Race and ethnic variation in proximal femur structure and BMD among older men.

Femoral neck dimensions and vBMD from QCT were compared among 3,305 black, Asian, Hispanic, and white men >or=65 yr of age. All had similar stature-adjusted mean femoral neck volume, but black and Asian men had thicker cortices and higher trabecular vBMD, which may increase bone strength. INTRODUCTION: Hip fracture rates among elderly U.S. black and Asian men are lower than rates among white men. Structural characteristics or volumetric BMD (vBMD), which confer advantages for femoral neck bone strength, may vary by race/ethnicity. However, this topic has not been studied in detail. MATERIALS AND METHODS: In a cross-sectional study, dimensions and vBMD in the femoral neck and shaft were obtained from QCT scans among 3,305 men >or=65 yr of age in the Osteoporotic Fractures in Men (MrOS) study. Femoral neck measures were cross-sectional area; integral, cortical, and medullary volumes and integral, cortical, and trabecular vBMD. Shaft measures were cross-sectional, cortical, and medullary areas and cortical vBMD. Self-reported race/ethnicity was classified as black, Asian, Hispanic, or white. We used multivariable linear regression models with adjustment for age, height, and body mass index to compare means of the outcome measures in black, Asian, and Hispanic men to those in whites. RESULTS: All groups had similar femoral neck integral volume. Among black and Asian men, mean cortical volume as a percent of integral volume was 6% greater, integral vBMD was 6-10% greater, and trabecular vBMD was 33-36% greater than means among whites. Shaft cross-sectional area was similar among blacks, but smaller among Asians, compared with whites. However, mean shaft cortical area was greater among blacks but similar among Asians and whites, resulting in mean cortical thickness being 5% greater among black and Asian men. Blacks also had greater mean cortical vBMD in both the femoral neck and shaft. CONCLUSIONS: Black and Asian men >or=65 yr of age have features in the proximal femur that may confer advantages for bone strength. Specifically, greater cortical thickness and higher trabecular vBMD among black and Asian men could help explain the lower hip fracture rates in these populations. Discerning the mechanisms underlying these differences could provide advances for the prevention and treatment of osteoporosis.     

Abaloparatide Effects on Cortical Volumetric BMD and Estimated Strength Indices of Hip Subregions by 3D-DXA in Women With Postmenopausal Osteoporosis

In ACTIVE, abaloparatide increased areal BMD (aBMD) of the hip and femoral neck vs teriparatide and placebo in women with osteoporosis. Previously, 3D-processing of dual X-ray absorptiometry (DXA) scans of a subgroup of ACTIVE subjects showed similar increases in trabecular volumetric BMD (Tb.vBMD) and greater increases in cortical vBMD (Ct.vBMD) of the total hip with abaloparatide vs teriparatide. The current analyses from this subgroup describe 2D- and 3D-DXA data for hip subregions. Randomly selected subjects from ACTIVE (n = 250/treatment group) who received 18 mo of placebo, abaloparatide 80 µg, or open-label teriparatide 20 µg by daily subcutaneous injection underwent hip DXA at baseline, and mo 6 and 18 of treatment. Areal BMD of the femoral neck, trochanter, and femoral shaft was determined using standard 2D-DXA and 3D-SHAPER software to retrospectively evaluate changes from baseline in volumetric parameters of these 3 hip subregions, including trabecular and cortical segmentation. Changes in biomechanical parameters cross-sectional moment of inertia (CSMI), section modulus (Z), and buckling ratio were also evaluated. Femoral neck, trochanter, and shaft aBMD increased in the abaloparatide and teriparatide groups at mo 6 and 18 vs placebo, with greater increases for abaloparatide vs teriparatide at the femoral neck at mo 6 and the shaft at mo 6 and 18. All 3 subregions showed similar significant increases in Tb.vBMD with abaloparatide and teriparatide vs placebo, whereas Ct.vBMD of all 3 subregions showed greater increases after 18 mo of abaloparatide vs teriparatide. Biomechanical parameters improved in all subregions with abaloparatide and teriparatide vs placebo, with greater improvements in CSMI and Z of the femoral neck and lower shaft after 6 and 18 mo of abaloparatide vs teriparatide. Differential femoral neck and shaft Ct.vBMD responses may explain the greater increases in CSMI and Z of those subregions with abaloparatide vs teriparatide.     

Measurement of bone mineral density at the spine and proximal femur by volumetric quantitative computed tomography and dual-energy X-ray absorptiometry in elderly women with and without vertebral fractures.

