title: Mechanical, biochemical and morphometric alterations in the femur of mdx mice.
abstract: The bone tissue abnormalities observed in patients with Duchenne muscular dystrophy are frequently attributed to muscle weakness. In this condition, bones receive fewer mechanical stimuli, compromising the process of bone modeling. In the present study we hypothesize that other factors inherent to the disease might be associated with bone tissue impairment, irrespective of the presence of muscle impairment. Mdx mice lack dystrophin and present cycles of muscle degeneration/regeneration that become more intense in the third week of life. As observed in humans with muscular dystrophy, bone tissue abnormalities were found in mdx mice during more intense muscle degeneration due to age. Under these circumstances, muscle deficit is probably one of the factors promoting these changes. To test our hypothesis, we investigated the changes that occur in the femur of mdx mice at 21 days of age when muscle damage is still not significant. The mechanical (structural and material) and biochemical properties and morphometric characteristics of the femur of mdx and control animals were evaluated. The results demonstrated a lower strength, stiffness and energy absorption capacity in mdx femurs. Higher values for structural (load and stiffness) and material (stress, elastic modulus and toughness) properties were observed in the control group. Mdx femurs were shorter and were characterized by a smaller cortical area and thickness and a smaller area of epiphyseal trabecular bone. The hydroxyproline content was similar in the two groups, but there was a significant difference in the Ca/P ratios. Thermogravimetry showed a higher mineral matrix content in cortical bone of control animals. In conclusion, femurs of mdx mice presented impaired mechanical and biochemical properties as well as changes in collagen organization in the extracellular matrix. Thus, mdx mice developed femoral osteopenia even in the absence of significant muscle fiber degeneration. This weakness of the mdx femur is probably due to genetic factors that are directly or indirectly related to dystrophin deficiency.
authors.affiliation: Department of Anatomy, Cell Biology and Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Wilson Romero
authors.initials: WR
authors.lastname: Nakagaki
authors.forename: Celso Aparecido
authors.initials: CA
authors.lastname: Bertran
authors.forename: Cintia Yuri
authors.initials: CY
authors.lastname: Matsumura
authors.forename: Humberto
authors.initials: H
authors.lastname: Santo-Neto
authors.forename: José Angelo
authors.initials: JA
authors.lastname: Camilli
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D005269:Femur / Q000033:anatomy & histology* / Q000378:metabolism / Q000503:physiopathology*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008853:Microscopy; D013696:Temperature; D013818:Thermogravimetry
chemical_list: D006909:Hydroxyproline