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Bone density: BMC, BMD, or corrected BMD?
Bone, VoL 16, No.1 January 1995:5-7
ELSEVIER
EDITORIAL
Bone Density: BMC, BMD, or Corrected BMD? J. E. COMPSTON Department of Medicine, Unh'ersity of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge, United Kingdom CB2 2QQ
The investigation and clinical management of osteoporosis have been revolutionised by the development of noninvasive techniques for the measurement of bone mass. These techniques, which include single- and dual-photon absorptiometry, dualenergy x-ray absorptiometry, quantitative computcd tomography, and broad-band ultrasound attenuation, have a number of proven and potential applications. In epidemiological studies, bone mass assessment is used to study determinants of peak bone mass and to assess the predictive value of a single bone mass measurement for future fracture risk. In clinical trials, changes in bone mass are commonly used as a surrogate for fracture risk, whereas in clinical practice, bone density assessment is used both to diagnose osteopenia and osteoporosis and to monitor the response to treatment. Absorptiometric methods, which are used most commonly, measure the bone mineral content (BMC) within a given area; the bone mineral density (BMO) is calculated as BMC/area and expressed in glcm2 • This is an areal density and not a true volume density; the correction of BMC for area removes some but not all of its dependency on bone size. In an effort to correct completely for bone size and thus derive a calculated volumetric density, investigators have devised correction factors or multiple regression models with BMO as the dependent variable and indices of body and bone size as independent variables (Miller et al. 1991; Prentice et al. 1991; Kroger et al. 1992; Peel & Eastell 1994). These manipulations result in a BMO value that is less dependent on bone size than the uncorrected areal BMO, although neither provides a true volumetric density. The latter can be achieved only by tomographic techniques, in which measurements are made in three dimensions. Bone size changes throughout life, increasing in longitudinal and transverse dimensions during childhood and adolescence. Longitudinal growth ceases after epiphyseal closure, but the transverse diameter of the long bones and the vertebrae continues to increase by subperiosteal appositional growth (Smith & Walker 1964; Mosekilde & Mosekilde 1990). Cortical thinning and expansion of the medullary cavity occur as a result of endosteal resorption, which proceeds at a faster rate than subperiosteal apposition. These changes in bone size affect linear and areal bone density values in both cortical and cancellous bone and may confound the interpretation of apparent age-related or treatment-induced changes in bone mass. The dependency of areal BMO values on bone size is seen most dramatically in growing children, in whom areal BMO closely reflects linear growth, at least up to the age of around 13-14 years (Glastre et al. 1990; Bonjour et al. 1991; Kroger et al. 1992). This steep increase in areal BMO values contrasts with the much greater stability of calculated (Kroger et al. 1992) or measured (Gilsanz et al. 1988; Schonau et al. 1993) volumetric bone density during this period, assessed by quantitative computed tomography. True volumetric data in children are sparse because of the higher radiation doses required. However, © 1995 by Elsevier Science Inc.
Gilsanz et al. (1988) reported that volumetric bone density of spinal trabecular bone remained stable between 2 and 12 years of age, with some increase between 12 and 15 years. In another study, both trabecular and combined cortical and trabecular volumetric bone densities in the distal radius in eight healthy children aged 4-11 years were similar to those found in normal young adults (Schonau et al. 1993). The lack of a relation between body size and volumetrie density also has been shown in adults (Compston et al. 1988), emphasising the independence of true bone density and bone size. Because age-related bone loss is associated with a reduction in true bone density, it is reflected by a reduction in both areal and volumetric bone density (Riggs et al. 1981; Genant et al. 1982; Ruegsegger et al. 1984). However, because subperiosteal appositional growth continues throughout adult life (Smith & Walker 1964; Mosekilde & Mosekilde 1990), the measured reduction in areal bone density that occurs with aging will underestimate the loss in true bone density (Kanis & Adami 1994). Prediction of fracture risk constitutes the rationale for bone densitometry in both epidemiological and clinical studies. In prospective studies, the demonstration of a relation between HMC or areal bone density and future risk of fracture (Wasnich et al. 1985; Hui et al. 1988; Cummings et al. 1990; Black et al. 1992; Cummings et al. 1993; Gardsell et al. 1993) provides justification for this approach. However, the contribution of bone size to this relation has not been established conclusively. The relative ability of BMC and areal HMO to predict hip fracture was reported to be similiar in the calcaneus, radius, or spine (Cummings et al. 1990), although areal BMO in the femoral neck was