scholarly journals FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women

2010 ◽  
Vol 163 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Domenico Rendina ◽  
Fernando Gianfrancesco ◽  
Gianpaolo De Filippo ◽  
Daniela Merlotti ◽  
Teresa Esposito ◽  
...  

ObjectiveFSH, via its receptor (FSHR), influences bone remodeling and osteoclast proliferation and activity. The aim of this study was to evaluate the influence of two single nucleotide polymorphisms (SNPs) of theFSHRgene on bone mineral density (BMD) and bone turnover markers (bone alkaline phosphatase and type I collagen C-telopeptides) in postmenopausal women.MethodsTwo hundred and eighty-nine unrelated postmenopausal women were genotyped for the SNPs rs1394205 and rs6166. BMD was estimated using dual-energy X-ray absorptiometry and quantitative ultrasound (QUS) methodologies.ResultsAA rs6166 women showed a lower BMD (femoral neck and total body), lower stiffness index (calcaneal QUS), and higher serum levels of bone turnover markers compared to GG rs6166 women. The prevalence of osteoporosis was significantly higher in AA rs6166 women compared with GG rs6166 women. These results were not influenced by circulating levels of FSH and estrogens.ConclusionThe SNP rs6166 of theFSHRgene significantly influences BMD in postmenopausal women. In particular, AA rs6166 women are at increased risk of postmenopausal osteoporosis compared with GG rs6166 women, independently of circulating levels of FSH and estrogens. Previous studies have demonstrated that this SNP influences cell and tissue response to hyperstimulation of FSHRin vivoandin vitro. Our study results appear in agreement with these experimental data and with known biological actions of FSH/FSHR system in bone homeostasis.

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-Wei Hu ◽  
Zeng Zhang ◽  
Jin-Wei He ◽  
Wen-Zhen Fu ◽  
Chun Wang ◽  
...  

The reference ranges of bone turnover markers (BTMs) were important during the treatment of osteoporosis, and the associations with bone mineral density (BMD) were controversial. The aim of this study was to establish the reference ranges of N-terminal procollagen of type l collagen (P1NP), osteocalcin (OC), and beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) in Shanghai area and to investigate the relationships between BTMs and BMD in postmenopausal women. 2,799 subjects recruited in Shanghai City were measured BTMs to establish the reference ranges. Additional 520 healthy postmenopausal women were also measured BTMs, these women measured BMD in addition. BTMs were measured using the Roche electrochemiluminescence system. We used the age range of 35 to 45-year-olds to calculate reference intervals. The reference range of OC was 4.91 to 13.90 ng/mL for women and 5.58 to 16.57 ng/mL for men, P1NP was 13.72 to 32.90 ng/mL for women and 16.89 to 42.43 ng/mL for men, andβ-CTX was 0.112 to 0.210 ng/mL for women and 0.100 to 0.378 ng/mL for men. BTMs significantly negatively correlated with lumbar spine and femoral and total hip in postmenopausal women ( = −0.157~−0.217,P< 0.001). We established the normal reference ranges of P1NP, OC, andβ-CTX in the Shanghai area. This study also found that BTMs correlated with BMD and suggested that BTMs were the key determining factors of early BMD decreases.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
A. Sánchez ◽  
L. R. Brun ◽  
H. Salerni ◽  
P. R. Costanzo ◽  
D. González ◽  
...  

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab.Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.


Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Jadwiga Ambroszkiewicz ◽  
Joanna Gajewska ◽  
Grazyna Rowicka ◽  
Witold Klemarczyk ◽  
Magdalena Chelchowska

Objective There is scant research examining the prevalence of thinness in early childhood, despite its potential negative consequences for health and development across the life course. The objective of this study was to assess bone status through measurement of bone mineral density and biochemical bone turnover markers, with special attention paid to carboxylated (c-OC) as well as undercarboxylated (uc-OC) forms of osteocalcin, in the groups of thin and normal-weight children. Design The study included 80 healthy prepubertal children (median age 7.0 years), who were divided (according to Cole’s international cutoffs) into 2 subgroups: thin children ( n = 40, body mass index [BMI] = 13.5 kg/m2) and normal-weight children ( n = 40, BMI = 16.1 kg/m2). Bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy x-ray absorptiometry method. Serum concentrations of C-terminal telopeptide of collagen type I (CTX), total osteocalcin (OC), and c-OC, and uc-OC forms of osteocalcin were determined using enzyme-linked immunosorbent assays. Results In thin children, we observed higher levels of bone resorption marker CTX compared with normal-weight peers. Total osteocalcin concentrations were comparable in both groups of children; however, in thin children we observed higher median values of uc-OC (34.40 vs. 29.30 ng/mL, P < 0.05) and similar c-OC levels (25.65 vs. 28.80 ng/mL). The ratio of c-OC to uc-OC was significantly lower ( P < 0.05) in thin than in normal-weight children. Total BMD and BMC were significantly decreased ( P < 0.0001) in thin children compared with normal-weight peers (0.724 ± 0.092 vs. 0.815 ± 0.060 g/cm2 and 602.7 ± 159.2 vs. 818.2 ± 220.1 g, respectively). Conclusion Increased concentrations of CTX and uc-OC might lead to disturbances in bone turnover and a decrease in bone mineral density in thin children.


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