Research progress on an autophagy-mediating AMPK pathway involving bone metabolism-related cells that regulate bone homeostasis in periodontitis / 口腔疾病防治

@#Osteoclasts are the only cells responsible for bone resorption in the body, and osteoblasts are the main cells responsible for bone regeneration in the body. Under physiological conditions, these cells maintain a dynamic balance to maintain bone homeostasis. It was widely believed that the imbalance of bone metabolism is mainly affected by the expression of related inflammatory factors. However, with the gradual expansion of related studies in recent years, autophagy has been shown to be closely related to the differentiation, apoptosis and functions of osteoclasts and osteoblasts. AMP-activated protein kinase (AMPK) is an important regulator of energy metabolism in vivo and is involved in the regulation of autophagy and bone homeostasis in bone metabolism-related cells. Periodontitis is a chronic infectious disease, and its typical symptoms are alveolar bone resorption. At present, controlling the level of periodontal inflammation and alveolar bone resorption more effectively in clinical practice remains a challenge. The detection of AMPK and autophagy levels in bone metabolism-related cells shows certain prospects for the clinical prevention and treatment of periodontitis in the future. Therefore, this article reviews the regulation of periodontal inflammation levels and bone homeostasis through cell autophagy related to AMPK-mediated bone metabolism.

Effects of selegiline phosphate combined with liraglutide and osteoporotic triol on glucolipid metabolism and PINP and S-CTX levels in patients with T2DM combined with osteoporosis / 中华内分泌外科杂志

Objective:To investigate the effects of selegiline phosphate combined with liraglutide and osteopontin on glucolipid metabolism, bone mineral density and bone metabolism in patients with type 2 diabetes mellitus (T2DM) combined with osteoporosis (OP) .Methods:A prospective randomized controlled trial was designed.130 patients with T2DM combined with OP admitted to the outpatient clinic of Yantai Yantaishan Hospital from Jan.2020 to Aug. 2021 were selected as study subjects and pregrouped according to the pre-visit serial number according to the random number table method, 65 cases each. The control group weregiven liraglutide and osteopontin combination therapy, and the observation group were treated with sitagliptin phosphate combined with liraglutide and osteopontin, and both groups were treated continuously for 3 months. The tests compared the glycolipid metabolism [glycosylated hemoglobin (HAb1c) , triacylglycerol (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , 2h postprandial glucose (2hPG) , high-density and low-density lipoprotein cholesterol (HDL-C, LDL-C) ], bone density [4 sites of femoral trochanter, lumbar orthostyle, femoral neck, forearm], before and after 3 months of treatment in the 2 groups. Changes in bone metabolism (osteocalcin (OC) , type I collagen C-terminal peptide (S-CTX) , 25-hydroxyvitamin [25 (OH) D], type I procollagen amino-terminal peptidogen (PINP) , and bone-specific alkaline phosphatase (b-ALP) ] levels were detected, and the adverse effects and efficacy of drug administration in the 2 groups were compared.Results:After 3 months of treatment, FBG (7.48±1.02) mmol/L, TG (2.01±0.31) mmol/L, PINP (43.72±4.86) ng/ml, HAb1c (7.43±0.65) %, S-CTX (0.27±0.09) ng/ml, 2hPG (9.08±1.34) mmol/L in the observation group, LDL-C (2.58±0.27) mmol/L were lower than those in the control group (7.86±0.97) mmol/L, (2.29±0.34) mmol/L, (46.55±4.19) ng/ml, (7.81±0.62) %, (0.32±0.10) ng/ml, (10.52±1.41) mmol/L, (2.89±0.31) mmol/L ( t=2.177, 5.968, 3.556, 3.481, 2.996, 5.968, 6.080, P<0.05) ; after 3 months of treatment, the bone density of each site in the observation group was (0.76±0.09) g/cm 3, (0.75±0.10) g/cm 3, (0.76±0.11) g/cm 3, (0.75±0.09) g/cm 3 and OC (20.87±2.33) μg/L, b-ALP (19.70±2.35) U/L were higher than those of the control group (0.70±0.10) g/cm 3, (0.68±0.09) g/cm 3, (0.69±0.10) g/cm 3, (0.70±0.10) g/cm 3, (18.45±3.66) μg/L, (18.09±2.14) U/L ( t=3.596, 4.195, 3.796, 2.996, 4.497, 4.084, P<0.05) ; the overall efficiency of the observation group was 96.92%, higher than that of the control group 84.61% ( χ2=5.876, P<0.05) . The difference was not statistically significant when comparing the incidence of adverse reactions in the 2 groups ( χ2=0.000, P>0.05) . Conclusion:Sitagliptin phosphate combined with liraglutide and osteopontin can further improve clinical efficacy and regulate glucolipid metabolism in patients with T2DM combined with OP, and it also has an important role in improving bone density and regulating bone metabolism level in patients.

