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The significance of high bone density in children
PEDIATRICS THE JOURNAL OF
October 2001
Volume 139
Number 4
EDITORIALS
The significance of high bone density in children Approximately a decade ago, Kreipe stated that “The prevention of osteoporosis, often deemed a geriatric disorder, may now be considered the legitimate domain of pediatricians.”1 The underlying assumption, widely shared despite the absence of direct evidence, is that peak bone mass achieved early in life is one of the major determinants of the risk for future osteoporosis. In recent years, the interest in the bone mineral content (BMC) of children, and in factors that affect BMC, has increased considerably. This issue of The Journal contains 3 articles that deal directly with bone measurements of children2-4 and 1 article that deals with calcium intake, a primary factor that enhances the bone accretion of children.5 Nutrition, physical activity, and genetics are the 3 major factors that influence bone growth and bone mineralization in childhood. Two of the articles deal with nutrition,2,5 one with the effect of physical activity,4 and one with a possible protective effect of high BMC and bone mineral density (BMD) on childhood fracture risk.3 Mora et al2 report findings from a longitudinal study assessing the effect of a gluten-free diet on BMD in chilReprint requests: Bonny L. Specker, PhD, E.A. Martin Program in Human Nutrition, South Dakota State University, Box 2204, EAM Building, Brookings, SD 57007.
J Pediatr 2001;139:473-5. Copyright © 2001 by Mosby, Inc. 0022-3476/2001/$35.00 + 0 9/18/118420 doi:10.1067/mpd.2001.118420
dren with celiac disease. BMD deficits present at the time celiac disease was diagnosed were corrected after 1 year of treatment. Normal BMD values were maintained when these children remained on a gluten-free diet. The introduction of a gluten-free diet resulted in an increase not only in BMD but also in bone area. These findings, combined with increases in markers of bone turnover, suggest that overall nutritional status improved, leading to a greater growth rate and increased bone mineralization.
See related articles, p 494, p 509, p 516, and p 522. In 1993, the Food and Drug Administration authorized a health claim for calcium in reducing osteoporosis risk. Since then, numerous calcium-fortified products have been appearing on grocery store shelves. Given the wide range of foods that are currently calcium-fortified, it is relatively easy for children to consume calcium in excess of the tolerable upper limit (UL) of intake set by the Food and Nutrition Board of the Institute of Medicine.6 The UL is defined as “the maximum level of total chronic daily intake of a nutrient judged to be likely to pose no risk of adverse health effects to the most sensitive members of the healthy population.”6 One of the reasons that the UL of calcium intake was set at 2500 mg/d for children was the risk of depletion of other minerals, in particular zinc and iron, associated with high calcium intakes.6
Thus, Abrams et al5 asked the appropriate question of whether harm might result from high calcium intakes from the consumption of fortified cereals. The mean calcium intake of the children consuming calcium-fortified cereal was 900 mg/d compared with 700 mg/d for children consuming non-fortified cereal. Both amounts are well below the UL. Reassuringly, Abrams et al5 found that consumption of calcium-fortified cereal resulted in increased calcium retention with no inhibition of iron absorption. The lack of an adverse effect of calcium-fortified cereal cannot, of course, be extrapolated to the potentially higher intakes that are possible through consumption of the wide variety of calcium-fortified foods appearing in the market. The long-term adaptation to high calcium intakes is not known, nor is the ability to adapt to a low calcium intake after long-term excessive intakes. The ramifications of long-term excessive calcium intakes during childhood are unknown. BMC BMD UL
Bone mineral content Bone mineral density Upper limit
The study by Nichols et al4 was designed to determine whether a 15month resistance training program could increase BMD in adolescent girls. Sixty-seven girls were randomly assigned to either a training program or a control group. The exercise program involved training 30 to 45 minutes per day, 3 days per week, for 15 months. An interesting aspect of the 473
EDITORIALS
study by Nichols et al4 was that of the 46 girls assigned to the resistance training group, only 5 (11%) actually completed the program. With such a small number of girls completing the program, the bone results are irrelevant. As mentioned by the authors, other investigators who conducted exercise intervention programs within school systems found significantly better retention and compliance rates and also found significant effects of exercise on bone and body composition. The importance of this study is the implication that for an exercise program to be effective in increasing BMD in adolescents, it should be incorporated within the school curriculum. Nichols et al4 also suggest that better motivators are needed if adolescents are to be persuaded to engage in physical activity. One possible motivator could be that increased BMD, obtained through regular exercise, provides protection against fractures. The study by Goulding et al3 suggests that it does. Their case-control study of boys with forearm fractures showed that case patients had greater body mass index and fat mass and less lean mass than control subjects. Case patients also had lower forearm (non-fractured), spinal, and femoral neck BMD than control subjects. The finding of reduced BMD and BMC among patients with fractures is similar to their previous report in girls7,8 and is consistent with adult studies showing an association between fracture occurrence and low BMD. However, it is not clear whether the association between fracture occurrence and increased body mass index is a result of weaker bones or a greater force on the skeleton when a fall occurs. Half the boys in the study by Goulding et al3 already had a history of fracture, and one might argue that their BMD was lower because of immobilization resulting from previous fractures. However, among the boys with fractures, the investigators did not find a lower BMD in those with a fracture history compared with those with no fracture history. 474
THE JOURNAL OF PEDIATRICS OCTOBER 2001 These studies in this issue of The Journal answer some important questions related to bone mass in children. However, many questions remain. What is the evidence that high BMD early in life is beneficial? There is no direct evidence that high childhood BMD is associated with high adulthood BMD and that high childhood BMD protects against osteoporotic fractures late in life. However, we know that children who participate in competitive sports have higher BMD than those who do not.9 We also know that retired gymnasts (mean age, 25 years) have higher BMD than similarly aged non-gymnasts.10 Longitudinal cohort studies show that adults who were physically active as children, and therefore likely to have higher childhood BMD, have higher BMD than adults who were not physically active as children.11,12 Therefore, there is indirect evidence that adults who had high BMD during childhood have high BMD as adults. The long-term significance of high BMD has been studied in adults. In postmenopausal women, BMD measurements made up to 11 years earlier predicted fracture risk as well as bone measurements made more recently.13 A second unknown is how calcium intake and physical activity affect different types of bone or fracture risk. Wosje and Specker recently summarized bone data available from pediatric calcium supplementation trials and found that the benefit of calcium on bone appears to be limited to cortical bone sites, whereas trabecular bone sites appear to be more influenced by age or hormonal status.14 Physical activity, on the other hand, appears to be site-specific, and benefits are seen mainly in bones that are loaded.10 Whether the bone response to an equivalent load is similar in cortical and trabecular bone is not known. Goulding et al3 reported slightly lower calcium intakes among boys aged 11 to 13 years who had fractures compared with those with no fracture. They did not observe a relationship between BMD and calcium intake, although the
mean intake was relatively high (approximately 1200 mg/d), which may have limited their ability to detect such a relationship. BMD at both cortical and trabecular sites was lower in the boys with fractures than in control subjects, but it was not clear whether the fractures occurred at cortical or trabecular bone sites. Increasing calcium intake may reduce fracture occurrence at cortical bone sites by increasing cortical BMD, but it may not reduce fracture risk at trabecular bone sites (ultra-distal forearm) among children. Studies defining predictors of fracture risk for specific bone sites are needed. Third, it is possible that the relationship between BMD and calcium intake and physical activity is influenced by other variables during childhood. Although physical activity has been shown to increase bone mineralization in older children,15 the response may not be the same in younger children or infants. A randomized 1-year trial of gross motor versus fine motor activity in infants showed no effect of bone loading