电针；CGRP；骨质疏松；骨代谢

Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.

Interoception is a core process through which the body perceives its internal state and regulates physiological homeostasis via bidirectional communication between the central and peripheral nervous system. Skeletal interoception is a specific circuitry for the brain control of the weight-bearing system, particularly responsible for sensing bone-derived internal signals to maintain skeletal homeostasis in response to mechanical loading. Recent studies uncovered that prostaglandin E2 (PGE2) plays a crucial role in skeletal interoception, and is therefore involved in major skeletal disorders and pain conditions such as low back pain, osteoarthritis and particularly ankle osteoarthritis (AOA). Ankle pain is clinically common, with a prevalence of 9%-15% among adults, severely impairing work productivity and quality of life. This article reviews the progress of skeletal interoception in skeletal pathogenesis and pain, with AOA as an example. Specifically, it discusses PGE2 and skeletal interoception in relation to pain and inflammation. We also attempted to interpret non-steroidal anti-inflammatory drugs (NSAIDs), surgical interventions and Traditional Chinese Medicine (TCM) therapies, especially acupuncture and electroacupuncture, in the therapy of pain and osteoarthritis from the viewpoint of skeletal interoception. Interoception is an emerging science in understanding how the brain regulates peripheral organs. Skeletal interoception mediated by PGE2 provides an opportunity to understand the potential of NSAIDs and acupuncture in regulating interoception for the treatment of skeletal disorders including ankle pain.

Abstract Knee osteoarthritis (KOA) is a common chronic degenerative joint disease marked by progressive cartilage loss, subchondral bone remodeling, and synovial inflammation, resulting in persistent pain, functional disability, and diminished quality of life. Electroacupuncture (EA), a modality combining traditional acupuncture with electrical stimulation, has gained attention as a non-pharmacological intervention for KOA. Growing evidence suggests that EA not only reduces pain and enhances joint mobility but also modulates diverse biological processes—such as neuroendocrine signaling, inflammatory cascades, cartilage metabolism, and local hemodynamics. Mechanistically, EA acts through multi-target mechanisms, including suppression of pro-inflammatory mediators, promotion of anti-inflammatory and chondroprotective factors, and regulation of critical signaling pathways such as NF-κB, MAPK, and Wnt/β-catenin. Additionally, EA engages central and peripheral neuromodulatory systems involving opioid, serotonergic, and cannabinoid receptors, underpinning its analgesic properties. Despite encouraging outcomes, current support derives predominantly from small-scale clinical trials with short follow-up periods, underscoring the necessity for large-scale, randomized controlled studies with rigorous designs to establish standardized protocols and validate long-term benefits. This review synthesizes contemporary understanding of EA’s mechanisms and efficacy in KOA management, addressing ongoing challenges and outlining future directions for refining EA-based strategies within integrated treatment frameworks.

Background Postmenopausal osteoporosis (PMOP) is a common metabolic disorder in middle−aged and older women, leading to fractures, disability, and increased mortality. Current treatments include bisphosphonates (BPs), calcitonin (CT), vitamin D (VD), and acupuncture (Acu), often used in combination, but comparative evidence on different combined strategies remain limited. Objective To systematically compare the efficacy and safety of acupuncture combined with various medications for PMOP, supporting evidence−based clinical decisions. Methods We searched eight databases from inception to April 11, 2026 for randomized controlled trials (RCTs) evaluating acupuncture plus pharmacotherapy for PMOP. Primary outcomes included lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), clinical efficacy, Traditional Chinese Medicine (TCM) syndrome scores, and Visual Analog Scale (VAS) pain scores. Secondary outcomes were procollagen type I N−terminal propeptide (PINP), C−terminal telopeptide (CTX), estradiol (E2), alkaline phosphatase (ALP), and osteocalcin (OCN). A Bayesian network meta−analysis was performed, ranking treatments by surface under the cumulative ranking curve (SUCRA). Results We included 112 RCTs (9, 908 patients, 83 treatment strategies). For LS−BMD, Calcitriol (Cal)_Electroacupuncture (ElecAcu) ranked highest. For FN−BMD, CT_VD_Traditional Chinese Medicine (TCM)_Fire dragon moxibustion (FDMox) (without BP) and CT_VD_BP_TCM_Acu (with BP) were best. TCM_Acu showed the best clinical efficacy. For TCM syndrome total score, CT_VD_ Du−moxibustion (DuMox) ranked lowest. For low back pain, TCM_Acu (without BP) and CT_VD_BP_Acu_Moxibustion (Mox) (with BP) were best. CT_VD_BP_Acu_Point Application Therapy (Pat) ranked lowest for VAS. CT_VD_BP_Acupoint injection (AcuInj) produced the lowest PINP, CT_VD_TCM_Acu the lowest CTX, and CT_VD_BP_TCM_Acupoint catgut embedding (ACE) the highest E2. For ALP, CT_VD_BP_Acu ranked lowest with BP, and CT_VD_Mox highest without BP. For OCN, CT_VD_Mox ranked highest without BP, and CT_VD_BP_TCM_Acu_Mox highest with BP. Conclusion Acupuncture combined with pharmacotherapy offers differential benefits across efficacy outcomes in PMOP. However, fracture data were nearly absent (only one trial reported two hip fractures) and follow−up was short (≤12 months), limiting any inference on fracture prevention. Treatment selection should be individualized based on therapeutic priorities and patient characteristics, supporting personalized integrative management strategies. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251233374.

