New form of hereditary osteoporosis identified

A research group led by the professor Outi Mäkitie, Unviersity of Helsinki, identified in families with mutations causing a disease of osteoporosis in children, in a gene that was previously unrelated to the skeletal system or osteoporosis.

"Through extensive genetic research, we have identified a genetic defect underlying osteoporosis in two Finnish families with multiple affected limbs, and in collaboration with Dutch and US researchers we have found four additional families with mutations. in the same gene leading to osteoporosis – as in the Finnish patients – or an even more serious bone disease badociated with a small and severe size and disturbed bone development, "explains Mäkitie.

"Mutations in the SGMS2 gene have been identified as the cause of the disease, SGMS2 encodes an enzyme involved in the metabolism of sphingolipids, mutations result in changes in enzyme function and, through mechanisms up to the present time. Not yet known, a serious disturbance of bone metabolism and mineralization, "says Minna Pekkinen, PhD, one of the principal investigators of the study.

Since childhood, mutation carriers have suffered limb and spine fractures, even as a result of minor injuries. Some subjects in the study also had neurological symptoms, with transient facial nerve palsy being particularly common and which, according to Mäkitie, could be one of the hallmarks of this form of osteoporosis.

The examination of bone samples taken from three patients showed that their bone tissue was different from normal bone tissue: the number of bone cells was atypical and the bone mineralization disrupted. The changes were particularly evident in the cortical bone – the outer layer of the bone – in the most abundant region of SGMS2 gene expression.

"Our discovery of genes is very important because it dramatically improves understanding of the mechanisms underlying osteoporosis and opens new avenues for the development of osteoporosis drug diagnoses and treatments," says Mäkitie. .

Osteoporosis is characterized by low bone mineral density and deteriorated bone microstructure, expressed by increased bone fragility and fracture propensity. According to current knowledge, genes are among the key factors that determine bone strength. However, researchers have so far identified only a few genes that have a significant effect on the risk of bone loss whose mutations are at the origin of familial osteoporosis.

The Mäkitie research group, active at the University of Helsinki, at the new children's hospital of the Helsinki and Uusimaa hospital districts and at the Folkhälsan research center, is studying the causes of early osteoporosis and, in particular, genetic abnormalities that predispose individuals to osteoporosis. . Previously, the group had already identified a new form of osteoporosis (Laine CM et al., NEJM 2013).