methasone and insulin on the synthesis of triacylglycerois and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes. Biochem J 1986;233:151-60 14. Graham A, Bennett AJ, McLean AAM, Zammit VA, Brindley DN. Factors regulating the secretion of lysophosphatidylcholine by rat hepatocytes compared with the synthesis and secretion of phosphatidylcholine and triacylglycerol. Biochem J 1988 ;253 1687-92 15. Baisted DJ, Robinson BS, Vance DE. Albumin
stimulates the release of lysophosphatidylcholine from cultivated rat hepatocytes. Biochem J 1988 ;253 :693- 701 16. Robinson BS, Yao Z, Baisted DJ, Vance DE. Lysophosphatidylcholine metabolism and lipoprotein secretion by cultured rat hepatocytes deficient in choline. Biochem J 1989;260:207-14 17. Yao Z. Vance DE. Head group specificity i n the requirement of phosphatidylcholine biosynthesis for very low density lipoprotein secretion from cultured hepatocytes. J Biol Chem 1989;264: 11373-80
LETTER TO THE EDITOR Will Calcium Supplementation Preserve Bone Integrity? Millions of American women now take calcium supplements in tablet, capsule, pill, or liquid form. Pharmacists report more questions about calcium supplements than about any other over-the-counter medication. It is hoped that increased calcium intakes, up to or beyond the present recommended daily allowance (RDA) will delay, arrest, or even reverse “involutional osteoporosis.” If such calcium supplementation is effective, the prevalence of round back (the dowagers’ hump) should decrease, and the incidence of forearm, femoral neck, trochanteric, and vertebral fractures should go down. Stature shrinkage after the fifth decade might not be an inevitable concomitant of aging, provided that calcium supplementation is effective. Dietary calcium is obviously necessary for bone-building. As much as 100 mg per day may be incorporated into new bone during late-adolescent bone growth. Some workers suggest an even larger amount, though retention of 100 mg per day accounts for 0.15 kg of new bone in a single year. Obviously the amount of dietary calcium necessary to preserve skeletal integrity is more difficult to estimate, since bone loss takes place among older adults in all populations studied, over a wide range of calcium intakes, and in both genders. Decreased estrogen and androgen levels, de26 NUTRITION REVlEWSlVOL 48,NO llJANUARY 1990
creased activity, and changes in absorptive efficiency all complicate attempts to identify calcium intake as the key factor in osteoporosis. New evidence suggests that the age-specific incidence of bone fractures is increasing, at least in Canada, despite dietary improvements in that country.’ The so-called “dietary hypothesis,” has long been associated with the name of Christopher Nordin, and many know it simply as the Nordin hypothesis. Over a period of three decades Nordin has held that an insufficient calcium intake, long maintained, is ultimately responsible for adult bone loss. Years ago Nordin initiated multinational radiographic comparisons, under the auspices of the World Health Organization, to test this hypothesis in places where calcium intakes were low and in regions where they were high. Although Nordin has considered other relevant variables, such as estrogen loss, he continues to reiterate the Nordin hypothesis, effectively summarized in Nufrition Reviews last year.2 At almost the same time, Kanis and P a s ~ m o r e , ~ in a two-part review in the British Medical Journal came to diametrically opposite conclusions. Moreover, a new working paper,4 prepared for the British Nutrition Foundation, similarly rejects the low-calcium hypothesis and the notion that calcium supplementation would be the answer to bone loss in adults. As Kanis and Passmore3 also observed, data on bone-fractures do not support the
low-calcium hypothesis. Fracture rates are not only higher in Scandinavia and the United States and lower in places like Singapore and Durban, but the still-limited international data actually suggest an inverse relationship between calcium intakes and fracture rates.’ In the United States, however, blacks (largely of African ancestry) stand out as relatively fracture-resistant even in ice-slicked northern cities. Blacks also have a larger skeletal mass from infancy onward, and elderly black women appear to maintain a larger skeletal mass even though they consume far less fluid milk than do white women.5 Moreover, international comparisons do not show greater rates of bone loss where calcium intakes are low and lower rates of bone loss where the calcium intake is 2800 mg per day. Even our fossil ancestors lost bone with advancing age, despite animal-joint gnawing and whole-fish eating.6 Adult bone loss or involutional osteoporosis is not a recent product of a sedentary modern life. Decades ago, experimental studies on rodents, canines, and primates fully confirmed the expectation that a drastically reduced calcium intake can diminish bone mass, cortical area, ash weight, and breaking strength. For ethical reasons calcium deprivation has not been repeated on human volunteers, and current investigations with humans involve calcium supplementation. Still, the results are not fully clear. Increased calcium retention, suggested in balance studies, has not been confirmed by radiography film-type densitometry, or absorptiometry. It is not known whether calcium “pushing” can increase the bone mass during the adolescent period of bone addition or restore bone lost from skeletal tissue with advancing years. Reported data on calcium intake may be at fault, since it is derived from short-term dietary records or long-term hazy memories. Very few studies had access to multidecade records of mineral intake and changes in mineral intake in older and aging subjects with necessarily changing diets. The bone measurements themselves
