运动；机械负荷；电针；针灸；骨质疏松；骨代谢

… Thus, the effects of exercise on bone metabolism in postmenopausal women are not well established, especially regarding the effects of aerobic exercise [15, 16]. Some studies have …

… There is evidence that exercise can regulate bone metabolism and MSC osteogenic differentiation through the BMP signaling pathways. It was reported that the BMP-2 mRNA levels …

Osteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.

Bone formation and resorption are ongoing phenomena. When bone resorption equals bone formation, bone mass remains stable. When resorption exceeds formation, bone mass is reduced--a process that leads to osteopenia or osteoporosis. Osteopenia is reduced bone mass and osteoporosis is reduced bone mass with resultant fractures. Reduced bone mass may be postmenopausal or related to ovarian failure (type I osteoporosis), it may be age-related (type II osteoporosis), or it may result from several other etiologic factors (secondary osteoporosis). Disuse and inactivity can cause bone loss, whereas weight-bearing exercises may maintain or improve bone mineral density. There is a significant correlation between muscle strength and bone mineral density. There is evidence that strengthening exercises may lead to an increase in the mineral density of the bones to which the muscles are attached. Currently, drug regimens are available to decrease or halt bone loss in osteoporotic patients. Properly designed exercise programs may prove to be effective for retarding age-related bone loss. In patients with osteoporosis, the cause should be investigated before treatment is commenced.

… to bone strength, hypothesized mechanisms of bone loss, the influence of physical activity on bone mass accretion, and the role of exercise in preventing and treating osteoporosis. …

… ) GBSA exercise may benefit bone metabolism and general health by down-regulating bone resorption … improving functional fitness in PMW with osteopenia or osteoporosis. The GBSA …

… Osteoporosis and osteopenia are defined by a decrease in bone mineral density and an increased risk of bone … the development of osteopenia and osteoporosis not only in the elderly …

… of disuse osteoporosis. This review refers to the mechanism, the diagnosis using imaging … and bone metabolism markers, and treatment and prophylaxis of disuse osteoporosis. …

… and energy metabolisms emerged in pathology: while diabetic patients experience an increased fracture risk due to reduced bone mineral density (BMD), in osteoporosis metabolic dys…

… A further 5 sedentary women, who were all at least 5 years postmenopausal, in good health and not using any medication thought to influence bone metabolism (users of menopausal …

… The role of ROS in bone metabolism is dual. It is a key modulator of bone cell function and also implicated in the pathophysiology of mineral tissues. Elevated production of ROS and/or …

The prevalence of chronic diseases including osteoporosis and sarcopenia increases as the population ages. Osteoporosis and sarcopenia are commonly associated with genetics, mechanical factors, and hormonal factors and primarily associated with aging. Many older populations, particularly those with frailty, are likely to have concurrent osteoporosis and sarcopenia, further increasing their risk of disease-related complications. Because bones and muscles are closely interconnected by anatomy, metabolic profile, and chemical components, a diagnosis should be considered for both sarcopenia and osteoporosis, which may be treated with optimal therapeutic interventions eliciting pleiotropic effects on both bones and muscles. Exercise training has been recommended as a promising therapeutic strategy to encounter the loss of bone and muscle mass due to osteosarcopenia. To stimulate the osteogenic effects for bone mass accretion, bone tissues must be exposed to mechanical load exceeding those experienced during daily living activities. Of the several exercise training programs, resistance exercise (RE) is known to be highly beneficial for the preservation of bone and muscle mass. This review summarizes the mechanisms of RE for the preservation of bone and muscle mass and supports the clinical evidences for the use of RE as a therapeutic option in osteosarcopenia.

… mass and geometric adaptations at load-bearing bone sites [1–4], and therefore presents an important part of osteoporosis prevention strategies. Bone metabolic responses to …

… exercise intensity (EI) on bone metabolism during and for 4 days after acute, weight-bearing endurance exercise… intensity of endurance exercise might influence bone metabolism. …

… exercise on bone metabolism and related hormones. The responses of calciotropic hormones and bone … in preventing osteoporosis [[7]], by either increasing the peak bone mass during …

… products of bone tissue has been of high value to investigate the complex pathways of bone metabolism and their alterations in bone diseases, especially in osteoporosis. They have …

… The activities of osteoblasts and osteoclasts are controlled by a variety of hormones and cytokines, as well as by mechanical loading. Most importantly, sex hormones are very crucial for …

… microscopic organization and volume of bones, an effect that may carry over to maturity (… osteoporosis).On the other hand, withdrawal of mechanical loading results in rapid bone loss (…

… mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss … bone remodeling. …

During evolution, the development of bone was critical for many species to thrive and function in the boundary conditions of Earth. Furthermore, bone also became a storehouse for calcium that could be mobilized for reproductive purposes in mammals and other species. The critical nature of bone for both function and reproductive needs during evolution in the context of the boundary conditions of Earth has led to complex regulatory mechanisms that require integration for optimization of this tissue across the lifespan. Three important regulatory variables include mechanical loading, sex hormones, and innervation/neuroregulation. The importance of mechanical loading has been the target of much research as bone appears to subscribe to the “use it or lose it” paradigm. Furthermore, because of the importance of post-menopausal osteoporosis in the risk for fractures and loss of function, this aspect of bone regulation has also focused research on sex differences in bone regulation. The advent of space flight and exposure to microgravity has also led to renewed interest in this unique environment, which could not have been anticipated by evolution, to expose new insights into bone regulation. Finally, a body of evidence has also emerged indicating that the neuroregulation of bone is also central to maintaining function. However, there is still more that is needed to understand regarding how such variables are integrated across the lifespan to maintain function, particularly in a species that walks upright. This review will attempt to discuss these regulatory elements for bone integrity and propose how further study is needed to delineate the details to better understand how to improve treatments for those at risk for loss of bone integrity, such as in the post-menopausal state or during prolonged space flight.