Combined effects of bee pollen supplementation and resistance training on aerobic capacity, muscular performance, antioxidant status, and bone metabolism markers in young men: A randomised controlled trial

@#Introduction: This study investigated the combined effects of bee pollen and resistance training on aerobic capacity, muscular performance, antioxidant status, and bone metabolism markers among young men. Methods: Forty young men were randomly assigned into four groups: sedentary control (C), bee pollen supplementation (BP), resistance training (RT), and combined bee pollen supplementation and resistance training (BPRT) groups. Bee pollen was consumed by participants in BP and BPRT groups (1500 mg daily for eight weeks). Resistance training was performed thrice per week for eight weeks in RT and BPRT groups. Participants’ anthropometry, aerobic capacity, isokinetic muscular peak torque (strength), and average power were measured. Concentrations of serum total antioxidant status (TAS), serum superoxide dismutase (SOD), serum alkaline phosphatase (ALP), and serum C-terminal telopeptide of type 1 collagen (1CTP) were determined. Results: After eight weeks of intervention, there was a significant decrease in 1CTP in BP group. In RT group, significant increases were observed in both muscular strength and power. In BPRT group, significant increases in both muscular strength and power, and a significant decrease in 1CTP were observed after 8 weeks. There were no significant changes in aerobic capacity, serum TAS, SOD, and ALP in all the study groups. Conclusion: Resistance training using dumbbells and elastic bands seemed to elicit beneficial effects on muscular strength and power, while bee pollen supplementation alone reduced the level of bone resorption marker. In addition, combining bee pollen with resistance training seemed to offer additive benefit in muscular strength and power.

Co-regulation of circadian clock genes and microRNAs in bone metabolism / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.

Sodium-glucose co-transporter 2 inhibitor: Cardiorenal benefit, bone metabolism, and fracture risk in type 2 diabetes mellitus / 中华内分泌代谢杂志

Type 2 diabetes mellitus is commonly associated with cardiovascular, renal complications, osteoporosis and other comorbidities. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) can reduce blood glucose level in patients with type 2 diabetes mellitus by promoting urine glucose excretion, and has the effect of weight loss and blood pressure reduction. Large randomized controlled clinical trials have shown that SGLT-2i can improve the prognosis of cardiovascular disease and diabetic nephropathy. This article focuses on the effects of SGLT-2i on cardiorenal outcomes and bone metabolism in addition to the glucose-lowering effect. SGLT-2i can improve the prognosis of patients with coronary atherosclerotic cardiovascular disease, reduce the risk of hospitalization for heart failure, reduce cardiovascular diseases and all-cause mortality, and has renal protective effect. Moreover, the cardiorenal protective effect is proved to be consistent in people without type 2 diabetes. SGLT-2i has a regulatory effect on bone mineral ions and bone metabolism related hormones, and its risk of osteoporosis and fracture deserves attention. Although data suggest that canagliflozin may increase fracture risk, meta-analyses of multiple clinical trials have concluded that SGLT-2i does not significantly increase fracture risk. However, for patients with high risk of fracture, bone mineral density and bone turnover biomarkers should be considered to assess the risk of fracture before prescription.

Effects of somatostatin receptor ligands on bone metabolism in acromegaly / 中华内分泌代谢杂志

Objective:To investigate the effect of somatostatin receptor ligands (SRLs) on bone metabolism in patients with acromegaly.Methods:Retrospective analysis of clinical data of acromegaly patients( n=100) received surgery or SRLs alone for 3 months. The changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), osteocalcin (OC), N-mid fragment of osteocalcin (N-MID), amino-terminal peptide of type I procollagen (P1NP) and C-terminal peptide degradation product of type I collagen(CTX) were compared before and after treatment. Patients were divided into drug treatment group and surgical group according to treatment methods. According to the decline of GH after medication, patients in the drug treatment group were further divided into drug sensitive group and drug insensitive group. Results:The average dynamic GH and IGF-1 indexes in the drug treatment group were significantly decreased after treatment compared with before treatment (both P<0.05), and CTX was also significantly decreased after treatment [1.25 (0.67, 1.40) ng/mL vs 1.34 (0.57, 1.68) ng/mL, P<0.05]. The mean dynamic GH, IGF-1 index, OC, N-MID, P1NP, and CTX in surgical group were significantly decreased after treatment compared with before treatment (all P<0.01). In the surgical group, there was a positive correlation between GH difference (ΔGH) and N-mid difference (ΔN-MID; r=0.454, P=0.026), and there was a positive correlation between IGF-1 index difference (ΔIGF-1 index) and CTX difference (ΔCTX; r=0.339, P=0.036). After treatment, the mean dynamic GH, IGF-1 index, CTX, P1NP, and N-MID in drug treatment group were significantly higher than those in surgical group (all P<0.001). CTX and N-MID decreased significantly after treatment in drug sensitive group compared with drug insensitive group (35.3% vs 7.2%, P<0.001; 24.1% vs 11.8%, P<0.05), and ΔGH was positively correlated with ΔCTX ( r=0.328, P=0.004). Conclusion:SRLs treatment can reduce bone formation marker N-MID and bone resorption marker CTX, improving the high turnover state of bone metabolism in patients with acromegaly, which may attribute to the reduction of GH and IGF-1 levels.