on bone accretion in infants consuming a high calcium diet but showed a detrimental affect of gross motor activity on bone accretion in infants consuming a moderate to low calcium diet.16 Infancy is one of the most rapid growth periods, and an increase in bone turnover resulting from increased bone loading may not be beneficial during this time of development. The fourth question is at what age high BMD is desirable. The age range studied by Goulding et al3 was 3 to 19 years (mean, 12 years). Forearm fracture incidence peaks in early adolescence, and according to the findings of Goulding et al,3 this is an age at which high BMD may be important in reducing fracture risk. Whether high BMD earlier in life has significant health implications is not known. If BMD early in life is found to track with age, high BMD in infancy or early childhood should imply reduced fracture risk in later childhood and possibly in adulthood. It is important to determine
EDITORIALS
THE JOURNAL OF PEDIATRICS
VOLUME 139, NUMBER 4 whether BMD tracking occurs and the age at which BMD tracking begins. In summary, this issue of The Journal provides relevant information on how a gluten-free diet may improve nutritional status and BMD in children with celiac disease and on the ability of calcium-fortified cereals to cause increases in net calcium absorption without adversely affecting iron absorption. The difficulty in retaining adolescents in a 15-month resistance training program is also illustrated, and findings of reduced BMD in children with fractures compared with children without fractures are presented. One might conclude that calcium fortification of foods that children prefer is beneficial and that activity programs designed to increase BMD should be instituted within schools. These simple interventions would lead to increased BMD and may decrease fracture risk. However, questions remain as to the potential harm to children from excessive calcium fortification of foods, possible dissimilarities in the effects of calcium intake and physical activity on different bone types, whether there are periods during growth when these interventions are not appropriate, and the age at which high BMD is desirable. Bonny L. Specker, PhD E.A. Martin Program in Human Nutrition South Dakota State University Brookings, SD 57007
REFERENCES 1. Kreipe RE. Bones of today, bones of tomorrow [editorial]. Am J Dis Child 1992;146:22-5. 2. Mora S, Barera G, Beccio S, Menni L, Proverbio MC, Bianchi C, et al. A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease. J Pediatr 2001;139:516-21. 3. Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ. Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy x-ray absorptiometry study. J Pediatr 2001;139:509-15. 4. Nichols DL, Sanborn CF, Love AM. Resistance training and bone mineral density in adolescent females. J Pediatr 2001;139:494-500. 5. Abrams SA, Griffin IJ, Davila P, Liang L. Calcium fortification of breakfast cereal enhances calcium absorption in children without affecting iron absorption. J Pediatr 2001;139:522-6. 6. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington (DC): National Academy Press; 1997. 7. Goulding A, Cannan R, Williams SM, Gold EJ, Taylor RW, Lewis-Barned NJ. Bone mineral density in girls with forearm fractures. J Bone Miner Res 1998;13:143-8. 8. Goulding A, Jones IE, Taylor RW, Manning PJ, Williams SM. More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. J Bone Miner Res 2000;15:2011-8.
9. Cassell C, Benedict M, Specker B. Bone mineral density in elite 7-9 year old female gymnasts and swimmers. Med Sci Sports Exerc 1996;28:1243-6. 10. Bass S, Pearce G, Bradney M, Hendrich E, Delmas PD, Harding A, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Miner Res 1998;13:500-7. 11. Welten DC, Kemper HCG, Post GB, Van Mechelen W, Twisk J, Lips P, et al. Weight-bearing activity during youth is a more important factor for peak bone mass than calcium intake. J Bone Miner Res 1994;9:1089-96. 12. Valimaki MJ, Karkkainen M, Lamberg-Allardt C, Laitinen K, Alhava E, Heikkinen J, et al. Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. BMJ 1994;309:230-1. 13. Huang C, Ross P, Wasnich RD. Short-term and long-term fracture prediction by bone mass measurements: a prospective study. J Bone Miner Res 1998;13:107-13. 14. Wosje KS, Specker BL. Role of calcium in bone health during childhood. Nutr Rev 2000;58:253-68. 15. Bradney M, Pearce G, Naughton G, Sullivan C, Bass S, Beck T, et al. Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study. J Bone Miner Res 1998; 13:1814-21. 16. Specker BL, Mulligan L, Ho ML. Longitudinal study of calcium intake, physical activity, and bone mineral content in infants 6-18 months of age. J Bone Miner Res 1999;14:569-76.
