Bone Abstracts

In recent years, the important role in bone remodelling Wnt/β-catenin pathway is highlighted. Key receptor of this pathway is LDL receptor-related protein 5 (LRP5). It was demonstrated in adults that polymorphism in LRP5 gene was associated with bone mineral density and fracture risk. So far no such studies were conducted in children.

The aim of the study was the analysis of LRP5 and COL1A1 genes in a patient with recurrent fractures and low bone mass of unknown aetiology.

Description of the patient and the method: A 14-year-old boy was admitted to the hospital because of recurrent low-trauma fractures. The patient sustained five fractures: the first took place at the age of 4, the last at 14 years of age; it was fracture of forearm (three times), humerus, and metatarsal bone. There was no fracture history in the family. The father of the patient suffered from pain in the extremities and in the spine; he was diagnosed with scoliosis. There were no abnormalities in the physical examination of the patient with exception of a slight scoliosis. We diagnosed low bone mass by DXA method: Z-score index in the AP spine was −2.2. Hormonal disorders, malabsorption syndrome, chronic inflammation, kidney and liver diseases were excluded. An analysis of the LRP5 and COL1A1 gene by direct sequencing was performed. LRP5 analysis was also conducted in the parents and siblings of the patient.

Results: We identified a new, not yet described in the literature, R1146C heterozygous mutation (c.3436 C> T, CGC> TGC) in the LRP5 gene sequences. The same mutation was found in the patient’s father, but it was not present in the mother and siblings. We did not identify COL1A1 gene mutation.

Conclusions: • LRP5 gene mutation may be the cause of recurrent fractures and low bone mass in the examined patient.

• It seems likely that the scoliosis, and bone pain in the patient’s father are also related to LRP5 mutation.

Acknowledgements: The study was financed as a grant NN407 060 938.