Effects of levetiracetam combined with low-dose topiramate on bone and lipid metabolism in children with epilepsy / 中国基层医药

Objective:To investigate the efficacy of levetiracetam combined with low-dose topiramate on epilepsy and its effects on bone metabolism and lipid metabolism in children.Methods:A total of 108 children with epilepsy who received treatment in the First People's Hospital of Yongkang from August 2016 to December 2019 were included in this study. They were randomly allocated to study and control groups ( n = 54/group). The study group was treated with levetiracetam combined with low-dose topiramate. The control group was treated with carbamazepine combined with low-dose topiramate. Before treatment and half a year after treatment, serum alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels, blood Ca 2+ and P 3- concentrations, and bone mineral density (BMD) were determined. Clinical efficacy was evaluated in each group. Results:Half a year after treatment, blood Ca 2+ concentration, blood P 3- concentration, and BMD in the study group were (2.41 ± 0.35) mmol/L, (1.57 ± 0.26) mmol/L, and (2.21 ± 0.52) g/cm2, respectively, which were significantly greater than those in the control group [(2.19 ± 0.27) mmol/L, (1.18 ± 0.15) mmol/L, (1.81 ± 0.38) g/cm, tca2+ = 4.20, tbloodP3- = 5.73, tBMD = 6.42, all P < 0.05). ALP level was significantly lower in the study group than in the control group [(129.78 ± 25.63) U/L vs. (181.55 ± 21.94) U/L, t = 15.39, P < 0.05). Half a year after treatment, TC, TG, and LDL-C levels in the study group were (4.38 ± 0.64) mmol/L, (1.71 ± 0.42) mmol/L, and (1.65 ± 0.32) mmol/L, respectively, which were significantly lower than those in the control group [(4.76 ± 0.83) mmol/L, (1.96 ± 0.45) mmol/L, (1.98 ± 0.34) mmol/L, tTC = 3.81, tTG = 4.14, tLDL-C = 5.58, all P < 0.05]. HDL-C level in the study group was significantly higher than that in the control group [(1.96 ± 0.38) mmol/L vs. (1.63 ± 0.27) mmol/L, tHDL-C = 7.39, P < 0.05]. Half a year after medication, clinical efficacy was significantly higher in the study group than that in the control group (94.44% vs. 81.48%, χ2 = 6.29, P < 0.05). Conclusion:Low-dose topiramate combined with levetiracetam is highly effective on epilepsy in children. The combined therapy has less impact on the levels of bone and lipid metabolism indicators and is suitable for clinical application.

Effect of atorvastatin combined with alendronate in the treatment of T2DM with osteoporosis on bone metabolism, TNF-α, IL-6, and 25- (OH) D levels / 中华内分泌外科杂志

