Severe osteoporosis with multiple spontaneous vertebral fractures in a young male carrying triple polymorphisms in the vitamin D receptor, collagen type 1, and low-density lipoprotein receptor-related peptide 5 genes

Osteoporosis is a common disease with a strong genetic component. Several studies have reported the vitamin D receptor (VDR), collagen type I (COL1A1), and LDL receptor-related protein 5 (LRP5) genes as the most likely candidates. However, most of the studies have been carried out in postmenopausal women and older men and show inconsistent results. CASE PRESENTATION: We report a case of a 26-year old male who presented with severe back pain of acute onset, unrelated to any kind of trauma, and diffuse myalgia. Imaging of the lumbar and the thoracic spine revealed two Grade 3, according to Genant’s semiquantitative method, vertebral fractures in T10 and T11 and multiple Grade 1 and 2 fractures from T8 to L2. Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy) showed severe osteoporosis of the lumbar spine (Z-score=−3.0, BMD = 0.866 gr/cm2). A complete laboratory and biochemical work-up was performed to exclude secondary causes of osteoporosis. Total genomic DNA was extracted from peripheral blood and was used as a template for genotype analysis. The patient was heterozygous for the p.V667M mutation of the LRP5 gene and for the BsmI [g.63980 G→A, rs1544410] and Sp1 polymorphisms fg.6252 G→T, rs1800012] of the VDR and COL1A1 genes, respectively. Further genotype analysis excluded types of osteogenesis imperfecta associated with mutations in the COL1A1 and COL1A2 genes. CONCLUSION: We herein show that the co-existence of three polymorphic sites in the VDR, COL1A1, and LPR-5 genes in a young male adult caused severe osteoporosis with multiple fractures, suggesting a combined effect and/or interaction between these genes.