<i>Polg</i> mtDNA mutator mice reveal limited involvement of vertebral bone loss in premature aging-related thoracolumbar hyperkyphosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36120646.
- Also identified by DOI 10.1016/j.bonr.2022.101618 and PMC identifier 9479024.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Age-related hyperkyphosis is multifactorial and involves alterations of vertebral bone, intervertebral discs (IVD) and paraspinal muscles. The relative contribution of these tissues remains unclear. Here, we compared differences in vertebral bone microarchitecture and IVD thickness between prematurely aging mice with spinal hyperkyphosis and wild type littermates. Thoracolumbar vertebral columns were dissected from homozygous <i>Polg</i> <sup><i>D257A</i></sup> and age-matched wild type littermates. Micro-computed tomography was performed to quantify cortical and trabecular bone parameters at anterior and posterior portions of T8-L4 vertebrae. In addition, vertebral shape, transaxial facet joint orientation and IVD thickness were quantified. Differences in anterior/posterior ratios between genotypes were compared by Student's <i>t-</i>test and association between vertebral bone and IVD parameters was investigated using Pearson correlation analysis. Hyperkyphotic homozygous mice displayed generalized osteopenia that was more pronounced at the posterior compared with anterior portion of thoracolumbar vertebrae. An increase in the anterior/posterior ratio of trabecular bone parameters was revealed at the thoracolumbar junction (T13-L1). <i>Polg</i> <sup><i>D257A</i></sup> displayed diffuse loss of cortical bone thickness, yet anterior/posterior ratios were unchanged. Despite generalized and regional bone loss, vertebral shape was unaffected. <i>PolG</i> <sup><i>D257A</i></sup> mice showed a 10-20 % reduction of IVD thickness at both thoracic and lumbar levels, with only minimal histopathological changes. IVD thickness was negatively correlated with anterior/posterior ratios of trabecular bone parameters, as well as with more coronally oriented facet joints, but negatively correlated with the anterior/posterior ratio of cortical bone thickness. Aging-induced regional changes of vertebral trabecular and cortical bone did not lead to altered vertebral shape in <i>Polg</i> <sup><i>D257A</i></sup> mice but may indirectly cause hyperkyphosis through reduction of IVD thickness. These findings suggest a limited role for aging-induced bone loss in spinal hyperkyphosis and warrants further research on the involvement of paraspinal muscle degeneration.