Objective:To investigate the effects of atorvastatin combined with alendronate in the treatment of type 2 diabetes mellitus (T2DM) with osteoporosis (OP) on bone metabolism, tumor necrosis factor alpha (TNF-α) , interleukin 6 (IL-6) , and 25-hydroxyvitamin D[25- (OH) D] level.Methods:A total of 152 patients with T2DM and OP who were diagnosed and treated in our hospital from Jul. 2017 to Jul. 2020 were selected. According to the different treatment methods, they were divided into control group (73 cases with alendronate treatment) and study group (79 cases receiving atova Statins combined with alendronate sodium treatment) . The two groups were compared in terms of bone metabolism indexes, bone mineral density, changes in serum TNF-α, IL-6, 25- (OH) D levels, and adverse reactions before and after treatment.Results:After treatment, osteocalcin (BGP) , bone-specific alkaline phosphatase (BAP) , lumbar spine L1-4 bone mineral density, femoral neck bone mineral density, and 25- (OH) D of the two groups increased ( P< 0.001) , and the study group was significantly higher than the control group (BGP: 7.68±0.89 vs 6.88±0.93; BAP: 18.62±3.97 vs 16.82±3.24; lumbar spine L1-4: 0.95±0.08 vs 0.92±0.05; femoral neck: 0.79±0.07 vs 0.75±0.06; 25- (OH) D: 31.35±10.1 vs 26.54±7.14; all P<0.05) . After treatment, the serum type I collagen C-terminal peptide (s-CTX) , human tartrate acid phosphatase (TRAP-5b) , TNF-α, IL-6 were decreased for both groups ( P<0.001) , and they were significantly lower in the study group than those in the control group (s-CTX:0.37±0.12 vs 0.55±0.12; TRAP-5b: 2.43±0.66 vs 2.99±0.75; TNF-α: 9.93±1.91 vs 11.77±2.69; IL-6: 10.65±1.26 vs 12.91±1.21; all P<0.001) . The incidence of adverse reactions in the study group was significantly lower than that in the control group (16.46% vs 39.73%, P=0.001) . Conclusion:Atorvastatin combined with alendronate in the treatment of T2DM patients with OP can effectively increase 25- (OH) D levels, reduce inflammation, and promote bone metabolism and bone density.

Correlation of TNFAIP3 gene polymorphism with osteoporotic fractures and bone metabolism in elderly patients / 中华内分泌外科杂志

Objective:To investigate the correlation between TNFAIP3 gene polymorphism and osteoporotic fractures in the elderly and bone metabolism indexes.Methods:A total of 115 patients with senile osteoporotic fractures admitted to Peace Hospital Affiliated to Shanxi Changzhi Medical College from Jan. 2019 to Jun. 2021 were enrolled as the observation group, and 120 patients with senile osteoporotic fractures matched with gender, age and body mass index of the observation group were selected as the control group. The levels of blood calcium, blood phosphorus, alkaline phosphatase, 25-hydroxyvitamin D and other bone metabolism indexes of all subjects were recorded. The genotypes of rs10499194 and rs13207033 in TNFAIP3 gene were analyzed by capillary electrophoresis and fragment analysis (SNaPshot) . The mRNA relative expression level of TNFAIP3 gene in peripheral blood of all subjects was determined by quantitative real-time fluorescence quantitative polymerase chain reaction.Results:There were statistically significant differences in genotype distribution and gene frequency of RS10499194 and RS13207033 between the observation group and the control group ( P<0.05) . For rs10499194, CT genotype carriers had a significantly higher risk of fracture than wild-type CC genotype carriers [OR=3.253 (1.223-8.652) , P=0.014]. The dominant model was also statistically significant ( P=0.003) . For rs13207033, GA carriers had a significantly higher risk of fracture than wild-type GG carriers [OR=3.775 (1.192-11.952) , P= 0.016]. The dominant model was statistically significant ( P=0.009) . The blood calcium level in AA+GA group was significantly higher than that in GG group at rs13207033 site ( P=0.006) . The mRNA expression level of TNFAIP3 gene in the observation group was 1.41±0.09, which was significantly lower than that in the observation group (2.07±0.12, t=6.69, P<0.001) . TNFAIP3 mRNA expression level of rs10499194 site TT+CT group was 1.35±0.11, significantly lower than CC group 1.43±0.13 ( t=2.82, P=0.007) . Conclusion:The polymorphism of TN-FAIP3 gene is related to the occurrence of osteoporotic fractures and bone metabolism, and may affect the gene expression level.