Calcitonin gene-related peptide (CGRP) has 37 amino acids. Initially, CGRP had vasodilatory and nociceptive effects. As research progressed, evidence revealed that the peripheral nervous system is closely associated with bone metabolism, osteogenesis, and bone remodeling. Thus, CGRP is the bridge between the nervous system and the skeletal muscle system. CGRP can promote osteogenesis, inhibit bone resorption, promote vascular growth, and regulate the immune microenvironment. The G protein-coupled pathway is vital for its effects, while MAPK, Hippo, NF-κB, and other pathways have signal crosstalk, affecting cell proliferation and differentiation. The current review provides a detailed description of the bone repair effects of CGRP, subjected to several therapeutic studies, such as drug injection, gene editing, and novel bone repair materials.

The peripheral nervous system may play an important role in normal bone maintenance and remodeling. Substance P (SP) is a neuropeptide associated with bone loss and formation that may mediate the effects of the nervous system. The purpose of this study is to determine if treadmill running combined with electro-acupuncture at Jiaji acupoints (Jiaji-EA) affects tibial bone mass and SP expression in rabbits with sciatic nerve injury. Twenty-four juvenile male New Zealand white rabbits were randomly assigned to one of 4 groups: sham injury control (sham), sciatic never crush control (SNCr), treadmill running (treadmill), and Jiaji-EA combined with treadmill running (ET group). The SNCr, treadmill, and ET groups all had an induced sciatic never crush injury of approximately 2mm. Control groups received no intervention; the treadmill and ET groups were trained by treadmill; the ET group also received Jiaji-EA. After the 4 weeks of treatment, toe-spreading index (TSI), BMD, bone strength, and SP expression in the tibia were significantly lower in the nerve injury groups (SNCr, treadmill, and ET) compared to the sham groups (p<0.05). Treatment (treadmill and ET groups) increased all measures compared to the SNCr group (p<0.05). Further, TSI, BMD, bone strength, and SP expression in the ET group were higher than the treadmill group (p<0.05). Our results indicate that treadmill therapy combined with electro-acupuncture at Jiaji acupoints prevents bone loss in rabbit tibias after sciatic nerve injury. This may occur in two ways: indirectly in association with axon regeneration and directly via loading on the bone mediated through increased SP expression. This study provides important evidence for the clinical treatment of bone loss after peripheral nerve injury.

Calcitonin gene-related peptide (CGRP) is an active peptide composed of 37 amino acids that functions through specific receptors. It is widely distributed in small-diameter dorsal root ganglion neurons, trigeminal ganglion neurons, and nerve fibers innervating the spinal cord and brainstem dorsal horn. CGRP regulates various physiological functions, including vasodilation, inflammation modulation, and cardiac protection, and plays a key role in pain transmission. Pain is a global health challenge closely associated with the activity of neuropeptides such as CGRP. Although progress has been made in the application of CGRP in treating various diseases, research in the field of rehabilitation remains in its early stages. This article summarizes the roles of CGRP in peripheral nerve injury, central injury, cardiovascular rehabilitation, and pain rehabilitation. In terms of treatment, common physical therapies such as laser therapy and shock wave therapy have been shown to influence CGRP expression levels. However, the specific effects of these physical interventions on CGRP require more systematic future research and analysis to achieve more efficient and personalized rehabilitation strategies.

The global aging crisis has increased the prevalence of skeletal disorders, necessitating innovative therapeutic strategies. This review employs the brain-bone axis (BBA) framework to examine the role of the sympathetic nervous system (SNS) in bone metabolism. The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters, such as norepinephrine, dopamine, neuropeptide Y, and leptin, regulating interactions between bone-related cells to maintain skeletal homeostasis. It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. By integrating current evidence, we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases. This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.

