Osteoporosis: Genetic Influences

Osteoporosis

Osteoporosis occurs frequently in postmenopausal women. This often leads to women having a fracture. Some of these fractures can lead to becoming life-threatening or at the very least cause loss of independence.

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Introduction
Fractures are a major contributor to healthcare costs and a societal burden as a result of an increasing aging population. Studies have shown one out of two women and one of five men age 50 yrs and older will have a fracture. Low bone mineral density and osteoporosis are linked with fractures in this age group. In this study, the prevelance of osteoporosis was 13% in postmenopausal Caucasian women age 60 to 85 yrs. Though this study did not determine that these specific biomarkers of osteoporosis. Clinical populations like osteoporosis patients with fracture are showing promise for future studies (Chen et al, 2019).
What causes this?
Observation of secondary osteoporosis suggests that the metabolic state of the body can be a major determinant of bone health. Causality can’t be inferred from observational studies and randomized controlled studies are needed to establish causal relationships. Circulating metabolites measured explained more than one-third of the variance in a large female population. They found 15 unique metabolites showed to be directly associated with osteoporosis. This direct association has been duplicated in an independent study done on a Chinese population. Combining both genetic and Metabolomics data provided a platform to determine the role of new pathways in pathogenesis and diagnosis of osteoporosis (Moayyeri et al, 2018).

Rapid bone accrual (come about as a natural growth) occurs during puberty. The process of sexual maturation is likely to impact lifelong bone health as bone mineral density tracks throughout life. Older girls who start their periods later than 12 years have been associated with an increased risk of osteoporosis as they age. This study examined the relationship between the timing of puberty and bone mineral density. The results showed that genetic risk for later than average puberty was associated with lower spine and bone density. This association between later puberty and increase osteoporosis risk was stronger in women than in men. It is felt this occurs because of the girls having a decrease in exposure to estrogen a known component of osteoporosis occurrence. Clearly during adolescence maturation and bone acquisition during puberty occurs at the same time. Further work, however, needs to be done. This study showed the ability to address the association between puberty and timing associated variations. In addition, the results showed clear genetic links between the age of puberty and bone mineral accrual during critical years of bone development. It also is suggested that in some cases, the adult bone mineral density may have been present in children but not detected due to limited samples (Cousminer et al, 2018).

Ways to address this
Exercise has been proposed as a potential strategy to manage osteoporosis. A study was done, LIFTMOR, to determine the usefulness of brief bone-targeted lifting for improving bone mineral density in postmenopausal women. Many exercise trials to improve bone health of this group of women have beea n conducted with corresponding variety of results. The study found some improvements in bone mineral density and results were better than what has been found in previous studies. The people of the study did voice a caustion that this type of protocol needs to be overseen by a doctor. If they are not, there is a potential for injury from the weights (Watson et al, 2018).

Osteoporosis is characterized by low bone mineral density and increase risk of fracture. It is a condition easily inherited and requires understanding of genetic basis of bone traits. Diseases of the bone inhibit the ability of the skeleton to provide support, protection, locomotion, or maintain blood production. Osteoporosis affects over 12 million individuals in the US and 200 millon worldwide. There are approximate 300,000 people in the US over the age 50 that suffer a hip fracture each year. One in five of these will die in the subsequent 12 months and half of the survivors will not return to their pre-fracture status. In the 1990’s genetic studies were conducted to explore the inheritable trait of osteoporosis. In the past decade advances in sequencing technology have completely revolutionized biological science. However the understanding of the underpinning of biological process and diseases is still far from complete. While bone mineral density is spoken of frequently the responsible genes continue to be elusive. And as biology is inherently complex, it is unreasonable to believe that a single or a few types of genetic analysis will be enough to understand the genetics of complex bone traits (Al-Barghouth & Farber, 2019).

Conclusion
Osteoporosis is an environmentally changeable bone disease. It results in fractures from fragile bones and places the person at high risk for low impact fracture. A range of medicines have been approved by FDA that inhibits bone resorption to be used to treat osteoporosis. Skeletal tissue represents a tissue that continues to change throughout our life span. Activity of bone cells are influenced directly or indirectly by a large variety of factors. In a healthy person, the balance of destruction and formations results in sufficient bone mass. In most people osteoporosis is caused by increase in reobsorption with decrease in formation, resulting in a decrease of bone mineral density. This condition affects an ever-growing number of people as our population ages. According to the CDC 16.2% over age 65 have osteoporosis; 48.3% exhibit low bone mass. This study has found that the number of people afflicted with osteoporosis will continue to increase. It is felt an individualized treatment regimens may result in more than one drug being used to help treat this disease. Further development and study of ways to treat osteoporosis is very necessary. More effective treatment options are needed as the total number of those afflicted continue to increase (Russow et al, 2019).

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Works Cited
Al-Barghouth, B.M. & Farber, C.R. (2019). Dissecting the genetics of osteoporosis using system approaches. Trends in Genetics, 35(1).

Chen, Z., Bemben, M.S. & Bemben, D.A. (2019). Bone and muscle-specific circulating microRNAs in postmenopausal women based on osteoporosis and sarcopenia status. Science Direct-Bone.

Cousminer, D.L. et al. (2018). Genetically determined later puberty impacts lowered bone mineral density in childhood and adulthood. Journal of Bone and Mineral Research, 33(3).

Moayyeri, A. et al. (2018). Metabolic pathways to in middle-aged women: A genome-metabolome-wide mendelian randomization study. Journal of Bone and Mineral Research, 33(4).

Russow,G. et al. (2019). Anabolic therapies in osteoporosis and bone regeneration. International Journal of Molecular Sciences, 20(1).

Watson, S.L. et al. (2018). High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: The LIFTMOR randomized controlled trial. Journal of Bone and Mineral Research.

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