… , bone remodelling was maintained at control levels,[62] indicating perhaps that the frequency of loading is an additional important mechanical … Mechanical loading attenuates bone loss …

… Modeling serves to adapt bones to changes in mechanical loading [1], and remodeling serves to thicken trabeculae in the growing skeleton [2], processes that are most effective during …

… defining feature of osteoporosis is the diminished skeletal response to mechanical loading. … for investigating how weak mechanical signals influence bone remodeling. However, its …

This review will define the role of collagen and within-bone heterogeneity and elaborate the importance of trabecular and cortical architecture with regard to their effect on the mechanical strength of bone. For each of these factors, the changes seen with osteoporosis and ageing will be described and how they can compromise strength and eventually lead to bone fragility.

… In this study, bone remodeling simulations with a mechanical … to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of …

… changes in the bone remodelling process. In this study, it is proposed that osteoporosis is due … The algorithm used to simulate bone cellular response to mechanical loading is based on …

… Bone remodelling is regulated by signals to these cells generated by mechanical loading. … Strains below the lower threshold (200 me) will result in remodelling that causes net bone loss…

Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis.

… the role mechanical loading plays in bone remodeling and cartilage … that regulate loading-induced bone remodeling and cartilage … Mechanical Loading and Bone Remodeling …

… Note that the extent of net bone loss resulting from a single cycle of remodeling, indicated by the difference between the new and old locations of the bone surface, can be the same, …

… or induced osteoporotic changes. … bone remodeling process and its possible effects on bone physiology and pathology, to examine bone histomorphometry as a means of studying bone …

… The plate transmits a substantial portion of the loads that are normally transmitted by the bone. Extensive bone remodeling and a net bone loss may occur which many researchers …

The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt-β-catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague-Dawley rats (4.5-months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non-acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three-point-bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme-linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription-quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, β-catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt-β-catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt-β-catenin signaling pathway.

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.

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.

The aim of the present study was to investigate the effectiveness of electroacupuncture (EA) on ovariectomy-induced osteoporotic rats to elucidate potential mechanisms by which EA regulates acetylation of histones in caput femoris. A total of 40 female Sprague-Dawley rats were randomly allocated into four groups: Sham operation, ovariectomy-induced osteoporosis (OVX), EA and 17β-estradiol (E2) treatments. After 8 weeks of intervention, the trabecular morphology of each group was measured by micro-computed tomography. Biomarkers of bone metabolism in serum were detected. The protein expression of histone deacetylase 2 (HDAC2), histone H3, Ac-histone H3 and downstream cytokines involved in osteoblast and osteoclast differentiation were detected. The results showed that EA and E2 both prevented bone loss and improved trabecular morphology in OVX rats. EA was found to suppress the protein expression of HDAC2 and promoted the acetylation of histone H3 compared with the OVX model group. The results indicated that EA promoted the differentiation of osteoblasts, and suppressed that of osteoclasts, thereby improving the trabecular morphology. E2 was shown to regulate the expression of runt-related transcription factor 2 and receptor activator of nuclear factor-κB ligand without modulating the expression of HDAC2, and therefore diverged mechanistically from EA. Overall, the results of the present study suggested that the mechanisms through which EA improved bone mineral density and trabecular morphology may involve the modulation of histone H3 acetylation and regulation of osteoblast and osteoclast differentiation.

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.

OBJECTIVE This aim of the study was to investigate whether electroacupuncture (EA) can mitigate osteoporosis (OP) in an ovariectomy (OVX)-induced rat model by affecting the ferroptosis-related pathway. METHODS Thirty-two 12-week-old female Sprague-Dawley rats were randomly allocated into four groups: CONTROL, SHAM, OVX and EA. We examined the effects of OVX and EA on markers of bone resorption and formation, iron content, malondialdehyde (MDA) levels, and the expression of ferritin heavy chain 1 (FTH1), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In addition, femoral morphology and immunofluorescence were analysed. RESULTS The OVX group exhibited a significant increase in bone resorption markers, iron and MDA levels, with a notable decrease in alkaline phosphatase (ALP) levels, FTH1, SLC7A11 and GPX4 expression, and impaired trabecular architecture. EA significantly reduced bone resorption markers, iron and MDA content while substantially elevating ALP levels and FTH1, SLC7A11 and GPX4 expression. At the same time, EA improved trabecular architecture. CONCLUSION EA ameliorated OVX-induced OP by decreasing iron accumulation and activating the SLC7A11/GPX4 axis.

Electroacupuncture has demonstrated established efficacy in treating postmenopausal osteoporosis, yet the central mechanisms underlying its action via the brain-bone axis remain incompletely understood. This study employed multimodal resting-state functional magnetic resonance imaging to investigate neurofunctional changes induced by electroacupuncture in a rat model of postmenopausal osteoporosis. Twenty-four female Sprague-Dawley rats were randomly allocated to electroacupuncture, sham, and model (ovariectomized) groups. The electroacupuncture group received an 8-week intervention at acupoints GB30, GB34, and GB39. We assessed brain function through amplitude of low-frequency fluctuation, regional homogeneity, and region-of-interest functional connectivity, while simultaneously measuring serum bone turnover markers via enzyme-linked immunosorbent assay. Our results demonstrated that electroacupuncture significantly improved bone microstructure and reduced bone resorption marker levels. Neuroimaging revealed enhanced cerebellar neural activity which correlated negatively with bone resorption, alongside decreased neural synchronization in the entorhinal cortex. Furthermore, strengthened functional connectivity between entorhinal and visual cortices positively correlated with bone formation markers, while weakened somatosensory-cerebellar connectivity correlated with reduced bone resorption. Bayesian mediation analysis provided strong statistical evidence for the role of the entorhinal-visual pathway involvement in bone formation regulation and cerebellar mediation of bone resorption suppression. These findings systematically reveal the association between electroacupuncture-induced brain functional reorganization and bone metabolic improvements, offering new insights into the role of the brain-bone axis in osteoporosis management.

