Plasminogen activator inhibitor-1 concentrations and bone mineral density in postmenopausal women with type 2 diabetes mellitus

Abstract

BackgroundWomen with type 2 diabetes mellitus (T2DM) have a higher risk of fractures despite increased bone mineral density (BMD). In experimental studies a potential role of plasminogen activator inhibitor-1 (PAI-1) in bone remodeling is suggested but studies in humans are lacking. This is a first study in humans investigating whether circulated levels of PAI-1 in postmenopausal women with T2DM are related to BMD and adiposity.MethodsAnthropometric variables, PAI-1 and insulin levels, serum lipids and bone turnover markers were measured in 127 postmenopausal women with T2DM. A total of 117 female patients were divided according to lumbar spine BMD measurements via dual-energy x-ray absorptiometry in three groups: 47 with osteopenia, 21 with osteoporosis and 49 with normal BMD.ResultsDiabetic patients with normal BMD had significantly higher BMI, greater waist circumference and lower bone turnover markers than diabetics with osteopenia and osteoporosis. PAI-1 was lower in diabetics with osteoporosis and osteopenia compared with diabetics with normal BMD. Multiple regression analysis revealed insulin, triglycerides levels, pyrilinks and beta blocker therapy to be the strongest predictors of PAI-1 levels. PAI-1 levels correlated with both L-BMD and hip BMD, but after adjustment for age and BMI association was no longer significant.ConclusionOur findings suggest that elevated PAI-1 levels are associated with higher BMD in obese diabetic patients but the possible implications of this finding and underlying mechanisms still remain unclear. Obviously, metabolic parameters, may affect both BMD and PAI-levels, and association of PAI-1 and BMD could be indirect. However, as pyrilinks is also independently and significantly negatively correlated to PAI-1 its direct involvement in bone metabolism is also plausible. Further investigations are needed to elucidate the nature of interaction of this matrix modulator in relation to energy and bone metabolism in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-016-0094-x) contains supplementary material, which is available to authorized users.

Bone Mineral Density in Relation to Metabolic Syndrome Components in Postmenopausal Women With Diabetes Mellitus Type 2

“…PAI-1 also negatively correlated with bone turnover markers, once again suggesting higher mineral density as a result of inhibited bone resorption. In a recently published study increased PAI levels were associated with higher BMD in obese diabetic female patients implicating direct involvement in bone metabolism 28 . Total femoral BMD was signifi cantly higher in the overweight group, whereas no signifi cant diff erence in the vertebral BMD was noted, implying that the effects of obesity and hyperinsulinemia on BMD varied by anatomic site, as shown in previous studies 29 .…”

Genistein treatment improves fracture resistance in obese diabetic mice

“…Leptin is a hormone that is secreted by white adipose tissue to aid in the regulation of obesity by inducing weight loss and homeostasis of bone. Although obesity alone is not linked with decreases in bone mass [ 6 ], obese individuals with T2DM often exhibit leptin resistance that likely plays a role in increased incidence of fractures [ 7 – 10 ]. The ob/ob mouse is leptin deficient due to a spontaneous mutation of the ob gene.…”

Effect of GSK-137647A, the first non-carboxylic FFA4 agonist, on the osteogenic and adipogenic differentiation of bone mesenchymal stem cells in db/db mice

“…However, the relationship between type 2 diabetes and BMD reduction has not been determined, and the results of various related studies are not consistent . Although the change in BMD in type 2 diabetes is uncertain, the connection between type 2 diabetes and osteoporotic fractures has been confirmed . Compared to healthy patients, the risks of fracture in type 2 diabetes are rising sharply.…”