Abstract
Type 2 diabetic patients have impaired bone quality, leading to increased fracture risk. Substantial evidence demonstrates that pulsed electromagnetic fields (PEMF) could resist osteopenia/osteoporosis induced by estrogen deficiency and disuse. However, the effects of PEMF on osteopenia/osteoporosis associated with diabetes, especially for more prevalent type 2 diabetes, remain poorly understood. We herein investigated the skeletal effects and mechanisms of PEMF (15 Hz, 20 Gs) on leptin receptor-deficient db/db mice with typical type 2 diabetic symptoms. Our µCT results showed that 12-week PEMF exposure significantly improved both cancellous and cortical bone microarchitecture in db/db mice. Three-point bending and biomechanical indentation testing demonstrated that PEMF improved whole-bone structural properties and tissue-level material properties in db/db mice. PEMF significantly promoted bone formation in db/db mice evidenced by increased serum osteocalcin and bone mineral apposition rate, whereas PEMF exerted no observable alteration in bone resorption. Real-time PCR showed that PEMF upregulated tibial gene expression of osteoblastogenesis-related of canonical Wnt/β-catenin signaling but not osteoclastogenesis-related RANKL-RANK signaling in db/db mice. Our findings demonstrate that PEMF improved bone quantity and quality with obvious anabolic activities in db/db mice, and imply that PEMF might become a clinically applicable treatment modality for improving bone quality in type 2 diabetic patients.
Highlights
Diabetes mellitus (DM), as an emerging epidemic in which the organism either does not produce enough or respond to insulin, afflicts approximately 350 million people worldwide[1]
The db/db group displayed significant elevation in serum Tartrate-resistant acid phosphatase 5b (TRACP5b) levels as compared with the WT group (P < 0.001); pulsed electromagnetic fields (PEMF) stimulation exhibited no significant alteration for the secretion of serum TRACP5b in db/db mice (P = 0.362)
The positive efficiency for resisting bone loss induced by estrogen deficient and disuse using PEMF has been proved by substantial previous studies; the potential effects of PEMF on bone structure and bone remodeling in DM, especially for more prevalent type 2 DM, are still poorly understood
Summary
Diabetes mellitus (DM), as an emerging epidemic in which the organism either does not produce enough or respond to insulin, afflicts approximately 350 million people worldwide[1]. Considering the high cost or adverse side effects of current available anti-osteoporosis drugs (e.g., hormones and bisphosphonates) and nutrients (e.g., calcium and vitamin D)[29,30,31,32,33], PEMF treatment might become a more promising alternative regimen for resisting osteoporosis due to its economic, safe and noninvasive nature In spite of these positive experimental and clinical findings of PEMF, little is understood about the potential effects of PEMF exposure on osteopenia/osteoporosis associated with DM, especially for more prevalent type 2 DM. In the present study, we hypothesize that PEMF exposure was capable of improving bone microstructure and regulating bone metabolism in type 2 DM db/db mice To examine this hypothesis, the effects of PEMF stimulation for 12 weeks on bone quantity, quality and turnover in db/db mice were systematically evaluated via serum biochemical, bone biomechanical, μCT and histomorphometric analyses. The potential regulatory mechanisms of bone turnover in db/db mice under the exposure of PEMF were preliminarily elucidated
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