human nutrition. III. Calcium, phosphorus and magnesium balance. Am J Clin Nutr 32:823-833, 1979 29. De Marchi S, Cecchin E, Renzo C et al: Calcium and alcohol induced hypertension. Ann Intern Med 104:728, 1986 30. De Marchi S, Basile A, Grimaldi F et al: Fractures and hypercalciuria: two markers of severe dependence in alcoholics. Br Med J 288:1457-1458, 1984 3 1. Deluca HF, Schnoes HK: Vitamin D: recent advances. Ann Rev Biochem 52:41 l-430,1983 32. Editorial: Hepatic osteomalacia and Vitamin D. Lancet 1:943-944, 1982 33. Feitelberg S, Epstein S, Ismail F, et al: Deranged bone mineral metabolism in chronic alcoholism. Metabolism 36: 322-326,1987 34. Dibble JB, Losowsky MS: Osteomalacia in chronic liver disease. Br Med J 285:157-158, 1982 35. Meyer M, Wechsler S, Shibolet S, et al: Malabsorption of Vitamin D in man and rat with liver cirrhosis. J Mel Med 3:29-37, 1978 36. Jung RT, Davie M, Hunter JO, et al: Abnormal Vitamin D metabolism in cirrhosis. Gut 19:290-293, 1978 37. Summerskill WHJ, Kelle PJ: Osteoporosis with fractures in anicteric cirrhosis: Observations supplemented by microradiographie evaluation of bone. Proc Mayo Clin 38:162l74,1963 38. Paterson CR, Losowsky MS: The bones in chronic liver disease. Stand J Gastroenterol2:293-300, 1967 39. Bikle DD, Halloran BP, Gee E, et al: Free 25hydroxyvitamin D levels are normal in subjects with liver disease and reduced total 25-hydroxivitamin D levels. J Clin Invest 78:748-752,1986 40. Verbanck M, Verbanck J, Brauman J, et al: Bone histology and 25-OH vitamin D plasma levels in alcoholics without cirrhosis. Calcif Tiss Res 22:538-541, 1977 41. Long RG, Meinhard E, Skinner RK, et al: Clinical biochemical and histological studies of osteomalacia, osteoporosis and parathyroid function in chronic liver disease. Gut 19:85-90,1978 42. Matloff DS, Kaplan MM, Neer RM, et al: Osteoporosis in primary biliary cirrhosis: Effects of 25hydroxyvitamin D treatment. Gastroenterology 83:97-102, 1982
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43. Mobarhan SA, Russell RM, Reeker RR, et al: Metabolic bone disease in alcoholic cirrhosis: A comparison of the effect of vitamin D2, 23-hydroxyvitamin D3. or supportive treatment. Hepatology 4:266-273, 1984 44. Raisz LG: Bone metabolism and its hormonal regulation: An update. Triangle 27:5-10, 1988 45. Williams GA, Bowser EN, Hargis GK, et al: Effect of ethanol on parathyroid hormone and calcitonin secretion in man. Proc Sot Exp Biol Med 159:187-191, 1978 46. Gallagher JC, Aaron J, Horsman A, et al: Corticosteroid osteoporosis. Clin Endocrinal Metab 2:355-362, 1973 47. Mendelson JH, Ogata M, Mello NK: Adrenal function and alcoholism. I. Serum cortisol. Psychosom Med 33:145-157,1971 48. Lamberts SWJ, Klijn JG, de Jong FH, et al: Hormone secretion in alcohol induced pseudo-Cushing syndrome. Differential diagnosis with Cushing disease. JAM A 242: 16401643.1979 49. Jackson JA, Kleerekoper M, Parfitt AM, et al: Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis. J Clin Endocrinal Met 65:53-58, 1984 50. Chappard D, Alexandre C, Fraisse H, et al: L’os du cirrhotique. Relation entre la masse osseuse et Ia testosteronemie. Nouv Presse Med 12:524, 1983 5 1. Diamond T, Stiel D, Lunzer M, et al: Ethanol reduces bone formation and may cause osteoporosis. Am J Med 86:282-287, 1989 52. Anderson RA, Willis BR, Oswald C, et al: Hormonal imbalance and alteration: Testicular morphology induced by chronic ingestion of ethanol. Biochem Pharmacol 29:14091419,198O 53. Baron DT, Teitelbaum SL, Berfield MA, et al: Effects of alcohol