may be at fault, depending (as most have) on a single bone site with inevitable positioning and repositioning errors. With total bone mineral now measurable by noninvasive in vivo techniques, and with attention to individual changes in dietary intakes, we may achieve more definitive answers. At six cents per 500-mg tablet (of the carbonate), calcium supplements rank among the less expensive generic medications. Even continued over four decades (i.e., 14,600 days) the cumulative cost at retail would be small, as compared with the cost of a femoral neck or trochanteric fracture. Since compliance may be a problem, the food fortification route has also been suggested, i.e., raising the calcium content of bread, ground meat, and even milk. However, there is no firm evidence that calcium supplementation does truly diminish fracture rates, and it is debatable whether the skeletal mass of adolescents can be expanded by an increased calcium intake. Nordin and Morris2 remain advocates of calcium supplementation. Kanis and Passmore3 question its effectiveness. The British Nutrition Foundation continues to hold to the 500-mg level as the “recommended” level of intake for the United Kingdom, rendering the Scottish verdict “nonproven.” Stanley M . Garn, Ph.D. Contributing Editor Martin AD, Silverthorn KG, Houston CS, Bernhardson S,Waida A, Roos LL. Hip fractures trends in two million Canadians, 1972 to 1984. Clin Orthop Re1 Res 1989 (in press) 2. Nordin BEC, Morris HA. The calcium deficiency model for osteoporosis. Nutr Rev 1989;47:65-72 3. Kanis JA, Passmore R. Calcium supplementatiorr of the diet. Br Med J 1989;298:137-40, 205-8 4. Calcium: the report of the British Nutrition Foundation’s Task Force. London: British Nutritioii Foundation, 1989 5. Garn SM, Solomon MA, Fried1 J. Calcium intake and bone quality in the elderly. Ecol Fd NL!tr 1989; 10: 131-3 6. Garn SM, Hawthorne VM. Calcium intake and bone loss in population context. In: Rubin RP, Weiss GB, Putney JW, eds. Calcium in biological systems. New York: Plenum, 1985:569-74 1.
NUTRfTiON REVIEWSIVOL 48, NO 11JANUARY 1990 27
stimulates the release of lysophosphatidylcholine from cultivated rat hepatocytes. Biochem J 1988 ;253 :693- 701 16. Robinson BS, Yao Z, Baisted DJ, Vance DE. Lysophosphatidylcholine metabolism and lipoprotein secretion by cultured rat hepatocytes deficient in choline. Biochem J 1989;260:207-14 17. Yao Z. Vance DE. Head group specificity i n the requirement of phosphatidylcholine biosynthesis for very low density lipoprotein secretion from cultured hepatocytes. J Biol Chem 1989;264: 11373-80
LETTER TO THE EDITOR Will Calcium Supplementation Preserve Bone Integrity? Millions of American women now take calcium supplements in tablet, capsule, pill, or liquid form. Pharmacists report more questions about calcium supplements than about any other over-the-counter medication. It is hoped that increased calcium intakes, up to or beyond the present recommended daily allowance (RDA) will delay, arrest, or even reverse “involutional osteoporosis.” If such calcium supplementation is effective, the prevalence of round back (the dowagers’ hump) should decrease, and the incidence of forearm, femoral neck, trochanteric, and vertebral fractures should go down. Stature shrinkage after the fifth decade might not be an inevitable concomitant of aging, provided that calcium supplementation is effective. Dietary calcium is obviously necessary for bone-building. As much as 100 mg per day may be incorporated into new bone during late-adolescent bone growth. Some workers suggest an even larger amount, though retention of 100 mg per day accounts for 0.15 kg of new bone in a single year. Obviously the amount of dietary calcium necessary to preserve skeletal integrity is more difficult to estimate, since bone loss takes place among older adults in all populations studied, over a wide range of calcium intakes, and in both genders. Decreased estrogen and androgen levels, de26 NUTRITION REVlEWSlVOL 48,NO llJANUARY 1990
