RESUMEN
Osteonecrosis of the femoral head （ONFH） is a painful and debilitating disease caused by impaired blood supply to the femoral head and cellular and tissue degeneration， leading to gradual destruction of the bone structure and progressive collapse of the femoral head. The main pathological mechanism of ONFH is the disruption of the balance between bone absorption and the reconstruction of new bone， resulting from microcirculation damage and decreased cellular tissue ability. This imbalance leads to biomechanical changes and accelerates the pathological progression of ONFH. In the early stages， clinical manifestations may not be obvious， mainly presenting as pain or discomfort in the hip or groin area， which can be relieved after rest. In the later stage of the disease， pain intensifies， and limb shortening， lower limb weakness， difficulty walking， or limping may occur. Currently， western medicine commonly uses osteogenic agents， anticoagulants， and artificial joint replacement for treatment， but there are also many issues such as prosthesis loosening and infection. Research has shown that traditional Chinese medicine （TCM） treatment of ONFH takes a holistic approach and employs multi-functional， multi-target， and multi-system Chinese medicine therapies， ensuring the safety and effectiveness of the treatment. The osteoprotegerin （OPG）/receptor activator of nuclear factor-κB （RANK）/RANK ligand （RANKL） signaling pathway plays a crucial role in maintaining the dynamic balance of bone remodeling. TCM treatments utilize this pathway to promote apoptosis of osteoclasts， reduce bone resorption， and accelerate bone formation， thereby playing an important role in the prevention and treatment of ONFH. This paper reviewed the role of OPG/RANK/RANKL signaling pathway and related cytokine expression in ONFH by reviewing relevant literature in China and abroad and research status of Chinese medicinal monomers， Chinese medicinal formulations， and combinations with physical therapy in increasing osteoblast secretion， promoting OPG expression， enhancing cytokine expression levels， and inhibiting osteoclast activity for the prevention and treatment of ONFH. This paper is expected to provide new ideas and directions for TCM in the prevention and treatment of ONFH.
RESUMEN
Although different types of drugs are available for postmenopausal osteoporosis, the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents. Here, we defined that norlichexanthone (NOR), a natural product, is a ligand of estrogen receptor-alpha (ER
RESUMEN
Objective:As the problem of global aging intensifies，postmenopausal osteoporosis （PMOP） has become a global health problem among females. At present，the commonly used biological agents have been proved not suitable for long-term use due to multiple adverse reactions. Several Meta-analyses have confirmed the good safety and effectiveness of kidney-tonifying method against PMOP，but its therapeutic mechanism remains unclear. The purpose of this Meta-analysis was to evaluate the effect of kidney-tonifying method on osteoclastogenesis inhibitory factor（OPG）/receptor activator of nuclear transcription factor （NF）-<italic>κ</italic>B （RANK）/receptor activator of NF-<italic>κ</italic>B ligand （RANKL） signaling pathway in PMOP animal model，so as to provide an experimental basis for the treatment of PMOP with kidney-tonifying method. Method:The related articles were retrieved from PubMed，Ovid Medline，Embase，China National Knowledge Infrastructure （CNKI），Chongqing Weipu Database for Chinese Technical Periodicals （VIP），and Wanfang Data Knowledge Service Platform with the retrieval time set from their inception to January 2020. The quality of each included article was evaluated using the SYRCLE's risk of bias tool. Then RevMan 5.3 was utilized for Meta-analysis according to the Cochrane systematic review methodology. Result:Thirty-two studies involving 619 rats were included. The quality score of these studies ranged from 3 to 5 points. The results of the Meta-analysis indicated obvious advantages of kidney-tonifying method in increasing bone mineral density （BMD）［standardized mean difference （SMD）=2.01，95% confidence interval（CI）=1.50-2.52，<italic>P</italic><0.000 01］），serum OPG level （SMD=3.33，95% CI=2.59-4.07，<italic>P</italic><0.000 01），and OPG mRNA expression （SMD=11.81，95% CI=7.49-16.13，<italic>P</italic><0.000 01），promoting OPG protein production （SMD=4.95，95% CI=3.09-6.81，<italic>P</italic><0.000 01），reducing serum RANKL（SMD=-4.88，95% CI=-6.01--3.75，<italic>P</italic><0.000 01） and RANK levels （SMD=-7.30，95% CI=-9.53--5.07，<italic>P</italic><0.000 01），and down-regulating RANKL （SMD=-6.22，95%CI=-8.95--3.49，<italic>P</italic><0.000 01） and RANK mRNA （SMD=-3.18，95% CI=-6.19--0.18，<italic>P</italic><0.05） expression and RANKL protein expression in bone tissue （SMD=-3.99，95% CI=-5.47--2.50，<italic>P</italic><0.000 01）. Conclusion:The kidney-tonifying method has been proved to possess potential advantages in regulating the balance of OPG/RANK/RANKL signaling pathway in PMOP animal model. Nevertheless，more large-sample sized，properly designed，and high-quality animal experiments are still needed for further verification.
