Genetic Insights Into Age-Related Bone Loss

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Genetic Insights Into Age-Related Bone Loss

Date of Content: May 12, 2024
Written by: Harvey Talento
Reviewed by: Maarit Tiirikainen, PhD


What is Age-Related Bone Loss?

Age-related bone loss, or osteopenia, refers to the gradual and progressive decline in bone mass and strength that occurs as individuals age. This process involves increased bone resorption and decreased bone formation, leading to a reduction in bone mineral density and an increased risk of severe bone loss; osteoporosis, and fractures.

Factors contributing to age-related bone loss include genetics, hormonal changes, alterations in cellular components, and lifestyle factors like nutrition and physical activity.

Research has shown that aging, combined with intrinsic and extrinsic factors, accelerates the decline in bone mass, predisposing individuals to fractures. Peak bone mass attainment plays a crucial role in later age-related bone loss, with those achieving higher peak bone mass being less likely to develop osteoporosis. Therapeutic approaches focus on understanding the mechanisms associated with an aging bone to develop treatments that can potentially reverse the adipogenic shift in the bone marrow and improve bone health.

Age-related bone loss

Symptoms of Age-Related Bone Loss

Age-related bone loss, and its severe form called osteoporosis, can manifest through various symptoms. These symptoms can include:

  • Gradual Loss of Height: A common sign of age-related bone loss is a gradual decrease in height over time, often due to compression fractures in the spine.
  • Back Pain: Back pain can occur as a result of broken or collapsed bones in the spine, which is a common symptom of osteoporosis.
  • Stooped Posture: Age-related bone loss can lead to a stooped or hunched posture, known as kyphosis, due to compression of the vertebrae in the spine.
  • Fractures: Fragile bones resulting from osteoporosis can lead to fractures, which can occur from minor movements like stepping off a curb or even from a strong sneeze or cough.
  • Receding Gums: Bone loss in the jaw can cause receding gums, which can be an indicator of weakening bones.
  • Weak Grip Strength: Low handgrip strength has been linked to low bone mineral density, indicating a potential sign of bone loss.
  • Weak and Brittle Fingernails: Changes in nail strength can sometimes signal bone health issues, although other factors can also affect nail health.

These symptoms can vary in severity and may indicate the need for further evaluation, especially in individuals at higher risk due to factors like advanced age, hormonal changes, family history, or certain medical conditions. Regular screening and early detection are crucial in managing age-related bone loss effectively.

How Age-Related Bone Loss May Affect Daily Living

Age-related bone loss can significantly impact daily living in various ways. Here are some effects of age-related bone loss on daily life:

  • Reduced Mobility: Bone loss can lead to fractures, especially in the spine and hips, which can result in pain and reduced mobility, affecting daily activities like walking and movement.
  • Posture Changes: Changes in bone structure, such as spinal compression fractures and a curved spine, can lead to stooped posture, discomfort, and limitations in movement, impacting daily tasks and overall quality of life.
  • Increased Risk of Falls: Weakened bones increase the risk of fractures from falls, making individuals more prone to injuries that can hinder independence and daily activities.
  • Muscle Weakness: Age-related bone loss can be accompanied by muscle weakness, contributing to fatigue, reduced strength, and limitations in physical activities, potentially affecting tasks that require strength and endurance.
  • Joint Stiffness: Changes in joints due to bone loss can lead to stiffness and reduced flexibility, affecting movements like bending, reaching, and overall joint function, impacting daily tasks and comfort.
  • Pain and Discomfort: Osteoporosis-related fractures and bone changes can cause chronic pain and discomfort, affecting daily comfort levels and the ability to engage in various activities.
  • Risk of Disability: Severe bone loss can increase the risk of disability, limiting independence and the ability to perform daily tasks without assistance, impacting overall quality of life.

These effects highlight the importance of preventive measures, such as exercise, proper nutrition, and medical interventions, to mitigate the impact of age-related bone loss on daily living and maintain overall health and well-being.

How Genetics May Influence Age-Related Bone Loss

Age-related bone loss, which can lead to conditions like osteoporosis, is a complex trait influenced by a variety of genetic factors. Recent research in genetics has provided new insights into the specific genes and genetic variants that contribute to bone mineral density (BMD), especially when associated with osteoporosis, and fracture risk.

Genetic Determinants of Bone Mineral Density

Bone loss is primarily diagnosed using bone mineral density (BMD) measurements, and significant progress has been made in identifying the genetic determinants of BMD. A comprehensive study from 2018 assessed genetic determinants of BMD using heel quantitative ultrasound in over 426,000 individuals, identifying 518 genome-wide significant loci, with 301 being novel discoveries. These loci collectively explain 20% of the variance in BMD. Additionally, the study identified 13 loci associated with bone fractures, all linked to estimated BMD (BMD). This research underscores the genetic complexity of osteoporosis and highlights specific genes, such as SLC8A1, FGFRL1, RSPO3, and TMEM135  that influence bone density and strength, providing valuable targets for drug development.

