Pulsed Electromagnetic Fields Partially Preserve Bone Mass, Microarchitecture, and Strength by Promoting Bone Formation in Hindlimb-Suspended Rats

Abstract

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 þ PEMF groups. The HU þ PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (mCT) 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, b-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.

Role of endoplasmic reticulum stress in disuse osteoporosis

“…The tail-suspended animal model has been widely accepted as an effective disuse osteoporosis model for simulating bone loss [15,22,41]. In the current tail suspension experiment, bone formation was mildly inhibited and bone resorption was markedly increased in unloaded mice, these 20 changes are in accord with previous study [14,[42][43][44].…”

“…In our study, we demonstrated that p-eIF2α/eIF2α was elevated in response to 22 short-term ER stress. For long-term stress, CCAAT/enhancer CHOP was elevated.…”

“…Food and water were provided on the cage floor. For the age-matched control group, mice were housed individually under the same conditions but were not subjected to hindlimb unloading [21][22][23].…”

Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats

“…As a safe and noninvasive physiotherapy, pulsed electromagnetic fields (PEMFs) have been suggested as a promising treatment for diabetic osteopenia. It has been reported that PEMFs can increase bone mineral density (BMD) in osteoporosis patients [5], prevent bone loss in ovariectomy-induced osteoporosis rats [6][7][8] and hindlimb-suspended rats [9], improve bone formation [10,11], and inhibit bone resorption [12] in vitro. It has reported that the cellular functions of bone marrow stromal cell [13], osteoblast [14,15], and osteoclast [16,17] are abnormal under diabetic conditions.…”

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

“…Furthermore, the enhanced Wnt/β-catenin signaling induced by PEMFs notably elevated the expression of proliferation phase related target genes, Ccnd 1 and Ccne 1, and differentiation phase related genes, ALP, OCN, COL1, and Runx2, in osteoblast cells, which accelerated the osteoblasts proliferation, differentiation, and mineralization, three pivotal processes of bone formation [31, 32]. On the other hand, according to in vivo assay studies, PEMFs effectively reversed the bone mass loss and deterioration of bone microarchitecture analyzed by microCT and attenuated biomechanical strength deterioration evaluated by three-point bending test in hind limb-suspended ovariectomized rats through the Wnt/Lrp5/β-catenin signal pathway [33, 34], indicating that activating this pathway by PEMF exposure is beneficial for bone disorders.…”