ingestion on bone and mineral metabolism in rats. Am J Physiol238:E507-E510, 1980 54. Duquesnoy B, Noel C, Hubaud P, et al: Metabolisme phosphocalcique et histomorphometrie osseuse dans I’ethylisme chronique. Revue du Rheumatisme 5 1:75-80, 1984 55. Bell NH, Turner RT, Greene VS: Demonstration that ethanol inhibits bone matrix synthesis and mineralization in the rat, in Cohn DV, Martin T, Meunier PT (eds): Calcium Regulation and Bone Metabolism. Amsterdam. Excerpta Medica 1987, p 636 56. Crilly RG, Anderson C, Hogan D, et al: Bone histomorphometry, bone mass and related parameters in alcoholic males. Calcif Tiss Int 43:269-276, 1988 57. Schnitzler CM, Solomon L: Bone changes after alcohol abuse. S Afr Med J 66:730-734, 1984 58. Bikle DD, Genant HK, Cann C, et al: Bone disease in alcohol abuse. Ann Intern Med 103:42-48, 1985 59. Schapira D: Physical exercise in the prevention and treatment of osteoporosis: A review. J R Sot Med 81:461463,1988 60. Wilson BE, Westlin NE: Changes in bone mass in alcoholics. Clin Orthop Rel Res 90:229-232, 1973 61. Hudgson P: Alcoholic myopathy. Br Med J 288:584585,1984 62. de Vernejoul MC, Bielakoff J, Herve M et al: Evidence for defective osteoblastic function. A role of alcohol and
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tobacco consumption in osteoporosis in middle aged men. ClinOrthopRelRes 179:107-115, 1983 63. de Vernejoul MC, Belenguer R, Halkidou H, et al: Histomorphometric evidence of deleterious effect of aluminium on osteoblasts. Metab Bone Dis Rel Res 6:15-20, 1985 64. Spencer H, Kramer L, Norris C, et al: Effect of small doses of aluminum-containing antacids on calcium and phosphorous metabolism. Am J Clin Nutr 36:32-40, 1982 65. Miller NS, Gold MS, Cocores JA: Alcohol dependence and its medical consequences. NY State J Med 88:476-481, 1988 66. Saville PD: Changes in bone mass with age and alcoholism. J Bone Joint Surg (Am) 47:492-499,1965 67. Dalen N, Feldreich AL: Osteopenia in alcoholism. Clin Orthop Rel Res 99:201-202, 1974 68. Jackson WP: Osteoporosis of unknown cause in younger people: Idiopathic osteoporosis. J Bone J Surg 40B:420-441, 1958 69. Perry HM III, Fallon MD, Bergfeld M, et al: Osteoporosis in young men: A syndrom of hypercalciuria and accelerated bone turnover. Arch Intern Med 142:1295-1298, 1982 70. Spencer H, Rubio N, Rubio R, et al: Chronic alcoholism. A frequently overlooked cause of osteoporosis in men. Am J Med 80:393-397.1986 71. Seeman E, Melton LJ III, O’Fallon WW, et al: Risk
factors for spinal osteoporosis 1983
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72. Nilsson BE: Conditions contributing to fractures the femoral neck. Acta Chir Stand 136:383-384, 1970
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Ann
75. Honkanen R, Visuri T: Blood alcohol levels in a series of injured patients with special references to accident and type of injury. Ann Chir Gynaec 65:287-294,1976 76. Israel Y, Orrego H, Holt S, et al: Identification of alcohol abuse: thoracic fractures, routine chest x-ray as an indication of alcoholism. Alcoholism 4:420-422, 1980 77. Holden C: Alcoholism and the medical Science235:1132-1133, 1987 78. Schuckit 64:78-84, 1978
MA: The disease alcoholism.
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79. Mossberg D, Liljeberg P, Borg S: Clinical conditions in alcoholics during long term abstinence: A descriptive longitudinal study. Alcohol 2:551-553, 1985 80. Martini GA, Teschke R: Alcohol abstinence in alcoholic liver disease. Acta Med Stand 703:185-194, 1985 (suppl)
Alcoholism;
osteoporosis.
