title: Devastation of bone tissue in the appendicular skeleton parallels the progression of neuromuscular disease.
abstract: A mouse model of spinal muscular atrophy with respiratory distress (SMARD1) was used to study the consequences of neuromuscular degenerative disease on bone quantity and morphology. Histomorphometry and micro-computed tomography were used to assess the cortical and cancellous bone in the tibia, femur and humerus of adult neuromuscular degeneration (nmd) mice (up to 21w) and age-matched wild-type controls (WT). At 21w, the average lengths of the humerus, tibia and femur were 15%, 10%, and 10% shorter in the nmd mice, respectively. The midshaft of the humerus, tibia and femur of nmd mice had 41%, 47% and 34% less cortical bone than the WT. In the humeral, tibial, and femoral metaphyses of the nmd mice, there was 50%, 78%, and 85% less trabecular bone volume, and 58%, 92%, and 94% less trabecular connectivity than the WT. NMD cortical bone had less than half of the 42% active surface measured in the WT, yet the mineral apposition rate of those surfaces were similar between strains (nmd: 1.80 microm x day(-1); WT: 2.05 microm x day(-1)). Osteoclast number and activity levels did not differ across strains. These data emphasize that neuromuscular degeneration as a result of immunoglobulin S-mu binding protein-2 (Ighmbp2) mutation will compromise several critical parameters of bone quantity and architecture, the most severe occurring in the trabecular compartment.
authors: Department of Biomedical Engineering, State University of New York, Stony Brook, New York 11794-2580, USA.
authors: B J
authors: BJ
authors: Lee
authors: G A
authors: GA
authors: Cox
authors: T P
authors: TP
authors: Maddatu
authors: S
authors: S
authors: Judex
authors: C T
authors: CT
authors: Rubin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D009154:Mutation; D009929:Organ Size / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology*; D010243:Paralysis / Q000235:genetics; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics / Q000473:pathology*; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics; D055114:X-Ray Microtomography
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors