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Abstract
The RANKL/RANK/OPG pathway regulates bone remodelling and turnover. However, the genetic background of bone mineral density (BMD) and osteopenia in Saudi postmenopausal women is yet to be studied. We studied the genetic polymorphism of RANKL/RANK/OPG with BMD and other associated factors in Saudi postmenopausal osteopenic women. A total of 439 (223 osteopenia and 216 control) postmenopausal women were recruited from the orthopaedic department of the King Khalid University Hospital, Riyadh, KSA. Genetic variants of RANK (rs1805034 and rs35211496), RANKL (rs2277438 and rs9533156), and OPG (rs2073618 and rs3102735) were genotyped using RT-PCR. Anthropometrics, bone mineral density, and other bone markers were measured. The levels of bone turnover markers, PTH, and RANKL were found to be significantly different between control and the osteopenia group. The odds ratio of 2.37 (1.00–5.69) for RANK SNP (rs1805034) indicates that subjects with CC genotype are more vulnerable to developing osteopenia as compared to subjects with TT genotype. Similarly, for RANKL SNP (rs2277438), the significant odds ratio of 20.56 (9.82–43.06) indicates that the subjects with GG genotype are at significantly higher risk of having osteopenia compared with the AA genotype subjects. In addition, G allele in rs2277438 also found to be a risk factor for osteopenia 4.54 (3.18–6.49) compared with A allele. However, none of the OPG genotypes shows association with osteopenia. The association of RANK polymorphisms with osteopenia shows its clinical importance in the diagnosis and prognosis of the bone diseases; here, we suggest that the subjects with RANK and RANKL polymorphisms may develop osteoporosis.
Highlights
Low bone mineral density may cause osteoporosis but not all osteopenia patients develop osteoporosis [1, 2]
Keeping in sight the function of the RANK/RANKL/OPG with bone mineral density (BMD), we studied the genetic polymorphism of these genes with BMD and other associated factors in Saudi postmenopausal osteopenic women
Osteopenia and control groups had no significant difference in the values of the Body mass index (BMI), waist and hip circumference ratio (WHR), and diastolic blood pressure (BP)
Summary
Low bone mineral density (osteopenia) may cause osteoporosis but not all osteopenia patients develop osteoporosis [1, 2]. Some other physical factors like nonweight-bearing sports such as bicycling or swimming can trigger osteopenia. Multiple studies indicated that various factors including genetic, environmental, and their mutual cross talks could cause osteoporosis and osteopenia [8, 9]. Previous genome-wide association studies identified several genetic regions that influence BMD [10]. These genetic variants explained a small fraction of the variations in bone density, and none was shown to have a definite influence on the risk of fracture. Keeping in sight the function of the RANK/RANKL/OPG with BMD, we studied the genetic polymorphism of these genes with BMD and other associated factors in Saudi postmenopausal osteopenic women
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