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.