… than electroacupuncture and needling for osteoporosis in … some differences of cycle of bone metabolism in humans and … has no effect on bone mineral density in osteoporosis patients …

… EA positively influenced bone metabolism. Radiographic analysis … , EA prevented osteoporosis, enhancing the number of bone … alveolar bone loss in sham-treated animals in this study. …

Background Warm needle acupuncture (WNA) is commonly used in primary osteoporosis (OP) management in China. The evidence of its effectiveness needs to be systematically reviewed. Objective The aim of the meta-analysis was to evaluate whether using WNA alone or combined with conventional medicine benefits primary OP. Methods PubMed, Embase, the Cochrane Central Register, Medline, China National Knowledge Infrastructure, Wanfang and VIP databases were searched from their inception through 30 June 2016. RCTs applying WNA independently or as an adjunct to conventional medicine, compared with conventional medicine alone, were included. Primary outcomes were bone mineral density (BMD) of the lumbar vertebrae, femoral neck, Ward's triangle and greater trochanter. The secondary outcome was chronic pain measured by VAS score. Meta-analysis was conducted using RevMan V.5.3 software. Results Nine RCTs involving 572 participants were included. When WNA was used as an adjunct to conventional medicine, meta-analysis revealed a statistical difference in favour of increasing BMD of the lumbar vertebrae (mean difference (MD)=0.06, 95% CI 0.03 to 0.08, P<0.001). WNA increased BMD of the femoral neck (MD 0.14, 95% CI 0.08 to 0.21, P<0.001) and greater trochanter (MD 0.09, 95% CI 0.04 to 0.15, P<0.001) when used alone, and additionally decreased VAS scores (MD=−1.10, 95% CI −1.14 to −1.06, P<0.001) when used as an adjunct to conventional medicine. However, the safety of WNA was not specifically reported. Conclusions WNA may have beneficial effects on BMD and VAS scores of patients with primary OP. However, all included trials were at high risk of bias and of low quality. Further rigorous studies are needed to determine the effectiveness of WNA for primary OP treatment.

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Background: The aim of this study was to investigate the effects of a combination of electroacupuncture (EA) and the Otago Exercise Program (OEP) for sarcopenia in older individuals and provide treatment recommendations for this patient population. Methods: In this assessor-blinded randomized controlled trial, 120 older patients with sarcopenia were randomly divided into an OEP group (n = 58) and an EA + OEP group (n = 62). The OEP group received OEP 5 times/week, with each session lasting 30 minutes, for a duration of 12 weeks. In addition to OEP treatment, the EA + OEP group was treated with EA at ST31, ST32, GB34 and ST36 for 30 minutes 3 times/week for 12 weeks. The appendicular skeletal muscle mass-height index (ASM/H2) was the primary outcome. The secondary outcomes included grip strength, 4-m gait speed and 6-min walk distance. Outcomes were measured before initiation and at 6 and 12 weeks after initiation. Results: Significant differences in ASM/H2, grip strength, 4-m gait speed and 6-min walk distance were detected between the 2 groups at week 12, whereas no differences were detected at weeks 0 and 6. In the EA + OEP group, as the treatment time increased, ASM/H2, grip strength, 4-m gait speed and 6-min walk distance increased significantly. In the OEP group, as the treatment time increased, no significant difference was found in ASM/H2, whereas grip strength, 4-m gait speed and 6-min walk distance increased significantly (P < .05). Conclusion: In older patients with sarcopenia, EA + OEP was associated with increased skeletal muscle mass, but no such effect was found for OEP alone. Moreover, EA + OEP was superior to OEP alone in terms of improving muscle strength and walking ability. EA + OEP may be considered an effective treatment for sarcopenia in older adults.

Abstract Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

Denosumab is an effective drug for treating postmenopausal osteoporosis (PMO), yet some patients experience inadequate pain relief and suboptimal rates of bone mineral density (BMD) increase. Warm acupuncture, a traditional Chinese therapy, shows potential in alleviating pain and improving bone metabolism. This study aimed to evaluate the efficacy and safety of warm acupuncture combined with denosumab versus denosumab alone for PMO. A prospective, randomized, open-label, controlled design was employed. 120 eligible PMO patients were randomly assigned to the Combination group (n = 60, receiving denosumab + warm acupuncture) or the Control group (n = 60, receiving denosumab only). The treatment period was 6 months. The primary outcome was the percentage change in lumbar spine (L1-L4) BMD. Secondary outcomes included changes in Visual Analogue Scale (VAS) pain score, serum bone turnover markers (β-CTX, PINP), 36-Item Short Form Health Survey (SF-36) scores, and adverse events. After treatment, the percentage change in lumbar BMD was significantly greater in the Combination group (+8.32 ± 3.15%) than in the Control group (+5.21 ± 2.78%) (P < 0.001). The Combination group also showed superior improvement in VAS score reduction (−4.45 ± 1.25 vs. −2.88 ± 1.42, P < 0.001), greater decrease in serum β-CTX (−0.40 ± 0.12 ng/mL vs. −0.32 ± 0.11 ng/mL, P < 0.001), and better scores in several SF-36 domains (notably Bodily Pain and Physical Function) (P < 0.05). No serious adverse events occurred in either group. The Combination group reported three cases of mild local burns from moxibustion, and the Control group reported 2 cases of mild flu-like symptoms. Warm acupuncture combined with denosumab more effectively increases lumbar spine BMD, alleviates bone pain, further inhibits bone resorption, and improves quality of life in PMO patients, with a favorable safety profile. Warm acupuncture may serve as a beneficial adjunctive therapy to denosumab for PMO.

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.

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.

… Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover. Osteoarthritis Cartilage 2011;19:466–73. 19 Imhof …

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.

Objective This study aimed to appraise the efficacy and safety of the tonifying-Shen (kidney) principle (TS (TK) principle) for primary osteoporosis (POP). Methods Randomized controlled clinical trials (RCTs) using the TS (TK) principle for POP were searched from eight electronic databases to search for relevant literature that was published from the initiation to September 2019. Two reviewers performed study selection, data extraction, data synthesis, and quality assessment independently. Review Manager 5.3 software was used to assess the risk of bias and conduct the data synthesis. We assessed the quality of evidence for outcomes by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results Thirty-six studies with 3617 participants were included. Meta-analysis showed a consistently superior effect of the TS (TK) principle combined with conventional Western medicine (CWM) in terms of total effectiveness rates (RR = 1.28; 95% CI (1.23, 1.33); P < 0.00001), BMD of the lumbar spine (SMD = 0.71; 95% CI (0.47, 0.95); P < 0.00001) and proximal femur (SMD = 0.94; 95% CI (0.49, 1.38); P < 0.00001), TCM symptom integral (SMD = −1.23; 95% CI (−1.43, −1.02); P < 0.00001), and VAS scores (SMD = −3.88; 95% CI (−5.29, −2.46); P < 0.00001), when compared to using CWM alone and with significant differences. Besides, in respect of adverse effects, it showed no significant statistical difference between the experimental and control groups, RR = 0.99 and 95% CI (0.65, 1.51), P=0.97. Conclusion Our meta-analysis provides promising evidence to suggest that using the TS (TK) principle combined with CWM for POP is more effective than using CWM alone. Also, both of them are safe and reliable for POP.