The goal of this study was to determine the effect of vertebral fracture status on trabecular bone mineral density (BMD) measurements obtained in the proximal femur and spine by helical volumetric quantitative computed tomography (vQCT). The study population consisted of 71 Italian women (average age 73 +/- 6) years. This group included 26 subjects with radiographically confirmed atraumatic vertebral fractures and 45 controls. The subjects received helical CT scans of the L1 and L2 vertebral bodies and the hip. The three-dimensional CT images were processed using specialized image analysis algorithms to extract measurements of trabecular, cortical, and integral BMD in the spine and hip. To compare the vQCT results with the most widely used clinical BMD measurement, dual X-ray absorptiometry (DXA) scans of the anteroposterior (AP) spine and proximal femur were also obtained. The difference between the subjects with vertebral fractures and the age-matched controls was computed for each BMD measure. All BMD measurements showed statistically significant differences, which ranged from 7% to 22% between subjects with fractures and controls. Although, given our small sample size, we could not detect statistically significant differences in discriminatory power between BMD techniques, integral BMD of the spine measured by vQCT and DXA tended to show stronger associations with fracture status (0.001 < p < 0.004). Measurements by QCT and DXA at the hip were also associated with vertebral fracture status, although the association of DXA BMD with fracture status was explained largely by differences in body weight between subjects with vertebral fractures and controls.     

Dimensions and volumetric BMD of the proximal femur and their relation to age among older U.S. men.

We measured femoral neck and shaft dimensions and volumetric BMD with QCT. Relations of these measures to age were quantified in a cross-sectional study among 3358 men 65-100 years old. Relations of femoral neck dimensions and vBMD to age differed from those in the shaft, indicating that patterns of bone modeling and remodeling in the neck and shaft are distinct. INTRODUCTION: Little is known about population variation in dimensions and volumetric BMD of the proximal femur or the relation of these measures to age among older men. MATERIALS AND METHODS: In a cross-sectional study, dimensions and volumetric BMD (vBMD) in the femoral neck and shaft were obtained from QCT scans among 3358 men 65-100 years of age in the Osteoporotic Fractures in Men cohort. Total bone size and size of the cortical and medullary compartments were measured with volumes in the femoral neck and with areas in the shaft. We quantified distributions of these measures and examined their relations to age with multivariable linear regression. RESULTS: Population variation in femoral neck and shaft dimensions and vBMD was substantial. In the femoral neck, total volume was minimally related to age, whereas cortical volume was 5% smaller and medullary volume was 10% larger (both p < 0.0001) in the oldest (85+ years) compared with the youngest (65-69 years) men. Across these ages, the percent of cortical bone declined from 46% to 42% (p < 0.0001). Integral and trabecular vBMD were 9% and 22% lower, whereas DXA femoral neck BMD was 4% lower, in the older men. Neck cortical vBMD was unrelated to age. In the shaft, cross-sectional area and medullary area were 9% and 22% larger, respectively, in the oldest men (both p < 0.0001), but cortical area was unchanged with age. The percent of cortical bone declined from 69% to 65% across these ages (p < 0.0001). Shaft cortical BMD was 4% lower in the older men (p < 0.0001). CONCLUSIONS: There is substantial diversity of femoral morphology and vBMD among older U.S. men. Patterns indicative of modeling and remodeling in the femoral neck were distinct from those in the shaft. Notably, changes in periosteal and endosteal dimensions that underlie cortical thinning appear to differ in the neck and shaft.     

Distribution of bone density and cortical thickness in the proximal femur and their association with hip fracture in postmenopausal women: a quantitative computed tomography study

Summary

The quantitative computed tomography (QCT) scans in an individually matched case–control study of women with hip fracture were analysed. There were widespread deficits in the femoral volumetric bone mineral density (vBMD) and cortical thickness of cases, and cortical vBMD and thickness discriminated hip fracture independently of BMD by dual-energy X-ray absorptiometry (DXA).

Introduction

Acknowledging the limitations of QCT associated with partial volume effects, we used QCT in an individually matched case–control study of women with hip fracture to better understand its structural basis.

Methods

Fifty postmenopausal women (55–89 years) who had sustained hip fractures due to low-energy trauma underwent QCT scans of the contralateral hip within 3 months of the fracture. For each case, postmenopausal women, matched by age (±5 years), weight (±5 kg) and height (±5 cm), were recruited as controls. We quantified cortical, trabecular and integral vBMD and apparent cortical thickness (AppCtTh) in four quadrants of cross-sections along the length of the femoral head (FH), femoral neck (FN), intertrochanter and trochanter and examined their association with hip fracture.