Objectives: Osteoporosis is widely regarded as a typical aged-related disease caused by impaired bone remodeling. This research was designed to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in a rat model and investigate the underlying mechanisms. Methods: Three-month-old rats were randomly selected as the youth group, and 24-month-old rats were randomly assigned to the elderly and EA groups. Rats in the EA group received 30 min of EA at bilateral SP10, ST36, K13 and GB34 daily, 5 days a week for 8 weeks. Bone mineral density (BMD), microstructure of the bone tissue, bone turnover biomarkers and expression level of autophagy-related proteins were detected. Results: Compared with the elderly group, EA treatment significantly increased BMD of the femur and ameliorated the microstructure. EA treatment increased trabecular bone volume ratio (= bone volume / total volume [BV/TV]) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) in senile osteoporosis rats. Compared with the elderly group, the serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment. Conclusions: EA can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms.

… responses and bone loss in postmenopausal osteoporosis rats,and its mechanism may be related to the activation of the PI3K/AKT pathway. [KEYWORDS] Electroacupuncture; Foot …

… or PEMF alone on osteoporotic bone have been documented… in rats with ovariectomy-induced osteoporosis. In the present … Effects of electroacupuncture on bone mass and cathepsin K …

Abstract Objective To observe the effect of electroacupuncture combined with low-frequency pulsed electromagnetic field on bone metabolism in patients with spinal cord injury (SCI). Methods The 60 SCI patients who met the inclusion criteria were randomly divided into 2 groups by means of a random number table. In the control group, 30 patients were treated with osteoporosis treatment apparatus. In the observation group, 30 patients were treated with osteoporosis treatment apparatus and electroacupuncture at the foot-shaoyangacupoints [Yanglingquan (阳陵泉GB 34) and Xuanzhōng (悬钟GB 39) of both sides].The treatment was applied once a day, 5 days a week, for 8 weeks.Before and after treatment, the changes of indexes in the two groups, including the bone mineral density (BMD), bone gla-containing protein (BGP), serum alkaline phosphatase (ALP), procollagen type I C-peptide (PICP), and 25‑hydroxy-vitamin D [25(OH)D], were observed for comparison. Results After treatment, in the two groups, the BMD and 25(OH)D indexes of the femoral neck, greater trochanter, and Ward's triangle region were not significantly changed in comparing with those before treatment (P>0.05), while the BGP, ALP, and PICP indexes were significantly higher than those before treatment (P 0.05). Conclusion The osteoporosis treatment apparatus can improve bone metabolism in SCI patients, and the curative effect can be enhanced when combined with electroacupuncture at foot-shaoyangacupoints.

Since the piezoelectric quality of bone was discovered in 1957, scientists have applied exogenous electrical stimulation for the purpose of healing. Despite the efforts made over the past 60 years, electronic bone growth stimulators are not in common clinical use. Reasons for this include high cost and lack of faith in the efficacy of bone growth stimulators on behalf of clinicians. The purpose of this narrative review is to examine the preclinical body of literature supporting electrical stimulation and its effect on bone properties and elucidate gaps in clinical translation with an emphasis on device specifications and mechanisms of action. When examining these studies, trends become apparent. In vitro and small animal studies are successful in inducing osteogenesis with all electrical stimulation modalities: direct current, pulsed electromagnetic field, and capacitive coupling. However, large animal studies are largely unsuccessful with the non-invasive modalities. This may be due to issues of scale and thickness of tissue planes with varying levels of resistivity, not present in small animal models. Additionally, it is difficult to draw conclusions from studies due to the varying units of stimulation strength and stimulation protocols and incomplete device specification reporting. To better understand the disconnect between the large and small animal model, the authors recommend increasing scientific rigor for these studies and reporting a novel minimum set of parameters depending on the stimulation modality.

The regeneration defect of bone is a long-term physiological process after bone injuries. To accelerate the bone remodeling process, the combination of chemical and physical stimulations provides an efficient strategy to allow maturation and to functionalize osteoclasts and osteoblasts. This study aims to investigate the dual effects of a tricalcium phosphate (TCP)-based gelatin scaffold (GGT) in combination with electroacupuncture stimulation on the activation of osteoclasts and osteoblasts, as well as new bone regrowth in vitro and in vivo. We demonstrated that electrical stimulation changes the pH of a culture medium and activates osteoblasts and osteoclasts in an in vitro co-culture system. Furthermore, we showed that electroacupuncture stimulation can enhance osteogenesis and new bone regrowth in vivo and can upregulate the mechanism among parathyroid hormone intact (PTH-i), calcium, osteoclasts, and osteoblasts in the bone-defected rats. Those results showed the potential interest to combine the electroacupuncture technique with GGT scaffolds to improve bone remodeling after injury.

