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

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.

Lei T ，Liang Z ，Li F ，Tang C ，Xie K ，Wang P ，Dong X ，Shan S ，Jiang M ，Xu Q ，Luo E ，Shen G ... -  《-》

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis.

Jing D ，Cai J ，Wu Y ，Shen G ，Li F ，Xu Q ，Xie K ，Tang C ，Liu J ，Guo W ，Wu X ，Jiang M ，Luo E ... -  《-》

Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/β-catenin signaling-associated mechanism.

Jing D ，Li F ，Jiang M ，Cai J ，Wu Y ，Xie K ，Wu X ，Tang C ，Liu J ，Guo W ，Shen G ，Luo E ... -  《PLoS One》

Effects of combined treatment with ibandronate and pulsed electromagnetic field on ovariectomy-induced osteoporosis in rats.

Ibandronate (IBN) and pulsed electromagnetic field (PEMF) have each shown positive effects for treating osteoporosis, but no study has evaluated the relative effects of these treatments combined. This study investigated the effects of IBN + PEMF on bone turnover, mineral density, microarchitecture, and biomechanical properties in an ovariectomized (OVX) rat model of osteoporosis. Fifty 3-month-old rats were randomly apportioned to receive a sham-operation (n = 10), or ovariectomy (n = 40). The latter group was equally divided as the model (OVX control) or to receive IBN, PEMF, or IBN + PEMF. Beginning the day after surgery, the IBN and IBN + PEMF groups received weekly subcutaneous IBN; the PEMF and IBN + PEMF groups were given daily PEMF during the same 12 weeks. After 12 weeks of treatments, biochemical parameters, bone mineral density (BMD), microarchitecture parameters, biomechanical properties, and some metabolic modulators that are involved in bone resorption were compared. The L5 lumbar vertebral body BMDs of the IBN, PEMF, and IBN + PEMF groups were 121.6%, 119.5%, and 139.6%; maximum loads were 111.4%, 112.7%, and 121.9%; and energy to failure was 130.8%, 129.2%, and 154.9% of the OVX model, respectively. The IBN + PEMF group had significantly lower levels of serum tartrate-resistant acid phosphatase 5b, and greater improvement in BMD, bone microarchitecture, and strength of the lumbar spine compared with monotherapy groups. Results showed that IBN + PEMF had a more favorable effect on the lumbar spine in this osteoporosis model than did either monotherapy. Bioelectromagnetics. 38:31-40, 2017. © 2016 Wiley Periodicals, Inc.

Zhou J ，Liao Y ，Xie H ，Liao Y ，Zeng Y ，Li N ，Sun G ，Wu Q ，Zhou G ... -  《-》

Effect of intervention initiation timing of pulsed electromagnetic field on ovariectomy-induced osteoporosis in rats.

The aim of this study is to explore the effect of timing of initiation of pulsed electromagnetic field (PEMF) therapy on bone mass, microarchitecture, and biomechanical properties, and to investigate receptor activator of NF-kB (RANK) expression in ovariectomized (OVX) rats. Sixty female Sprague-Dawley rats were randomly divided into two equal batches of three groups each (10 rats in each group). The first batch comprised of sham-operated (Sham-0 group), ovariectomized (OVX-0 group), and ovariectomized plus treated with PEMF starting from the day of OVX (Early PEMF group). The second batch comprised of sham-operated (Sham-12 group), ovariectomized (OVX-12 group), and ovariectomized plus treated with PEMF starting 12 weeks after OVX (Late PEMF group). Rats (whole body) in the early and late PEMF groups were exposed to PEMF (3.8 mT peak, 8 Hz pulse burst repetition rate). After 12 weeks of PEMF therapy, Early PEMF prevented OVX-induced deterioration in bone mineral density (BMD) and mechanical properties in lumbar vertebral body and femur, and deterioration in bone microarchitecture in lumbar vertebral body and proximal tibia. Late PEMF intervention only inhibited deterioration of BMD, bone microarchitecture, and mechanical properties in lumbar vertebral body. Both early and late PEMF therapy suppressed RANK protein expression in OVX rats without a concomitant effect on RANK mRNA expression. These results demonstrate that timing of initiation of PEMF therapy plays an important role in achieving optimal beneficial effects. The specific PEMF parameters may exert these favorable biological responses, at least partially, via inhibition of protein expression of RANK. Bioelectromagnetics. 38:456-465, 2017. © 2017 Wiley Periodicals, Inc.

Zhou J ，Liao Y ，Zeng Y ，Xie H ，Fu C ，Li N ... -  《-》