Results

Women with hip or intracapsular (IC) fracture had significantly (p?<?0.05) lower vBMD and AppCtTh than the controls in the majority of cross-sections and quadrants of the proximal femur, and both cortical and trabecular compartments are involved. Cortical vBMD and AppCtTh in the FH and FN were associated with hip and IC fractures independent of hip areal BMD (aBMD). The combination of AppCtTh and trabecular or integral vBMD discriminated hip fracture, whereas the combination of FH and FN AppCtTh discriminated IC fracture significantly (p?<?0.05) better than the hip aBMD.

Conclusion

Deficits in vBMD and AppCtTh in cases were widespread in the proximal femur, and cortical vBMD and AppCtTh discriminated hip fracture independently of aBMD by DXA.     

Correlates of trabecular and cortical volumetric bone mineral density at the femoral neck and lumbar spine: The osteoporotic fractures in men study (MrOS)

The objective of this cross‐sectional analysis was to examine the correlates of trabecular and cortical volumetric bone mineral density (vBMD) in 3670 community‐dwelling men, mean age 73.6 ± 5.9 years. vBMD was measured by quantitative computed tomography (QCT) and areal BMD by dual‐energy X‐ray absorptiometry (DXA). Demographic, historical, and lifestyle information was obtained by interview, and height, weight, and neuromuscular function were determined by examination. To express the strength of the associations, percent differences (95% confidence interval) were calculated from multivariable linear regression models using the formula 100 (β × unit/mean BMD). Units for continuous variables were chosen to approximate 1 standard deviation (SD). The multivariable linear regression models predicted 15%, 21%, and 20% of the overall variance in trabecular and cortical vBMD of the femoral neck and vBMD of the lumbar spine, respectively. Diabetes was associated with a 16.5% greater trabecular vBMD at the femoral neck and 11% at the lumbar spine but less than 2% for cortical vBMD. For femoral neck trabecular vBMD, the strongest negative correlates were past smoking (?9%), fracture history (?15%), kidney stones (?7%), corticosteroids (?11%), and insulin therapy (?26%). For cortical vBMD, the strongest negative correlate was use of thyroid medication (?2.8%). The strongest negative correlates for lumbar spine trabecular vBMD were fracture history (?5%), antiandrogen use (?19%), height (?8%), and thiazoliainedione use (?22%). Bioavailable estradiol and testosterone levels were positively related and sex hormone–binding globulin was negatively related to trabecular vBMD of the spine. There was no relationship between sex hormones and femoral neck trabecular vBMD. Our conclusion is that correlates of trabecular vBMD and cortical vBMD appear to differ in older men. © 2010 American Society for Bone and Mineral Research     

Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid‐femoral neck: The AGES‐Reykjavik longitudinal study

The risk of hip fracture rises rapidly with age, and is notably higher in women. After falls and prior fragility fractures, the main clinically recognized risk factor for hip fracture is reduced bone density. To better understand the extent to which femoral neck density and structure change with age in each sex, we carried out a longitudinal study in subjects not treated with agents known to influence bone mineral density (BMD), to investigate changes in regional cortical thickness, as well as cortical and trabecular BMD at the mid‐femoral neck. Segmental quantitative computed tomography (QCT) analysis was used to assess bone measurements in two anatomic subregions, the superolateral (superior) and inferomedial (inferior). A total of 400 older individuals (100 men and 300 women, aged 66–90 years) who were participants in the Age Gene/Environment Susceptibility‐Reykjavik Study (AGES‐Reykjavik), were studied. Participants had two QCT scans of the hip over a median follow‐up of 5.1 years (mean baseline age 74 years). Changes in bone values during follow‐up were estimated from mixed effects regression models. At baseline women had lower bone values in the superior region than men. At follow‐up all bone values were lower in women, except cortical volumetric bone mineral density (vBMD) inferiorly. The relative losses in all bone values estimated in the superior region were substantially (about threefold) and significantly greater compared to those estimated in the inferior region in both sexes. Women lost cortical thickness and cortical vBMD more rapidly than men in both regions; and this was only weakly reflected in total femoral neck dual‐energy X‐ray absorptiometry (DXA)‐like results. The higher rate of bone loss in women at critical locations may contribute materially to the greater femoral neck fracture incidence among women than men. © 2013 American Society for Bone and Mineral Research.     

