Association of Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms with Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women

Kim, Jung Oh; Han, Soo-Hong; Lee, Yeonho; Ahn, Tae Keun; Lim, Jae Joon; Chung, Young Sun; Shin, Dong Eun; Lee, Woo Sik; Han, In Ho; Kim, Nam Keun

doi:10.3390/ijms17122062

Cited by 11 publications

(12 citation statements)

References 39 publications

(45 reference statements)

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“…PAI‐1 is expressed by osteoblasts and osteoclasts, and its expression is stimulated by several cytokines . Polymorphisms in PAI‐1 are associated with the incidence of osteoporotic vertebral compression fractures , although serum PAI‐1 levels and functional studies for PAI‐1 single nucleotide polymorphisms (SNPs) were not examined in this study. Several studies using PAI‐1‐deficient mice have indicated involvement of the plasminogen activator/PAI‐1 system in bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

et al. 2018

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Osteoporosis is a progressive bone disease caused by an imbalance between bone resorption and formation. Recently, plasminogen activator inhibitor‐1 (PAI‐1) was shown to play an important role in bone metabolism using PAI‐1‐deficient mice. In this study, we evaluated the therapeutic benefits of novel, orally available small‐molecule PAI‐1 inhibitor (iPAI‐1) in an estrogen deficiency‐induced osteoporosis model. Eight‐week‐old C57BL/6J female mice were divided into three groups: a sham + vehicle (Sham), ovariectomy + vehicle (OVX + v), and OVX + iPAI‐1 (OVX + i) group. iPAI‐1 was administered orally each day for 6 weeks starting the day after the operation. Six weeks of iPAI‐1 treatment prevented OVX‐induced trabecular bone loss in both the femoral bone and lumbar spine. Bone formation activity was significantly higher in the OVX + i group than in the OVX + v and Sham groups. Unexpectedly, OVX‐induced osteoclastogenesis was partially, but significantly reduced. Fluorescence‐activated cell sorting analyses indicated that the number of bone marrow stromal cells was higher in the OVX + i group than that in the OVX + v group. A colony‐forming unit‐osteoblast assay indicated enhanced mineralized nodule formation activity in bone marrow cells isolated from iPAI‐1‐treated animals. Bone marrow ablation analysis indicated that the remodeled trabecular bone volume was significantly higher in the iPAI‐1‐treated group than that in the control group. In conclusion, our results suggest PAI‐1 blockade via a small‐molecule inhibitor is a new therapeutic approach for the anabolic treatment of postmenopausal osteoporosis.

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Section: Discussionmentioning

confidence: 99%

A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

et al. 2018

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“…OVCFs have a profound impact on patients with spinal kyphosis and lumbar back pain; if not treated in time, patients will suffer persistent pain, needing treatment with analgesic drugs daily to maintain normal life; not only does it increase the financial burden, but it also has a serious impact on the physical and mental health and the quality of life ( 16 ). The results of this study show that there were no significant differences in preoperative ODI, MPQ and JOA scores between the two groups (P>0.05), and after operation, the scores of ODI, MPQ and JOA in the two groups were significantly improved, which were more obvious in the observation group than those in the control group (P<0.05).…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of PVP and PKP in the treatment of OVCFs after bilateral resection of ovarian cancer

Wang

Niu

2018

Oncol Lett

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The clinical efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer was investigated. Eighty-six patients with osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer admitted to the Second People's Hospital of Hefei from September, 2015 to August, 2016 were selected and randomly divided into control group (n=43) and observation group (n=43). The control group was treated with PVP, while the observation group received PKP. The operation time, fluoroscopy times, bone cement volume and leakage rate of patients in the two groups were recorded; the postoperative pain of patients was compared using Short-form McGill Pain Questionnaire; the changes in height of injured vertebra and Cobb angle of patients in two groups were compared; the efficacy of patients in the two groups was compared in accordance with Oswestry dysfunction index (ODI) and Japanese Orthopedic Association (JOA) low back pain scoring; and the quality of life was compared. The fluoroscopy times and bone cement leakage were significantly less in observation group than those in control group (P<0.05). After operation, the scores of ODI, MPQ and JOA in the two groups were significantly improved (P<0.05). The postoperative height of injured vertebra and the Cobb angle of patients in two groups were significantly different than those before the operation (P<0.05). The quality of life of patients in the observation group was higher than that in the control group one year after operation (P<0.05). In conclusion, PKP and PVP are effective in the treatment of osteoporotic vertebral compression fractures after bilateral resection of ovarian cancer; however, PKP is more conducive to lumbar stability and maintenance of intervertebral height thus greatly correcting the kyphosis, which is beneficial to improving the quality of life of patients.

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“…A probability ( p ) value of 0.05 was considered to indicate statistical significance. ORs were adjusted by possible confounders, including age, hypertension, and DM [ 58 ]. These parameters were selected as adjustment variables because they are directly or potentially associated with OVCF.…”

Section: Methodsmentioning

confidence: 99%

3′-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women

Ahn

Kim

et al. 2018

IJMS

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Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.

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Association of Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms with Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women

Cited by 11 publications

References 39 publications

A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

A small‐molecule PAI‐1 inhibitor prevents bone loss by stimulating bone formation in a murine estrogen deficiency‐induced osteoporosis model

Clinical efficacy of PVP and PKP in the treatment of OVCFs after bilateral resection of ovarian cancer

3′-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women

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