There are several factors that contribute to bone health, including gender, hormone levels, ethnicity, physical activity, medications, nutrient uptake and genetics.
Women have an increased risk of osteoporosis, due to a lower bone mass and decreased estrogen levels that occur at menopause. Variations in male hormones also influence the risk, as men with lower testosterone levels can have a lower bone mass.
Hispanics and African-Americans tend to have higher bone densities and a reduced risk of osteoporosis compared to Caucasians and Asians. Weight-bearing exercises (e.g. running, walking and dancing) help to strengthen bones, hence a sedentary lifestyle increases the risk of poor bone health. The long-term use of many medications (e.g. corticosteroids) can also reduce bone mass.
Strong bones require adequate calcium in the diet. Vitamin D is also essential, as the calcium cannot be absorbed without healthy vitamin D levels. A poor diet or a decreased ability to absorb these essential nutrients increases the risk of osteoporosis. Gastrointestinal issues (e.g. Crohn’s and celiac disease) impact an individual’s ability to absorb nutrients from the diet. Lactose intolerance is also associated with a lower bone mass, as these individuals are unable to digest dairy products that are a rich source of calcium.
Genetic variation is a major factor influencing bone health. Genetic changes affect the risk for gastrointestinal issues that affect mineral absorption (e.g. HLA-DQA1 and HLA-DQB1 changes increase the risk of celiac disease and common variations in the MCM6 gene cause lactose intolerance).
Variations in the CYP2R1 and GC genes affect vitamin D activity (and the ability to absorb calcium) and changes in the WNT16 gene interrupt cell-to-cell signaling. This genetic analysis identifies common variations in the CYP2R1, GC and WNT16 genes that are associated with an increased risk of osteoporosis. Genetrace also offers genetic testing for celiac disease risk and lactose intolerance.
Vitamin D is an essential fat-soluble vitamin required for the absorption of other nutrients, particularly calcium and phosphate. Ultraviolet B radiation (from sunlight) triggers the synthesis of vitamin D in the body. Vitamin D can also be obtained from some foods, including fatty fish, fish liver oils and fortified foods (e.g. infant formula, milk and cereals). Decreased levels of active vitamin D and inefficient vitamin D transport around the body result in reduced calcium absorption and increased risk of osteoporosis.
Vitamin D from the diet or triggered by sun exposure must be converted to the physiologically active form (calcitriol) by a two-step process. Cytochrome P450 2R1 (CYP2R1) is the enzyme responsible for the first conversion step from vitamin D to calcidiol. Variants of this enzyme are associated with reduced enzyme activity and reduced levels of active vitamin D.
The vitamin D binding protein (encoded by the GC gene) is required to transport active vitamin D around the body and into the cells. Variations of this protein reduce the efficiency of vitamin D transport and cellular uptake.
The Wnt Signaling Pathway
The Wnt signaling pathway is one of the most important pathways in several biological processes, including embryonic development, postnatal development, adult tissue homeostasis and bone biology. The Wnt cascade is especially important for signaling the differentiation of mesenchymal stem cells into osteoblasts – the cells responsible for bone formation. Disruption of the Wnt cascade results in reduced osteoblasts and bone formation.
The WNT16 gene encodes a protein from the Wnt signaling pathway. Inactivating variations in this gene have been linked to decreased bone density and an increased risk of osteoporosis.
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