Femoral Volumetric Bone Density,Geometry, and Strength in Relation to 25‐Hydroxy Vitamin D in Older Men

Low serum 25‐hydroxy vitamin D (25(OH)D) concentrations are associated with increased hip fracture risk and decreased femoral areal bone mineral density (BMD) among elderly men. Structural dimensions of the proximal femur and volumetric BMD in cortical and trabecular compartments are also associated with hip fracture risk. However, associations of volumetric BMD or structural dimensions with serum 25(OH)D concentrations among older men remain unclear. In a random sample of 1608 men aged ≥65 years from the Osteoporotic Fractures in Men Study (MrOS), baseline serum 25(OH)D concentrations were measured by liquid chromatography/mass spectrometry assays. Femoral neck geometry and volumetric BMD derived from quantitative computed tomography included integral, cortical, and trabecular volumetric BMD; cross‐sectional area; integral and cortical volume; and cortical volume as a percent of integral volume. We studied 888 men with vitamin D, parathyroid hormone (PTH), femoral neck geometry, and BMD measures. Whole‐bone femoral strength and load‐strength ratio from finite element (FE) analysis were also available for 356 men from this sample. Multivariable linear regression was used to estimate least square means of each femoral measure within quartiles of 25(OH)D adjusted for age, race, body mass index, height, latitude, and season of blood draw. Tests of linear trend in the means were performed across increasing quartile of serum 25(OH)D levels. Mean cortical volume (p trend = 0.006) and cortical volume as a percent of integral volume (p trend < 0.001) increased across increasing quartile of 25(OH)D level. However, overall femoral neck size (area and integral volume) did not vary by 25(OH)D level. Femoral neck volumetric BMD measures increased in a graded manner with higher 25(OH)D levels (p trend < 0.001). Femoral strength, but not load‐strength ratio, increased with increasing 25(OH)D. Adjustment for PTH did not materially change these associations. We conclude that in older men, higher levels of endogenous 25(OH)D may increase whole‐bone strength by increasing femoral volumetric BMD and cortical volume. © 2014 American Society for Bone and Mineral Research.     

Densitometric and geometric measurement of the proximal femur in elderly women with and without osteoporotic vertebral fractures by volumetric quantitative multi-slice CT

There is a lack of research on volumetric multi-slice CT (MSCT) application in hip densitometric assessment and geometric measures in elderly women with osteoporotic vertebral fractures. A total of 237 elderly women were divided into three groups based on BMD values of the lumbar spine (AP-SPINE) and/or the femoral neck (NECK) by dual energy X-ray absorptiometry (DXA): osteoporosis with (OP_FX, 53 cases) or without vertebral fracture (OP_NONFX, 94 cases), or normal BMD (CONTROL, 90 cases). Volumetric BMD of trabecular bone (TRAB), integral bone (INTGL) and cortical bone (CORT) with neck axis length (NAL) and minimum cross-section area (mCSA) measures of the left femoral neck were calculated, respectively, by using OsteoCAD software based on MSCT scans of the abdominal-pelvic region of all participants, then the index of femoral neck strength (FNSI) was estimated. The values of TRAB, CORT and INTGL of OP_FX were significantly lower than those of OP_NONFX, with the decrease in 6.8–21.8%, as well as being lower than those in CONTROL, whereas no significant differences in the values of AP-SPINE and NECK were found between OP_FX and OP_NONFX. No significant difference of the value of mCSA was found among these three groups. The NAL value of OP_NONFX was larger than that of CONTROL. FNSI of femoral neck in OP_FX (0.42 ± 0.15 g²/cm⁴) was significantly lower than OP_NONFX (0.50 ± 0.14 g²/cm⁴) (p < 0.05). vQCT measurement seemed to be more effective than DXA in evaluating hip densitometric changes and discriminating osteoporotic elderly subjects with fractured vertebrae from the non-fractured in a group of Chinese women.     

Selective reduction in trabecular volumetric bone mineral density during treatment for childhood acute lymphoblastic leukemia

During treatment of childhood acute lymphoblastic leukemia (ALL) fracture incidence is increased. Studies using DXA, which measures a composite of both trabecular and cortical BMD, have shown reduced BMD during treatment. We investigated changes in compartmental (cortical and trabecular) volumetric BMD (vBMD) and bone geometry using peripheral quantitative computed tomography. These outcomes were also analysed in relation to adiposity and treatment factors. Thirty nine patients with ALL (64% male, median age 7.2years (4.1-16.9)) were compared to 34 healthy controls (50% male, median age 9.1years (4.4-18.7)). DXA-derived age-specific standard deviation scores (SDS) of the lumbar spine (LS) and femoral neck (FN) were reduced in subjects with ALL compared to controls (p≤0.01). This persisted following adjustment for body size using height-specific SDS (LS -0.72±1.02 vs -0.18±0.72, p=0.01; FN -1.53±0.96 vs -0.74±0.74, p=0.001) and bone mineral apparent density (BMAD) SDS (LS -0.76±1.14 vs 0.04±1.08, p=0.01; FN -1.63±1.38 vs -0.16±1.20, p<0.001). Radial and tibial trabecular vBMD was also reduced (196.5±54.9mg/cm(3) vs 215.2±39.9mg/cm(3), p=0.03 and 232.8±60.3mg/cm(3) vs 267.5±60.2mg/cm(3), p=0.002, respectively), but cortical vBMD at the radius and tibia was similar in patients and controls. A lowered tibial bone strength index (BSI) was identified in patients with ALL (53.9±23.1mg/mm(4) vs 82.5±27.8mg/mm(4), p<0.001) suggesting lower fracture threshold from compressive forces. No relationships with measures of adiposity, duration of treatment or cumulative corticosteroid dose were identified. Our findings therefore suggest that reduction in trabecular vBMD during childhood ALL treatment may contribute to the observed increased fracture incidence and bony morbidity in this group.     