… the acupuncture groups as compared to the model control group. Our findings showed that acupuncture … group p < 0.05) conforms to the high bone turnover expected after ovariectomy. …

… Acupuncture, a form of Traditional Chinese Medicine (TCM), has also been used for the treatment of osteoporosis. The validity of acupuncture treatment for osteoporosis has been …

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.

Purpose This meta-analysis and data mining aimed to investigate the effectiveness of Acupuncture-Related Therapies for animal models with Postmenopausal Osteoporosis (POMP) and to summarize the acupoints involved. Methods This systematic review was conducted a comprehensive search of animal experiments using acupuncture-related therapies for the treatment of PMOP up to April 1, 2025. The primary outcome was bone mineral density (BMD). The secondary outcome indicators were estradiol(E2), blood calcium, osteocalcin(OC) and alkaline phosphatas(ALP).Meta-analysis was used to evaluate its efficacy, and data mining was used to explore the protocol for acupoint selection. Results 27 Animal Experiments encompassing 548 animals with PMOP were analyzed. Meta-analysis displayed that compared with the conventional drug group, the acupuncture-related therapy group significantly increased the Estradiol (mean difference [MD] 2.37,95% confidence interval [95%CI] 1.15 to 3.58), Femoral BMD (mean difference [MD] 1.25,95% confidence interval [95%CI] 0.65 to 1.87), lumbar BMD (mean difference [MD] 1.88,95% confidence interval [95%CI] 1.27 to 2.49), Tibia BMD (mean difference [MD] 1.63,95% confidence interval [95%CI] 0.56 to 2.69). Data mining revealed that Zusanli (ST36), Shenshu (BL23), Guanyuan (CV4), and Sanyinjiao (SP6) were the core acupoints for PMOP treated by Acupuncture-Related Therapies. Conclusion Acupuncture improved BMD and estrogen levels in animal models of PMOP. ST36, BL23, CV4, and SP6 are the core acupoints for acupuncture in PMOP, and this program is expected to become a supplementary treatment for PMOP.

Acupuncture has gained growing attention in the management of osteoporosis (OP). However, a comprehensive review has not yet been conducted on the efficacy and challenges of acupuncture in preliminary research and clinical trials. Therefore, an extensive literature search was conducted using electronic databases, including PubMed (http://www.ncbi.nlm.nih.gov/pubmed), CNKI (http://www.cnki.net), and Web of Science, for studies published from the beginning of 2000 to the end of May 2022. Combinations of synonyms for OP, acupuncture, traditional Chinese medicine, clinical trial, preclinical study, and animal experiments were searched. A total of 290 papers were consulted, including 115 reviews, 109 clinical observations, and 66 preclinical studies. There is accumulating evidence to support the beneficial role of acupuncture in preserving bone quality and relieving clinical symptoms based on clinical and preclinical investigations. The top ten most commonly used acupoints are BL23, ST36, BL20, BL11, CV4, GV4, SP 6, KI3, BL18, and GB39. The underlying mechanisms behind the benefits of acupuncture may be linked with the regulation of the hypothalamic-pituitary-gonadal (adrenal) axis and activation of the Wnt/β-catenin and OPG/RANKL/RANK signaling pathways. In summary, strong evidence may still come from prospective and well-designed clinical trials to shed light on the potential role of acupuncture in preserving bone loss. Future investigations are needed to explore the potential underlying mechanisms, long-term clinical efficacy, and compliance of acupuncture in OP management.

Introduction To compare and analyze the clinical effects of acupuncture-related therapies for postmenopausal osteoporosis (PMOP) and propose the optimal scheme, we utilized a network meta-analysis to evaluate the therapeutic effects of various commonly used acupuncture methods for PMOP. Methods Randomized controlled trials of acupuncture-related therapies for PMOP were searched in eight databases (PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Science and Technology Journal Database, China Biomedical Literature Database, and Wanfang database) from January 1, 2002 to December 31, 2023. Our primary outcomes included overall clinical effectiveness rate, bone mineral density (BMD), and visual analog scale scores (VAS). The secondary outcome is adverse events. The entire process of literature screening and data analysis was conducted by 2 independent investigators. Results A total of 30 studies with 2,342 participants provided data suitable for analysis. We compared six interventions: manual acupuncture, electroacupuncture, acupoint catgut embedding, moxibustion, acupoint application, and warm acupuncture. The results of the network meta-analysis revealed that, when compared to conventional Western medication (CWM), multiple acupuncture therapies had a greater impact on the overall clinical effectiveness rate. Electroacupuncture combined with CWM demonstrated superior clinical effectiveness and lumbar spine BMD improvement. Moxibustion with CWM ranked highest for femoral neck BMD, while warm acupuncture showed optimal effects on Ward’s triangle and trochanter BMD. Acupoint catgut embedding provided the greatest pain reduction. The most prevalent minor adverse effects included hematoma, discomfort, and scorching. Conclusion The results suggest that several acupuncture-related therapies, either alone or in conjunction with CWM, outperform CWM alone and may be regarded as an alternative or supplementary therapy to PMOP, though higher-quality trials are needed.