RESUMEN
OBJECTIVE：To investigate the effects of curcumin on bone metabolism balance in ovariectomized osteoporosis model rats ，and to investigate its potential mechanism. METHODS ：Totally female Wistar rats were randomly divided into blank group（group A ），model group （group B ），estradiol group [group C （positive control ），estradiol valerate 50 μg（/ kg·d）]， curcumin low-dose ，medium-dose and high-dose groups [group D-F ，55，110，165 μg（/ kg·d）]，with 15 rats in each group. Except for group A ，other rats were ovariectomized to establish osteoporosis model. After modeling ，group A and B were given normal saline intrgastrically ，and administration groups were given relevant medicine intrgastrically 30 mL/kg，once a day ，for consecutive 12 weeks. The contents of serum bone metabolism markers [BALP ，CBF-α1，CTX-Ⅰ，PINP and OC] were determined by ELISA. The bone mineral density （BMD）and trabecular structure indexes [relative bone volume fraction （BV/TV），trabecular number （Tb.N），trabecular thickness （Tb.Th），connectivity density （Conn. D ），trabecular separation （Tb.Sp）and structure model index （SMI）] were determined by micro CT imaging system. The mRNA and protein expression of OPG and RANKL in hypothalamus and femur were determined by RT-PCR and Western blotting assay. RESULTS ：Compared with group A ，the contents of serum bone metabolism markers ，BMD，BV/TV，Tb.N，Tb.Th，Conn.D，mRNA and protein expression of OPG were decreased significantly in group B ，while Tb.Sp ，SMI，mRNA and protein expression of RANKL were increased significantly @qq.com （P＜0.05）. Compared with group B ，the contents of serum bone metabolism markers ，BMD，BV/TV，Tb.N，Tb.Th，Conn.D，mRNA and protein expression of OPG were increased significantly in administration groups ；Tb.Sp，SMI，mRNA and protein expression of RANKL were decreased significantly ，in a dose-dependent manner among curcumin groups （P＜0.05 or P＜0.01）. CONCLUSIONS ：Curcumin can improve the level of bone metabolism，increase BMD ，improve the trabecular microstructure and inhibit bone absorption in ovariectomized osteoporosis model rats. Its mechanism may be related to the regulation of OPG/RANKL signaling pathway.
RESUMEN
OBJECTIVE: To observe the effect of electroacupuncture (EA) on histopathological changes of cartilage and subchondral bone and osteoprotegerin (OPG)，receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) (OPG/RANK/RANKL) signaling and the expression of matrix metalloproteinase-13 (MMP-13) in ovariectomized(OVX)rats, so as to explore its mechanism underlying improvement of osteoporosis. METHODS: Three-month female SD rats were randomly divided into sham operation, model and EA groups (n＝8 in each group). The ovoariectomy model was established by resection of bilateral ovaries. Rats of the sham group were treated by simple removal of a piece of adipose tissue around the bilateral ovaries. EA (3 Hz/15 Hz, 1 mA) was applied to bilateral "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34), "Yinlingquan" (SP 9) and "Zusanli" (ST 36) for 30 min, once daily (except the weekends) for 12 weeks. The histopathological changes of the subchondral bone of the right knee-joint were observed after Saffron O dyeing and evaluated by Mankin's score, and its anatomical structure including the bone volume fraction (bone volume/tissue volume, BV/TV), trabecular bone number (Tb. N) and trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) was observed by using Micro CT imaging. The urine C-terminal cross-linking telopeptide of type Ⅰ collagen (CTX-Ⅰ), CTX-Ⅱ (two bone resorption markers) and serum estrogen (E 2) contents were assayed by ELISA, and the expression levels of OPG, RANKL and MMP-13 mRNAs in the cartilage tissue of the left knee-joint were detected by quantitative RT-PCR. RESULTS: Following modeling, the BV/TV, Tb. N and Tb.Th levels were significantly decreased (P<0.01) and Tb.Sp and Mankin's score obviously increased in the model group compared with the sham group (P<0.01), suggesting a formation of osteoporosis and degeneration of the cartilage tissue. The serum E 2 content and OPG mRNA level in the cartilagetissue were significantly down-regulated (P<0.01), and urine CTX-Ⅰ and CTX-Ⅱ contents and RANKL mRNA and MMP-13 mRNA expression levels cartilagetissue were considerably up-regulated in the model group relevant to the sham group (P<0.01). After EA intervention, modeling-induced decrease of BV/TV, Tb.N, Tb.Th, E 2 and OPG mRNA levels and OVX-induced increase of Tb.Sp, Mankin's score, CTX-Ⅰ， CTX-Ⅱ， RANKL mRNA and MMP-13 mRNA levels were all completely reversed in the EA group relevant to the model group (P<0.01，P<0.05)．. CONCLUSION: EA intervention can inhibit subchondral bone osteoporosis and articular cartilage degeneration of knee-joint in OVX rats, which is closely associated with its effects in inhibiting the down-regulation of serum E 2 and OPG mRNA expression and up-regulation of CTX-Ⅰ， CTX-Ⅱ， RANKL mRNA and MMP-13 mRNA levels, including adjusting OPG/RANK/RANKL signaling.
RESUMEN
In recent years, due to the irregular and abused use of glucocorticoid in clinical treatment, the incidence of steroid induced avascular necrosis of femoral head (SANFH) is gradually increasing. TCM for the prevention and treatment of SANFH has received much attention from many scholars. However, due to the lack of the scientific explanation of molecular biology level for its pharmacodynamics mechanism, it is difficult to achieve the purpose of standardized treatment. The discovery of OPG/RANK/RANKL signaling pathway has opened up new shortcuts for the prevention and treatment of bone metabolic diseases. OPG/RANK/RANKL signaling pathway is associated with the pathogenesis of spleen deficiency and phlegm - blood stasis caused by phlegm-blood stasis due to paralysis of SANFH. The treatment efficacy based on the phlegm theory can eventually axial control of the system through the micro-information to express. This article discussed the relevance between the phlegm in the treatment of SANFH and molecular biology mechanism of OPG/RANK/RANKL signal regulation mechanism, and combined the system of bone metabolism regulation mechanism to discuss TCM differentiation of SANFH, with a purpose to provide references for clinical and further study.