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Osteoporosis Genetics

Osteoporosis Genetics

What is Osteoporosis ?

Osteoporosis is a skeletal disorder in which bones become weak and brittle and the risk of fracture increases due to the decrease in bone tissue strength, which reflects the composition of bone quality and quantity. It results in first bone pain, then bone weakness and eventually bone fractures.

Osteoporosis is a medical condition in which one becomes more susceptible to fractures. It occurs when the body loses too much bone tissue or does not create enough new bone tissue..

How common is osteoporosis?

Osteoporosis can affect both men and women, but it is more common in women, especially after menopause. Osteoporosis is seen in 30-50% of women and 15-30% of men. The incidence of osteoporosis, which does not differ much according to ethnic groups, is 10-15% in White Europeans and North Americans, while its prevalence is higher in Asians.

Why does osteoporosis occur?

Osteoporosis is in the group of multifactorial diseases in which genetic factors and environmental effects play a role together. In multifactorial diseases, quantitative phenotype changes in societies emerge with the interaction of genotype with the environment. While genetics may play a role in the development of osteoporosis, it is not typically considered a purely genetic disease. Many factors can contribute to the development of osteoporosis, including diet, exercise, and lifestyle factors such as smoking, as well as hormonal and environmental factors.

Is Osteoporosis genetic condition?

In addition to the influence of environmental factors, there are certain genetic factors that can increase an individual's risk of developing osteoporosis. Genetic factors affect bone mass and composition by 50-80%. For example, research has identified more than 50 genetic variants associated with bone mineral density and fracture risk. Apart from these, variants in genes related to vitamin D metabolism, estrogen receptors and collagen synthesis are all included in the risk of osteoporosis.

We can define the several gene polymorhisms that effects osteoporosis as follows;

Bone Gla Protein (BGLAP) Gene: Osteocalcin is the most abundant non-collagen protein in the bone tissue matrix. BGLAP gene promoter region -298 C/T polymorphism has been associated with osteoporosis.

Collagen Type1 alfa 1 (Col1A1) and (Col1A2) Genes: The Sp1 transcription region in the 1st intron of the COL1A1 gene is important in the control of collagen transcription. The single nucleotide polymorphism in this region increases the binding efficiency of the Sp1 transcription factor and increases the COL1A1 transcript level.

Estrogen Receptor α and ß (ESR1 and ESR2) Genes: The main cause of rapid bone loss in menopause is estrogen deficiency. Studies investigating the relationship between polymorphisms in the ESR1 gene and various clinical phenotypes focused on PvuII, XbaI and TA repeat polymorphisms in the control region. ESR2 AluI (rs4986938, 1730G>A) polymorphism has been associated with bone mineral density (BMD) in postmenopausal women.

VDR Gene: It is important to regulate bone cell function and maintain serum calcium homeostasis. Active metabolites of vitamin D bind to the vitamin D receptor and fulfill these duties. The VDR gene has been studied as a potential candidate in osteoporosis genetic susceptibility studies. ApaI (rs7975232), BsmI (rs 1544410) and TaqI (rs731236) polymorphisms in the VDR gene were associated with bone mineral density.

CYP27B1 gene polymorphism: It has been reported that Vitamin D level is significantly lower in individuals carrying the T allele (CT and TT genotypes) for the rs4646536 SNP in the CYP27B1 gene.

CYP24A1 gene polymorphism: The CYP24A1 gene encodes the enzyme 24-hydroxylase, which degrades active Vitamin D. It has been reported that although the serum calcium level is elevated in those carrying the rs1570669 (G/A) polymorphism, G allele located near the CYP24A1 gene, it has a negative effect on bone mineral density.

Calcitonin Receptor (CALCR) Gene: Calcitonin inhibits bone resorption by stimulating, CALCR located on the surface of osteoclasts. The human CALCR gene has at least six splice site variants, two of which are proteins known as CALCR1(CTR-1) and CALCR-2 (CTR2).

Receptor Activator Nuclear Kappa B (RANK) and (RANKL) Gene: Two different proteins have been discovered that control physiological and pathological bone resorption. Of these, receptor activator nuclear kappa B (RANK) is the receptor found in osteoclasts and stimulates bone resorption by RANK ligand (RANKL). Bone mass is determined by the working together of osteoblasts and osteoclasts. The two main pathways that determine this in osteoblasts are the RANKL/RANK and Wnt/β-catenin system.

TGFß1 Gene: Transforming Growth Factor acts as a binding factor between bone resorption and formation. Many studies with the TGFß1 gene have been associated with osteoporosis-associated phenotypes.

Lipoprotein receptor-associated protein (LRP5) Gene: It is a protein that has been found to have a key role in regulating bone mass as a result of linkage analysis studies performed in osteoporosis and high bone mass syndromes.

Sclerostin Gene (SOST): The SOST gene encodes the protein sclerostin, which is produced by osteocytes and inhibits bone formation. Inactivating mutations in the SOST gene cause sclerostosis and va Buchems diseases with high bone mass. These results make the SOST gene a strong candidate for genetic regulation of BMD.

Genes related to bone nutrition: These are the genes that cause hypercoagulation and vascular occlusion. These are FV Leiden, FII Prothrombin mutation, MTHFR C677T and A1298C polymorphisms

The results of studies related to the genetics of osteoporosis are extremely important in the prediction of bone density and quality, they are especially guide in the estimation of fracture risk. This will be useful both for the diagnosis of osteoporosis and for the determination of personal profiles in nutrition and drug therapy.

Gene polymorphisms examined in the bone resorption panel in our center: FV Leiden, FII Prothrombin mutation, MTHFR C677T and A1298C polymorphisms VDR Gene Polymorphisms (ApaI (rs7975232), BsmI (rs 1544410) TaqI (rs731236) polymorphisms in the VDR gene), ESR1 Gene Polymorphisms, COL1A1 Gene Polymorphisms.


1. Tural Ş, Kara N, Alaylı G. Osteoporoz Genetiği Turk J Osteoporos 2011;17(3):0-0

2. Van Driel M, van Leeuwen JPTM. Vitamin D and Bone: A Story of Endocrine and Auto/Paracrine Action in Osteoblasts. Nutrients. 2023 Jan 17;15(3):480. doi: 10.3390/nu15030480. PMID: 36771187; PMCID: PMC9919888.

3. Kow M, Akam E, Singh P, Singh M, Cox N, Bhatti JS, Tuck SP, Francis RM, Datta H, Mastana S. Vitamin D receptor (VDR) gene polymorphism and osteoporosis risk in White British men. Ann Hum Biol. 2019 Aug;46(5):430-433. doi: 10.1080/03014460.2019.1659851. Epub 2019 Sep 11. PMID: 31448632.

4. Serrano-Toledano D, Del Río-Arteaga M, Ribera-Zabalbeascoa J. Transient Familial Factor V Leiden-Linked Hip Osteoporosis. Rev Esp Cir Ortop Traumatol (Engl Ed). 2020 Jul-Aug;64(4):286-289. English, Spanish. doi: 10.1016/j.recot.2019.12.005. Epub 2020 Mar 27. PMID: 32229104.

Last Update: 2023-04-18 16:21:33