The differing tempo of growth in bone size, mass, and density in girls is region-specific.

The differing tempo and direction of growth of the periosteal and endocortical surfaces, and the differing tempo of growth of the axial and appendicular skeleton, may predispose to regional deficits in bone size, bone mineral content (BMC), and volumetric bone mineral density (vBMD). These traits were measured during 2 years by dual x-ray absorptiometry in 109 girls. By 7 years of age, bone size was approximately 80% of its maturational peak, and BMC was approximately 40% of its peak. Before puberty, the legs grew more rapidly than the trunk. During puberty, the growth spurt was truncal. Between 7 and 17 years, femoral and lumbar spine BMC increased by 50-150% because bone size increased. vBMD increased by 10-30%. Thus, growth builds a bigger, but only moderately denser, skeleton. Regions growing rapidly, or distant from their peak, may be more severely affected by illness than those growing slowly or nearer completion of growth. Depending on the age of exposure to disease, deficits may occur in limb dimensions (prepuberty), spine dimensions (early puberty), or vBMD by interference with mineral accrual (late puberty). As vBMD is independent of age before puberty, the position of an individual's vBMD in the population distribution is established early in life. Bone fragility in old age may have its foundations in growth.

The contribution of reduced peak accrual of bone and age-related bone loss to osteoporosis at the spine and hip: insights from the daughters of women with vertebral or hip fractures.

The genetic hypothesis states that a daughter will resemble her mother by about 50% in a given trait because she shares, on average, half her genes. We used this trait resemblance in mothers and daughters to determine whether abnormalities in volumetric bone mineral density (vBMD) or bone size in women with fractures originate in growth or aging. vBMD and volume of the third lumbar vertebra and femoral neck were estimated using posteroanterior (PA) scanning by dual-energy X-ray absorptiometry (DXA). Vertebral volume was estimated as (scan area)(3/2) and femoral neck volume was pi* (width/2)(2)* height. vBMD was bone mineral content (BMC)/volume. The data were expressed as age-specific SD or Z scores (mean +/- SEM). Vertebral vBMD was reduced by -0.98 +/- 0.14 SD (p < 0.001) in 34 women with vertebral fractures, and by -0.36 +/- 0.13 SD (p < 0.05) in their 44 premenopausal daughters. The vBMD deficit in the daughters (relative to age-matched controls) was no different from one-half their mothers' deficit (relative to their age-matched controls). Vertebral volume was reduced in the women with vertebral fractures relative to age-matched controls (-0.77 +/- 0.15 SD; p < 0.001), but not in their daughters (-0.17 +/- 0.13 SD, NS). The 31 women with hip fractures and their 41 premenopausal daughters had no deficits in vertebral volume or vBMD. Femoral neck vBMD was reduced in the women with hip fractures (-1.24 +/- 0.12 SD; p < 0.001) but not in their daughters (-0.17 +/- 0.13 SD, NS). Femoral neck volume was increased by 0.98 +/- 0.30 SD (p < 0.05) in women with hip fractures (relative to age-matched controls) and by 0.54 +/- 0.14 SD (p < 0.001) in their daughters (relative to age-matched controls); that is, about one-half that of their mothers. We propose that women with vertebral fractures have reduced vertebral vBMD because of, in large part, reduced accrual of bone during growth (because the deficit in their daughters was almost one-half their mothers' deficit); reduced vertebral volume in women with vertebral fractures is caused by reduced periosteal apposition during aging (because their daughters have no deficit in vertebral volume). Women with hip fractures have reduced vBMD because of age-related bone loss (because their daughters have no deficit in vBMD) but the increased femoral neck volume is growth related (because their daughters' femoral neck size is increased by one-half as much). The pathogenesis of bone fragility at the axial and appendicular skeleton is heterogeneous and has its origins in growth and aging.

Bone mass, areal, and volumetric bone density are equally accurate, sensitive, and specific surrogates of the breaking strength of the vertebral body: an in vitro study.