0
STEOPOROSIS is a clinical condition characterized by a reduced amount of bone per unit volume and a tendency to fracture bone with only moderate trauma.’ It is the most common skeletal disorder and a major health, social, and economic problem in developed countries.2 A better understanding of its pathophysiology, sophisticated new methods for measuring bone mass, and the successful combination of nutritional measures, physical activity, and drug therapy are factors that have changed the outlook on osteoporosis from pessimism to research interest and therapeutic hope.3 Alcohol abuse is defined as a pattern of pathological use that continues for at least 1 month and that impairs social or occupational functioning.4 This disaster of modern society involves up to 10% of the mature population, its incidence continuously increasing among adolescents of both sexes.536Besides deleterious effects on the gastrointestinal, hepatic, cardiovascular, hematopoietic, genitourinary, and neuromuscular systems, prolonged use of excessive alcohol may affect bone metabolism.’ Chronic alcoholism is associated with aseptic necrosis (osteonecrosis) of the hip and with peripheral neuroarthropathies.8*9 The object of this study is to elucidate the effects of alcohol on bone and to inculpate chronic alcohol abuse as a cumulative, but potentially remediable, risk factor for osteoporosis.
in the production of acetaldehyde, considered to be noxious to various body tissues, which is oxidized to acetate.” NUTRITION AND ALCOHOL
Malnutrition is often present in chronic alcoholics as assessed from dietary histories, anthropometric measures (weight to height ratio, mid arm circumference, skinfold thickness, and lean muscle mass) and biochemical indices. Its etiology is multifactorial. Alcohol provides 29.8 kJ/g. Its abuse may supply a main part of the daily energy requirements of a mature person. However, it does not supply equivalent caloric food value and contains only minimal amounts of nutrients and minerals, inadequate for daily requirements.” Poor dietary intake is common among alcoholics so that alcoholism is considered by some as the major cause of malnutrition in the western world.‘2,‘3 Frequent nonspecific digestive disorders, malabsorption (due to hyperosmolarity and accelerated intestinal transit), direct deleterious effects of alcohol on the intestinal mucosa, inhibition of pancreatic and biliary excretion, and impaired nutrient metabolism (alcohol induced inhibition of albumin synthesis, of gluconeogenesis, of protein release from the liver and of vitamin D use),-all contribute to the malnutrition of chronic alcoholism.14-‘7 These changes may be partially reversed by alcohol abstinence.‘* CHRONIC EFFECTS OF ALCOHOL ON BONE-ETIOLOGICAL
ABSORPTION AND METABOLISM
FACTORS
OF ETHANOL
Ethanol is a molecule that easily moves through cell membranes. It is absorbed (in decreasing amounts) from the proximal portion of the small intestine, the stomach, the large intestine, the buccal and esophageal mucosa and it rapidly equilibrates between blood and tissues. Gastric emptying as well as the absence of nutrients such as fats, carbohydrates, or proteins enhance the absorption of alcohol. Ethanol is predominately metabolized by the liver. It involves two main routes, dehydrogenation of alcohol in the cell cytosol and ethanol oxidation in the microsomes of the smooth endoplasmic reticulum. Both result
Seminars in Arthritis and Rheumatism, Vol 19, No 6 (June), 1990:
Bone and mineral metabolism are disturbed during prolonged alcohol excess. Several factors are responsible for the resulting osteoporosis or osteomalacia:
From the Department of Rheumatology, Rambam Medical Center, and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Daniel Schapira, MD: Consultant in Rheumatology. Address reprint requests to: Daniel Schapira, MD. The B Shine Department of Rheumatology. Rambam Medical Center, Haifa 35254, Israel. 0 1990 by W.B. Saunders Company. 0049-0172/90/1906-0006%5.0000/0
pp 37 l-376
371
372
Disturbances of Mineral Metabolism
Calcium is a main constituent of bone and more than 99% of the mineral in the body is concentrated in the skeleton. Adequate calcium intake is important for skeletal health and integrity. The impact of dietary calcium on skeletal mass is maximal in childhood, adolescence and early adulthood. Nevertheless it seems to have a beneficial influence on the prevention of osteoporosis during the second half of life.‘9,20Milk and dairy products are the main dietary source of calcium. In alcoholics, calcium deficient diets are part of the general malnutrition and calcium malabsorption is present along with impaired absorption of other nutrients and minerals. These factors seem to be the main causes of low body calcium. However, calcium deficiency may be potentiated by the following mechanisms: hypomagnesemia, frequently encountered in alcohol abusers through impaired production and release of parathyroid hormone (PTH), decreases intestinal calcium absorption and results in hypocalcemia21’22; low protein diet (which may be responsible for reduced bone formation and enhanced bone loss) diminishes intestinal absorption of calcium23; furthermore, since serum calcium is highly bound to albumin, decreased serum albumin may also contribute to hypocalcemia24; and, phosphate, the other significant component of bone mineral, may be depleted because of inadequate intake, chronic antacid abuse, and malabsorption.25 Excessive use of antacids also enhances hypercalciuria. 26Increased urinary loss of minerals (calcium, phosphate, and magnesium) occurs during chronic or sporadic alcohol ingestion.27*28 In patients with alcohol associated hypertension, a common problem among heavy drinkers, serum phosphate and ionized calcium concentration decrease, while urinary excretion increases.29 The magnitude of hypercalciuria is a valuable marker for estimating the severity of alcohol dependence.”
