What you carry at this position in your DNA and what research says about it.
Bone and Joint Health: 9/10 evidence, 30 publications.
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Sample genotype (not yours): A/A
Higher Osteoporosis Risk and Lower Bone Density
This genotype is associated with lower bone mineral density and an increased risk of developing osteoporosis. However, it may offer some protection against developing osteoarthritis in the hips.
What this genotype means: Lower bone mineral density; Increased risk of osteoporosis; Lower risk of osteoarthritis.
Sample genotype (not yours): A/C
Typical Bone Density and Osteoarthritis Risk
This genotype is associated with average bone mineral density and a typical risk of developing osteoporosis or osteoarthritis. It represents a balanced genetic profile for bone and joint health.
What this genotype means: Typical bone mineral density; Average osteoporosis risk; Typical osteoarthritis risk.
Sample genotype (not yours): C/C
Stronger Bones but Higher Osteoarthritis Risk
This genotype is associated with higher bone mineral density, which protects against osteoporosis, but it also carries an increased risk of developing osteoarthritis. It represents a classic biological trade-off between bone strength and joint wear.
What this genotype means: Higher bone mineral density; Lower risk of osteoporosis; Increased risk of osteoarthritis.
Gene function and biological role
Gene Function: The TNFRSF11A gene encodes the RANK receptor, a key regulator of bone remodeling [1]. RANK interacts with its ligand to stimulate the formation and activation of osteoclasts, the cells responsible for breaking down bone tissue [2]. This process is essential for maintaining calcium balance and bone strength throughout life [1]. Genetic variations in this gene can alter the balance between bone formation and bone resorption, influencing susceptibility to skeletal disorders [3].
Variant Impact: The rs884205 variant is located in the 3 prime untranslated region of the TNFRSF11A gene, where it may influence gene expression [3]. This genetic change alters the binding of regulatory molecules, thereby affecting the levels of the RANK protein [4]. Specifically, the A allele is associated with higher levels of the RANK protein, which can accelerate bone breakdown [4]. Conversely, the C allele is linked to lower RANK levels, promoting higher bone mineral density across multiple skeletal sites [5].
Key Insight: This variant highlights a direct biological trade-off where genetic factors that strengthen bones also increase the risk of joint wear and tear.
Location: TNFRSF11A. Chromosome 18 · 18q21.33 · 62.4 Mb
Estimated prevalence by population
Global 4.2%; European 6.3%; African 0.4%; East Asian 4.4%; South Asian 4.2%; Americas 3.0%; Ashkenazi 3.0%; Finnish 7.9%; Middle Eastern 1.5%; Amish 12.2%.
Estimated AA genotype frequency.
Global 29.1%; European 37.6%; African 11.5%; East Asian 33.3%; South Asian 32.7%; Americas 28.5%; Ashkenazi 28.6%; Finnish 40.4%; Middle Eastern 21.5%; Amish 45.5%.
Estimated AC genotype frequency.
Global 66.6%; European 56.1%; African 88.1%; East Asian 62.3%; South Asian 63.1%; Americas 68.5%; Ashkenazi 68.4%; Finnish 51.7%; Middle Eastern 77.0%; Amish 42.3%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoporosis. Evidence: 6/10. Source: PMID 39024449. Increased Risk.
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. Decreased Risk.
Bone Mineral Density. Evidence: 9/10. Source: PMID 41206123. Lower Density.
RANK Protein Levels. Evidence: 6/10. Source: PMID 29875488. Increased Levels.
Showing effects for A/C genotype
Osteoporosis. Evidence: 6/10. Source: PMID 39024449. Typical Risk.
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. Typical Risk.
Bone Mineral Density. Evidence: 9/10. Source: PMID 41206123. Typical Density.
RANK Protein Levels. Evidence: 6/10. Source: PMID 29875488. Typical Levels.
Showing effects for C/C genotype
Osteoporosis. Evidence: 6/10. Source: PMID 39024449. Decreased Risk.
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. Increased Risk.
Bone Mineral Density. Evidence: 9/10. Source: PMID 41206123. Higher Density.
RANK Protein Levels. Evidence: 6/10. Source: PMID 29875488. Decreased Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying two copies of the A allele is linked to lower bone mineral density across several skeletal sites, including the spine, hip, and heel [1]. This reduction in bone density significantly increases the lifetime risk of developing osteoporosis and experiencing bone fractures [2]. The biological mechanism involves higher levels of the RANK protein, which accelerates the activity of bone-resorbing cells [3]. Interestingly, this lower bone density is associated with a lower risk of developing osteoarthritis, representing a biological trade-off [4].
Lower bone mineral density; Increased risk of osteoporosis; Lower risk of osteoarthritis.
Sample genotype: AC (Heterozygous)
Carrying one copy of each allele results in intermediate levels of the RANK protein and typical bone remodeling activity [1]. Bone mineral density measurements at the spine, hip, and heel generally fall within the average range for the population [2]. Consequently, the risk of developing osteoporosis or experiencing bone fractures is not significantly elevated [3]. Similarly, the risk of developing osteoarthritis in the hips or other joints remains at baseline levels [4].
Typical bone mineral density; Average osteoporosis risk; Typical osteoarthritis risk.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is strongly associated with higher bone mineral density throughout the skeleton, including the spine, hip, and heel [1]. This increased bone density provides robust protection against osteoporosis and reduces the likelihood of fractures [2]. The underlying mechanism is linked to lower levels of the RANK protein, which slows down the rate of bone resorption [3]. However, this denser bone structure is also associated with a higher risk of developing osteoarthritis, particularly in the hips [4]. This trade-off occurs because stiffer, denser bone transmits more mechanical stress directly to the joint cartilage, accelerating wear and tear [4].
Higher bone mineral density; Lower risk of osteoporosis; Increased risk of osteoarthritis.
Variants with shared genetic architecture
rs3018362 · TNFRSF11A Gene · Chr 18 · Bone Health Risk
rs11898505 · SPTBN1 Gene · Chr 2 · Bone Density
rs4252548 · IL11 Gene · Chr 19 · Osteoarthritis Risk
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Content updated August 2026.
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