The validity of the bone mineral density (BMD) measurement depends on its accuracy as a predictor of the breaking strength of bone. As the breaking strength is proportional to the square of the apparent density, a small error in the calculation of BMD may result in a larger error in the predicted bone strength. The aims of this study were (i) to determine whether inaccuracies in the measurement of the dimensions, projected area, and volume of the vertebral body (used to derive the areal and volumetric BMD) result in errors in the predicted breaking strength and (ii) to compare the accuracy, sensitivity, and specificity of bone mineral content (BMC), areal BMD, volumetric BMD, and volumetric bone mineral apparent density (BMAD) as surrogates of bone strength. We measured the BMC (by densitometry), dimensions and volume (using calipers, densitometry, the Carter et al. and Peel and Eastell methods), and breaking strength (using the Instron 1114 apparatus, Newtons, N) of 22 vertebral body specimens. All methods resulted in errors in height, width, and depth between -11.3 +/- 1.0 and 30.4 +/- 1.8% relative to the "gold" standard caliper method. The vertebral body volume (of 38.0 +/- 1.2 cm3) measured by submersion was used as the gold standard to derive the volumetric BMD gold standard (of 0.162 +/- 0.01 g/cm3). All methods, except the Peel and Eastell method, resulted in errors ranging between -10.7 +/- 1.5 and 56.9 +/- 3.4% in vertebral body volume and -35.6 +/- 1.5 to 12.6 +/- 1.8% in volumetric BMD (all p < 0.0005). The same absolute value for volumetric BMD predicted a breaking strength that differed according to the method used to derive BMD. For example, a volumetric BMD of 0.162 g/cm3 predicted a breaking strength of 6208 N (submersion method), 5473 N (caliper method), 6095 N (Peel and Eastell method), 7697 N (DXA method), and 9470 N (Carter et al. method). The mean volumetric BMD derived by each method differed (0.181, 0.165, 0.133, and 0.104 g/cm3, respectively). However, all were accurate; each predicted a similar breaking strength (6177, 6217, 6209, and 6221 N respectively). Likewise, breaking strengths predicted by the mean BMC, areal BMD by calipers, and areal BMD by dual-energy X-ray absorptiometry (DXA) were 6267, 6214, and 6244 N, respectively. The methods were equally sensitive; a 1 standard deviation (SD) decrease in volumetric BMD resulted in a similar decrease in the breaking strength of 1818 (caliper), 2080 (Peel and Eastell), 2001 (DXA), and 1625 N (BMAD by Carter et al). A 1 SD decrease in BMC, areal BMD (using calipers) and areal BMD (using DXA) predicted a decrease in the breaking strength of 2019, 1738, and 1825 N, respectively. All methods were equally specific; the variance in bone strength explained by bone mass did not differ for volumetric BMD (38-61% depending on the method), BMC (58%), or areal BMD (48%). In conclusion, despite errors in the measurement of the dimensions of the vertebral body, bone mass, areal, and volumetric bone density are equally accurate, sensitive, and specific surrogates of the breaking strength of bone in vitro.

The benefit of hormone replacement therapy on bone mass is greater at the vertebral body than posterior processes or proximal femur.

The aim of this study was to determine whether the higher vertebral bone mass in women receiving hormone replacement therapy (HRT) is confined to the trabecular rich vertebral body rather than the predominantly cortical posterior processes, and to determine whether the protective effect of HRT at the proximal femur, a predominantly cortical site, is less than at the spine. Bone mass (g) of the third lumbar vertebra (total, vertebral body and posterior processes, measured by lateral scanning), and bone mineral density (g/cm2) of the femoral neck, Ward's triangle, and trochanter were measured using dual X-ray absorptiometry in a cross-sectional study of 71 women receiving HRT for 5.7 +/- 0.4 years (mean +/- SEM), ranging from 1 to 21 years, 69 age-matched controls, and 42 premenopausal controls aged 20 to 40 years. Relative to untreated postmenopausal controls, total bone mass of the third lumbar vertebra (body plus posterior processes) by postero-anterior (PA) scanning was 0.4 +/- 0.1 SD or 9.6 +/- 3.0% higher in HRT treated women (p < 0.01). By lateral scanning, total bone mass was higher than age-matched controls (z score 0.4 +/- 0.1 SD or 11.2 +/- 3.4%, p < 0.01). This difference was confined to the vertebral body (z score 0.6 +/- 0.1 SD, p < 0.001), which was 17.1 +/- 3.3% higher than in age-matched controls (p < 0.001). Bone mass of the posterior processes was no higher [z score 0.1 +/- 0.1, not significant (NS)]. The deficit at the vertebral body in HRT-treated women, relative to premenopausal controls, was half the deficit at the vertebral body in untreated postmenopausal women (t score -0.7 +/- 0.1 vs. -1.4 +/- 0.1 SD, respectively; p < 0.001) but no less at the posterior processes (t score -1.6 +/- 0.2 vs. -1.9 +/- 0.2 SD, respectively; NS). Similarly, the deficit in the vertebral body in the HRT treated group was half the deficit at their posterior processes (t score -0.7 +/- 0.1 SD vs. -1.6 +/- 0.2, respectively; p < 0.001). In HRT-treated women, bone mass diminished significantly with age at the posterior processes (r = -0.31, p < 0.01), but not at the vertebral body (r = -0.21, p = 0.07). Bone mass diminished significantly with age at the vertebral body and posterior processes in untreated women (r = -0.55, p < 0.001; r = -0.45, p < 0.001, respectively). Bone density (g/cm2) diminished at all femoral sites with advancing age in HRT-treated women. A protective effect was seen at the femoral neck and Ward's triangle, but not trochanter (z score 0.2 +/- 0.1, p = 0.06; 0.3 +/- 0.1, p < 0.05; 0.0 +/- 0.1, NS, respectively). In conclusion, the protective effect of HRT against bone loss at the vertebral body, the site of fracture in osteoporosis, may be underestimated by PA scanning. The greater benefit at the vertebral body, and more modest effect at the proximal femur, suggests that HRT may be a more effective means of reducing the risk of spine than hip fractures.