475
October 2001
Volume 139
Number 4
EDITORIALS
The significance of high bone density in children Approximately a decade ago, Kreipe stated that “The prevention of osteoporosis, often deemed a geriatric disorder, may now be considered the legitimate domain of pediatricians.”1 The underlying assumption, widely shared despite the absence of direct evidence, is that peak bone mass achieved early in life is one of the major determinants of the risk for future osteoporosis. In recent years, the interest in the bone mineral content (BMC) of children, and in factors that affect BMC, has increased considerably. This issue of The Journal contains 3 articles that deal directly with bone measurements of children2-4 and 1 article that deals with calcium intake, a primary factor that enhances the bone accretion of children.5 Nutrition, physical activity, and genetics are the 3 major factors that influence bone growth and bone mineralization in childhood. Two of the articles deal with nutrition,2,5 one with the effect of physical activity,4 and one with a possible protective effect of high BMC and bone mineral density (BMD) on childhood fracture risk.3 Mora et al2 report findings from a longitudinal study assessing the effect of a gluten-free diet on BMD in chilReprint requests: Bonny L. Specker, PhD, E.A. Martin Program in Human Nutrition, South Dakota State University, Box 2204, EAM Building, Brookings, SD 57007.
J Pediatr 2001;139:473-5. Copyright © 2001 by Mosby, Inc. 0022-3476/2001/$35.00 + 0 9/18/118420 doi:10.1067/mpd.2001.118420
dren with celiac disease. BMD deficits present at the time celiac disease was diagnosed were corrected after 1 year of treatment. Normal BMD values were maintained when these children remained on a gluten-free diet. The introduction of a gluten-free diet resulted in an increase not only in BMD but also in bone area. These findings, combined with increases in markers of bone turnover, suggest that overall nutritional status improved, leading to a greater growth rate and increased bone mineralization.
See related articles, p 494, p 509, p 516, and p 522. In 1993, the Food and Drug Administration authorized a health claim for calcium in reducing osteoporosis risk. Since then, numerous calcium-fortified products have been appearing on grocery store shelves. Given the wide range of foods that are currently calcium-fortified, it is relatively easy for children to consume calcium in excess of the tolerable upper limit (UL) of intake set by the Food and Nutrition Board of the Institute of Medicine.6 The UL is defined as “the maximum level of total chronic daily intake of a nutrient judged to be likely to pose no risk of adverse health effects to the most sensitive members of the healthy population.”6 One of the reasons that the UL of calcium intake was set at 2500 mg/d for children was the risk of depletion of other minerals, in particular zinc and iron, associated with high calcium intakes.6
Thus, Abrams et al5 asked the appropriate question of whether harm might result from high calcium intakes from the consumption of fortified cereals. The mean calcium intake of the children consuming calcium-fortified cereal was 900 mg/d compared with 700 mg/d for children consuming non-fortified cereal. Both amounts are well below the UL. Reassuringly, Abrams et al5 found that consumption of calcium-fortified cereal resulted in increased calcium retention with no inhibition of iron absorption. The lack of an adverse effect of calcium-fortified cereal cannot, of course, be extrapolated to the potentially higher intakes that are possible through consumption of the wide variety of calcium-fortified foods appearing in the market. The long-term adaptation to high calcium intakes is not known, nor is the ability to adapt to a low calcium intake after long-term excessive intakes. The ramifications of long-term excessive calcium intakes during childhood are unknown. BMC BMD UL
Bone mineral content Bone mineral density Upper limit
The study by Nichols et al4 was designed to determine whether a 15month resistance training program could increase BMD in adolescent girls. Sixty-seven girls were randomly assigned to either a training program or a control group. The exercise program involved training 30 to 45 minutes per day, 3 days per week, for 15 months. An interesting aspect of the 473
EDITORIALS
