Cystic fibrosis-related bone disease in children: Examination of peripheral quantitative computed tomography (pQCT) data.

The investigation of skeletal health data beyond dual X-ray absorptiometry (DXA) is limited in young individuals with CF. We assessed volumetric bone mineral densities (BMD), and bone and muscle parameters using peripheral quantitative computed tomography (pQCT) in individuals with CF and controls, 7.00-17.99 years. Peripheral QCT (XCT 3000, Stratec) measurements were made in 53 individuals with CF and 53 controls. Bone mineral content (BMC), total volumetric BMD (vBMD) and cross sectional area (CSA) of the bone were measured at the 4% and 66% sites of the non-dominant tibia and radius. Additionally, trabecular vBMD and bone strength index (BSIc) were measured at the 4% sites, and cortical vBMD, muscle CSA (mCSA) and strength strain index (SSI) were measured at the 66% sites. Pre-pubertal males with CF had greater trabecular vBMD (p=0.01) and total vBMD (p=0.00) at 4% tibia, and greater total vBMD (p=0.02) at 4% radius. Pre-pubertal females with CF had greater total vBMD at 66% tibia (p=0.02) and radius (p=0.04), and cortical vBMD (p=0.04) at the radius. At puberty, the CF cohort had less BMC at 4% tibia (males, p=0.02; females, p=0.01), and smaller mCSA at 66% tibia (males, p=0.02; females, p=0.01). Pubertal CF females had a smaller bone CSA (p=0.01) at 4% tibia, and lower bone strength (SSI) at the tibia (p=0.00) and radius (p=0.05) sites. Bone strength parameters were not compromised prior to puberty in this CF cohort. At puberty, the bone phenotype changed for this CF cohort, showing several deficits compared to the controls. However, bone strength was adapting to the mechanical demands of the muscle. Altered bone parameters and their implications for lowered bone strength with increased age may be greatly influenced by: the CF cohort remaining smaller for age and/or a reduced bone strain, secondary to reduced muscle force.

Brookes DS ，Briody JN ，Munns CF ，Davies PS ，Hill RJ ... -  《-》

Bone geometry and density in the skeleton of pre-pubertal gymnasts and school children.

Ward KA ，Roberts SA ，Adams JE ，Mughal MZ ... -  《-》

Adults with cystic fibrosis have deficits in bone structure and strength at the distal tibia despite similar size and measuring standard and relative sites.

Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race. To assess the effect of limb length and minimize the confounding effects of size on HR-pQCT outcomes, we scanned participants at both the standard fixed HR-pQCT measurement sites and at a subject-specific relative site that varied according to limb length. CF participants did not differ significantly in age, height, weight, or BMI from controls. Ulnar and tibial lengths were 9mm shorter in CF patients, though differences were not significant. CF patients had significantly lower BMI-adjusted aBMD by DXA at the lumbar spine (8.9%, p<0.01), total hip (11.5%, p<0.01) and femoral neck (14.5%, p<0.01), but not at the forearm. At the fixed radius site, thickness of trabecular plates and torsional stiffness were significantly lower in CF participants than controls. At the relative radius site, only torsional stiffness was significantly lower in CF participants. At the tibia, total, trabecular and cortical vBMD were significantly lower at both fixed and relative sites in CF participants, with fewer, more widely-spaced trabecular plates, lower trabecular connectivity, and lower axial and torsional stiffness. Our results confirm that aBMD is lower at the spine and hip in young adults with CF, independent of BMI and body size. We also conclude that vBMD and stiffness are lower at the weight-bearing tibia. The pathogenesis of these differences in bone density and strength at the tibia appear to be related to trabecular drop-out and reduced trabecular connectivity and to be independent of differences in limb length, as assessed by scanning participants at both standard and relative sites. We concluded that significant deficits in bone structure and strength persist in young adults with CF, despite advances in care that permit them to attain relatively normal height and weight.

Nishiyama KK ，Agarwal S ，Kepley A ，Rosete F ，Hu Y ，Guo XE ，Keating CL ，DiMango EA ，Shane E ... -  《-》

Compromised bone microarchitecture and estimated bone strength in young adults with cystic fibrosis.

Putman MS ，Milliren CE ，Derrico N ，Uluer A ，Sicilian L ，Lapey A ，Sawicki G ，Gordon CM ，Bouxsein ML ，Finkelstein JS ... -  《-》

Trabecular and cortical bone deficits are present in children and adolescents with cystic fibrosis.

Osteopenia and increased fracture rates are well-recognized in adults with CF, but neither the specific contributions of cortical and trabecular bone deficits to bone fragility nor their presence in youth with CF are well-characterized. This study sought to characterize cortical and trabecular volumetric bone mineral density (vBMD), geometry, and biomechanical competence in children with CF and determine their relationship to growth, body composition, and disease severity. Peripheral quantitative computerized tomography (pQCT) measures of total, cortical, and trabecular vBMD, cortical, muscle, and fat cross-sectional areas (CSA), periosteal and endosteal circumferences, and the polar unweighted section modulus (Zp) of the tibia were converted to age- and tibial length-adjusted Z-scores in 97 CF and 199 healthy children (aged 8-21y). Effects of body composition and pulmonary function (forced expiratory volume in 1s, FEV1) upon pQCT outcomes were determined using linear regression. Children with CF (FEV1%-predicted: 84.4+19.7) had lower weight-, height-, BMI-, and whole body lean mass (LBM)-Z and tibial length. Females with CF had lower (p<0.01) total and trabecular vBMD; cortical, muscle, and fat CSA; Zp and periosteal circumference than females in the healthy reference group. These bone differences persisted after adjustment for BMI-Z and to a great extent following adjustment for muscle CSA. Males with CF had lower (p<0.01) cortical, muscle, and fat CSA and their trabecular vBMD deficit approached significance (p=0.069). Deficits were attenuated by adjustment for BMI-Z and to a greater extent adjustment for muscle CSA-Z. The relationship between FEV1%-predicted and pQCT outcomes persisted only in males following adjustment for age and BMI-Z. The CF cohort had lower tibial muscle CSA than expected for their LBM. In this relatively healthy, young CF cohort, deficits in trabecular and multiple cortical bone parameters were present. In females, deficits were greater at older ages and were not fully explained by alterations in body composition. In males worsening pulmonary function was associated with greater deficits that was not explained by increasing age or compromised nutritional status. The occurrence of these differences in CF youth highlights the importance of instituting measures to optimize peak bone mass early in the course of CF.

Kelly A ，Schall J ，Stallings VA ，Zemel BS ... -  《-》