DANIEL SCHAPIRA
irradiation, diminished dietary intake,33,34chronic liver disease, intestinal malabsorption,35 a low capacity of formation of 250H D, and an accelerated rate of cholecalciferol metabolism.36 The literature is contradictory concerning the impact of hepatic damage and of its extent on vitamin D mediated skeletal metabolism.37v38Total vitamin D metabolite measurements may be misleading in evaluating vitamin D status of patients with liver disease; determination of serum free 250H D levels is recommended.39 Osteoporosis, osteomalacia, or both are the histological manifestations of deficient bone metabolism in chronic alcoholism, in which vitamin D deficiency plays a major ro1e.7S40g41 Osteoporosis is the predominant bone condition in most patients with cirrhosis.42v43 Parathyroid hormone mediated bone resorption is another cause of decreased bone density.44 Parathyroid hormone levels increase during acute alcohol ingestion,45 abnormal secretion being attributed to hypomagnesemia and to deficient 250H D levels.32 Increased serum corticosteroids levels are associated with negative calcium balance.46 With chronic alcohol abuse adrenal hyperplasia and increased levels of plasma cortisol occur. A pseudo Cushing syndrome results, characterized by elevated plasma cortisol levels that normalize following alcohol withdrawal, insufficient suppression by the administration of 1 mg to 2 mg of dexamethasone, and the absence of a diurnal rhythm.47348 Testosterone deficiency is associated with osteopenia.49 During short- and long-term alcohol ingestion reduced levels of serum testosterone are found in linear correlation with trabecular bone volume and with increased urinary hydroxyproline excretion rates. 50~5’A direct effect of alcohol on the testicles results in decreased production of anabolic steroids.52 Clinical and laboratory findings show that these hormones do not act independently but have an added deleterious effect on bone tissue.
Impaired Hormonal Metabolism
Vitamin D affects the homeostasis of calcium through intestinal absorption, bone resorption, and renal reabsorption. 31 In chronic alcoholics serum levels of vitamin D metabolites are reduced.32*33This deficiency is attributed to several factors including: reduced exposure to solar
Toxic Effect of Alcohol on Bone Tissue
A direct toxic effect of alcohol on bone tissue has been reported in human and animal studies. This results in reduced bone formations (represented by lesser osseous matrix, osteoblast perimeters, and reduced serum levels of bone
ALCOHOL ABUSE AND DSTEDF’CMOSIS
glaprotein-the vitamin K dependent protein synthesized by osteoblasts), uncoupling of the normal association between resorption and formation, increased bone resorption, diminished trabecular bone volume (TBV), and defective mineralization.7*40~s’~53~s6 Reduced bone formation and mineralization rate seem to be the main causes of osteopenia in alcoholism.57 Other investigators report severe inhibition of bone remodeling independent of the calciotropic hormones’s Other Factors
The correlation between the body muscle and bone mass is well known and physical activity is generally accepted as efficient prevention and treatment of osteoporosis.59 Reduced body weight and muscle mass, as well as physical inactivity, are considered risk factors for osteoporosis. Some studies found that alcoholic patients are leaner than controls.60 Also, the medical consequences of alcoholism may prevent regular physical activity in part of this population. In cases of chronic alcoholic myopathy, muscle weakness and atrophy may contribute to reduced bone mass.6’ Increased bone loss in the appendicular skeleton occurs in chronic smokers, attributable to depressed plasma estrogen or testosterone levels. Heavy smoking is commonly associated with chronic alcohol abuse.* Both addictions have a negative influence on bone formation, probably a result of defective osteoblastosis6* As mentioned, aluminum containing antacid may induce osteoporosis by inducing calcium loss. The deleterious effect of this metal on osteoblast function may further inhibit bone formation.63 Excessive use of antacids by alcoholics enhances bone loss in this population.M ALCOHOL ABUSE-A “IDIOPATHIC”
RISK FACTOR FOR
373