study by Nichols et al4 was that of the 46 girls assigned to the resistance training group, only 5 (11%) actually completed the program. With such a small number of girls completing the program, the bone results are irrelevant. As mentioned by the authors, other investigators who conducted exercise intervention programs within school systems found significantly better retention and compliance rates and also found significant effects of exercise on bone and body composition. The importance of this study is the implication that for an exercise program to be effective in increasing BMD in adolescents, it should be incorporated within the school curriculum. Nichols et al4 also suggest that better motivators are needed if adolescents are to be persuaded to engage in physical activity. One possible motivator could be that increased BMD, obtained through regular exercise, provides protection against fractures. The study by Goulding et al3 suggests that it does. Their case-control study of boys with forearm fractures showed that case patients had greater body mass index and fat mass and less lean mass than control subjects. Case patients also had lower forearm (non-fractured), spinal, and femoral neck BMD than control subjects. The finding of reduced BMD and BMC among patients with fractures is similar to their previous report in girls7,8 and is consistent with adult studies showing an association between fracture occurrence and low BMD. However, it is not clear whether the association between fracture occurrence and increased body mass index is a result of weaker bones or a greater force on the skeleton when a fall occurs. Half the boys in the study by Goulding et al3 already had a history of fracture, and one might argue that their BMD was lower because of immobilization resulting from previous fractures. However, among the boys with fractures, the investigators did not find a lower BMD in those with a fracture history compared with those with no fracture history. 474
THE JOURNAL OF PEDIATRICS OCTOBER 2001 These studies in this issue of The Journal answer some important questions related to bone mass in children. However, many questions remain. What is the evidence that high BMD early in life is beneficial? There is no direct evidence that high childhood BMD is associated with high adulthood BMD and that high childhood BMD protects against osteoporotic fractures late in life. However, we know that children who participate in competitive sports have higher BMD than those who do not.9 We also know that retired gymnasts (mean age, 25 years) have higher BMD than similarly aged non-gymnasts.10 Longitudinal cohort studies show that adults who were physically active as children, and therefore likely to have higher childhood BMD, have higher BMD than adults who were not physically active as children.11,12 Therefore, there is indirect evidence that adults who had high BMD during childhood have high BMD as adults. The long-term significance of high BMD has been studied in adults. In postmenopausal women, BMD measurements made up to 11 years earlier predicted fracture risk as well as bone measurements made more recently.13 A second unknown is how calcium intake and physical activity affect different types of bone or fracture risk. Wosje and Specker recently summarized bone data available from pediatric calcium supplementation trials and found that the benefit of calcium on bone appears to be limited to cortical bone sites, whereas trabecular bone sites appear to be more influenced by age or hormonal status.14 Physical activity, on the other hand, appears to be site-specific, and benefits are seen mainly in bones that are loaded.10 Whether the bone response to an equivalent load is similar in cortical and trabecular bone is not known. Goulding et al3 reported slightly lower calcium intakes among boys aged 11 to 13 years who had fractures compared with those with no fracture. They did not observe a relationship between BMD and calcium intake, although the
mean intake was relatively high (approximately 1200 mg/d), which may have limited their ability to detect such a relationship. BMD at both cortical and trabecular sites was lower in the boys with fractures than in control subjects, but it was not clear whether the fractures occurred at cortical or trabecular bone sites. Increasing calcium intake may reduce fracture occurrence at cortical bone sites by increasing cortical BMD, but it may not reduce fracture risk at trabecular bone sites (ultra-distal forearm) among children. Studies defining predictors of fracture risk for specific bone sites are needed. Third, it is possible that the relationship between BMD and calcium intake and physical activity is influenced by other variables during childhood. Although physical activity has been shown to increase bone mineralization in older children,15 the response may not be the same in younger children or infants. A randomized 1-year trial of gross motor versus fine motor activity in infants showed no effect of bone loading on bone accretion in infants consuming a high