Background To date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism. Method This trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded. Discussion CEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

Introduction: Internal heat-type acupuncture therapy is a new therapeutic method that integrates acupuncture and heat therapy and effectively reduces local muscle inflammation. It has a good effect on the clinical application of osteoporosis. The purpose of this study was to assess the improvement of glucocorticoid-induced osteoporosis (GIOP) after internal heat-type acupuncture treatment as well as its role in promoting the balance of bone remodeling in the GIOP rabbit model by regulating the triplet of osteoprotegerin(OPG)-receptor activator of nuclear factor-KB ligand (RANKL)-receptor activator of nuclear factor-KB (RANK). Methods: The rabbits were divided into the control, model (GIOP), GIOP+Alendronate, and GIOP+Internal heat-type acupuncture groups, with 8 rabbits in each group. At the end of the treatment, all rabbits were sacrificed. The pathologic changes of lumbar vertebrae were observed by x-ray, the morphology of lumbar trabecular bone was observed by HE staining, and the apoptosis of lumbar vertebrae was detected by Tunel. The protein expressions of OPG, RANKL, and RANK in lumbar vertebrae were detected by immunohistochemistry staining, immunofluorescence staining, and Western blotting. Results: Internal heat-type acupuncture partly prevented osteopenia among GIOP-induced rabbits, improved the morphology of lumbar vertebrae, and inhibited the apoptosis of lumbar vertebrae osteocytes. Moreover, by increasing the protein expression level of OPG and reducing the protein expression of RANKL and RANK, internal heat-type acupuncture effectively promoted the balance of bone remodeling and eventually achieved the treatment of GIOP. Conclusion: Internal heat-type acupuncture therapy may promote the balance of bone remodeling by regulating the triplet of osteoprotegerin-receptor activator of nuclear factor-KB ligand-receptor activator of nuclear factor-KB, thereby treating osteoporosis which was induced by glucocorticoid.

… level, inhibiting hyperactive bone remodeling, thus restoring normal bone metabolism, increasing the BD and relieving clinical symptoms. Unlike estrogen-replacement therapy that may …

… Effects of electroacupuncture on bone mass and cathepsin K expression in ovariectomised rats. Acupunct Med 32:478–485. Zhou J, Liao Y, Xie H, Liao Y, Zeng Y, Li N, Sun G, Wu Q, …

ABSTRACT Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

… procedure could alleviate subchondral bone remodeling, mainly bone resorption, by inhibiting osteoclast activity. Moreover, acupotomy and electroacupuncture had more advantages …

OBJECTIVE To explore short-term changes in dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) after a standardized acupuncture program in Mexican postmenopausal women and to generate hypotheses regarding osteoporosis-related transcriptomic pathways and candidate peripheral-blood genes. METHODS This exploratory pre-post pilot study included 19 women selected in two extreme-phenotype strata: low BMD (n = 13; T-score ≤ -2.5 at the lumbar spine or hip) and normal BMD (n = 6; T-score ≥ -1.0 at both sites). Women with intermediate T-scores were not enrolled. All participants received 24 acupuncture sessions over 3 months. Femoral neck and lumbar spine BMD and anthropometric variables were assessed before and after treatment. A published osteoporosis-versus-normal microarray dataset was reanalyzed, followed by pathway and network analyses and reverse transcription quantitative polymerase chain reaction (RT-qPCR) assessment of three prespecified candidate genes in peripheral blood mononuclear cells. RESULTS The low-BMD stratum was older and had higher glucose and lipid concentrations at baseline. In the low-BMD stratum, measured femoral neck BMD was higher after treatment (nominal p < 0.001), as were lumbar spine BMD (nominal p = 0.037) and hip circumference (nominal p = 0.046). After Bonferroni correction across these three focal comparisons, only the femoral neck BMD difference remained below the corrected threshold of p < 0.0167. The exploratory microarray screen retained 478 probe-set records using an absolute log₂ fold-change threshold > 0.5 and nominal p < 0.05; none met an FDR threshold < 0.05. Pathway enrichment was therefore considered hypothesis-generating, and RT-qPCR differences involving FNIP2, SAMD9L, and FGD2 were observed. After Bonferroni correction for nine tests, eight comparisons remained significant, whereas the FNIP2 pre-post comparison was significant only at the nominal level (p = 0.032). CONCLUSIONS The program was feasible and was associated with short-term changes in measured DXA values and candidate molecular signals. However, the small nonrandomized sample, extreme-phenotype selection, absence of a sham or untreated comparator, baseline imbalance, and lack of a facility- and site-specific least significant change preclude causal or definitive efficacy conclusions. Larger randomized, sham-controlled trials with validated DXA precision estimates are required.

… Long-term electroacupuncture stimulation prevents osteoporosis in … Electroacupuncture stimulation at BL20, BL23 and SP6 prevents hind limb unloading-induced osteoporosis …

Osteoporosis (OP) is one of the most serious health problems, causing a huge economic burden to patients, families, and society. OP rehabilitation treatment plays an important role in …

Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies.