creased activity, and changes in absorptive efficiency all complicate attempts to identify calcium intake as the key factor in osteoporosis. New evidence suggests that the age-specific incidence of bone fractures is increasing, at least in Canada, despite dietary improvements in that country.’ The so-called “dietary hypothesis,” has long been associated with the name of Christopher Nordin, and many know it simply as the Nordin hypothesis. Over a period of three decades Nordin has held that an insufficient calcium intake, long maintained, is ultimately responsible for adult bone loss. Years ago Nordin initiated multinational radiographic comparisons, under the auspices of the World Health Organization, to test this hypothesis in places where calcium intakes were low and in regions where they were high. Although Nordin has considered other relevant variables, such as estrogen loss, he continues to reiterate the Nordin hypothesis, effectively summarized in Nufrition Reviews last year.2 At almost the same time, Kanis and P a s ~ m o r e , ~ in a two-part review in the British Medical Journal came to diametrically opposite conclusions. Moreover, a new working paper,4 prepared for the British Nutrition Foundation, similarly rejects the low-calcium hypothesis and the notion that calcium supplementation would be the answer to bone loss in adults. As Kanis and Passmore3 also observed, data on bone-fractures do not support the
low-calcium hypothesis. Fracture rates are not only higher in Scandinavia and the United States and lower in places like Singapore and Durban, but the still-limited international data actually suggest an inverse relationship between calcium intakes and fracture rates.’ In the United States, however, blacks (largely of African ancestry) stand out as relatively fracture-resistant even in ice-slicked northern cities. Blacks also have a larger skeletal mass from infancy onward, and elderly black women appear to maintain a larger skeletal mass even though they consume far less fluid milk than do white women.5 Moreover, international comparisons do not show greater rates of bone loss where calcium intakes are low and lower rates of bone loss where the calcium intake is 2800 mg per day. Even our fossil ancestors lost bone with advancing age, despite animal-joint gnawing and whole-fish eating.6 Adult bone loss or involutional osteoporosis is not a recent product of a sedentary modern life. Decades ago, experimental studies on rodents, canines, and primates fully confirmed the expectation that a drastically reduced calcium intake can diminish bone mass, cortical area, ash weight, and breaking strength. For ethical reasons calcium deprivation has not been repeated on human volunteers, and current investigations with humans involve calcium supplementation. Still, the results are not fully clear. Increased calcium retention, suggested in balance studies, has not been confirmed by radiography film-type densitometry, or absorptiometry. It is not known whether calcium “pushing” can increase the bone mass during the adolescent period of bone addition or restore bone lost from skeletal tissue with advancing years. Reported data on calcium intake may be at fault, since it is derived from short-term dietary records or long-term hazy memories. Very few studies had access to multidecade records of mineral intake and changes in mineral intake in older and aging subjects with necessarily changing diets. The bone measurements themselves
may be at fault, depending (as most have) on a single bone site with inevitable positioning and repositioning errors. With total bone mineral now measurable by noninvasive in vivo techniques, and with attention to individual changes in dietary intakes, we may achieve more definitive answers. At six cents per 500-mg tablet (of the carbonate), calcium supplements rank among the less expensive generic medications. Even continued over four decades (i.e., 14,600 days) the cumulative cost at retail would be small, as compared with the cost of a femoral neck or trochanteric fracture. Since compliance may be a problem, the food fortification route has also been suggested, i.e., raising the calcium content of bread, ground meat, and even milk. However, there is no firm evidence that calcium supplementation does truly diminish fracture rates, and it is debatable whether the skeletal mass of adolescents can be expanded by an increased calcium intake. Nordin and Morris2 remain advocates of calcium supplementation. Kanis and Passmore3 question its effectiveness. The British Nutrition Foundation continues to hold to the 500-mg level as the “recommended” level of intake for the United Kingdom, rendering the Scottish verdict “nonproven.” Stanley M . Garn, Ph.D. Contributing Editor Martin AD, Silverthorn KG, Houston CS, Bernhardson S,Waida A, Roos LL. Hip fractures trends in two million Canadians, 1972 to 1984. Clin Orthop Re1 Res 1989 (in press) 2. Nordin BEC, Morris HA. The calcium deficiency model for osteoporosis. Nutr Rev 1989;47:65-72 3. Kanis JA, Passmore R. Calcium supplementatiorr of the diet. Br Med J 1989;298:137-40, 205-8 4. Calcium: the report of the British Nutrition Foundation’s Task Force. London: British Nutritioii Foundation, 1989 5. Garn SM, Solomon MA, Fried1 J. Calcium intake and bone quality in the elderly. Ecol Fd NL!tr 1989; 10: 131-3 6. Garn SM, Hawthorne VM. Calcium intake and bone loss in population context. In: Rubin RP, Weiss GB, Putney JW, eds. Calcium in biological systems. New York: Plenum, 1985:569-74 1.
NUTRfTiON REVIEWSIVOL 48, NO 11JANUARY 1990 27
