title: Children with nephrotic syndrome have greater bone area but similar volumetric bone mineral density to healthy controls.
abstract: BACKGROUND
  Glucocorticoid use has been associated with an increased fracture risk and reduced bone mineral density (BMD), particularly in the trabecular compartment. However the contribution of the underlying inflammatory disease process to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) typically follows a relapsing-remitting course often requiring recurrent courses of glucocorticoids, but with low systemic inflammation during remission. NS therefore represents a useful clinical model to investigate the effects of glucocorticoids on BMD and bone geometry in childhood.
  
  
  METHODS
  Children with NS were compared to age and sex matched healthy controls. Body composition and areal BMD (whole body, lumbar spine and hip) were assessed by DXA. Peripheral quantitative computed tomography (pQCT) scans were obtained at metaphyseal (4%) and diaphyseal (66%) sites of the tibia to determine volumetric BMD and bone cross-sectional geometry. Lifetime cumulative glucocorticoid exposure was calculated from medical records.
  
  
  RESULTS
  29 children with NS (55% male, age 10.7±3.1years) were compared to 29 healthy controls (55% male, age 11.0±3.0years). The children with NS were of similar height SDS to controls (p=0.28), but were heavier (0.65±1.28SDS vs -0.04±0.89SDS, p=0.022) and had greater body fat percentage SDS (0.31±1.01 vs -0.52±1.10, p=0.008). Tibial trabecular and cortical vBMD were similar between the two groups but bone cross-sectional area (CSA) was significantly greater in children with NS at both the metaphysis (954±234mm(2) vs 817±197mm(2), p=0.002) and diaphysis (534.9±162.7mm(2) vs 463.2±155.5mm(2), p=0.014). Endosteal and periosteal circumferences were greater in children with NS than controls (both p<0.01), resulting in reduced cortical thickness (2.4±0.7mm vs 2.8±0.7mm, p=0.018), but similar cortical CSA (p=0.22). The differences in cortical geometry were not statistically significant when weight was included as a confounding factor. There were no associations between cumulative steroid exposure, duration of NS or number of relapses and any bone parameter.
  
  
  CONCLUSIONS
  Tibial bone CSA is increased in children with NS. We speculate that this is a compensatory response to increased body weight. Defects in trabecular BMD were not identified in this cohort of children with NS.
authors.affiliation: Paediatric Endocrinology, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, University Hospital Southampton, Tremona Road, Southampton SO16 6YD, UK. Electronic address: rm@mrc.soton.ac.uk.
authors.forename: R J
authors.initials: RJ
authors.lastname: Moon
authors.forename: R D
authors.initials: RD
authors.lastname: Gilbert
authors.forename: A
authors.initials: A
authors.lastname: Page
authors.forename: L
authors.initials: L
authors.lastname: Murphy
authors.forename: P
authors.initials: P
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: E M
authors.initials: EM
authors.lastname: Dennison
authors.forename: J H
authors.initials: JH
authors.lastname: Davies
mesh_terms: D015502:Absorptiometry, Photon; D015519:Bone Density / Q000502:physiology*; D016022:Case-Control Studies; D002648:Child; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009404:Nephrotic Syndrome / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D013977:Tibia / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed
keywords: Bone geometry; Bone mineral density; Glucocorticoids; Nephrotic syndrome; pQCT