Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice

Abstract

Pulsed electromagnetic fields (PEMF) has been investigated as a noninvasive alternative method to prevent bone loss for postmenopausal osteoporosis (OP), and the bone tissue involved in these studies are usually long bones such as femur and tibia in OP patients or rat models. However, few studies have investigated the effects of PEMF on the vertebral bone in mice with OP. This study aimed to investigate whether PEMF preserve lumbar vertebral bone mass, microarchitecture and strength in ovariectomized (OVX) mouse model of OP and its associated mechanisms. Thirty 3-month-old female BALB/c mice were randomly divided into three groups (n=10): sham-operated control (Sham), ovariectomy (OVX), and ovariectomy with PEMF treatment (OVX+PEMF). The OVX+PEMF group was exposed to 15Hz, 1.6 mT PEMF for 8h/day, 7days/week. After 8weeks, the mice were sacrificed. The OVX+PEMF group showed lower body weight gain of mice induced by estrogen deficiency compared with OVX group. Biochemical analysis of serum demonstrated that serum bone formation markers including bone specific alkaline phosphatase (BALP), serum osteocalcin (OCN), osteoprotegerin (OPG) and N-terminal propeptide of type I procollagen (P1NP) were markedly higher in OVX+PEMF group compared with OVX group. Besides, serum bone resorption markers including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal crosslinked telopeptides of type I collagen (CTX-I) were markedly lower in OVX+PEMF group compared with OVX group. Biomechanical test observed that OVX+PEMF group showed higher compressive maximum load and stiffness of the lumbar vertebrae compared with OVX group. Micro-computed tomography (μCT) and histological analysis of lumbar vertebrae revealed that PEMF partially prevented OVX-induced decrease of trabecular bone mass and deterioration of trabecular bone microarchitecture in lumbar vertebrae. Real-time PCR showed that the canonical Wnt signaling pathway of the lumbar vertebrae, including Wnt3a, LRP5 and β-catenin were markedly up-regulated in OVX+PEMF group compared with OVX group. Moreover, the mRNA expressions of RANKL and OPG were markedly up-regulated in OVX+PEMF group compared with OVX group, whereas no statistical difference in RANKL/OPG mRNA ratio was found between OVX+PEMF group and OVX group. Besides, our study also found that the RANK mRNA expression was down-regulated in OVX+PEMF group compared with OVX group. Taken together, we reported that long-term stimulation with PEMF treatment was able to alleviate lumbar vertebral OP in postmenopausal mice through a combination of increased bone formation and suppressed bone resorption related to regulating the skeletal gene expressions of Wnt3a/LRP5/β-catenin and OPG/RANKL/RANK signaling pathways.

Keywords: Lumbar; Osteoporosis; Ovariectomized; Pulsed electromagnetic fields; Vertebrae.