The regenerative repair after bone trauma is not merely an osteogenic process but a dynamic reconstruction involving the coordinated participation of multiple systems, including the nervous, immune, and vascular systems. In recent years, the regulatory role of the neuro-immune axis in bone regeneration has attracted increasing attention. Existing studies indicate that this axis may influence the quality of bone regeneration and functional recovery outcomes by modulating inflammation initiation, facilitating the transition from the inflammatory clearance phase to the reparative phase, and contributing to the remodeling of the local microenvironment. Specifically, neural signal-mediated regulation of early immune cell recruitment, macrophage polarization, and angiogenesis-osteogenesis coupling represents a critical upstream mechanism in post-traumatic bone regeneration. Conversely, an imbalance in the neuro-immune axis may be associated with adverse outcomes such as nonunion, chronic pain, and functional impairment. This article reviews the main mechanisms by which the post-traumatic neuro-immune axis regulates bone regeneration from four aspects: inflammation initiation, inflammation switching, microenvironment remodeling, and functional repair, and summarizes the research progress of related intervention strategies. Overall, targeting the neuro-immune axis may provide novel therapeutic strategies for promoting bone healing and improving functional recovery; however, most current evidence is derived from animal experiments, mechanistic studies, or early translational explorations, and its clinical value remains to be further validated.

The peripheral sensory nervous system (PNS) has been widely recognized for its role in the collection, processing, and transmission of sensory information, including thermal, mechanical, chemical, and proprioceptive stimuli. In recent years, there has been a growing scholarly interest in the PNS attributable to its multiple physiological and pathophysiological non-sensory roles in the organs it innervates. The PNS exerts regulatory functions within the organs it innervates through direct interactions with local cells or through microbe-nerve-cell interactions that differ from the traditional feedback regulatory modes used by the hormonal and sensory brain-sympathetic/parasympathetic systems. The release of the neuropeptide calcitonin gene related peptide (CGRP) by nerves, through its action on CGRP receptors in peripheral cells, constitutes a primary molecular axis for PNS regulation of organ cells, maintaining tissue homeostasis, facilitating pathological processes, and modulating innate and adaptive immunity. This review highlights the non-sensory functions of the peripheral sensory nervous system in various tissues and organs, focusing on phenotypes, molecular mechanisms and their significance, while also exploring future research directions, methodologies and potential preclinical studies aimed at targeting these pathways for the development of novel therapies.

This study evaluated the participation of CB1 and CB2 receptors in the antiresorptive effect of electroacupuncture (EA) on an experimental model of inflammatory bone loss in rats. 30 rats were divided into five groups: C (control); EP (experimental periodontitis); EA (C+ EA); EP-EA (EP+ EA in the acupoints LI4, LG11, ST36, ST44); EP - EA-sham (EP+ EA in sham acupoints). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. Animals were euthanized at day 11. Histometric analysis was performed to evaluate the percentage of bone area in the furcation area. Immunolabeling patterns in the periodontal tissues and immunofluorescent staining in the trigeminal ganglia and in the trigeminal spinal tract for CB1 and CB2 receptors were performed. It was observed increased bone loss in the furcation in the EP and EP-EA-sham groups, in comparison to the other groups (p < 0.05). Enhanced CB2 immunolabeling was observed in the periodontal tissues in the EP-EA group, when compared to the EP and EP-EA-sham groups (p < 0.05). Increased CB1 immunofluorescent staining was observed in the neural tissues in the EA treated group in comparison with the other groups (p < 0.05), while no expression of CB2 was observed in those regions. Our study showed that in the presence of inflammatory bone disease, EA treatment reduced bone erosion and increased the immunoexpression of CB1 in the neural tissues and CB2 in the periodontal tissues.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene‐related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type‐H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES‐enhanced osteoporotic fracture healing. This proof‐of‐concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP). The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective.

Background: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. Methods: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at −30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. Results: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). Conclusions: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

… bone mineral density in postmenopausal women with differentiated thyroid cancer and osteoporosis, thereby substantiating its distinct therapeutic potential for skeletal protection. [ 3,4 ] …

