Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation

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Introduction: Short-stature homeobox (. SHOX) gene haploinsufficiency may cause skeletal dysplasia including Léri-Weill Dyschondrosteosis (LWD), a clinical entity characterised by the triad of low height, mesomelic disproportion and Madelung's deformity of the wrist. Bone microarchitecture and estimated strength in adult SHOX mutation carriers have not been examined. Methods: Twenty-two subjects with a SHOX mutation including 7 males and 15 females with a median age of 38.8 [21.1-52.2] years were recruited from five unrelated families. The control group consisted of 22 healthy subjects matched on age and sex. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric density, microarchitecture and finite element estimated (FEA) bone strength were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). A full region of interest (ROI) image analysis and height-matched ROI analyses adjusting for differences in body height between the two groups were performed. Results: Areal BMD and T-scores showed no significant differences between cases and controls. Total radius area was smaller in cases than controls (207 [176-263] vs. 273 [226-298] mm, p<0.01). Radius cortical bone area (74±20 vs. 58±17mm 2, p=0.01) and thickness (1.16±0.30 vs. 0.84±0.26mm, p<0.01) as well as total density (428±99 vs. 328±72mg/cm 3, p<0.01) were higher in SHOX mutation carriers compared to controls. Radius trabecular bone area (119 [103-192] vs. 202 [168-247] mm 2, p<0.01) and trabecular number (1.61 [1.46-2.07] vs. 1.89 [1.73-2.08] mm -1, p=0.01) were smaller in SHOX mutation carriers. Tibia trabecular thickness was lower in cases (0.067±0.012 vs. 0.076±0.012mm, p=0.01). These results remained significant after adjustment for differences in body height and when restricting analyses to females. There were no differences in BMD, radius and tibia cortical porosity or FEA failure load between groups. A segment of cortical bone defect was identified in the distal radius adjacent to ulna in five unrelated SHOX mutation carriers. Conclusion: Subjects with a SHOX mutation presented with a different bone geometry in radius and tibia while there were no differences in BMD or failure load compared to controls, suggesting that mutations in SHOX gene may have an impact on bone microarchitecture albeit not bone strength.

Original languageEnglish
Pages (from-to)23-29
Publication statusPublished - Dec 2014


  • Bone microarchitecture
  • HR-pQCT
  • Léri-Weill Dyschondrosteosis
  • SHOX
  • Radius/diagnostic imaging
  • Bone Density
  • Humans
  • Middle Aged
  • Male
  • Tomography, X-Ray Computed
  • Absorptiometry, Photon
  • Short Stature Homeobox Protein
  • Young Adult
  • Homeodomain Proteins/genetics
  • Adult
  • Female
  • Mutation


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