Changes in pediatric DXA measures of musculoskeletal outcomes and correlation with quantitative CT following treatment of acute lymphoblastic leukemia.

We previously reported significant gains in pQCT measures of tibia trabecular bone mineral density (BMD) and cortical structure following completion of therapy in children and adolescents with acute lymphoblastic leukemia (ALL). The objective of this study was to examine changes in DXA measures used in clinical practice and expressed as Z-scores using robust national reference data. Children and adolescents, ages 5 to 18 years were enrolled within 2 (median 0.8) years of completing ALL therapy. DXA total-body less-head bone mineral content (TBLH-BMC), and spine, total hip, femoral neck, and 1/3rd radius areal BMD (aBMD) were assessed in 45 participants at enrollment and 12-months later. Linear regression models examined correlates of changes in DXA Z-scores. Changes in DXA outcomes were compared to changes in tibia pQCT trabecular and cortical volumetric BMD (vBMD) and cortical area. At enrollment, DXA TBLH-BMC, spine and radius aBMD Z-scores were not significantly reduced in ALL survivors; however, total hip [median -0.74 (IQ range -1.51 to -0.04)] and femoral neck [-0.51 (-1.24 to 0.14)] aBMD Z-scores were lower (both p < 0.01) compared to reference data. DXA Z-scores at all skeletal sites increased over 12 months. Despite improvement, total hip Z-score remained lower at -0.55 (-1.05 to 0.18). The increases in TBLH-BMC, total hip and femoral neck aBMD Z-scores were more pronounced in those enrolled within 6 months of completing ALL therapy, compared to those enrolled at >6 months. Gains in TBLH-BMC, total hip, femoral neck and radius aBMD Z-scores were significantly associated with gains in tibia cortical area Z-scores (R = 0.56 to 0.67, p ≤ 0.001). Changes in TBLH and proximal femur sites were associated with gains in trabecular vBMD Z-scores (R = 0.37 to 0.40; p ≤ 0.01); these associations were not significant when adjusted for gains in cortical area. In summary, gains in DXA measures were most pronounced in total hip and femoral neck following ALL therapy. The gains in all DXA measures, with the exception of lumbar spine, reflected gains in cortical area. Overall, ALL survivors demonstrate skeletal recovery following completion of therapy; a small sub-group continue to demonstrate deficits and benefit from continued observation to ensure improvement over time.

Mostoufi-Moab S ，Kelly A ，Mitchell JA ，Baker J ，Zemel BS ，Brodsky J ，Long J ，Leonard MB ... -  《-》

A multi-imaging modality study of bone density, bone structure and the muscle - bone unit in end-stage renal disease.

End stage renal disease (ESRD) is associated with sarcopenia and skeletal fragility. The objectives of this cross-sectional study were to (1) characterize body composition, bone mineral density (BMD) and bone structure in hemodialysis patients compared with controls, (2) assess whether DXA areal BMD (aBMD) correlates with peripheral quantitative CT (pQCT) measures of volumetric BMD (vBMD), cortical dimensions and MRI measures of trabecular microarchitecture, and (3) determine the magnitude of bone deficits in ESRD after adjustment for muscle mass. Thirty ESRD participants, ages 25 to 64 years, were compared with 403 controls for DXA and pQCT outcomes and 104 controls for MRI outcomes; results were expressed as race- and sex- specific Z-scores relative to age. DXA appendicular lean mass index (ALMI kg/m2) and total hip, femoral neck, ultradistal and 1/3rd radius aBMD were significantly lower in ESRD, vs. controls (all p < 0.01). pQCT trabecular vBMD (p < 0.01), cortical vBMD (p < 0.001) and cortical thickness (due to a greater endosteal circumference, p < 0.02) and MRI measures of trabecular number, trabecular thickness, and whole bone stiffness were lower (all p < 0.01) in ESRD, vs. controls. ALMI was positively associated with total hip, femoral neck, ultradistal radius and 1/3rd radius aBMD and with tibia cortical thickness (R = 0.46 to 0.64). Adjustment for ALMI significantly attenuated bone deficits at these sites: e.g. mean femoral neck aBMD was 0.79 SD lower in ESRD, compared with controls and this was attenuated to 0.33 with adjustment for ALMI. In multivariate models within the dialysis participants, pQCT trabecular vBMD and cortical area Z-scores were significant and independently (all p < 0.02) associated with DXA femoral neck, total hip, and ultradistal radius aBMD Z-scores. Cortical vBMD (p = 0.01) and cortical area (p < 0.001) Z-scores were significantly and independently associated with 1/3rd radius areal aBMD Z-scores (R2 = 0.62). These data demonstrate that DXA aBMD captures deficits in trabecular and cortical vBMD and cortical area. The strong associations with ALMI, as an index of skeletal muscle, highlight the importance of considering the role of sarcopenia in skeletal fragility in patients with ESRD.