According to World Health Organization (WHO), osteoporosis is a systematic bone disability marked by reduced bone mass and microarchitectural degeneration of osseous cells, which leads to increased bones feebleness and fractures vulnerability. It is a polygenetic, physiological bone deformity that frequently leads to osteoporotic fractures and raises the risk of fractures in minimal trauma. Additionally, the molecular changes that cause osteoporosis are linked to decreased fracture repair and delayed bone regeneration. Bones have the ability to regenerate as part of the healing mechanism after an accident or trauma, including musculoskeletal growth and ongoing remodeling throughout adulthood. The principal treatment approaches for bone loss illnesses, such as osteoporosis, are hormone replacement therapy (HRT) and bisphosphonates. In this review, we searched literature regarding the Traditional Chinese medicines (TCM) in osteoporosis and bone regeneration. The literature results are summarized in this review for osteoporosis and bone regeneration. Traditional Chinese medicines (TCM) have grown in popularity as a result of its success in curing ailments while causing minimal adverse effects. Natural Chinese medicine has already been utilized to cure various types of orthopedic illnesses, notably osteoporosis, bone fractures and rheumatism with great success. TCM is a discipline of conventional remedy that encompasses herbal medication, massage (tui na), acupuncture, food, and exercise (qigong) therapy. It is based on more than 2,500 years of Chinese healthcare profession. This article serves as a comprehensive review summarizing the osteoporosis, bone regeneration and the traditional Chinese medicines used since ancient times for the management of osteoporosis and bone regeneration.

Introduction. The aim of this study was to investigate the efficacy of herbal formula QiangGuYin (QGY) in postmenopausal women. Materials and Methods. A total of 240 participants from six clinical centers were randomly to receive alendronate 70 mg/week, QGY granules 20 g/day, and placebo. Primary end points were BMD changes over 6 and 12 months; secondary end points were bone turnover markers changes at 3, 6, 9, and 12 months. Safety was monitored by clinical adverse events reported during the follow-up. Results. Of 240 women recruited, 218 completed the study. Significant BMD increases from baseline were observed over 6 and 12 months at each observed part both in QGY and alendronate compared with placebo (p < 0.01). Alendronate-treated subjects had significant decreases in β-CTX compared to QGY-treated subjects at each time point assessed (p < 0.01). Reduction in t-P1NP was only observed in the QGY group at 3 and 6 months (−23.81% and −3.07%, resp.). No significant difference was observed in the overall incidence of clinical adverse events among the alendronate group and the QGY group (5.0% versus 7.5%, p = 0.513). Conclusion. 1-Year treatment with QGY demonstrated a safe statistical increase in BMD and new balance may be rebuilt after 9 months. This trail is registered with ChiCTR-POC-16008026.

Many clinical trials and meta-analyses related to acupuncture for osteoporosis (OP) have been published. However, identifying the evidence from these studies still remains a challenge for acupuncturists. We conducted a systematic search of the Chinese Biomedical Medicine (CBM), VIP Database, Wanfang Data, China National Knowledge Infrastructure (CNKI), PubMed, Springer, Cochrane Library, and Embase to identify relevant trials, systematic reviews, and/or meta-analyses up to October 31, 2018. Data were extracted to assess the methodological quality using Veritas plots and to explore potential acupuncture prescriptions using the Traditional Chinese Medicine inheritance support system (TCMISS). In addition, potential mechanisms of core acupoints identified by data mining were summarized based on published studies. A total of 218 clinical trials and ten meta-analyses were included, involving 212 acupuncture prescriptions, 102 acupoints, 13 meridians, three extra meridians, and one Ashi point. The mean Veritas score of publication year, type of study, Assessment of Multiple Systematic Reviews 2, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, heterogeneity, and publication bias were 5.5, 7.2, 6, 5.6, 5.8, and 7.5, respectively. The study of Pan et al. received the highest Veritas score of 8.67 points. The most frequently used meridian was BL. Acupoint combinations BL23 and BL20, BL23 and GV4, and BL23 and ST36 were used frequently. The core acupoints association networks were acupoints BL23, BL20, ST36, GV4, SP6, CV4, and KI3. The potential mechanisms of core acupoints involved upregulated expression of members in OPG/RANKL, Wnt/β-catenin, and MAPK pathways, such as LRP5, β-catenin, Runx2, and OPG. In conclusion, our Veritas plots enable acupuncturists to evaluate key attributes of meta-analysis quality related to acupuncture for primary OP and to improve the quality of evidence-based medicine relating to acupuncture. Data mining analysis revealed an association network of meridians, acupoint combinations, core acupoints, and the underlying mechanisms of acupuncture for primary OP.

Wolff’s law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis. Mechanical forces induce bone remodeling, but how bone cells sense mechanical signaling is unclear. Here, the authors show that loss of the mechanotransduction channel Piezo1 in osteoblastic cells impairs osteoclast activity via YAP signaling and collagen expression, leading to reduced bone mass and spontaneous fractures.

… to mechanical loading. However, while osteoblasts play an important role in regulating osteoclast … , insight into bone loss in postmenopausal osteoporosis, whereby estrogen-deficient …

In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed.

Low bone mass is a pervasive global health concern, with implications for osteoporosis, frailty, disability, and mortality. Lifestyle factors, including sedentary habits, metabolic dysfunction, and an aging population, contribute to the escalating prevalence of osteopenia and osteoporosis. The application of mechanical load to bone through physical activity and exercise prevents bone loss, while sufficient mechanical load stimulates new bone mass acquisition. Osteocytes, cells embedded within the bone, receive mechanical signals and translate these mechanical cues into biological signals, termed mechano-transduction. Mechano-transduction signals regulate other bone resident cells, such as osteoblasts and osteoclasts, to orchestrate changes in bone mass. This review explores the mechanisms through which osteocyte-mediated response to mechanical loading regulates osteoblast differentiation and bone formation. An overview of bone cell biology and the impact of mechanical load will be provided, with emphasis on the mechanical cues, mechano-transduction pathways, and factors that direct progenitor cells toward the osteoblast lineage. While there are a wide range of clinically available treatments for osteoporosis, the majority act through manipulation of the osteoclast and may have significant disadvantages. Despite the central role of osteoblasts to the deposition of new bone, few therapies directly target osteoblasts for the preservation of bone mass. Improved understanding of the mechanisms leading to osteoblastogenesis may reveal novel targets for translational investigation.

