Camp, Jon J.

Abstract We used QCT scans obtained in 687 men and women, 21–97 years of age, to estimate the factor of risk for vertebral fracture, Φvert, defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Φvert increased significantly more in women than men. Age- and sex-specific differences in Φvert closely resembled previously reported vertebral fracture incidence. Introduction: Despite the high prevalence of vertebral fractures, little is known about the interaction between spinal loading and vertebral fragility. Materials and Methods: We assessed the ratio of spinal loading to vertebral strength (i.e., the factor of risk, Φvert) in an age- and sex-stratified population-based sample of 700 women and men 21–97 years of age. We measured volumetric BMD (vBMD, mg/cm3) and cross-sectional area (CSA, cm2) of the midvertebral bodies of L1–L3 using QCT and computed vertebral compressive strength from these data using engineering beam theory. A biomechanical model of the trunk was used to estimate compressive forces applied to the L3 vertebral body during standing, bending forward, and bending forward while lifting 10 kg. The factor of risk for fracture, Φvert, was computed as the ratio of spinal compressive force to vertebral strength for each activity. Results: Men had a higher vertebral strength at all ages, largely because of their greater CSA. Whereas both sexes exhibited a marked decline in vertebral compressive strength with age (p < 0.001), the decline was greater in women than men (−43% versus −31%, p = 0.008). Compressive forces on L3 were greater in men than women, because of their greater body weight and height. For both sexes, forces during bending and lifting were 8-fold higher than those experienced during upright standing. For all activities, Φvert increased with age, but significantly more so in women than men (p < 0.001). For bending and lifting, Φvert-bending exceeded 1.0 in 30% of women and 12% of men ≥50 years of age, values that are similar to the reported frequency of vertebral fracture. Conclusion: These findings illustrate potential mechanisms underlying vertebral fractures and provide strong rationale for further evaluation of this QCT-based biomechanical approach for assessment of fracture risk.

Abstract In a population-based, cross-sectional study, we related age-associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated “threshold” for skeletal estrogen deficiency was most evident at cortical sites. Introduction: Serum sex steroids, particularly estrogen levels, are associated with bone mass in men, and previous work has suggested that there may be a “threshold” bioavailable estradiol (bio E2) level below which the male skeleton becomes estrogen deficient. However, previous studies addressing this issue have exclusively used DXA, which cannot separate trabecular from cortical bone or provide information on bone geometry or structure. Materials and Methods: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E2 and bio testosterone (T) levels. Results: Compared with young men (age, 20-39 years), middle-aged men (age, 40-59 years) had significantly lower bio T (−26%, p < 0.001) and bio E2 (−9%, p = 0.038) levels, and these decreases were even greater in the elderly men (age ≥ 60 years, −60% and −38% for bio T and bio E2, respectively, p < 0.001 for both). Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E2 levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E2 and bio T at some sites. At all cortical sites, vBMD was associated with bio E2 at low (<30 pM, R = 0.27-0.41, p < 0.05-0.001) but not high (≥30 pM, R = −0.003 to 0.12, p = not significant) levels; no such differences were evident at trabecular sites. Conclusions: In men, bio E2 is the most consistent predictor of vBMD and some bone geometric variables as assessed by QCT. We also extend our previous findings on a possible “threshold” for skeletal estrogen deficiency by showing that this is most evident for cortical sites.

Abstract In a population-based, cross-sectional study, we assessed age- and sex-specific changes in bone structure by QCT. Over life, the cross-sectional area of the vertebrae and proximal femur increased by ∼15% in both sexes, whereas vBMD at these sites decreased by 39–55% and 34–46%, respectively, with greater decreases in women than in men. Introduction: The changes in bone structure and density with aging that lead to fragility fractures are still unclear. Materials and Methods: In an age- and sex-stratified population sample of 373 women and 323 men (age, 20–97 years), we assessed bone geometry and volumetric BMD (vBMD) by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia. Results: In young adulthood, men had 35–42% larger bone areas than women (p < 0.001), consistent with their larger body size. Bone area increased equally over life in both sexes by ∼15% (p < 0.001) at central sites and by ∼16% and slightly more in men at peripheral sites. Decreases in trabecular vBMD began before midlife and continued throughout life (p < 0.001), whereas cortical vBMD decreases began in midlife. Average decreases in trabecular vBMD were greater in women (−55%) than in men (−46%, p < 0.001) at central sites, but were similar (−24% and −26%, respectively) at peripheral sites. With aging, cortical area decreased slightly, and the cortex was displaced outwardly by periosteal and endocortical bone remodeling. Cortical vBMD decreased over life more in women (∼25%) than in men (∼18%, p < 0.001), consistent with menopausal-induced increases in bone turnover and bone porosity. Conclusions: Age-related changes in bone are complex. Some are beneficial to bone strength, such as periosteal apposition with outward cortical displacement. Others are deleterious, such as increased subendocortical resorption, increased cortical porosity, and, especially, large decreases in trabecular vBMD that may be the most important cause of increased skeletal fragility in the elderly. Our findings further suggest that the greater age-related decreases in trabecular and cortical vBMD and perhaps also their smaller bone size may explain, in large part, why fragility fractures are more common in elderly women than in elderly men.

Abstract In an age- and sex-stratified population sample (n = 700), we estimated fall-related loads and bone strength indices at the UDR and FN. These load/strength ratios more closely simulated patterns of wrist and hip fractures occurring in the same population than did measurement of vBMD. Introduction: Areal BMD measurements, although associated with fracture risk, incompletely explain patterns of fragility fractures. Moreover, population-based assessments relating applied loads and whole bone strength to fracture patterns have not been made. Materials and Methods: Using QCT, we assessed volumetric BMD (vBMD), cross-sectional geometry, and axial (EA) and flexural (EI) rigidities (indices of bone's resistance to compressive and bending loads, respectively) at the ultradistal radius (UDR) and femoral neck (FN) and estimated the loads applied to the wrist and hip during a fall. We used fall load (FL)/bone strength ratios to estimate fracture risk. Results: vBMD in young adults was similar between sexes. Decreases in vBMD over life were also similar (30% and 28%) at UDR but were somewhat greater (46% and 34%) at FN in women versus men, respectively. In young adults, FL/strength ratios at UDR were 32–51% lower (better) in men than in women and increased (worsened) over life less in men (+4% to +22%) than in women (+20% to +33%). In young adults, FL/strength ratios at FN were only marginally better in men than in women but worsened less over life in men (+22% to +36%) than in women (+40% to +62%). Conclusions: The 6:1 female preponderance and the virtual immunity of men for age-related increases in wrist fractures are largely explained by the more favorable FL/strength ratios at UDR in young adult men (because of larger bone size and more favorable geometry) versus women and to maintaining this advantage over life. The 2-fold lower incidence of hip fractures in men versus women is largely explained by age-related increases (worsening) of FL/bone strength ratios that are only one-half of the increases in women. The moderate increases in these ratios with aging are insufficient to explain the >4-fold increase in hip fracture incidence after age 75 in both sexes, suggesting contributions of other factors, especially the well-documented increased frequency of injurious falls among the elderly.