degree of osteoporosis, the cumulative dietary and social risk factors for alcoholism, and the severity of liver disease correlate positively.‘.(” The classification of involutional osteoporosis into senile and postmenopausal types has camouflaged the existence of osteopenia in relatively young men. Idiopathic osteoporosis has been reported in young men but alcohol was not incriminated as a precipitating factor.68.69Other studies have shown reduced bone mass and skeletal demineralization in male alcoholics. In nearly half of chronic alcohol abusers, one third of whom were younger than 50 years, extensive radiological bone loss was demonstrated; and in some cases osteoporosis was histologically confirmed.” Vice versa, alcohol use was more prevalent and individual consumption greater in a large cohort of male patients with vertebral fractures than in the control group. Alcohol related bone loss adds to that induced by aging. Fracture risk is increased by the other cumulative risk factors for osteoporosis.” CLINICAL REFLECTIONS
Fractures are the ominous hallmark of advanced osteoporosis, and an increased fracture frequency is found with chronic alcoholism.7’~73 Usually fractures are attributed to trauma due to confusional states, neurological and musculoskeleta1 disturbances, hypoglycemia, or seizures following alcohol withdrawal.24 Alcohol inducedosteopenia increases the frequency of spontaneous fractures or that associated with minimal trauma.67’7676 Alcohol consumption augments the risk of fracture in patients with disturbances of calcium and bone metabolism. Alcohol-related traumatic and spontaneous fractures constitute an important health problem and a significant economic burden to society.”
OSTEOPOROSIS
Unlike some systemic medical disorders caused by chronic alcoholism, osteoporosis may advance for many years without clinical manifestations; therefore, this condition may be overlooked or forgotten.6s The incidence and the severity of osteoporosis among alcoholics is increased. Chronic alcohol abusers of both sexes have reduced axial and appendicular bone mass as compared with the normal population.60*M*67 Alcohol-associated osteopenia may appear at a relatively young age and progress with time. The
PREVENTION AND TREATMENT
The prevention and treatment of osteoporosis in alcoholics are similar to idiopathic osteoporosis. Nevertheless, several points deserve emphasis. Osteoporosis should be suspected in every chronic alcohol abuser, regardless of the other medical consequences of alcoholism. Sporadic alcohol ingestion should arouse suspicion. Osteoporosis should be diagnosed by techniques for precise bone mass and bone mineral measure-
374
DANIEL SCHAPIRA
ment. Patients with “idiopathic” osteoporosis should be routinely and thoroughly questioned about drinking habits. Once a connection between alcohol overuse and osteoporosis has been established the following measures are recommended: medical and psychiatric treatment may interrupt the cycle of chronic alcohol ingestion and diminish the risk of further skeletal deterioration; the patient should be given adequate social and economic support. A careful dietary history should be followed by an adequate, wellbalanced diet, rich in milk and calcium containing products. Exposure to sunlight and physical exercise should be encouraged. Excessive antacid and tobacco use should be avoided. Other risk factors for osteoporosis should be identified and minimized. If senile or postmenopausal osteoporosis is present concomittantly specific treatments (calcium supplements, estrogen, fluoride, calcitonin, etc) are prescribed. The personality disturbances and low compliance of some alcohol abusers reduces the therapeutic success ratio.78*79 Nervous system and liver function improve-
ment are possible beneficial effects of alcohol abstinence.24’80 However, the effects of ethanol withdrawal on bone tissue are uncertain. Elevated serum bone glaprotein levels and histological parameters of increased bone formation were found in alcoholic abstainers as compared with active drinkers. Bone mineral content, bone density, and the histological parameters of bone resorption did not change; however, the relatively short period of abstinence makes these results unconclusive.51v33 CONCLUSIONS
The relation between chronic alcoholism and osteoporosis is not fortuitous. The link between these two widespread conditions is supported by biochemical, histological, and clinical evidence. Osteoporosis should be suspected in alcohol abusers and alcohol dependence should be considered in osteoporotic patients. Alcohol is detrimental to skeletal integrity and its abuse is an important risk factor for the development of osteoporosis. The influence of alcohol withdrawal on bone tissue is uncertain.
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