Effects of 275 nm and 310 nm ultraviolet irradiation on bone metabolism in ovariectomized osteoporotic rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of 275 nm and 310 nm ultraviolet irradiation on ovariectomized rats' bone metabolism.@*METHODS@#Twenty four 3-month-old female Sprague-Dawley (SD) rat were randomly divided into control group, sham operated group, 275 nm ultraviolet (UV) irradiation group and 310 nm UV irradiation group. Each group contained 6 rats. The rats in the two irradiation groups were treated with bilateral ovariectomy. The rats in sham operated group received sham operation (They were given the same back incision and a bit of par-ovarian fat were removed). Control group received no disposition. About 24 weeks after operation, all the rats received detailed bone mineral density (BMD) detection again. Detection regions include cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur. Next, osteopenia rats in 275 nm irradiation group were UV irradiated 275 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The osteopenia rats in 310 nm irradiation group were UV irradiated 310 nm with fixed illumination intensity (15 μW/cm2) everyday for 16 weeks. The backs of the rats were shaved regularly as irradiation area (6 cm×8 cm). After 16-week irradiation, all the rats' BMD of cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur were measured. At the end of the trial, all the rats' blood specimens were obtained and serum 25(OH)D, procollagen type Ⅰ N-peptide (PINP) and osteocalcin (OC) were measured.@*RESULTS@#Compared with control group [(238.78±26.74) mg/cm3], the BMD of the whole body were significantly lower in 275 nm [(193.34±13.28) mg/cm3] and 310 nm [(191.19±18.48) mg/cm3] irradiation groups (P=0.002, P=0.001). There were no significant difference between sham operated group [(227.20±14.32) mg/cm3] and control group. After 16-week ultraviolet irradiation, the BMD of the whole body were significantly increased in 275 nm [(193.34±13.28) mg/cm3 vs. (221.68±25.52) mg/cm3, P=0.005] and 310 nm groups [(191.19±18.48) mg/cm3 vs. (267.48±20.54) mg/cm3, P < 0.001] after corresponding irradiation. The BMD of the four body regions (lumbar vertebra, proximal femur, mid femur and distal femur) had significantly increased after irradiation in 275 nm irradiation group. For 310 nm irradiation group, the BMD in cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur also had increased significantly after 310 nm ultraviolet irradiation. The concentration of serum 25(OH)D and OC was higher in 275 nm irradiation group than in control group [(46.78±5.59) μg/L vs. (21.32±6.65) μg/L, P=0.002;(2.05±0.53) U/L vs. (1.32±0.07) U/L, P=0.022]. Compared with the control, the concentration of serum 25(OH)D [(58.05±12.74) μg/L], OC [(2.04±0.53) U/L] and PINP [(176.16±24.18) U/L] was significantly higher (P < 0.001, P=0.015, P=0.005) in 310 nm irradiation group. However, there were no significantly difference between sham operated group and the control.@*CONCLUSION@#Both 275 nm and 310 nm ultraviolet could improve rats' vitamin D synthesis. Both 275 nm and 310 nm ultraviolet could improve osteopenia rats' bone condition. The irradiation of 310 nm might be more effective on bone condition improvement.

Changes of serum immunoregulatory cytokines in patients with rheumatoid arthritis complicated with osteoporosis / 中国医师杂志

Objective:To investigate the changes and clinical significance of serum immunoregulatory cytokines in patients with rheumatoid arthritis (RA) complicated with osteoporosis (OP).Methods:The clinical data of 420 patients with RA admitted to Mianyang Central Hospital from January 2019 to December 2019 were analyzed. According to their bone mineral density, they were divided into OP group (220 cases) and non OP group (200 cases). The immunoregulatory cytokines and bone metabolism indexes of the two groups were compared, and the correlation between them was analyzed.Results:The age, course of disease, glucocorticoid use history, fracture history, swelling joint number and tenderness joint number of OP group were significantly higher than those of non OP group ( P<0.05). In OP group, the serum levels of interleukin (IL)-6, IL-17, tumor necrosis factor-α (TNF-α) and C-terminal peptide cross-linking (CTX) of type Ⅰ collagen were significantly higher than those in control group ( P<0.05), while the IL-10 and transforming growth factor-β1 (TGF-β1) were significantly higher than that of non OP group ( P<0.05). The serum level of CTX in patients with RA complicated with OP was positively corrected with IL-6, IL-17, TNF-α ( r=0.913, 0.915, 0.921, P<0.001), and negatively correlated with IL-10 and TGF-β1 ( r=-0.921, -0.920, P<0.001). Conclusions:RA patients complicated with OP have higher age, longer course of disease, history of fracture, history of glucocorticoid use, more joint swelling and pain, higher IL-6, IL-17, TNF-α levels, lower IL-10 and TGF-β1 levels. Immunoregulatory cytokines may regulate the proliferation and differentiation of osteoclasts and osteoblasts, and play an important role in RA complicated with OP.