Primary osteoporosis (POP) is a common metabolic bone disorder that has a devastating effect on their quality of life in patients. Acupuncture, a traditional Chinese therapy, has been used to treat osteoporosis for over 2000 years. This study aimed to determine the efficacy of acupuncture in treating POP compared to conventional medicine or placebo. We searched for potentially relevant studies in PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang database and ClinicalTrials.gov up to December 20, 2024. Randomized controlled trials investigating treatment of POP for which acupuncture was administered as a stand-alone treatment or combined with conventional medicine compared to conventional medicine or placebo, were included. The outcomes included bone mineral density (BMD), visual analogue scale (VAS) scores, clinical effectiveness rate, estradiol (E2), Oswestry Disability Index (ODI), and levels of serum alkaline phosphatase (ALP). Data were synthesized using a random-effects meta-analysis model, and the observed heterogeneity was investigated using subgroup analyses. Study quality was appraised using the Cochrane RoB 2 tools, and the quality of the aggregated evidence was evaluated using the GRADE guidelines. Publication bias was assessed by funnel plots and validated by Egger's test. Forty eligible articles with 2654 participants were identified. Compared to the control group, acupuncture effectively increased the BMD (MD 0.04 [0.03–0.06], P < 0.001, I2 = 92%), clinical efficacy (RR 1.24 [1.14–1.34], P < 0.001, I2 = 81%), and levels of E2 (SMD 0.30 [0.09–0.52], P = 0.006, I2 = 0%), and reduced the VAS scores (SMD − 1.79 [− 2.29 to − 1.29], P < 0.001, I2 = 95%). Data on ODI and ALP were insufficient for meta-analysis. The current evidence suggests that the efficacy of acupuncture in improving the symptoms of POP are encouraging for its use in clinical practice as a physical intervention for patients with POP. However, since the included patients were all from China, there was a risk of sample bias, high-quality multicenter studies in different countries or regions should be conducted in the future.

… in a decrease in the strength and bone mineral density (BMD) of the femur [… osteoporosis by promoting insulinlike growth factor I system, which plays an important role in BMD and bone …

Bone diseases are the leading causes of disability and severely compromised quality of life. Neuropeptide Y (NPY) is a multifunctional neuropeptide that participates in various physiological and pathological processes and exists in both the nerve system and bone tissue. In bone tissue, it actively participates in bone metabolism and disease progression through its receptors. Previous studies have focused on the opposite effects of NPY on bone formation and resorption through paracrine modes. In this review, we present a brief overview of the progress made in this research field in recent times in order to provide reference for further understanding the regulatory mechanism of bone physiology and pathological metabolism.

A predominant number of diseases affecting women are related to female hormones. In most of the cases, these diseases are reported to be associated with menstrual problems. These diseases affect female reproductive organs such as the breast, uterus, and ovaries. Estrogen is the main hormone responsible for the menstrual cycle, so irregular menstruation is primarily due to a disturbance in estrogen levels. Estrogen imbalance leads to various pathological conditions in premenopausal women, such as endometriosis, breast cancer, colorectal cancer, prostate cancer, poly cysts, intrahepatic cholestasis of pregnancy, osteoporosis, cardiovascular diseases, obesity, etc. In this review, we discuss common drug targets and therapeutic strategies, including acupuncture and compounds of natural origin, for the treatment of diseases caused by estrogen deficiency.

Abstract Recent studies have reported that electroacupuncture (EA) can treat osteoporosis, but most of which were based on the “kidney governing bones” theory. However, the ancient Chinese medical textbook Huangdi Neijing pointed out that “Gallbladder Meridian of Foot Shaoyang” correlates with bone diseases, including osteoporosis, although the therapeutic regimens were lost after the Tang Dynasty. Here, we explored whether EA at GB points improves osteoporosis and its underlying mechanism. We constructed ovariectomized mice and treated them with EA at GB30 (Huantiao), GB34 (Yanglingquan), and GB39 (Xuanzhong) acupoints. EA treatment significantly improved bone parameters in osteoporotic mice, as evidenced by micro-computed tomography and histological assessment. Additionally, EA treatment elevated the serum levels of estradiol and SOD that were downregulated in osteoporotic mice. Transcriptome and qPCR results verified that EA treatment upregulated the expression of genes associated with bone formation. Moreover, transcriptome analysis revealed differential enrichment of the PI3K–Akt pathway. Furthermore, Western blot analysis demonstrated that estradiol partially counteracted a reduction in p-AKT expression induced by hydrogen peroxide. These findings indicate that EA treatment increases serum estradiol levels in mice, thus inhibiting osteoporosis induced by oxidative stress. This effect is achieved by activating the PI3K–Akt signaling pathway.

