Journal of Osteoporosis and Physical Activity
Open Access

Genetic Architecture of Osteoporosis

Florenc Clabaut^{* *}Correspondence: Florenc Clabaut, Department of Osteology, University of Wroclaw, Wroclaw, Poland, Email:

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Description

Osteoporosis is a common disease characterized by low bone mass and defects within the microarchitecture of bone tissue, which impairs bone strength and results in a hyperbolic risk of fragility fractures. Osteoporosis is outlined to exist once Bone Mineral Density (BMD) values at the lumbar spine or hip fall a minimum of 2.5 sd values below the population average in young healthy people (BMD T-score of -2.5 or less). The term osteopenia is used to explain matters whereby the BMD T-score is above -2.5, but below -1.0, whereas subjects with BMD T-score values of bigger than -1.0 and fewer than +2.5 are said to have normal BMD. Though the chance of fracture will increase with decreasing levels of BMD, it's important to notice that a lot of patients with osteoporosis don't go on to have a fracture which most fractures within the general population occur in patients without osteoporosis. Several factors influence the risk of osteoporosis, as well as diet, physical activity, medication use, and coexistent diseases; however one among the foremost vital clinical risk factors may be a positive family history, accenting the importance of genetic science within the pathological process of the disease [1,2]. The clinical and economic importance of osteoporosis lies in its association with fracture. Though the risk of fracture will increase as BMD values fall, about two-thirds of individuals that suffer a fracture don't have osteoporosis as defined on the basis of BMD values. Apart from this, the age-related increase in the fracture is largely independent of changes in BMD.

The foremost probable reason for this is often an increased risk of aging becau se of factors like reduced muscle power, postural instability, and reduced vision. Different factors conjointly have an effect on the risk of fracture by mechanisms that are independent of BMD. For instance, biochemical markers of bone turnover as well as the bone resorption markers, urinary C-telopeptide cross-links of scleroprotein type I, and free urinary deoxypyridinoline, and therefore the bone formation marker undercarboxylated osteocalcin are shown to predict fractures severally of BMD. Similarly, varied aspects of femoral neck geometry including hip axis length have conjointly been shown to act as predictors of fracture, significantly hip fracture [3]. Indeed, it's been instructed that variations in femoral neck geometry may explain, in part, variations in the rate of hip fractures between Caucasians and a few different ethnic groups. Twin and family studies have shown that between 50 % and 80% of the variance in peak BMD is genetically determined. Studies in twins have typically yielded higher estimates for heritability than family-based studies wherever individuals are compared across generations, presumptively due to nongenetic influences on rates of bone loss. In most studies, the heritability of BMD at axial sites like the spine and hip has been on top of the forearm, however, this has not continually been the case.

The genetic design of osteoporosis is typical of a complex disease with contributions from many genes, most of that have little effect; however many of them have large effects. Genetic variants are often divided into 2 broad categories, supported by their frequency within the functional effect on the target gene. The term “polymorphism” is used to explain common genetic variants that occur frequently (>1%) within the population. The most common type is a Single Nucleotide Polymorphism (SNP) during which one nucleotide in DNA is substituted for an additional however deletions and duplications also occur.

Another category of polymorphism is the variable number of closely repeats, which were previously used for linkage analysis in families. Deletions and duplications of large segments of DNA (typically 10 kb to 1 million bp) also are illustrious to occur throughout the genome, and these are named Copy Number Variants (CNVs). Current estimates suggest that there are 25 million polymorphisms within the human genome. Only a little fraction of these have to this point been investigated to determine whether or not they have functional effects [4,5]. Those polymorphisms that are studied typically are found to possess modest effects on gene function either by altering the protein structure of the factor product or by altering gene expression. Though the resulting changes in expression or function of an individual gene are small, it is thou ght that common disease like osteoporosis are attributab le due to a substantial extent to the combined effects of many hundreds to thousands of those polymorphisms.

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