superior to BMC at this site (Cummings et al. 1993). If bone size is an important and independent determinant of bone strength, mathematical manipulation of areal bone density values to remove any contribution of bone size will reduce, rather than enhance, the information about fracture risk obtained from bone density measurements. In support of this hypothesis, Mazess et al. (1994) reported recently that Z scores for areal bone density of the spine were significantly better than calculated volumetric Z scores in discriminating between patients with vertebral fracture and age-matched control subjects; in contrast, areal bone density and estimated volumetric bone density of the hip were shown to have very similar predictive values for hip fracture in the Study of Osteoporotic Fractures (Cummings et al. 1994). In two other, smaller studies, calculated volumetric bone density was reported to provide diagnostic accuracy similar to areal bone density (Uebel hart et al. 1990; Peel & Eastell 1994). At an earlier stage in life, there is evidence linking genetic factors, exercise, and calcium intake to peak bone mass, expressed as areal bone density, but the extent to which these influences arc mediated through effects on bone size has not been determined. Genotype clearly has an important influence on body size, and there is evidence that areal bone density differs according to vitamin 0 receptor genotype (Morrison et al. 1994), 5
8756-3282/951$9.50 8756-3282(9~)OOOO7-M
I, ,I
6
Bone, Vol. 16, No.1 January 1995:5-7
J. E. Compston Bone density
although the relative importance of bone size as opposed to bone density in this relation has not been defined. Several studies have shown a positive association between calcium intake and peak bone mass (Kanders et al. 1988; Kelly et al. 1990; Matkovic et al. 1990; Recker et al. 1992). In a recent study (Prentice et al. [in press]), the association between calcium intake and areal bone density in young adults disappeared when bone density was corrected for body size; this suggests that the effect of calcium on peak bone mass might be mediated through effects on bone size rather than bone density. However, in a prospective study of calcium supplementation in prepubertal twins (Johnston et al. 1992), BMC and areal BMD in the supplemented children increased in the absence of significant changes in the area or width of the site measured. Further studies are required in which accurate and precise measurements of bone size (Sievlinen et al. 1994) are combined with assessment of bone density. In the case of physical activity, there is direct evidence for effects on both bone size and true bone density. Jones et al. (1977) reported that the lateral and anteroposterior diameters of the humerus were increased in the dominant arm of professional tennis players; this was associated with an increase in cortical thickness and narrowing of the medullary cavity. More recently, BMC and areal BMD have been compared in the right and left humerus, radius, and ulna of professional tennis and squash players (Kannus et al. 1994; Haapasalo et al. 1994). Both measurements of bone mass were higher in the dominant than the nondominant arm, but the difference was always greater for BMC than for areal BMD, indicating an effect on bone size. Similar comparisons in the dominant and nondominant arms of control subjects revealed much smaller differences. In these studies, the effects of exercise were site-specific, being greatest in the humerus and least in the ulna. Exercise-induced increases in bone size at nonloaded sites have also been reported (Sandler et al. 1987), suggesting that systemic factors may operate. Differences in volumetric bone density between dominant and nondominant upper limbs have been reported in normal subjects, implying that activity affects true bone density as well as bone size (Rico et al. 1994). The association between fracture risk and low body mass is well established. An inverse relation between bone size and fracture risk also seems intuitively likely because, given the same mechanical stresses, a small bone is more likely to break than a large one of similar volumetric density, although bone geometry (Faulkner et al. 1993) clearly influences this relation. Studies of differenthil changes in BMC and areal BMD should provide more information about the relative contributions of bone size and bone density to skeletal strength in adults, although in the growing skeleton changes in bone size will dominate both these indices. The demonstrated relation between areal bone density and both bone strength (Dempster et al. 1993) and fracture risk (Wasnich et al. 1985; Cummings et al. 1990; Black et al. 1992; Cummings et al. 1993) provides justification for the use of areal density in clinical and epidemiological practice. The ability of these measurements to capture elements of both bone size and density may prove to be an advantage rather than a disadvantage. Finally, the differential effects of determinants of peak bone mass on bone size and true bone density and the potential of life-style, dietary, and pharmacological interventions to increase bone size in the adult skeleton merit wider consideration.
Acknowledgment: J.E.C. is supported by the Wellcome Trust.
