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Understanding Your TNFSF11 (RANKL) Result and Bone Health

Osteoporosis occurs when bones become weaker and more fragile because the balance between bone breakdown and formation shifts toward breakdown. The TNFSF11 gene makes a protein called RANKL that helps control osteoclasts, the cells that resorb bone. Variations in TNFSF11 can influence how much bone is broken down over time, which in turn can affect bone mineral density (BMD) and fracture risk.

Your genetic result for the rs2277439 variant in TNFSF11 provides context about one pathway that influences bone health. Genetics can explain roughly 50 to 80 percent of the differences in BMD between people, but lifestyle, nutrition, and certain medical conditions also have a major impact. Regardless of genotype, there are practical steps you can take to support stronger bones and reduce fracture risk.

Practical Actions to Support Bone Health

  • Calcium intake — Aim for the recommended daily intake for your age and sex. Choose calcium-rich foods such as dairy, fortified plant milks, leafy greens, tofu set with calcium, and canned fish with bones. Spread calcium intake across the day for better absorption.
  • Vitamin D — Vitamin D helps your body absorb calcium and supports bone remodeling. Get safe sun exposure when possible and include vitamin D–rich foods (fatty fish, fortified foods). Consider a supplement if blood levels are low or sun exposure is limited.
  • Vitamin K2 and magnesium — Both nutrients support bone strength and mineralization. Include foods like fermented dairy, natto (fermented soy), nuts, seeds, whole grains, legumes, and leafy greens. Discuss supplementation with your healthcare provider if dietary intake is inadequate.
  • Protein — Adequate protein supports bone matrix and muscle strength. Include a variety of protein sources across meals.
  • Weight-bearing and resistance exercise — Activities such as walking, jogging, stair climbing, strength training, and impact exercises stimulate bone formation and maintain muscle that protects bones.
  • Limit alcohol and avoid smoking — Excessive alcohol and tobacco use are linked to lower BMD and higher fracture risk.
  • Fall prevention — Improve home safety, maintain good balance and muscle strength, review medications that may cause dizziness, ensure proper vision correction, and consider physical therapy for balance training if needed.
  • Maintain a healthy weight — Underweight increases fracture risk, while obesity has mixed effects. Aim for a stable, healthy weight that supports mobility and muscle mass.
  • Consider strength and balance programs — Tai chi, targeted resistance classes, and supervised exercise reduce fall risk and support bone health.

When to Talk to Your Healthcare Provider

  • Ask about a bone density test (DEXA) if you have risk factors for low bone density, a family history of osteoporosis, history of fractures from minor falls, or prolonged use of medications that affect bone (for example, glucocorticoids).
  • Request blood testing if you or your clinician suspect nutrient deficiencies that affect bone: 25-hydroxyvitamin D, calcium, magnesium, and markers of bone turnover when clinically indicated.
  • Discuss medication options if you have low bone density or fractures. Several prescription therapies can reduce fracture risk by altering bone resorption or formation.
  • Review medications you are taking with your clinician to identify those that may lower bone density or increase fall risk.

Genetic Interpretation: rs2277439 (TNFSF11)

2 effect alleles (GG) — Two copies of the G variant

You have the GG genotype at rs2277439 in the TNFSF11 gene. This means you carry two copies of the effect allele that has been associated with lower bone mineral density. TNFSF11 produces RANKL, a key regulator of osteoclasts, the cells that break down bone. Changes in RANKL activity can shift the balance toward more bone resorption, which over time may lower bone strength and increase fracture risk.

What this means for you:

  • Genetic risk is one factor. Lifestyle and medical factors matter a lot and can often be modified.
  • Prioritize calcium and vitamin D intake, include vitamin K2 and magnesium, and follow a regular weight-bearing and resistance exercise routine.
  • Consider earlier or more frequent bone density screening with your provider, especially if you have other risk factors such as family history, low body weight, chronic steroid use, or prior fractures.
  • Work with your healthcare provider on fall prevention and review medications that may harm bone or increase fall risk.
1 effect allele (AG) — One copy of the G variant

You have the AG genotype at rs2277439, carrying one copy of the effect allele associated with likely lower bone mineral density. This suggests a modest genetic predisposition toward increased bone resorption through RANKL-mediated pathways, which could contribute to reduced BMD over time.

What this means for you:

  • Your genetic profile indicates a possible, but not certain, increased risk. Many people with this genotype maintain healthy bones with the right lifestyle choices.
  • Emphasize nutrition: calcium-rich foods, adequate vitamin D, and nutrients like vitamin K2 and magnesium.
  • Make weight-bearing and resistance exercises part of your routine to preserve bone and muscle strength.
  • Talk to your clinician about baseline bone density testing if you have additional risk factors or family history.
0 effect alleles (AA) — No G variant

You have the AA genotype at rs2277439, meaning you do not carry the G variant that has been linked to altered RANKL activity and lower bone mineral density. Your result indicates typical bone mineral density levels for this specific genetic site.

What this means for you:

  • This particular genetic risk factor is not present, but bone health is influenced by many genes and by environment and lifestyle.
  • Continue the bone-supporting habits: adequate calcium and vitamin D, vitamin K2 and magnesium when appropriate, regular weight-bearing and resistance exercise, and fall prevention measures.
  • Discuss screening with your clinician if you have other risk factors, such as family history, low body weight, smoking history, long-term steroid use, or early menopause.

Supplement Considerations

  • Consider a vitamin D supplement if testing shows low 25-hydroxyvitamin D or if sun exposure is limited. Your clinician can advise an appropriate dose and follow-up testing.
  • Calcium supplements may be useful if dietary intake is insufficient, but aim to meet most needs through food when possible. Discuss total daily calcium with your provider to avoid excessive intake.
  • Magnesium and vitamin K2 supplements may be considered when diet is inadequate. Discuss interactions with other medications and conditions with your clinician.

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult your healthcare provider before making changes to diet, supplements, exercise, or medical care. Your clinician can integrate your genetic result with your medical history, medications, and test results to create a plan tailored to your needs.