Drug Discovery Opinion

….not the skull bone, according to researchers in the UK led by scientists at Queen Mary, University of London. Writing in PLoS ONE, the team describe fundamental differences between bone that makes up the skull and bone in limbs. Although bones in the limbs become progressively weaker as people age, bone mass in the protective skull vault is maintained. Bone mass in weight bearing bones is maintained by a mechanically driven feedback mechanism but, when this fails, bone mass no longer matches demand and fractures are likely to occur. Although parietal bones of the skull are subject to low levels of strain that would cause ‘disuse’ bone loss in limbs, paradoxically skull bones do not lose strength. The skull bones are also resistant to post-menopausal hormonal changes and to glucocorticoid treatment-induced osteoporosis which occur in other bones.

Previous research has generally addressed the question ‘why is bone mass lost from weight-bearing limb bones despite continued usage?’ but the new study instead asks ‘how is bone mass and mechanical competence achieved in low weight-bearing skull bones despite continued ‘disuse’?’ Previous evidence had suggested differences between bones in the skull and the rest of the skeleton: mineral density and calcium concentration are greater in the skull and osteocytes in the skull have a more rounded appearance than osteocytes from long bones. The authors of the present study suggest that cell lineage may contribute, at least in part, to the differences between the skull and other bones. Investigation of basal gene expression identified 1236 genes (approximately 4% of the genome), including genes known to be involved in the formation of healthy bones, that were at least two-fold differentially expressed between ulnar limb and parietal skull bone. Since genes associated with bone mass and mineral density are differentially expressed in functionally distinct skeletal sites, better clinical outcomes following grafts and tissue engineering/regeneration protocols might be achieved by site matching of bone source to recipient site. The authors hope that it may also be possible to exploit their findings to develop new ways to treat or prevent osteoporosis.

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