References Black, D. M.; Cummings, S. R.; Genant, H. K.; Nevitt, M. c.; Palermo, L.; Browner, W. Axial and appendicular bone density predict fractures in older women. 1 Bone Miner Res 7:633-638; 1992. Bonjour, l·P.; Theintz, G.; Buchs, B.; Slosman, D.; Rizzoli, R. Critical years and stages of pubeny for spinal and femoral bone mass accumulation during adolescence. 1 C1in Endoncrinol Metab 73:555-563; 1991. Compston, 1. E.; Evans, W. D.; Crawley, E. 0.; Evans, C. Bone mineral content in normal UK subjects. Br 1 Radiol 61:631-636; 1988. Cummings, S. R.; Black, D. M.;Nevitt, M. C.; Browner, W.; Cauley, 1.; Ensrud, K.; Genant, H. K.; Palermo, L.; Scott, T.; Vogt, T. M. Bone density at various sites for prediction of hip fractures. Lancet 3·t! :72-75; 1993. Cummings, S. R.; Black, D. M.; Nevitt, M. C.; Browner, W. S.; Cauley, 1. A.; Genant, H. K.; Mascioli, S.; Scott, 1. c.; Seeley, D. G.; Steiger, P.; Vogt, T. M.; and the Study of Osteoporotic Fractures Research Group. Appendicular bone density and age predict hip fracture in women. lAMA 263:665-668; 19%. . Cummings, S. R.; Marcus, R.; Palermo, L.; Ensrud, K. E.; Genant, H. K. Does estimating volumetric bone density of the femoral neck improve the prediction of hip fracture? A prospective study. 1 Bone Miner Res 9:1429-1432; 1994. Dempster. D. W.; Ferguson·Pell. M. W.; Mellish. R. W. E.; Cochran. G. V. B.; Xie, F.; Fey, C.; Horben, W.; Parisien. M.; Lindsay, R. Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine. Osteoporosis Int 3:90-96; 1993. Faulkner, K. G.; Cummings, S. R.; GlUer, C. c.; Palermo. L.; Black, D. M.; Genant. H. K. Simple relationship of femoral geometry predicts hip fracture: The Study of Osteoporotic Fractures. 1 Bone Miner Res 8:1211-1217; 1993. Gardsell, P.; 10hnell. 0.; Nilsson, B. E.; Gullberg, B. Predicting various fragility fractures in women by forearm bone densitometry: A follow-up study. Calcif Tissue Int 52:348-353; 1993. Genant, H. K.; Cann. C. E.; Ettinger. B.; Gordan, G. S. Quantitative computed tomography of venebral spongiosa: A sensitive method of detecting early bone loss after oophorectomy. Ann Intern Med 97:699-705; 1982. Gilsanz, V.; Gibbens. D. T.; Roe, T. F.; Carlson, M.; Senac, M. 0.; Boechat, M. I.; Huang, H. K.; Schulz. E. E.; Libarati, C. R.; Cann. C.C. Venebral bone density in children; effects of pubeny. Radiology 166:847-850; 1988. G1astre, C.; Braillon, P.; Cochat, P.; Meunier. P. 1.; Delmas. P. D. Measurement of bone mineral content of the lumbar spine by dual energy x-ray absorptiometry in normal children: Correlations with growth parameters. 1 C1in Endocrinol Metab 70:1330-1333, 19%. Haapasalo, H.; Kannus. P.; Sieviinen, II.; Heinonen, A.; Oja, P.; Vuori, I. Longterm unilateral loading and bone mineral density and content in female squash players. Calcif Tissue Int 54:249-255; 1994. Hui, S. L.; Slemenda, C. W.; 10hnston. C. C. Age and bone mass as predictors of fracture in a prospective study. 1 Clin Invest 81:1804-1809; 1988. 10hnston. C. C.; Miller, 1. Z.; Slemenda, C. W.; Reister, T. K.; lIui, S.; Christian, 1. C.; Peacock, M. Calcium supplementation and increases in bone density in children. Engll Med 327:82-87; 1992. lones, H. H.; Priest, 1. D.; Hayes, W. C.; Tichenor, C. C.; Nagel, D. A. Humeral hypenrophy in response to exercise. 1 Bone 10int Surg 59A:204-208; 1977. Kanders, B.; Dempster, D.; Lindsay, R. Interaction of calcium nutrition and physical activity on bone mass in young women. 1 Bone Miner Res 3: 145-149; 1988. Kanis. 