Osteoporosis is a major health problem, making bones fragile and susceptible to fracture. Previous works showed that mechanical loading stimulated bone formation and accelerated fracture healing. Focusing on the role of Wnt3a (wingless/integrated 3a), this study was aimed to assess effects of mechanical loading to the spine, using ovariectomized (OVX) mice as a model of osteoporosis. Two‐week daily application of this novel loading (4N, 10Hz, 5 min/d) altered bone remodeling with an increase in Wnt3a. Spinal loading promoted osteoblast differentiation, endothelial progenitor cell migration, and tube formation and inhibited osteoclast formation, migration, and adhesion. A transient silencing of Wnt3a altered the observed loading effects. Spinal loading significantly increased bone mineral density, bone mineral content, and bone area per tissue area. The loaded OVX group showed a significant increase in the number of osteoblasts and reduction in osteoclast surface/bone surface. Though expression of osteoblastic genes was increased, the levels of osteoclastic genes were decreased by loading. Spinal loading elevated a microvascular volume as well as VEGF expression. Collectively, this study supports the notion that Wnt3a‐mediated signaling involves in the effect of spinal loading on stimulating bone formation, inhibiting bone resorption, and promoting angiogenesis in OVX mice. It also suggests that Wnt3a might be a potential therapeutic target for osteoporosis treatment. —Li, X., Liu, D., Li, J., Yang, S., Xu, J., Yokota, H., Zhang, P. Wnt3a involved in the mechanical loading on improvement of bone remodeling and angiogenesis in a postmenopausal osteoporosis mouse model. FASEB J. 33, 8913–8924 (2019). www.fasebj.org

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis.

… continues to adapt to changes in mechanical loads [1–4]. Its growth is mediated by the continuous activity of osteoblasts (OB) (bone deposition) and osteoclasts (OCs) (bone resorption), …

… local mechanical environment of osteocytes and osteoblasts … osteoclasts to orchestrate an adaptive response when the … This initial bone loss likely alters the micromechanical loading of …

Lack of physical activity causes bone loss and fractures not only in elderly people, but also in bedridden patients or otherwise inactive youth. This is fast becoming one of the most serious healthcare problems in the world. Osteocytes, cells buried within our bones, stimulate bone formation in the presence of mechanical stimuli, as well as bone degradation in the absence of such stimuli. As yet, we do not fully comprehend how osteocytes sense mechanical stimuli, and only know a fraction of the whole range of molecules that osteocytes subsequently produce to regulate bone formation and degradation in response to mechanical stimuli. This dramatically hampers the design of bone loss prevention strategies. In this review we will focus on the first step in the cascade of events leading to adaptation of bone mass to mechanical loading, i.e., on how osteocytes are able to perceive mechanical stimuli placed on whole bones. We will place particular emphasis on the role of the osteocyte cytoskeleton in mechanosensing. Given the crucial importance of osteocytes in maintaining a proper resistance against bone fracture, greater knowledge of the molecular mechanisms that govern the adaptive response of osteocytes to mechanical stimuli may lead to the development of new strategies towards fracture prevention and enhanced bone healing.

Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre‐osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/β‐catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.

… Bone remodeling results from the coordinated and balanced activities of osteoblasts and osteoclasts. Osteoblasts functions are intimately linked to osteoclast activity via the osteoblastic …

… osteoblasts with each other via canaliculi and appears to play a role in response to mechanical loading… imbalance between the activity of osteoclasts and osteoblasts. If the processes of …

… The effect of bone loss due to reduced loading has been noted in … actions of osteoblasts, osteoclasts, and osteocytes. … While parameters of in vivo skeletal mechanical loading that result …

… resistance of the skeleton to mechanical loads as a result of … by its opposite effects on osteoclasts and osteoblasts. Both … of the bone cell response to mechanical stimulation because …

IntroductionBones are subjected to a variety of mechanical loads duringdaily activities. In the nineteenth century, Julius Wolffproposed that bones adapt their mass and 3D structure tothe loading conditions in order to optimize their load-bearing capacity, and that this process is driven bymechanical stress [1]. For the past centuries, an increasingnumber of theoretical and experimental results reveal thatosteocytes are the pivotal cells orchestrating this bio-mechanical regulation of bone mass and structure, whichis accomplished by the process of bone remodeling [2–5]Osteocytes are terminally differentiated cells of theosteogenic lineage that are derived from mesenchymalprecursor cells. A number of molecules have been iden-tified as important markers of osteocytes, such as matrixextracellular phosphoglycoprotein [6] sclerostin [7], dentinmatrix protein-1 [8], and phex protein [8]. The osteocytesare the most abundant cells in adult bone and are constantlyspaced throughout the mineralized matrix. Mature osteo-cytes have a characteristic dendritic cell shape, with pro-cesses radiating from the cell body through the canaliculi indifferent directions. These processes form an intercellularnetwork through gap and adherent junctions with surround-ing osteocytes, the cells lining the bone surface and bonemarrow. Through this unique 3D network, osteocytes areanatomically placed in a prime position not only to sensedeformations driven by stresses placed upon bone, butalso to respond with passage of signals to the neighboringcells [9].For more than a decade now, it is known that theosteocytes are very sensitive to stress applied to intact bonetissue [10–16]. Computer simulation models have shownthat mechanosensors lying at the surface of bone, asosteoblasts and bone lining cells do, would be less sensitiveto changes in the loading pattern than the osteocytes, lyingwithin the calcified matrix [3]. Interestingly, targetedablation of osteocytes in mice disturbs the adaptation ofbone to mechanical loading [16].Osteocytes as key players in the process of bonemechanotransductionIt is currently believed that when bones are loaded, theresulting deformation will drive the thin layer of interstitialfluid surrounding the network of osteocytes to flow fromregions under high pressure to regions under low pressure[17, 18]. This flow of fluid is sensed by the osteocyteswhich in turn produce signaling molecules that can regulatebone resorption through the osteoclasts, and bone formationthrough the osteoblasts, leading to adequate bone remodel-ing [17, 18]. This concept is known as the fluid flowhypothesis. Evidence has been increasing for the flow ofcanalicular interstitial fluid as the likely factor that informsthe osteocytes about the level of bone loading [2, 5, 17, 18].Nevertheless, Vatsa and colleagues [19, 20] proposed thatif osteocytes could sense matrix strains directly, the cellshape, cytoskeletal alignment and distribution of adhesionsites in osteocytes in situ would bear alignment to themechanical loading patterns. Indeed, it was shown that the