Genetic BMD Associations in Diverse Populations

Genetic studies have historically focused on populations of European ancestry, potentially limiting the generalizability of findings across different ethnic groups. To address this, a 2020 genome-wide association study (GWAS) involving 212,453 Japanese individuals across 42 diseases was conducted. This study identified 320 independent signals in 276 loci for 27 diseases, with 25 novel loci. Two previously found loci and 1 novel locus, at gene STK39 (SNP rs578031265), were found to be associated with BMD. The identification of East Asian–specific missense variants as candidate causal variants for several loci emphasizes the importance of including diverse populations in genetic research to uncover unique genetic contributions to disease susceptibility.

Genetic Loci for Osteoporotic Fractures and BMD

An early GWAS in the Chinese Han population examined the genetic basis of osteoporotic fractures (OF) and BMD. This study involved 700 elderly individuals and identified a significant SNP, rs13182402, within the ALDH7A1 gene on chromosome 5q31, which was strongly associated with OF. Follow-up replication studies confirmed this association in both Chinese and Caucasian populations, demonstrating the cross-ethnic relevance of this genetic variant. The ALDH7A1 gene’s role in degrading acetaldehyde, a compound that inhibits osteoblast proliferation, suggests a potential mechanism for its effect on bone formation and strength. This finding highlights the importance of specific genetic variants in understanding the pathogenesis of osteoporosis and provides a new avenue for potential therapeutic interventions.

Advancements in Genome-Wide Association Studies

Standard genome-wide association studies (GWAS) often have limitations, such as testing only additive models and excluding the X chromosome. An advanced GWAS strategy, GUIDANCE, addresses these limitations by incorporating multiple reference panels for genotype imputation and analyzing non-additive models and the X chromosome. Applying this methodology in a recent study of 62,281 subjects across 22 age-related diseases identified 94 genome-wide associated loci, including 26 previously unreported. This comprehensive approach uncovered novel low-frequency recessive variants with significant impact, underscoring the benefits of innovative strategies in elucidating the genetic architecture of complex diseases, including age-related bone loss. Specifically for osteoporosis, the study identified SNPs in genes CCDC170 (rs4869742),  WNT16 (rs3779381), LRP5 (rs880610), and near HOXC4 (rs7308105) 

Genetic research continues to unravel the complex genetic landscape of age-related bone loss. By incorporating diverse populations and employing advanced methodologies, scientists are identifying new genetic variants and mechanisms that contribute to bone health, offering promising targets for future therapeutic development.

Non-Genetic Factors Influencing Age-Related Bone Loss

Age-related bone loss is a multifaceted issue influenced by a variety of factors aside from genetics. Understanding these factors is crucial for developing effective strategies to mitigate bone loss and maintain skeletal health.

Hormonal Changes

Hormonal fluctuations play a pivotal role in age-related bone loss. In women, the decline in estrogen levels following menopause is one of the primary causes of accelerated bone loss. Estrogen is crucial for bone density maintenance, and its reduction can lead to significant bone mass decrease. Similarly, men experience a gradual decline in testosterone levels as they age, which also contributes to bone loss. Both hormones are vital for the regulation of bone metabolism, and their decrease disrupts this balance, leading to increased bone resorption and decreased bone formation.


Nutritional intake is another critical factor affecting bone health. Diets deficient in calcium and vitamin D are particularly detrimental. Calcium is essential for the development and maintenance of strong bones, while vitamin D facilitates the absorption of calcium from the diet. Insufficient levels of these nutrients can impair bone formation and accelerate bone loss. Ensuring adequate intake of calcium and vitamin D through diet or supplements is vital for maintaining bone health, especially in older adults.

Physical Inactivity

Regular physical activity is integral to bone health. Weight-bearing exercises, such as walking, running, and dancing, are particularly beneficial as they stimulate bone formation and strengthen the musculoskeletal system. Inactivity, on the other hand, can lead to a reduction in bone density and an increased risk of fractures. Incorporating regular exercise into one’s routine is essential for mitigating age-related bone loss and enhancing overall skeletal strength.

Medical Conditions

Certain medical conditions can exacerbate bone loss. Diseases such as thyroid disorders, rheumatoid arthritis, and celiac disease have been linked to increased bone resorption and decreased bone formation. These conditions often involve chronic inflammation or hormonal imbalances, which can negatively impact bone health. It is important for individuals with these conditions to be vigilant about their bone health and seek appropriate medical management to minimize bone loss.