1. A.; Adami, S. Bone loss in the elderly. Osteoporosis Int 4(Suppl 1):5965; 1994. Kannus, P.; Haapasalo, H.; Sieviinen, H.; Oja. P.; Vuori. I. The site-specific effects of long-term unilateral activity on bone mineral density and content. Bone 15:279-284; 1994. Kelly. P.; Eisman, 1.; Sambrook. P. Interaction of genetic and environmental influences on peak bone density. Osteoporosis Int 1:56-tiO; 1990. Kroger, H.; Kotaniemi. A.; Vainio, P.; Alh3\·a. E. Bone densitometry of the spine and femur in children by dual energy x-ray absorptiomctry. Bone Miner 17: 75-85; 1992. Matkovic, V.; Fontana, D.; Rominac. C.; Goel, P.; Chesnut, C. Factors which influence peak bone mass formation: A study of calcium balance and the inheritance of bone mass in adolescent females. Am 1 Clin Nutr 52:878-888; 19%. Mazess, R. B.; Barden, II.; Mautalcn, C.; Vega, E. Normalisation of spine densitometry. 1 Bone Miner Res 9:541-548; 1994. Miller, 1. Z.; Slemenda, C. W.; Meaney. F. 1.; Reister, T. K.; Hui, S.; lohnston,
Bone, Vol. 16, No. January 1995:5-7 C. C. The relationship of bone mineral density and anthropometric variables in healthy male and female children. Bone Miner 14:137-152; 1991. Morrison, N. A.; Qi, J. C.; Tokita, A.; Kelly, P. J.; Crofts, L.; Nguyen, T. V.; Sambrook, P. N.; Gisman, J. A. Prediction of bone density from vitamin D receptor alleles. Nature 367:284-287; 1994. Mosekilde, L. I.; Mosekilde, L. Sex differences in age-related changes in vertebral body size, density and biomechanical competence in normal individuals. Bone 11:67-73; 1990. Peel, N. F. A.; Eastell, R. Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis. J Bone Miner Res 9:3 I 7-320; 1994. Prentice, A.; Parsons, T. J.; Cole, T. J. Uncritical use of B~ID in absorptiometry may lead to size-related artefacts in the identification of bone mineral determinants. Am J Clin Nutr 60:837-842; 1994. Prentice, A.; Shaw, J.; Laskey, M. A.; Cole, T. J.; Fraser, D. R. Bone mineral content of British and rural Gambian women aged 18-80+ years. Bone Miner 12:201-214; 1991. Recker, R. R.; Davies, M.; Hinders, S. M.; Heaney, R. P.; Stegman, M. R.; Kimmel, D. B. Bone gain in young adult women. JAMA 268:2403-2408; 1992. Rico, H.; Gonzalez-Riola, J.; Revilla, M.; ViIIa, L. F.; G6mez-Castresana, F.; Escribano, J. Cortical versus trabecular bone mass: Influence of activity on both bone components. Calcif Tissue Int 54:470-472; 1994. Riggs, B. L.; Wahner, H. W.; Dunn, W. L.; Mazess, R. B.; Offord, K. P.; Melton, L. J. Differential changes in bone mineral density of the appendicular and axial skeleton with aging. J Clin Invest 67:328-335; 1981.
J. E. Compston Bone density
7
Ruegsegger, P.; Dambacher, M. A.; Fischer, J. A.; Anliker, M. Bone loss in premenopausal and postmenopausal women. J Bone Joint Surg 66-A:10151023; 1984. Sandler, R. B.; Cauley, J. A.; 110m, D. L.; SashirCD.; Kriska. A. M. The effects of walking on the cross-sectional rlime~ions of the radius in postmenopausal women. CalcifTissue Int 41:65-69; 1987. SchOnaii. E.; Wentzlik, U.; Michalk, D.; Scheidhauer, K.; Klein, K. Is there an increase of bone density in children? Lancet 342:689-690; 1993. Sieviinen. H.; Kannus, P.; Oja, P.; Vuori, I. Dual energy x-ray absorptiometry is also an accurate and precise method to measure the dimensions of human long bones. Calcif Tissue Int 54:101-105; 1994. Smith, R. W.; Walker, R. R. Femoral expansion in aging women: Implications for osteoporosis and fractures. Science 145:156-157; 1964. Uebelhart, D.; Duboeuf, F.; Meunier, P. J.; Delmas, P. D. Lateral dual-photon absorptiometry: A new technique to measure the bone mineral density measured laterally at the lumbar spine. J Bone Miner Res 5:525-531; 1990. Wasnich, R. D.; Ross, P. D.; Heilbrun, L. K.; Vogel, J. M. Prediction of postmenopausal fracture risk with use of bone mineral measurements. Am J Obstet Gynecol 153:745-751; 1985.