The effect of hypoglycemic drugs on bone metabolism and dental implantation in type 2 diabetes mellitus patients / 口腔疾病防治

@#Patients with type 2 diabetes mellitus (T2DM) have a large demand for dental implants, but the pathologic state of T2DM patients could compromise the efficacy of implant treatment. Glycemic control can improve the success rate of implants in the T2DM population, but the early osseointegration of individuals still needs to be improved. Strengthening early osseointegration in patients with T2DM is one of the urgent problems for clinicians. The pharmacological mechanisms of hypoglycemic drugs on the market for bone metabolism are different and may require different interventions on the bone around the implant, but there is a lack of direct clinical evidence of the protective effect of hypoglycemic drugs. This review integrated the bone metabolic effect of drugs in clinical medical research and dental implant research. The aim was to provide medication guidance for T2DM patients who require implant surgery, and it is recommended to avoid the use of drugs with negative effects on bone as far as possible without violating the clinical medication guidelines, including SGLT-2 inhibitors and thiazolidinediones. Instead, they should choose glucose-lowering drugs that are beneficial to bone metabolism, such as insulin, metformin and GLP-1 receptor agonists. However, the comparative clinical effects of these drugs on periimplant bone need to be further elucidated. The researcher should select appropriate drugs (incretin drugs) to enhance the early osseointegration of implants in patients with T2DM.

Differences in implant osseointegration in the jaw and femur in animal experiments / 口腔疾病防治

@#The jaw and femur are commonly used sites in basic research for modeling bone defects or inserting implants. An increasing number of studies have identified that the jaw and femur indeed show great differences in embryonic development and growth, histomorphology and bone metabolism. A literature review showed that, compared with the femur, the main osteogenic pathway of the jaw may have better osteogenic ability, and its stem cells have better proliferation and osteogenic differentiation ability. However, the jaw structure is less regular, the osteogenic differentiation ability of its osteoblasts is mineralization slightly weak, and the immune cells of the jaw are more sensitive to cytokines. These may be the reasons why the osseointegration of the jaw implant is different from that of the femur in animal experiments, but its specific mechanism has not been clarified.

Effects of Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction on bone metabolism and inflammation response in osteoporosis patients / 国际中医中药杂志

Objective:To explore the effects of Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction on bone metabolism and inflammation response in osteoporosis patients. Methods:A total of 82 patients with osteoporosis of spleen-kidney deficiency, meeting the inclusion criteria in the hospital, were enrolled between June 2018 and October 2019. They were divided into observation group and control group by random number table method, 41 in each group. The control group was treated with oral calcium carbonate D3 tablets and alendronate sodium, while the observation group was treated with Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction on basis of control group. Both groups were treated for 6 months. Before and after treatment, scores of TCM symptoms were conducted. The bone mineral density (BMD) values of lumbar vertebra L 2-4, femoral neck and distal radius1/3 site were detected by dual-energy X-ray BMD analyzer. The levels of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and type I C-terminal cross linked peptide (CTX-I) were detected by electrochemiluminescence analyzer. The level of bone gla protein (BGP) was detected by radioimmunoassay. The levels of interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were detected by full-automatic biochemical analyzer. The adverse events during treatment were observed. And clinical curative effect was evaluated. Results:The differences in response rate between observation group and control group was statistically significant [95.1% (39/41) vs. 78.0% (32/41); χ2=5.145, P=0.023]. After treatment, scores of clinical symptoms (pain in back and loin, soreness and weakness of waist and knees, limb fatigue, debilitation, dizziness and tinnitus, frequent nocturia, loose stools, poor complexion) in observation group were significantly lower than those in the control group ( t=14.268, 10.732, 20.720, 7.564, 9.055, 15.975, 10.826, 6.552, all Ps<0.001). After treatment, BMD values of lumbar vertebra L 2-4 (0.89 ± 0.06 g/cm 3vs. 0.81 ± 0.04 g/cm 3, t=7.104), femoral neck (0.80 ± 0.08 g/cm 3vs. 0.72 ± 0.06 g/cm 3, t=5.122) and distal radius 1/3 site (0.65 ± 0.12 g/cm 3vs. 0.56 ± 0.14 g/cm 3, t=3.125) in observation group were significantly greater than those in the control group ( P<0.01). After treatment, levels of serum BGP and IL-10 in observation group were significantly higher than those in the control group ( t=3.875, 3.714, P<0.01), while levels of TRACP-5b, CTX-I, IL-6, TNF-α and CRP were significantly lower than those in the control group ( t=3.169, 5.849, 9.412, 4.606, 5.430, all Ps<0.001). Conclusion:Shenling-Baizhu Powder combined with modified Guilu-Erxian Decoction can improve clinical symptoms in patients with primary osteoporosis of spleen-kidney deficiency, increase BMD, regulate bone metabolism, alleviate inflammatory response and improve clinical curative effect.