Leonard MB ，Wehrli FW ，Ziolkowski SL ，Billig E ，Long J ，Nickolas TL ，Magland JF ，Nihtianova S ，Zemel BS ，Herskovitz R ，Rajapakse CS ... -  《-》

Impaired bone mineral density and microarchitecture in female adolescents with IgE-mediated cow's milk allergy.

This study compared the bone parameters of adolescents with persistent cow's milk allergy (CMA) with those of healthy adolescents. Adolescents with CMA had compromised bone parameters (lower bone mineral density, impaired trabecular microarchitecture, and lower bone strength). Partial exclusion diet was associated with better bone parameters than total exclusion diet. Persistent immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) may impair bone parameters and increase the risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel methodology that not only assesses trabecular and cortical bone compartments and volumetric density measurements, but also evaluates bone microarchitecture and estimates biomechanical properties through finite element analysis (FEA). Both HR-pQCT and bone strength parameters derived from FEA have shown a strong correlation with fracture risk. To assess the bone density, microarchitecture, and bone strength of adolescents with persistent IgE-mediated CMA (IgE-CMA). This was an observational, cross-sectional study with female adolescents with persistent IgE-CMA and healthy control participants matched by female sex and sexual maturation. Bone parameters were assessed by areal bone mineral density (aBMD) through dual-energy X-ray absorptiometry (DXA), bone microarchitecture by HR-pQCT at the radius and tibia, and laboratory markers related to bone metabolism. The median age of adolescents with persistent IgE-CMA (n = 26) was 13.0 years (interquartile range (IQR) 11.4-14.7) and of healthy control participants (n = 28) was 13.6 years (IQR 11.9-14.9). Adolescents with IgE-CMA ingested 27.4% less calcium (p = 0.012) and 28.8% less phosphorus (p = 0.009) than controls. Adolescents with IgE-CMA had lower bone mineral content (BMC) (38.83 g vs. 44.50 g) and aBMD (0.796 g/cm2 vs. 0.872 g/cm2) at lumbar spine, and lower BMC (1.11 kg vs. 1.27 kg) and aBMD (0.823 g/cm2 vs. 0.877 g/cm2) at total body less head (TBLH) (p < 0.05). However, Z-scores BMC and Z-scores aBMD at lumbar spine and TBLH, when adjusted for Z-score height/age, were not significantly different between the groups. Moreover, CMA adolescents had lower bone strength at the distal tibia (S 169 kN/mm vs. 194 kN/mm; F Load 8030 N vs. 9223 N) (p < 0.05). Pairing of groups by the presence of menarche showed compromised parameters at the tibia-lower total volumetric BMD (Tt.vBMD) (293.9 mg HA/cm3 vs. 325.9 mg HA/cm3) and trabecular vBMD (Tb.vBMD) (170.8 mg HA/cm3 vs. 192.2 mg HA/cm3), along with lower cortical thickness (Ct.th) (1.02 mm vs. 1.16 mm) and bone strength (S 174 kN vs. 210 kN; F Load 8301 N vs. 9950 N)-and at the radius (S 61 kN/mm vs. 71 kN/mm; F Load 2920 N vs. 3398 N) (p < 0.05) among adolescents with IgE-CMA. Adolescents with IgE-CMA on a total exclusion diet (n = 12) showed greater impairment of bone features than those on a partial exclusion diet (n = 14), with lower lumbar spine Z-score BMC (- 0.65 vs. 0.18; p = 0.013), lumbar spine trabecular bone score (TBS) (1.268 vs. 1.383; p = 0.005), Z-score TBS (0.03 vs. 1.14; p = 0.020), TBLH Z-score BMC (- 1.17 vs. - 0.35; p = 0.012), TBLH Z-score aBMD (- 1.13 vs. - 0.33; p = 0.027), Tt.vBMD at the tibia (259.0 mg HA/cm3 vs. 298.7 mg HA/cm3; p = 0.021), Ct.th at the tibia (0.77 mm vs. 1.04 mm; p = 0.015) and Ct.th at the radius (0.16 mm vs. 0.56 mm; p = 0.033). Adolescents with persistent IgE-CMA had lower aBMD and compromised microarchitecture (impaired trabecular microarchitecture and lower bone strength). Adolescents on a partial exclusion diet had better bone parameters than those on a total exclusion diet.