Dare Receh'ed: April 20, 1994 Date Rel"ised: July I, 1994 Date Accepted: July 19, 1994
ELSEVIER
EDITORIAL
Bone Density: BMC, BMD, or Corrected BMD? J. E. COMPSTON Department of Medicine, Unh'ersity of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge, United Kingdom CB2 2QQ
The investigation and clinical management of osteoporosis have been revolutionised by the development of noninvasive techniques for the measurement of bone mass. These techniques, which include single- and dual-photon absorptiometry, dualenergy x-ray absorptiometry, quantitative computcd tomography, and broad-band ultrasound attenuation, have a number of proven and potential applications. In epidemiological studies, bone mass assessment is used to study determinants of peak bone mass and to assess the predictive value of a single bone mass measurement for future fracture risk. In clinical trials, changes in bone mass are commonly used as a surrogate for fracture risk, whereas in clinical practice, bone density assessment is used both to diagnose osteopenia and osteoporosis and to monitor the response to treatment. Absorptiometric methods, which are used most commonly, measure the bone mineral content (BMC) within a given area; the bone mineral density (BMO) is calculated as BMC/area and expressed in glcm2 • This is an areal density and not a true volume density; the correction of BMC for area removes some but not all of its dependency on bone size. In an effort to correct completely for bone size and thus derive a calculated volumetric density, investigators have devised correction factors or multiple regression models with BMO as the dependent variable and indices of body and bone size as independent variables (Miller et al. 1991; Prentice et al. 1991; Kroger et al. 1992; Peel & Eastell 1994). These manipulations result in a BMO value that is less dependent on bone size than the uncorrected areal BMO, although neither provides a true volumetric density. The latter can be achieved only by tomographic techniques, in which measurements are made in three dimensions. Bone size changes throughout life, increasing in longitudinal and transverse dimensions during childhood and adolescence. Longitudinal growth ceases after epiphyseal closure, but the transverse diameter of the long bones and the vertebrae continues to increase by subperiosteal appositional growth (Smith & Walker 1964; Mosekilde & Mosekilde 1990). Cortical thinning and expansion of the medullary cavity occur as a result of endosteal resorption, which proceeds at a faster rate than subperiosteal apposition. These changes in bone size affect linear and areal bone density values in both cortical and cancellous bone and may confound the interpretation of apparent age-related or treatment-induced changes in bone mass. The dependency of areal BMO values on bone size is seen most dramatically in growing children, in whom areal BMO closely reflects linear growth, at least up to the age of around 13-14 years (Glastre et al. 1990; Bonjour et al. 1991; Kroger et al. 1992). This steep increase in areal BMO values contrasts with the much greater stability of calculated (Kroger et al. 1992) or measured (Gilsanz et al. 1988; Schonau et al. 1993) volumetric bone density during this period, assessed by quantitative computed tomography. True volumetric data in children are sparse because of the higher radiation doses required. However, © 1995 by Elsevier Science Inc.
Gilsanz et al. (1988) reported that volumetric bone density of spinal trabecular bone remained stable between 2 and 12 years of age, with some increase between 12 and 15 years. In another study, both trabecular and combined cortical and trabecular volumetric bone densities in the distal radius in eight healthy children aged 4-11 years were similar to those found in normal young adults (Schonau et al. 1993). The lack of a relation between body size and volumetrie density also has been shown in adults (Compston et al. 1988), emphasising the independence of true bone density and bone size. Because age-related bone loss is associated with a reduction in true bone density, it is reflected by a reduction in both areal and volumetric bone density (Riggs et al. 1981; Genant et al. 1982; Ruegsegger et al. 1984). However, because subperiosteal appositional growth continues throughout adult life (Smith & Walker 1964; Mosekilde & Mosekilde 1990), the measured reduction in areal bone density that occurs with aging will underestimate the loss in true bone density (Kanis & Adami 1994). Prediction of fracture risk constitutes the rationale for bone densitometry in both epidemiological and clinical studies. In prospective studies, the demonstration of a relation between HMC or areal bone density and future risk of fracture (Wasnich et al. 1985; Hui et al. 1988; Cummings et al. 1990; Black et al. 1992; Cummings et al. 1993; Gardsell et al. 1993) provides justification for this approach. However, the contribution of bone size to this relation has not been established conclusively. The relative ability of BMC and areal HMO to predict hip fracture was reported to be similiar in the calcaneus, radius, or spine (Cummings et al. 1990), although areal BMO in the femoral neck was superior to BMC at this site (Cummings et al. 1993). If bone size is an important and independent