Effect of eldecalcitol, an active vitamin D analog, on hip structure and biomechanical properties: 3D assessment by clinical CT

The effects of an active vitamin D analog, eldecalcitol (ELD), on bone mineral density (BMD), bone geometry, and biomechanical properties of the proximal femur were investigated by using clinical CT. The subjects--a subgroup of a recent randomized, double-blind study comparing anti-fracture efficacy of ELD with alfacalcidol (ALF) - constituted 193 ambulatory patients with osteoporosis (189 postmenopausal women and 4 men aged 52-85 years, average ± SD: 70.9 ± 6.92 years) enrolled at 11 institutions. Multidetector-row CT data was acquired at baseline and at completion of 144 weeks' treatment. Cross-sectional densitometric and geometric parameters of the femoral neck were derived from three-dimensional CT data. Biomechanical properties including cross-sectional moment of inertia (CSMI), section modulus (SM) and buckling ratio (BR) of the femoral neck, and CSMI of the femoral shaft were also calculated. We found that, (1) with respect to the femoral neck cross-sectional parameters (total bone), in the ALF group, volumetric BMD (vBMD) decreased but bone mass was maintained and cross-sectional area (CSA) increased. In contrast, ELD maintained vBMD with a significant increase in bone mass and a trend toward increased CSA. (2) With respect to the femoral neck cross-sectional parameters (cortex), cortical thickness decreased in the ALF group, but was maintained in the ELD group. In the ALF group, vBMD and bone mass increased, and CSA was maintained. In the ELD group, vBMD, CSA, and bone mass increased. (3) With respect to the biomechanical properties of the femoral neck, ELD improved CSMI and SM to a greater extent than did ALF. BR increased in both the ALF and ELD groups. (4) With respect to the femoral shaft parameters, overall the results of bone geometry and CSMI of the femoral shaft were very consistent with the results for the femoral neck; however, cortical vBMD of the femoral shaft decreased significantly in both the ELD and ALF groups. In conclusion, our longitudinal analysis of hip geometry by clinical CT revealed the unexpected potential of ELD to increase cortical CSA, vBMD, and bone mass, and to maintain cortical thickness, probably through the more potent effect of ELD in mitigating endocortical bone resorption than ALF. By improving the biomechanical properties of the proximal femur, ELD may have the potential to reduce the risk of hip fractures.     

Increased Trabecular Volumetric Bone Mass Density in Familial Hypocalciuric Hypercalcemia (FHH) Type 1: A Cross-Sectional Study

Familial Hypocalciuric Hypercalcaemia (FHH) Type 1 is caused by an inactivating mutation in the calcium-sensing receptor (CASR) gene resulting in elevated plasma calcium levels. We investigated whether FHH is associated with change in bone density and structure. We compared 50 FHH patients with age- and gender-matched population-based controls (mean age 56 years, 69 % females). We assessed areal BMD (aBMD) by DXA-scans and total, cortical, and trabecular volumetric BMD (vBMD) as well as bone geometry by quantitative computed tomography (QCT) and High-Resolution peripheral-QCT (HR-pQCT). Compared with controls, FHH females had a higher total and trabecular hip vBMD and a lower cortical vBMD and hip bone volume. Areal BMD and HRpQCT indices did not differ except an increased trabecular thickness and an increased vBMD at the transition zone between cancellous and cortical bone in of the tibia in FHH. Finite element analyses showed no differences in bone strength. Multiple regression analyses revealed correlations between vBMD and P-Ca²⁺ levels but not with P-PTH. Overall, bone health does not seem to be impaired in patients with FHH. In FHH females, bone volume is decreased, with a lower trabecular volume but a higher vBMD, whereas cortical vBMD is decreased in the hip. This may be due to either an impaired endosteal resorption or corticalization of trabecular bone. The smaller total bone volume suggests an impaired periosteal accrual, but bone strength is not impaired. The findings of more pronounced changes in females may suggest an interaction between sex hormones and the activity of the CaSR on bone.     