The use of certain medications can also contribute to bone loss. Corticosteroids, commonly prescribed for inflammatory conditions, can interfere with bone regeneration and increase bone resorption. Similarly, some antidepressants have been associated with decreased bone density. Patients on long-term medication regimens should discuss potential side effects with their healthcare providers and explore strategies to protect their bone health.

Preventing Age-Related Bone Loss

As we age, maintaining bone health becomes increasingly important to prevent osteoporosis and fractures. Here are some actionable lifestyle optimizations to help prevent age-related bone loss:

Avoid Smoking and Limit Alcohol Intake

Smoking and excessive alcohol consumption are significant risk factors for bone loss. Smoking can reduce blood flow to the bones and hinder the body’s ability to absorb calcium. Alcohol, when consumed in large amounts, can interfere with the balance of calcium in the body and hinder the production of bone-forming cells. By quitting smoking and moderating alcohol intake, you can protect your bones and improve overall health.

Maintain a Well-Balanced Diet

A nutrient-rich diet is essential for bone health. Ensure your diet includes:

  • Calcium-Rich Foods: Incorporate dairy products like milk, cheese, and yogurt, along with leafy green vegetables, almonds, and tofu. Calcium is vital for maintaining bone density and strength.
  • Vitamin D: This vitamin is crucial for calcium absorption. Include foods such as fatty fish (salmon, mackerel), fortified cereals, and eggs in your diet.
  • Fruits and Vegetables: These provide essential vitamins and minerals that support bone health, including vitamin C, which is important for collagen formation in bones.

Consider Supplements

If your diet does not provide sufficient calcium and vitamin D, consider supplements. Consult with a healthcare provider to determine the appropriate dosage and type of supplements that suit your needs. Adequate intake of these nutrients is key to maintaining bone mass and preventing bone-related diseases.

Stay Physically Active

Regular physical activity is one of the best ways to maintain bone health. Engage in exercises that help strengthen bones, such as:

  • Weight-Bearing Exercises: Activities like walking, running, and hiking force you to work against gravity, which strengthens bones.
  • Strength Training: Lifting weights or using resistance bands helps build muscle mass, which supports and strengthens bones.
  • Balance and Flexibility Exercises: Yoga and tai chi improve balance and coordination, reducing the risk of falls and fractures.

Get Adequate Sun Exposure

Sunlight is a natural source of vitamin D, which is crucial for bone health. Spending time outdoors helps your body synthesize vitamin D. Aim for about 10-30 minutes of sun exposure several times a week, depending on your skin type and local climate. Always use sun protection to avoid skin damage.

By integrating these lifestyle practices, you can significantly reduce the risk of age-related bone loss and maintain strong, healthy bones well into your later years. Prioritizing bone health today will help ensure a more active and independent lifestyle tomorrow.

About the LifeDNA Aging Report

As we age, maintaining bone wellness becomes increasingly vital to our overall well-being and quality of life. The LifeDNA Aging Report offers a comprehensive and personalized approach to understanding how your genetic makeup influences age-related bone loss. With the Age-Related Bone Loss trait report included, you can gain valuable insights into your genetic predisposition to conditions like osteopenia and osteoporosis. This knowledge empowers you to take proactive steps in managing your wellness, from tailored dietary recommendations to specific exercises that strengthen bones, all personalized to your unique genetic profile. 

Investing in the LifeDNA Aging Report today means investing in your future. By understanding your genetic risks, you can work with your healthcare provider to create a customized plan that addresses your specific needs.

Don’t leave your wellness to chance—equip yourself with the knowledge to protect and enhance your well-being for years to come.


  • Age-related bone loss increases osteoporosis and fracture risk, impacting overall health.
  • Factors contributing to bone loss include genetics, hormones, lifestyle, and medical conditions.
  • Symptoms include height loss, back pain, stooped posture, fractures, weak grip, and brittle nails.
  • Bone loss affects daily life by reducing mobility, altering posture, increasing fall risk, and causing pain.
  • Genetics plays a crucial role, with recent research identifying specific genes and their variants.
  • Studies now include diverse populations, revealing unique genetic contributions.
  • Advances in genome-wide studies uncover novel genetic loci and potential therapeutic targets.
  • Non-genetic factors like hormones, diet, inactivity, and medications also influence bone loss.
  • Preventive measures include lifestyle changes and ensuring adequate nutrient intake.
  • Prioritizing bone health through lifestyle optimizations can mitigate age-related bone loss and promote overall well-being.



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*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

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