Mitochondrial DNA copy number in peripheral blood is associated with femoral neck bone mineral density in postmenopausal women.

Abstract

It has been suggested that mitochondrial dysfunction is related to aging and metabolic disorders. Yet there are few studies of the relationship between bone mineral density (BMD) and mitochondrial content in humans. We investigated the relationship between BMD and mitochondrial DNA (mtDNA) copy number in peripheral blood of postmenopausal women. The study included 146 postmenopausal women. Enrolled subjects were taking no medications and had no disorders that altered bone metabolism. We measured BMD using dual-energy x-ray absorptiometry and leukocyte mtDNA copy number using real-time polymerase chain reaction. Anthropometric evaluations and biochemical tests were performed. Patients with osteopenia or osteoporosis had lower mtDNA copy numbers than normal subjects (p < 0.0001). Femoral neck BMD was negatively correlated with age (r = -0.01, p = 0.04) and with serum levels of adiponectin (r = -0.22, p = 0.01) and osteocalcin (r = -0.31, p = 0.0001). Serum levels of 25-OH vitamin D (r = 0.32, p < 0.0001) and mtDNA copy number (r = 0.36, p < 0.0001) were positively correlated with femoral neck BMD. Multiple regression analysis showed that mtDNA copy number (ß = 0.156, p < 0.001) was an independent factor associated with femoral neck BMD after adjustment for age, body mass index, waist circumference, waist-hip ratio, blood pressure, homeostatic model assessment of insulin resistance, high-sensitivity C-reactive protein, adiponectin, osteocalcin, homocysteine, lipid profiles, 25-OH vitamin D, and regular exercise. mtDNA copy number was not related to lumbar BMD. Low mtDNA content in peripheral blood is related to decreased femoral neck BMD in postmenopausal women. Our findings suggest that mitochondrial dysfunction may be a potential pathophysiologic mechanism of osteoporosis in postmenopausal women.