Proximal Femoral Structure and the Prediction of Hip Fracture in Men: A Large Prospective Study Using QCT

The structure of the femoral neck contributes to hip strength, but the relationship of specific structural features of the hip to hip fracture risk is unclear. The objective of this study is to determine the contribution of structural features and volumetric density of both trabecular and cortical bone in the proximal femur to the prediction of hip fracture in older men. Baseline QCT scans of the hip were obtained in 3347 men ≥65 yr of age enrolled in the Osteoporotic Fractures in Men Study (MrOS). All men were followed prospectively for an average of 5.5 yr. Areal BMD (aBMD) by DXA was also assessed. We determined the associations between QCT‐derived measures of femoral neck structure, volumetric bone density, and hip fracture risk. Forty‐two men sustained incident hip fractures during follow‐up: an overall rate of 2.3/1000 person‐years. Multivariable analyses showed that, among the QCT‐derived measures, lower percent cortical volume (hazard ratio [HR] per SD decrease: 3.2; 95% CI: 2.2–4.6), smaller minimal cross‐sectional area (HR: 1.6; 95% CI: 1.2–2.1), and lower trabecular BMD (HR: 1.7; 95% CI: 1.2–2.4) were independently related to increased hip fracture risk. Femoral neck areal BMD was also strongly related to hip fracture risk (HR: 4.1; 95% CI: 2.7–6.4). In multivariable models, percent cortical volume and minimum cross‐sectional area remained significant predictors of hip fracture risk after adjustment for areal BMD, but overall prediction was not improved by adding QCT parameters to DXA. Specific structural features of the proximal femur were related to an increased risk of hip fracture. Whereas overall hip fracture prediction was not improved relative to aBMD, by adding QCT parameters, these results yield useful information concerning the causation of hip fracture, the evaluation of hip fracture risk, and potential targets for therapeutic intervention.     

Adaptation of the proximal femur to skeletal reloading after long-duration spaceflight.

We studied the effect of re-exposure to Earth's gravity on the proximal femoral BMD and structure of astronauts 1 year after missions lasting 4-6 months. We observed that the readaptation of the proximal femur to Earth's gravity entailed an increase in bone size and an incomplete recovery of volumetric BMD. INTRODUCTION: Bone loss is a well-known result of skeletal unloading in long-duration spaceflight, with the most severe losses occurring in the proximal femur. However, there is little information about the recovery of bone loss after mission completion and no information about effect of reloading on the structure of load-bearing bone. To address these questions, we carried out a study of the effect of re-exposure to Earth's gravity on the BMD and structure of the proximal femur 1 year after missions lasting 4-6 months. MATERIALS AND METHODS: In 16 crew members of the International Space Station (ISS) making flights of 4.5-6 months, we used QCT imaging to measure the total, trabecular, and cortical volumetric BMD (vBMD) of the proximal femur. In addition to vBMD, we also quantified BMC, bone volume, femoral neck cross-sectional area (CSA), and femoral neck indices of compressive and bending strength at three time-points: preflight, postflight, and 1 year after mission. RESULTS: Proximal femoral bone mass was substantially recovered in the year after spaceflight, but measures of vBMD and estimated bone strength showed only partial recovery. The recovery of BMC, in the absence of a comparable increase in vBMD, was explained by increases in bone volume and CSA during the year after spaceflight. CONCLUSIONS: Adaptation of the proximal femur to reloading entailed an increase in bone size and an incomplete recovery of vBMD. The data indicate that recovery of skeletal density after long-duration space missions may exceed 1 year and supports the evidence in the aging literature for periosteal apposition as a compensatory response for bone loss. The extent to which this compensatory effect protects against fracture remains to be seen.     

Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight.