Background: Sclerostin, encoded by the SOST gene, has been implicated in the response to mechanical loading in bone. Some studies demonstrated that unloading leads to up-regulated SOST expression, which may induce bone loss. Purpose: Most reported studies regarding the changes caused by mechanical unloading were only based on a single site. Considering that the longitudinal bone growth leads to cells of different age with different sensitivity to unloading, we hypothesized that bone turnover in response to unloading is site specific. Methods: We established a disuse rat model by sciatic neurectomy in tibia. In various regions at two time-points, we evaluated the bone mass and microarchitecture in surgically-operated rats and control rats by micro-Computed Tomography (micro-CT) and histology, sclerostin/SOST by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (qPCR), tartrate resistant acid phosphatase 5b (TRAP 5b) by ELISA and TRAP staining, and other bone markers by ELISA. Results: Micro-CT and histological analysis confirmed bone volume in the disuse rats was significantly decreased compared with those in the time-matched control rats, and microarchitecture also changed 2 and 8 weeks after surgery. Compared with the control groups, SOST mRNA expression in the diaphysis was down-regulated at both week 2 and 8. On the contrary, the percentage of sclerostin-positive osteocytes showed an up-regulated response in the 5 - 6 mm region away from the growth plate, while in the 2.5 - 3.5 mm region, the percentage was no significant difference. Nevertheless, in 0.5 - 1.5 mm region, the percentage of sclerostin-positive osteocytes decreased after 8 weeks, consistent with serum SOST level. Besides, the results of TRAP also suggested that the expression in response to unloading may be opposite in different sites or system. Conclusion: Our data indicated that unloading-induced changes in bone turnover are probably site specific. This implies a more complex response pattern to unloading and unpredictable therapeutics which target SOST or TRAP 5b.

Sclerostin, encoded by the Sost gene, is an important negative regulator of bone formation that has been proposed to have a key role in regulating the response to mechanical loading. To investigate the effect of long‐term Sclerostin deficiency on mechanotransduction in bone, we performed experiments on unloaded or loaded tibiae of 10 week old female Sost−/− and wild type mice. Unloading was induced via 0.5U botulinum toxin (BTX) injections into the right quadriceps and calf muscles, causing muscle paralysis and limb disuse. On a separate group of mice, increased loading was performed on the left tibiae through unilateral cyclic axial compression of equivalent strains (+1200 µe) at 1200 cycles/day, 5 days/week. Another cohort of mice receiving equivalent loads (−9.0 N) also were assessed. Contralateral tibiae served as normal load controls. Loaded/unloaded and normal load tibiae were assessed at day 14 for bone volume (BV) and formation changes. Loss of BV was seen in the unloaded tibiae of wild type mice, but BV was not different between normal load and unloaded Sost−/− tibiae. An increase in BV was seen in the loaded tibiae of wild type and Sost−/− mice over their normal load controls. The increased BV was associated with significantly increased mid‐shaft periosteal mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS), and endosteal MAR and BFR/BS. Notably, loading induced a greater increase in periosteal MAR and BFR/BS in Sost−/− mice than in wild type controls. Thus, long‐term Sclerostin deficiency inhibits the bone loss normally induced with decreased mechanical load, but it can augment the increase in bone formation with increased load. © 2014 American Society for Bone and Mineral Research.

… studies suggest that mechanical loading can reduce … bone loss may be due to increased survival of osteoclasts [22], whereas the second phase may be due to osteocyte and osteoblast …

… architectural deterioration of bone tissue, resulting in reduced bone strength and increased … osteoporosis as a bone mineral density that lies ≥2.5 SDs below the mean peak bone mass (…

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.

… increase the bone mass density and alleviate pain in patients with primary osteoporosis.… Acupuncture treatment 2 included electroacupuncture (EA) (2cun needle) at SP6 (bilateral), …

… due to poor compliance; bone mineral density test showed osteoporosis, and CT scan showed no compression or compression fractures not exceeding 1/4 of the vertebral body. …

Spinal cord injury (SCI) is one of the most common causes of death and disability worldwide, and it can result in both permanent disability and serial complications in patients. Research shows that patients with SCI complications are often interested in acupuncture for symptomatic relief. Therefore, the issue of physicians advising their patients regarding the use of acupuncture to alleviate SCI complications becomes pertinent. We review and summarize two types of relevant publications: (1) literature concerning acupuncture for SCI and its complications and (2) underlying mechanisms of acupuncture therapy for SCI. Clinical trials and reviews have suggested that acupuncture effectively manages a range of post-SCI complications, including motor and sensory dysfunction, pain, neurogenic bowel and bladder, pressure ulcers, spasticity, and osteoporosis. The effect of acupuncture on post-SCI orthostatic hypotension and sexual dysfunction remains unclear. Decreased oxidative stress, inhibition of inflammation and neuronal apoptosis, regulation of the expression and activity of endogenous biological mediators, and increased regenerative stem cell production are the possible mechanisms of acupuncture therapy for SCI. Although many limitations have been reported in previous studies, given the evidence for the efficacy of acupuncture, we recommend that physicians should support the use of acupuncture therapy for SCI complications.

The prevalence of obesity and osteoporosis (OP) represents a significant public health concern on a global scale. A substantial body of evidence indicates that there is a complex relationship between obesity and OP, with a correlation between the occurrence of OP and obesity. In recent years, sirtuins have emerged as a prominent area of interest in the fields of aging and endocrine metabolism. Among the various research avenues exploring the potential of sirtuins, the effects of these proteins on obesity and OP have garnered significant attention from numerous researchers. Sirtuins regulate energy balance and lipid balance, which in turn inhibit the process of adipogenesis. Additionally, sirtuins regulate the balance between osteogenic and osteoblastic activity, which protects against the development of OP. However, no study has yet provided a comprehensive discussion of the relationship between the three: sirtuins, obesity, and OP. This paper will therefore describe the relationship between sirtuins and obesity, the relationship between sirtuins and OP, and a discussion focusing on the possibility of treating OP caused by obesity by targeting sirtuins. This will be based on the common influences on the occurrence of obesity and OP (such as mesenchymal stem cells, gut microbiota, and insulin). Finally, the potential of SIRT1, an important member of sirtuins, in polyphenolic natural products for the treatment of obesity and OP will be presented. This will contribute to a better understanding of the interactions between sirtuins and obesity and bone, which will facilitate the development of new therapeutic strategies for obesity and OP in the future.