Yonamine GH ，Domiciano DS ，Takayama L ，Castro APBM ，Pereira RMR ，Pastorino AC ... -  《-》

Bone microstructure in healthy men measured by HR-pQCT: Age-related changes and their relationships with DXA parameters and biochemical markers.

The primary purpose of this cross-sectional study was to investigate the characteristics of age-related changes in bone microstructure on high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) on dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers in men. The secondary purpose of this study was to examine how bone microstructure is related to aBMD and biochemical markers. The subjects were 128 healthy Japanese men (20-97 years old). Bone microstructure was measured in the distal radius and tibia using second-generation HR-pQCT; aBMD in the proximal femur and lumbar spine was measured with DXA; and tartrate-resistant acid phosphatase-5b (TRACP-5b), type I procollagen-N-propeptide (P1NP), 25(OH) vitamin D, and pentosidine concentrations were measured by blood tests. In trabecular bone, the trabecular volumetric BMD (Tb.vBMD) and trabecular number (Tb.N) were lower with age (r = -0.23, -0.35) (r = -0.36,-0.33), and trabecular separation (Tb.Sp) and the star volume of marrow space (V*ms) were higher with age (r = 0.29, 0.41) (r = 0.34, 0.38) in both the radius and tibia. In cortical bone, cortical volumetric BMD (Ct.vBMD) was lower with age (r = -0.25, -0.52), and cortical porosity (Ct.Po) was higher with age (r = 0.67, 0.62) in both the radius and tibia. In the tibia, cortical thickness (Ct.Th) and cortical area (Ct.Ar) were lower with age (r = -0.40) (r = -0.43), whereas, in the radius, they were maintained, and periosteal perimeter (Ct.Pm) was higher with age (r = 0.35). aBMD in the proximal femur and P1NP were lower, and pentosidine was higher with increased age, whereas aBMD in the lumbar spine, TRACP-5b, and 25(OH) vitamin D had no relationships with age. DXA and HR-pQCT showed strong correlations particularly with femoral aBMD and tibial Tb.vBMD and Ct.Ar (r = 0.61) (r = 0.61), whereas no DXA parameters were related with Ct.Po. In correlations between biochemical markers and HR-pQCT, TRACP-5b and total P1NP were negatively correlated with Ct.vBMD (r = -0.31) (r = -0.35), but almost no other correlations were seen. Age-related changes of the bone microstructure in men were characterized by decreases in trabecular and cortical vBMD associated with decreased trabecular number, cavitation of the trabecular structure, and increased cortical porosity. Femoral aBMD was strongly related to bone microstructure in the tibia, whereas both lumbar aBMD and femoral aBMD were not related to Ct.Po, and biochemical markers showed almost no relationships with bone microstructure.

Doi M ，Chiba K ，Okazaki N ，Kondo C ，Yamada S ，Yokota K ，Yonekura A ，Tomita M ，Osaki M ... -  《-》

Catch up in bone acquisition in young adult men with late normal puberty.

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5-year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual-energy X-ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R(2) aBMD 11.7%; BMC 4.3%), radius (R(2) aBMD 23.5%; BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow-up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years.

Darelid A ，Ohlsson C ，Nilsson M ，Kindblom JM ，Mellström D ，Lorentzon M ... -  《-》