We measured cortical and trabecular bone loss using QCT of the spine and hip in 14 crewmembers making 4- to 6-month flights on the International Space Station. There was no compartment-specific loss of bone in the spine. Cortical bone mineral loss in the hip occurred primarily by endocortical thinning. INTRODUCTION: In an earlier study, areal BMD (aBMD) measurements by DXA showed that cosmonauts making flights of 4- to 12-month duration on the Soviet/Russian MIR spacecraft lost bone at an average rate of 1%/month from the spine and 1.5%/month from the hip. However, because DXA measurements represent the sum of the cortical and trabecular compartments, there is no direct information on how these bone envelopes are affected by spaceflight. MATERIALS AND METHODS: To address this, we performed a study of crewmembers (13 males and 1 female; age range, 40-55 years) on long-duration missions (4-6 months) on the International Space Station (ISS). We used DXA to obtain aBMD of the hip and spine and volumetric QCT (vQCT) to assess integral, cortical, and trabecular volumetric BMD (vBMD) in the hip and spine. In the heel, DXA was used to measure aBMD, and quantitative ultrasound (QUS) was used to measure speed of sound (SOS) and broadband ultrasound attenuation (BUA). RESULTS AND CONCLUSIONS: aBMD was lost at rates of 0.9%/month at the spine (p < 0.001) and 1.4-1.5%/month at the hip (p < 0.001). Spinal integral vBMD was lost at a rate of 0.9%/month (p < 0.001), and trabecular vBMD was lost at 0.7%/month (p < 0.05). In contrast to earlier reports, these changes were generalized across the vertebrae and not focused in the posterior elements. In the hip, integral, cortical, and trabecular vBMD was lost at rates of 1.2-1.5%/month (p < 0.0001), 0.4-0.5%/month (p < 0.01), and 2.2-2.7%/month (p < 0.001), respectively. The cortical bone loss in the hip occurred primarily by cortical thinning. Calcaneal aBMD measurements by DXA showed smaller mean losses (0.4%/month) than hip or spine measurements, with SOS and BUA showing no change. In summary, our results show that ISS crewmembers, on average, experience substantial loss of both trabecular and cortical bone in the hip and somewhat smaller losses in the spine. These results do not support the use of calcaneal aBMD or QUS measurements as surrogate measures to estimate changes in the central skeleton.     

A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

Children with chronic kidney disease (CKD) have multiple risk factors for impaired accretion of trabecular and cortical bone. CKD during childhood poses an immediate fracture risk and compromises adult bone mass, resulting in significantly greater skeletal fragility throughout life. High-turnover disease initially results in thickened trabeculae, with greater bone volume. As disease progresses, resorption cavities dissect trabeculae, connectivity degrades, and bone volume decreases. Increased bone turnover also results in increased cortical porosity and decreased cortical thickness. Dual-energy X-ray absorptiometry (DXA)-based measures of bone mineral density (BMD) are derived from the total bone mass within the projected bone area (g/cm²), concealing distinct disease effects in trabecular and cortical bone. In contrast, peripheral quantitative computed tomography (pQCT) estimates volumetric BMD (vBMD, g/cm³), distinguishes between cortical and trabecular bone, and provides accurate estimates of cortical dimensions. Recent data have confirmed that pQCT measures of cortical vBMD and thickness provide substantially greater fracture discrimination in adult dialysis patients compared with hip or spine DXA. The following review considers the structural effects of renal osteodystrophy as it relates to fracture risk and the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, such as pQCT, micro-CT (μCT), and micro magnetic resonance imaging (μMRI) for fracture risk assessment.     

DXA-Based 3D Analysis of the Cortical and Trabecular Bone of Hip Fracture Postmenopausal Women: A Case-Control Study

Methods using statistical shape and appearance models have been proposed to analyze bone mineral density (BMD) in 3D from dual energy X-ray absorptiometry (DXA) scans. This paper presents a retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporotic hip fracture in postmenopausal women. Patients who experienced a hip fracture between 1 and 6 years from baseline and age-matched controls were included in this study. The 3D-SHAPER software (version 2.7, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from hip DXA scans at baseline. DXA and 3D measurements were compared between groups. Total hip areal BMD of hip fracture group as measured by DXA was 10.7% lower compared to control group. Differences in volumetric BMD (total hip) as measured by 3D-SHAPER were more pronounced in the trabecular compartment (−23.3%) than in the cortex (−8.2%). The area under the receiver operating curve was 0.742 for trabecular volumetric BMD, 0.706 for cortical volumetric BMD, and 0.712 for total hip areal BMD. Differences in the cortex were locally more pronounced at the medial aspect of the shaft, the lateral aspect of the greater trochanter, and the superolateral aspect of the neck. Marked differences in volumetric BMD were observed in the greater trochanter. This case-control study showed the association of DXA-derived 3D measurements with hip fracture. Analysis of large cohorts will be performed in future work to determine if DXA-derived 3D measurements could improve fracture risk prediction in clinical practice.     

Fracture risk in children with a forearm injury is associated with volumetric bone density and cortical area (by peripheral QCT) and areal bone density (by DXA)

Summary

Children who sustain a forearm fracture when injured have lower bone density throughout their skeleton, and have a smaller cortical area and a lower strength index in their radius. Odds ratios per SD decrease in bone characteristics measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) were similar (1.28 to 1.41).