Regulation Effect and Clinical Efficacy of Addition and Subtraction Therapy of Jinkui Shenqiwan Combined with Buzhong Yiqitang on Immune Inflammatory Factors of Patients with Postmenopausal Osteoporosis and Deficiency of Spleen and Kidney / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang to postmenopausal osteoporosis （PMO） with deficiency of spleen and kidney， and to investigate its regulation effect on immune inflammatory factors. Method:One hundred and sixty patients were randomly divided into observation group and control group， with 80 cases in each group. Both groups got comprehensive western medicine treatment measures. Patients in control group additionally got Zhuanggu Zhitong capsule， 4 capsules/time， 3 times/day. Patients in observation group additionally got addition and subtraction therapy of Jinkui Shenqiwan combined with Buzhong Yiqitang， 1 dose/day. The treatment was continued for 24 weeks. Before and after treatment， lumbar L2-4 bone mineral density （BMD） was detected by Dual energy X-ray absorptiometry （DXA） and lumbar BMD was detected by quantitative CT （QCT）. Scores of traditional Chinese medicine（TCM） syndromes and Chinese osteoporosis-targeted quality of life questionnaire （COQOL） were graded. Levels of Estradiol （E₂）， type Ⅰ procollagen amino terminal pro peptide （PINP）， serum osteocalcin （OC）， osteoprotegerin （OPG）， type Ⅰ collagen cross-linked C-terminal peptide （S-CTX）， tartrate resistant acid phosphatase （TRACP） and urinary pyridinoline （PYD） were detected. Levels of CD4⁺ T cells， CD8⁺ T cells， interleukin-17 （IL-17）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， <italic>γ-</italic>interferon（IFN-<italic>γ</italic>） and interleukin-4 （IL-4） were calculated. The proportion of T helper cell （Th）17 and regulatory T cell （Treg） in CD4⁺ T cells was calculated. Besides， the safety was evaluated. Result:Bone density was detected by DXA in observation group， and its T-value and bone density detected by QCT were all higher than those in control group （<italic>P</italic><0.01）. After treatment， scores of TCM syndrome and COQOL were lower than those in control group （<italic>P</italic><0.01）. Levels of PINP， OC， S-CTX， TRACP and PYD/Cr were all lower than those in control group （<italic>P</italic><0.01）. Levels of OPG， CD8⁺ and Treg were higher than those in control group （<italic>P</italic><0.05）， levels of Th17， Th17/Treg， CD4⁺/CD8⁺， IL-17， TNF-<italic>α</italic> and IFN-<italic>γ </italic>were lower （<italic>P</italic><0.01）， and levels of IL-4 and E₂ were higher than those in control group （<italic>P</italic><0.01）. The clinical efficacy in observation group was better than that in control group （<italic>Z</italic>=2.103， <italic>P</italic><0.05）. Conclusion:On the basis of calcium and vitamin D supplementation， Jinkui Shenqiwan combined with Buzhong Yiqitang can improve levels of E₂ and bone density， reduce clinical symptoms， improve quality of life， regulate bone metabolism index and immune inflammation reaction， with better clinical efficacy and safety.

Effect of Zuoguiwan on Wnt/β-catenin Signaling Pathway in Ovariectomized Osteoporosis Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/<italic>β</italic>-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg^-1·d^-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg^-1·d^-1）.After successful establishment of the model in the 13^th week， intragastric administration （<italic>ig</italic>） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E₂） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，<italic>β</italic>-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3<italic>β</italic>（GSK-3<italic>β</italic>） in rat tibia. Result:Compared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（<italic>P</italic><0.01）， the contents of E₂ and PINP in serum decreased significantly（<italic>P</italic><0.01）， the content of BALP，BGP，TRAP increased significantly（<italic>P</italic><0.01）， the expression levels of Wnt2，p-GSK-3<italic>β </italic>Ser9，LRP5 and <italic>β</italic>-catenin protein in bone tissue decreased significantly（<italic>P</italic><0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the contents of serum E₂ and PINP were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the content of BALP，BGP，TRAP was significantly decreased （<italic>P</italic><0.01）， and the expression level of Wnt2，p-GSK-3<italic>β</italic> Ser9，LRP5， <italic>β</italic>-catenin protein in bone tissue was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/<italic>β</italic>-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3<italic>β</italic>， reducing the degradation of <italic>β</italic>-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.