calcium diet but showed a detrimental affect of gross motor activity on bone accretion in infants consuming a moderate to low calcium diet.16 Infancy is one of the most rapid growth periods, and an increase in bone turnover resulting from increased bone loading may not be beneficial during this time of development. The fourth question is at what age high BMD is desirable. The age range studied by Goulding et al3 was 3 to 19 years (mean, 12 years). Forearm fracture incidence peaks in early adolescence, and according to the findings of Goulding et al,3 this is an age at which high BMD may be important in reducing fracture risk. Whether high BMD earlier in life has significant health implications is not known. If BMD early in life is found to track with age, high BMD in infancy or early childhood should imply reduced fracture risk in later childhood and possibly in adulthood. It is important to determine
EDITORIALS
THE JOURNAL OF PEDIATRICS
VOLUME 139, NUMBER 4 whether BMD tracking occurs and the age at which BMD tracking begins. In summary, this issue of The Journal provides relevant information on how a gluten-free diet may improve nutritional status and BMD in children with celiac disease and on the ability of calcium-fortified cereals to cause increases in net calcium absorption without adversely affecting iron absorption. The difficulty in retaining adolescents in a 15-month resistance training program is also illustrated, and findings of reduced BMD in children with fractures compared with children without fractures are presented. One might conclude that calcium fortification of foods that children prefer is beneficial and that activity programs designed to increase BMD should be instituted within schools. These simple interventions would lead to increased BMD and may decrease fracture risk. However, questions remain as to the potential harm to children from excessive calcium fortification of foods, possible dissimilarities in the effects of calcium intake and physical activity on different bone types, whether there are periods during growth when these interventions are not appropriate, and the age at which high BMD is desirable. Bonny L. Specker, PhD E.A. Martin Program in Human Nutrition South Dakota State University Brookings, SD 57007
REFERENCES 1. Kreipe RE. Bones of today, bones of tomorrow [editorial]. Am J Dis Child 1992;146:22-5. 2. Mora S, Barera G, Beccio S, Menni L, Proverbio MC, Bianchi C, et al. A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease. J Pediatr 2001;139:516-21. 3. Goulding A, Jones IE, Taylor RW, Williams SM, Manning PJ. Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy x-ray absorptiometry study. J Pediatr 2001;139:509-15. 4. Nichols DL, Sanborn CF, Love AM. Resistance training and bone mineral density in adolescent females. J Pediatr 2001;139:494-500. 5. Abrams SA, Griffin IJ, Davila P, Liang L. Calcium fortification of breakfast cereal enhances calcium absorption in children without affecting iron absorption. J Pediatr 2001;139:522-6. 6. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington (DC): National Academy Press; 1997. 7. Goulding A, Cannan R, Williams SM, Gold EJ, Taylor RW, Lewis-Barned NJ. Bone mineral density in girls with forearm fractures. J Bone Miner Res 1998;13:143-8. 8. Goulding A, Jones IE, Taylor RW, Manning PJ, Williams SM. More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. J Bone Miner Res 2000;15:2011-8.
9. Cassell C, Benedict M, Specker B. Bone mineral density in elite 7-9 year old female gymnasts and swimmers. Med Sci Sports Exerc 1996;28:1243-6. 10. Bass S, Pearce G, Bradney M, Hendrich E, Delmas PD, Harding A, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Miner Res 1998;13:500-7. 11. Welten DC, Kemper HCG, Post GB, Van Mechelen W, Twisk J, Lips P, et al. Weight-bearing activity during youth is a more important factor for peak bone mass than calcium intake. J Bone Miner Res 1994;9:1089-96. 12. Valimaki MJ, Karkkainen M, Lamberg-Allardt C, Laitinen K, Alhava E, Heikkinen J, et al. Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. BMJ 1994;309:230-1. 13. Huang C, Ross P, Wasnich RD. Short-term and long-term fracture prediction by bone mass measurements: a prospective study. J Bone Miner Res 1998;13:107-13. 14. Wosje KS, Specker BL. Role of calcium in bone health during childhood. Nutr Rev 2000;58:253-68. 15. Bradney M, Pearce G, Naughton G, Sullivan C, Bass S, Beck T, et al. Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study. J Bone Miner Res 1998; 13:1814-21. 16. Specker BL, Mulligan L, Ho ML. Longitudinal study of calcium intake, physical activity, and bone mineral content in infants 6-18 months of age. J Bone Miner Res 1999;14:569-76.
475