… on bone mass density and biochemical indexes of bone metabolism in patients of postmenopausal osteoporosis… Effects of acupuncture plus acupoint sticking on bone mass density …

… In the present study, we observed BMC and BMD by a dynamic filtration double-energy X-ray (DFDE-X) bone mineral density instrument, and tested the levels of serum estrodiol (E2), …

Background Based on a description of acupuncture to treat a bone disease resembling osteoporosis in the ancient text of Huangdi Neijing, we aimed to assess the effects of electroacupuncture (EA) at GB points in ovariectomised (OVX) rats. Methods 40 female Wistar rats were randomly divided into four groups (n=10 each): ovariectomised model group (OVX); ovariectomised group treated with EA at GB points (OVX+GB); ovariectomised group treated with EA at non-GB points (OVX+N) in the hindlimb; and a sham surgery group (Sham). Three months after ovariectomy, rats in the OVX+GB and OVX+N groups received EA treatment for 3 months. Urine, blood and femur samples were collected from each animal for analysis. Results Bodyweight (BW) in the OVX+GB group decreased after EA treatment, reaching a minimum of ∼12% below the OVX and OVX+N groups at 1 month. Concentrations of urine deoxypyridinoline, a bone resorption marker, were significantly elevated in the OVX and OVX+N groups but not the OVX+GB group. Concentrations of serum bone specific alkaline phosphatase, a bone formation marker, were significantly higher in the OVX+GB group versus the Sham and OVX groups. Bone mineral density (BMD) did not differ between the OVX, OVX+GB and OVX+N groups, but was ∼10% lower than the Sham group. However, BMD/BW in the OVX+GB group was significantly higher than in the OVX and OVX+N groups and similar to the Sham group. Histological assessment of the femur showed that EA at GB points improved the bone architecture. Conclusions EA treatment at GB points had anti-osteoporotic effects in a rat model of osteoporosis.

Osteoporosis is a common condition among breast cancer patients, characterized by decreased bone density due to chemotherapy and hormone therapy. However, the application of electroacupuncture (EA) stimulation at Guanyuan (CV4) sites has been found to be beneficial in enhancing bone mineral density. In this study, we aimed to investigate the efficacy of EA stimulation at CV4 sites in breast cancer-induced osteoporosis and elucidate the potential underlying mechanisms. A breast cancer model in mice was established, EA stimulation at CV4 sites was performed, and hematoxylin-eosin (HE) stain was conducted to assess the bone mineral density and trabecular bone volume of femur tissues. Additionally, Tartrate-resistant acid phosphatase (TRAP) staining was performed to identify and visualize osteoclasts. Furthermore, Western blots were used to evaluate the expression levels of various proteins, including c-src, Cathepsin K (CtSK), matrix metalloproteinase 9 (MMP9), Collagen 1A1 (COL1A1), Osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), Wnt3a and β-catenin, and Enzyme Linked Immunosorbent Assay (ELISA) to measure the concentration of Alkaline phosphatase (ALP), NO synthase 2 (NOS2), glutathione reductase (GSR), superoxide dismutase (SOD), reactive oxygen species (ROS) and lactate dehydrogenase (LDH) in the serum. The results revealed that EA stimulation in the breast cancer model resulted in higher bone mineral density and trabecular bone volume, along with a reduction in the number of osteoclasts. EA stimulation at CV4 site significantly decreased the protein levels of c-src, CtSK and MMP9, while also reducing ROS and LDH production. Conversely, it promoted the expression of COL1A1, OPN, RUNX2, Wnt3a and β-catenin. Additionally, it elevated the concentration of ALP, NOS2, GSR and SOD in the serum. Overall, EA stimulation at the CV4 site may inhibit bone loss and promote bone differentiation by activating the Wnt/β-catenin pathway, indicating its potential use for breast cancer-induced osteoporosis treatment.

… effective therapy for treating osteoporosis. Warm acupuncture seemed to more effective than electroacupuncture and needling for osteoporosis in comparison to sole Western medicine. …

Objective To systematically evaluate the efficacy and safety of acupuncture as an adjuvant therapy for osteoporosis (OP) through a comprehensive synthesis of recent randomized controlled trial (RCT) evidence. Methods A systematic literature search was conducted across PubMed, Web of Science, CNKI, and Wanfang databases (2014 – 2024) to identify RCTs investigating acupuncture combined with conventional therapy for OP. Study quality was appraised using the Cochrane Risk of Bias tool, and meta-analyses were performed using RevMan 5.4 and Stata 15.0, with subgroup analyses stratified by intervention type, population characteristics, and treatment duration. Results 28 RCTs (n=2,758) were included. Meta-analysis revealed acupuncture significantly enhanced bone mineral density (BMD) versus controls: total (SMD = 0.47, p = 0.03), femoral neck (MD = 0.05, p = 0.01), lumbar spine (SMD = 0.40, p < 0.001), Ward’s triangle (MD = 0.07, p = 0.02), and hip (SMD = 0.55, p < 0.001), with particularly marked improvements in the postmenopausal osteoporosis subgroup. Acupuncture demonstrated significant improvements in treatment efficacy, biochemical markers, pain scores, and symptom assessments, while reducing adverse events. Warm needle moxibustion outperformed controls in femoral neck (MD = 0.07, p = 0.002) and hip BMD (SMD = 0.87, p < 0.001), while electroacupuncture significantly elevated serum calcium (MD = 0.18, p = 0.02). Short-term interventions (≤ 3 months) demonstrated optimal efficacy. Conclusion Acupuncture demonstrates efficacy and safety as an OP adjuvant therapy. Current evidence is limited by regional bias and methodological heterogeneity. Multicenter, large-sample RCTs are needed to standardize protocols and validate long-term therapeutic efficacy. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024499354.