Background Data from the 2010–2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen. Objective This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats. Methods Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO 3 (OVX-LC-H). CaCO 3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed. Results The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO 3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO 3 supplementation ( p  < 0.01). The administration of 2800 mg/kg CaCO 3 decreased serum triglyceride and high-density lipoprotein levels ( p  < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced. Conclusions The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

… TCM compound … Among TCM formulations, GSK 22, 23 and LWDHP 24, 25, 26, 27, 28 have shown clinical efficacy in improving bone mineral density and modulating bone metabolism. …

Liuwei Dihuang Wan (LWDHW), a classic traditional Chinese medicine formula, is widely used to treat various diseases associated with kidney deficiency and has shown satisfactory clinical efficacy in postmenopausal osteoporosis (PMOP). However, its pharmacological mechanisms remain unclear. To address this, we first analyzed the chemical components of LWDHW using LC-MS/MS, which identified 1,615 components. Network pharmacology then predicted that inflammation and the NF-κB signaling pathway are potential therapeutic mechanisms underlying LWDHW's effects on PMOP. Subsequently, 27 female C57BL/6J mice were randomly assigned to the Sham, Model, and LWDHW groups. Mice in the latter two groups underwent bilateral ovariectomy (OVX), and those in the LWDHW group received oral LWDHW at 9.75 g/kg/day for 8 weeks. Serum and femur samples were collected for Enzyme-Linked Immunosorbent Assay (ELISA), Micro-Computed Tomography (µCT), histological examination, and immunohistochemistry (IHC). Primary bone marrow-derived macrophages (BMMs) were treated with LWDHW and then subjected to TRAP staining and qRT-PCR. In OVX mice, LWDHW significantly alleviated bone loss and deterioration of bone microarchitecture, accompanied by reduced serum β‑CTX levels and decreased osteoclast numbers in femoral tissues. IHC staining revealed notably lower expression of TNF-α, IL-1β, and p-P65 in femoral tissues of LWDHW-treated mice compared to the model group. In vitro, TRAP staining demonstrated that LWDHW inhibited RANKL/M-CSF-induced osteoclast differentiation of BMMs and downregulated the expression of Ctsk, MMP9, and Nfatc1. Western blot analysis further showed that protein levels of P65, p-P65, IκBα, and p-IκBα were significantly decreased in BMMs following LWDHW treatment. Collectively, LWDHW alleviates postmenopausal osteoporosis, possibly by suppressing NF-κB signaling‑mediated osteoclastogenesis.

Postmenopausal osteoporosis (PMO) significantly increases the risk of fragility fractures. The profound estrogen deficiency, compounded by severe oxidative stress, ferroptosis, and an impaired osteoimmune microenvironment, disrupts the vital coupling of angiogenesis and osteogenesis. This disruption frequently leads to delayed fracture union and implant failure. This narrative review aims to consolidate the current literature regarding both conventional pharmacological interventions and specific alternative therapeutic strategies, providing a comprehensive conceptual framework for optimizing bone healing in PMO fractures. An extensive literature search of databases including the systematic-review and evidence-synthesis database, biomedical and pharmacological bibliographic database, multidisciplinary citation-indexing database, and public biomedical literature database was conducted for relevant studies published up to March 2026. While conventional antiresorptive and anabolic agents remain the gold standard for long-term secondary fracture prevention, their inherent limitations and "double-edged sword" effects during the acute fracture healing phase pose significant clinical challenges. Emerging evidence suggests that multi-target alternative therapies, particularly natural bioactive compounds and traditional Chinese medicine (TCM) formulas, offer a synergistic approach. By ameliorating systemic metabolic dysregulation and inhibiting lipid peroxidation-induced ferroptosis, these alternative therapies reshape localized immune-bone homeostasis. Addressing the delayed healing of postmenopausal fractures requires an evolution toward an integrative sequential management model. Although current supporting data predominantly derive from robust preclinical models, combining these alternative therapeutic strategies with conventional agents-and potentially utilizing advanced targeted biomaterial delivery systems-represents a highly promising frontier to optimize perioperative fracture management and enhance long-term skeletal integrity.

Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

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.

The pathogenesis of prevalent metabolic diseases such as obesity, atherosclerosis, metabolic dysfunction-associated steatotic liver disease, and diabetes is intricately linked to dysregulated lipid metabolism. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcriptional regulator of lipid homeostasis and a well‑researched therapeutic target. Although biochemical signaling pathways have been the traditional focus, recent studies now highlight the mechanical microenvironment (matrix stiffness, fluid shear stress, and tensile strain) as a pivotal physical metabolism regulator. However, how mechanical signals integrate with PPARγ to control lipid metabolism across tissues and diseases remains poorly defined. This review details the molecular mechanisms by which mechanical cues influence PPARγ expression, activity, and post‑translational modifications, focusing on Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination, and protein kinase Cα (PKCα)-extracellular signal-regulated kinase (ERK) pathways. We further explore the critical role of PPARγ in mechano‑metabolic coupling in adipose tissue, liver, and vasculature. Under normal physiological conditions, mechanical loading suppresses PPARγ to promote osteogenesis and vascular homeostasis; under pathological conditions, aberrant signals and PPARγ dysfunction establish a vicious cycle of "mechanical imbalance-metabolic disorder-tissue remodeling." This review suggests that PPARγ may function as a mechano‑metabolic downstream transcriptional transducer linking the mechanical microenvironment to metabolic reprogramming, thereby offering a novel theoretical framework and translational perspective for the physical intervention and targeted therapy of common metabolic diseases.

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 mechanoreceptors of chondrocytes are responsible for the mechanotransduction of the mechanical signals into intracellular signals and comprise the primary cilium, ion channels …