determinant of bone strength, mathematical manipulation of areal bone density values to remove any contribution of bone size will reduce, rather than enhance, the information about fracture risk obtained from bone density measurements. In support of this hypothesis, Mazess et al. (1994) reported recently that Z scores for areal bone density of the spine were significantly better than calculated volumetric Z scores in discriminating between patients with vertebral fracture and age-matched control subjects; in contrast, areal bone density and estimated volumetric bone density of the hip were shown to have very similar predictive values for hip fracture in the Study of Osteoporotic Fractures (Cummings et al. 1994). In two other, smaller studies, calculated volumetric bone density was reported to provide diagnostic accuracy similar to areal bone density (Uebel hart et al. 1990; Peel & Eastell 1994). At an earlier stage in life, there is evidence linking genetic factors, exercise, and calcium intake to peak bone mass, expressed as areal bone density, but the extent to which these influences arc mediated through effects on bone size has not been determined. Genotype clearly has an important influence on body size, and there is evidence that areal bone density differs according to vitamin 0 receptor genotype (Morrison et al. 1994), 5
8756-3282/951$9.50 8756-3282(9~)OOOO7-M
I, ,I
6
Bone, Vol. 16, No.1 January 1995:5-7
J. E. Compston Bone density
although the relative importance of bone size as opposed to bone density in this relation has not been defined. Several studies have shown a positive association between calcium intake and peak bone mass (Kanders et al. 1988; Kelly et al. 1990; Matkovic et al. 1990; Recker et al. 1992). In a recent study (Prentice et al. [in press]), the association between calcium intake and areal bone density in young adults disappeared when bone density was corrected for body size; this suggests that the effect of calcium on peak bone mass might be mediated through effects on bone size rather than bone density. However, in a prospective study of calcium supplementation in prepubertal twins (Johnston et al. 1992), BMC and areal BMD in the supplemented children increased in the absence of significant changes in the area or width of the site measured. Further studies are required in which accurate and precise measurements of bone size (Sievlinen et al. 1994) are combined with assessment of bone density. In the case of physical activity, there is direct evidence for effects on both bone size and true bone density. Jones et al. (1977) reported that the lateral and anteroposterior diameters of the humerus were increased in the dominant arm of professional tennis players; this was associated with an increase in cortical thickness and narrowing of the medullary cavity. More recently, BMC and areal BMD have been compared in the right and left humerus, radius, and ulna of professional tennis and squash players (Kannus et al. 1994; Haapasalo et al. 1994). Both measurements of bone mass were higher in the dominant than the nondominant arm, but the difference was always greater for BMC than for areal BMD, indicating an effect on bone size. Similar comparisons in the dominant and nondominant arms of control subjects revealed much smaller differences. In these studies, the effects of exercise were site-specific, being greatest in the humerus and least in the ulna. Exercise-induced increases in bone size at nonloaded sites have also been reported (Sandler et al. 1987), suggesting that systemic factors may operate. Differences in volumetric bone density between dominant and nondominant upper limbs have been reported in normal subjects, implying that activity affects true bone density as well as bone size (Rico et al. 1994). The association between fracture risk and low body mass is well established. An inverse relation between bone size and fracture risk also seems intuitively likely because, given the same mechanical stresses, a small bone is more likely to break than a large one of similar volumetric density, although bone geometry (Faulkner et al. 1993) clearly influences this relation. Studies of differenthil changes in BMC and areal BMD should provide more information about the relative contributions of bone size and bone density to skeletal strength in adults, although in the growing skeleton changes in bone size will dominate both these indices. The demonstrated relation between areal bone density and both bone strength (Dempster et al. 1993) and fracture risk (Wasnich et al. 1985; Cummings et al. 1990; Black et al. 1992; Cummings et al. 1993) provides justification for the use of areal density in clinical and epidemiological practice. The ability of these measurements to capture elements of both bone size and density may prove to be an advantage rather than a disadvantage. Finally, the differential effects of determinants of peak bone mass on bone size and true bone density and the potential of life-style, dietary, and pharmacological interventions to increase bone size in the adult skeleton merit wider consideration.
Acknowledgment: J.E.C. is supported by the Wellcome Trust.
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Dare Receh'ed: April 20, 1994 Date Rel"ised: July I, 1994 Date Accepted: July 19, 1994