Abstract Background Primary osteoporosis is a common disease in the elderly, often causing low back pain and limited mobility. Electroacupuncture is considered a combination of traditional acupuncture and modern transcutaneous electrical nerve stimulation. Due to its strong stimulation, it has shown certain efficacy in relieving low back pain associated with primary osteoporosis (POP). It has the potential to be a complementary or alternative treatment for drug therapy of POP-related low back pain. However, the underlying mechanisms have not been fully elucidated. Therefore, this study, by evaluating the efficacy of electroacupuncture in treating POP-related low back pain, aims to explore the potential central mechanisms using resting-state functional magnetic resonance imaging (rs-fMRI). Methods This study is a randomized controlled trial in which 60 patients were randomly divided into two groups: the calcium group (n = 30) and the calcium + electroacupuncture group (n = 30). The study lasted for 17 weeks, including a 1-week baseline, 4 weeks of treatment, and 12 weeks of follow-up (at the 4th and 12th week after treatment). The primary outcome measure is McGill Pain Questionnaire (MPQ), and secondary outcome measures include the Oswestry dysfunction index(ODI), Young's Modulus, and the use of analgesic medications after treatment. These measures will be used to evaluate the clinical efficacy of the two intervention methods for treating low back pain associated with primary osteoporosis (POP). Twenty patients from each group will be randomly selected for rs-fMRI examinations to observe changes in brain functional activity and correlate them with changes in pain severity. Discussion This study aims to evaluate the clinical efficacy and potential central mechanisms of electroacupuncture in treating low back pain associated with POP. Provided that we obtain imaging-based evidence of the effectiveness of electroacupuncture intervention for POP-related low back pain, this study will provide supporting evidence for the clinical application of electroacupuncture in the treatment of low back pain associated with POP. Trial registration: Chinese Clinical Trial Registry ChiCTR2300075736. Registered on 14 September 2023

… This study on the treatment of osteoporosis-associated back pain demonstrated a clinically significant reduction in pain and improvement in quality of life with acupuncture treatment. At …

… the pain of postmenopausal osteoporosis.The study by … osteoporosis. A further study demonstrated that gonadotrophin releasing hormone is downregulated after electroacupuncture (EA…

Background The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. Methods Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group). Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, β-catenin, runt-related transcription factor (Runx) 2 involving Wnt/β-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting. Results The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, β-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group. Conclusion EA attenuates PMOP and it appears that the mechanism involves the regulation of multiple targets and pathways.

Objectives: The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms. Methods: This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague–Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks. Results: EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups. Conclusion: EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.

Background Electroacupuncture (EA) is widely used for osteoarthritis (OA), but its mechanisms remain unclear. This study investigated the therapeutic effects of EA on OA in rats and its potential mechanisms. Methods A rat model of knee OA was established via intra-articular injection of sodium monoiodoacetate. The effects of EA on behavioral indices (paw withdrawal threshold (PWT), body weight, knee width), cartilage pathology (HE staining, Safranin O-fast green staining, TUNEL), and inflammatory factors (IL-6, IL-1β, TNF-α) were assessed. Gut microbiota and metabolites were analyzed using 16S rRNA sequencing and metabolomics. Finally, integrative analysis of differential gut microbiotas and metabolites was conducted. Results EA alleviated joint pain, increased PWT, reduced knee swelling, promoted cartilage repair, and inhibited chondrocyte apoptosis in OA rats. Additionally, EA decreased IL-6, IL-1β, and TNF-α levels in both serum and synovial fluid. EA altered gut microbiota composition, increasing Muribaculaceae and Lachnospiraceae at the family level, and Clostridia and Campylobacteria at the class level, while decreasing Alphaproteobacteria and Actinobacteria. Functional analysis showed changes in pathways like Biosynthesis of vancomycin group antibiotics, Folate biosynthesis, and Vitamin B6 metabolism. Metabolomics revealed that EA modulated metabolic pathways in OA rats, particularly the Steroid biosynthesis pathway. Specifically, 7-Dehydrocholesterol was decreased in the OA group compared to the Control group, while EA treatment increased its levels. Integrated analysis revealed associations between 41 gut microbiotas and 47 metabolites. Conclusion EA alleviated OA and was associated with changes in gut microbiota composition and steroid biosynthesis-related metabolites. These findings suggest that the gut microbiota–metabolite axis may be involved in the effects of EA on OA.