The TNFRSF11B (OPG) 163 T>C polymorphism genetic test analyzes a specific variation in the TNFRSF11B gene, which encodes osteoprotegerin (OPG), a crucial regulator of bone remodeling and osteoclast inhibition. This test detects a thymine (T) to cytosine (C) substitution at nucleotide position 163, a genetic variation associated with differences in OPG expression levels, bone mineral density (BMD), and susceptibility to osteoporosis. As OPG functions as a decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL), genetic alterations affecting its expression influence bone resorption, skeletal strength, and fracture risk.
OPG is an essential glycoprotein that regulates the balance between bone formation and degradation by binding to RANKL and preventing it from interacting with its receptor RANK on osteoclast precursors. This inhibition reduces osteoclast activation and limits bone resorption, preserving bone mass and structural integrity. The 163 T>C polymorphism, located in a regulatory region of the TNFRSF11B gene, has been associated with variations in OPG production, influencing bone homeostasis and skeletal health. Studies suggest that individuals carrying the C allele may exhibit lower circulating OPG levels, leading to increased osteoclast activity, enhanced bone turnover, and a greater likelihood of osteoporosis-related fractures, particularly in postmenopausal women and elderly populations.
Bone remodeling is a tightly regulated process influenced by genetic, hormonal, and environmental factors, with OPG playing a central role in skeletal integrity. The 163 T>C polymorphism has been extensively studied in osteoporosis, where decreased OPG levels accelerate bone loss and increase fracture risk. Carriers of the C allele may experience a greater decline in BMD over time, particularly in weight-bearing bones such as the hip, spine, and femur. Genetic influences on OPG function also contribute to differences in peak bone mass acquisition during early adulthood, affecting long-term skeletal strength and fracture susceptibility.
Beyond osteoporosis, genetic variations in TNFRSF11B have been implicated in other bone-related disorders, including osteoarthritis and Paget’s disease, where abnormal bone remodeling contributes to structural damage and joint degeneration. OPG has also been recognized as a key factor in vascular calcification, with lower circulating levels associated with an increased risk of atherosclerosis, arterial stiffness, and cardiovascular disease. The involvement of OPG in inflammatory bone diseases such as rheumatoid arthritis has been explored, as altered RANK/RANKL/OPG signaling contributes to excessive osteoclast-mediated bone destruction.
Genetic testing for the TNFRSF11B (OPG) 163 T>C polymorphism provides valuable insight into an individual’s genetic predisposition to osteoporosis, bone fragility, and metabolic bone disorders. Identifying this variant allows for assessing bone resorption activity and skeletal health, contributing to a deeper understanding of bone metabolism and fracture susceptibility.
The TNFRSF11B (OPG) 163 T>C polymorphism genetic test is also included in:
