The relation between osteoprotegerin gen mutation/polymorphism and pathologic fractures in multiple myeloma patients

Multiple Myeloma is a malignant plasma cell disorder which derived from single clone of plasma cells in the bone marrow and produces monoclonal immunglobulins. Osteopenia, bone destruction and pathological fractures are often observed in the course of disease due to increased activity of osteoclasts and decreased activity of osteoblasts. The Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) transforms precursor cells to osteoclasts in the bone marrow and Osteoprotogerin (OPG) acts as a decoy receptor for RANKL. The levels of RANKL increase while OPG levels decrease in MM. However, decreased levels of OPG may lead to the development of bone lesions regardless of RANKL, is not yet known. In this study, the effects of OPG gene (TNFRSF11B) mutations and/or single nucleotide polymorphism (SNP) on the development of bone lesions in MM were investigated.Fifty-two MM patients, 36 cases with pathological fractures and/or destructive bone lesion, 16 cases with no pathological fractures and/or destructive bone lesion) were enrolled into the study (admitted to Black Sea Technical University Hospital between January 2010-January 2012). After DNA isolation, OPG gene was sequenced. No OPG gene mutations were observed, but SNPs were detected in the DNA sequence analysis. The most common SNPs were homozygous and heterozygous rs2073617 C/T and rs2073618 C/G in exon 1. OPG gene homozygous and/or heterozygous rs 2073617 and rs 2073618 SNPs or association of heterozygous and homozygous rs 2073618 and rs 2073617 SNPs were found to have no effect on the development of pathological fractures and/or destructive bone lesions in patients with MM. However, association of homozygous rs2073617 and rs2073618 SNPs were found to be significantly higher in patients with pathological fractures and/or destructive bone lesion. Therefore, it was shown that the association of homozygous rs 2073617 and rs 2073618 SNPs may play a role in the development of destructive bone lesions and/or pathological fractures.It was concluded that, association of homozygous rs 2073617 and rs 2073618 SNPs in the OPG gene may lead to pathological fractures and/or destructive bone lesions, due to the reduced function of OPG and the activated RANKL-RANK pathway.