Introduction

Forearm fractures are common in children. Bone strength is affected by bone mineral density (BMD) and bone geometry, including cross-sectional dimensions and distribution of mineral. Our objective was to identify bone characteristics that differed between children who sustained a forearm fracture compared to those who did not fracture when injured.

Methods

Children (5–16 years) with a forearm fracture (cases, n?=?224) and injured controls without fracture (n?=?200) were enrolled 28?±?8 days following injury. Peripheral QCT scans of the radius (4% and 20% sites) were obtained to measure volumetric BMD (vBMD) of total, trabecular and cortical bone compartments, and bone geometry (area, cortical thickness, and strength strain index [SSI]). DXA scans (forearm, spine, and hip) were obtained to measure areal BMD (aBMD) and bone area. Receiver operating characteristic (ROC) analyses were used to assess screening performance of bone measurements.

Results

At the 4% pQCT site, total vBMD, but not trabecular vBMD or bone area, was lower (?3.4%; p?=?0.02) in cases than controls. At the 20% site, cases had lower cortical vBMD (?0.9%), cortical area (?2.8%), and SSI (?4.6%) (p?<?0.05). aBMD, but not bone area, at the 1/3 radius, spine, and hip were 2.7–3.3% lower for cases (p?<?0.01). Odds ratios per 1 SD decrease in bone measures (1.28–1.41) and areas under the ROC curves (0.56–0.59) were similar for all bone measures.

Conclusions

Low vBMD, aBMD, cortical area, and SSI of the distal radius were associated with an increased fracture risk. Interventions to increase these characteristics are needed to help reduce forearm fracture occurrence.     

Association of amount of physical activity with cortical bone size and trabecular volumetric BMD in young adult men: the GOOD study.

In this population-based study, amount of PA was associated with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones in young men. The lowest effective amount of PA was > or = 4 h/week. INTRODUCTION: Physical activity (PA) is believed to have positive effects on the skeleton and possibly help in preventing the occurrence of osteoporosis. Neither the lowest effective amount of PA needed to induce an osteogenic response nor its effect on the BMD and size of the different bone compartments (i.e., trabecular and cortical bone) has yet been clarified. MATERIALS AND METHODS: In this population-based study, we investigated the amount of all types of PA in relation to areal BMD (aBMD), trabecular and cortical volumetric BMD (vBMD), and cortical bone size in 1068 men (age, 18.9 +/- 0.02 years), included in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. aBMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT. RESULTS AND CONCLUSIONS: The amount of PA was associated with aBMD of the total body, radius, femoral neck, and lumbar spine, as well as with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones. The lowest effective amount of PA was > or = 4 h/week. aBMD, cortical bone size, and trabecular vBMD were higher in subjects who started their training before age 13 than in subjects who started their training later in life. Our data indicate that > or = 4 h/week of PA is required to increase bone mass in young men and that exercise before and during the pubertal growth is of importance. These findings suggest that PA is imperative for the augmentation of cortical bone size and trabecular vBMD but does not affect the cortical vBMD in young men.     

Reproducibility of Volume-Adjusted Bone Mineral Density of Spine and Hip from Dual X-ray Absorptiometry

Skeletal size has a confounding effect on areal bone mineral density (aBMD) related to differences in skeletal volume. Several methods have been proposed for calculating volumetric BMD (vBMD), but in vivo precision data are limited for the spine and have not been published for the hip. We prospectively performed duplicate dual X-ray absorptiometry measurements of the anteroposterior spine and hip (n = 121) in a diverse female population referred for initial clinical BMD testing. Each scan pair was performed and analyzed by two different technologists (mean interval of 4 d) to obtain standard aBMD. Scan data were reprocessed at a later date to calculate vBMD for the lumbar spine (L2-L4), femoral neck, and total hip in the 87 spines and 82 hips for which we had complete analyzable scan data. We found much worse precision in femoral neck volume (5.2% coefficient of variation [CV]) than in spine volume (2.6% CV; p < 0.003). This contributed to greater error in femoral neck vBMD (3.9% CV) than aBMD (2.3= CV; p < 10(-6)). Total hip aBMD had better precision than vBMD (1.0 and 1.3-2.5% CV; p < 10(-5)). The reverse pattern was seen in the spine with slightly better precision for vBMD than aBMD (1.1 and 1.5% CV; p < 0.002). Volumetric measures of lumbar spine density can be obtained with high precision. Because of poor reproducibility in the femoral neck, the total hip region may be preferable for measuring volumetric bone density in the proximal femur.