Increased cortical area and thickness in the distal radius in subjects with SHOX-gene mutation |
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| Affiliation: | 1. Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark;2. Department of Endocrinology, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense, Denmark;1. Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;2. Department of Orthopedic Surgery, Boston Children''s Hospital, Harvard Medical School, Boston, MA, USA;3. Pediatric Nephrology Unit, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;1. Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Heinrich Collin Str. 30, A-1140 Vienna, Austria;2. Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, Quebec H3G 1A6, Canada;3. Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany;1. Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;2. Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;3. Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu 803-8580, Japan;1. Orthopaedic Surgery, University Paris East, Hôpital Henri Mondor, 94010 Creteil, France;2. University Paris East, Hôpital Henri Mondor, 94010 Creteil, France;3. EFS Cell Therapy Facility, University Paris East, Hôpital Henri Mondor, 94010 Creteil, France;1. Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia;2. Orthopaedic Research & Biotechnology Unit, The Children''s Hospital at Westmead, Sydney, Australia;3. Tissue Department of Biochemistry, Rush University Medical Center, USA;4. Institute of General Zoology and Endocrinology, University of Ulm, Ulm, Germany;5. Department of Endocrinology & Metabolism, Concord Hospital, Sydney, Australia |
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| Abstract: | IntroductionShort-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.MethodsTwenty-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.ResultsAreal 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 ± 17 mm2, p = 0.01) and thickness (1.16 ± 0.30 vs. 0.84 ± 0.26 mm, p < 0.01) as well as total density (428 ± 99 vs. 328 ± 72 mg/cm3, p < 0.01) were higher in SHOX mutation carriers compared to controls. Radius trabecular bone area (119 [103–192] vs. 202 [168–247] mm2, 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 ± 0.012 mm, 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.ConclusionSubjects 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. |
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