Effect of Modified Shiquan Dabutang on Inflammatory and Bone Metabolism Indexes in Elderly Patients with Osteoporotic Intertrochanteric Fractures Due to Qi and Blood Deficiency / 中国实验方剂学杂志

Objective:To explore the application value of modified Shiquan Dabutang in the treatment of elderly patients with osteoporotic intertrochanteric fractures （OIFs） due to Qi and blood deficiency by observing its impacts on inflammatory and bone metabolism indexes. Method:Ninety-eight elderly patients admitted to our hospital for OIFs of Qi and blood deficiency syndrome from April 2018 to April 2020 were randomized into an observation group （<italic>n</italic>=49） and a control group （<italic>n</italic>=49）. Following the proximal femoral nail antirotation （PFNA） fixation， patients in the control group were treated with Guipiwan， while those in the observation group received the modified Shiquan Dabutang. The clinical efficacy， inflammatory and bone metabolism indexes， and complications were compared between the two groups after four weeks of treatment. Result:The levels of such serum indexes as fibroblast growth factor-2 （FGF-2）， osteoprotegerin （OPG）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>β</italic>-endorphin （<italic>β</italic>-EP）， bone-specific alkaline phosphatase （BALP）， and osteocalcin （BGP） in the observation group after treatment were significantly elevated as compared with those in the control group （<italic>P</italic><0.05）， whereas the serum tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and <italic>D</italic>-dimer （<italic>D</italic>-D） declined （<italic>P</italic><0.05）. The TCM symptom score in the observation group after treatment was obviously lower than that in the control group， while the Harris Hip Score （HHS） was higher （<italic>P</italic><0.05）. The overall response rate of the observation group was 93.88% （46/49）， higher than 75.51% （37/49） of the control group （<italic>χ²</italic>=6.376， <italic>P</italic><0.05）. The total incidence of incision infection， deep vein thrombosis of lower limbs， and pulmonary infection in the control group was 24.49% （12/49）， significantly higher than 6.12% （3/49） in the observation group （<italic>χ²</italic>=6.607， <italic>P</italic><0.05）. Conclusion:The modified Shiquan Dabutang is able to alleviate inflammation， regulate bone metabolism， promote bone repair， and reduce the incidence of complications in elderly patients with OIFs due to Qi and blood deficiency.

Effect of Modified Anshentang on Serum Inflammatory Factors, Immune Function, Bone Metabolism on Treatment of Patients with Ankylosing Spondylitis in Early and Middle Stages / 中国实验方剂学杂志

Objective:This study aims to investigate the clinical efficacy of modified Anshentang on the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome and its effect on serum inflammatory factors， immune function， and bone metabolism indexes of patients. Method:In this study， 120 patients were randomly divided into control group and observation group， 60 cases in each group. On the basis of ethotrexate treatment， patients in control group took Bushen Shuji granule orally， while patients in observation group took modified Anshentang orally for 8 weeks. Before and after treatment， patients in two groups were observed for clinical symptoms ［ bath ankylosing spondylitis patient global score （BAS-G）， bath ankylosing spondylitis disease activity index （BASDAI）， spondyloarthritis research consortium of Canada （SPARCC）， traditional Chinese medicine symptoms （TCM symptoms）<italic> </italic>］， serum inflammatory factors ［ tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， macrophage migration inhibitory factor （MIF）， interleukin-23 （IL-23）］， immune function ［ immunoglobulin A（IgA）， immunoglobulin G（IgG）， immunoglobulin M（IgM）］， bone metabolic indicators ［osteocalcin （BGP）， bone morphogenetic protein-2 （BMP-2）， bonespecific alkaline phosphatase （BALP）］. The clinical efficacy， adverse reactions and recurrence rates of 12 months in two groups were observed. Result:During the study， 4 cases dropped out from control group and 2 cases from observation group. The total effective rate of 96.55% （56/58） in observation group was higher than 80.36% （45/56） in control group （<italic>χ</italic>²=4.827，<italic>P</italic><0.05）. The recurrence rate of 5.17% （3/58） in observation group was lower than 19.64% （11/56） in control group （<italic>χ</italic>²=5.187， <italic>P</italic><0.05）. Compare with control group after treatment， BAS-G，BASDAI， SPARCC， TCM symptoms， TNF-<italic>α</italic>， MIF and IL-23 in observation group were significantly decreased （<italic>P</italic><0.05）， while BGP， BMP-2， BALP， IgA， IgG and IgM were significantly increased （<italic>P</italic><0.05）. The incidence of adverse reactions was 12.07%（7/58） in observation group， which was lower than 32.14%（18/56） in control group （<italic>χ</italic>²=4.826，<italic>P</italic><0.05）. Conclusion:Modified Anshentang is effective in the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome， and the incidence of adverse reactions is low.

Clinical Efficacy of Modified Bushen Huoxuetang Combined with LCP in Treatment of Nonunion of Limb Long Bone Shaft Fracture / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of modified Bushen Huoxuetang combined with autologous bone grafting and locking compression plate （LCP） in treating nonunion of long bone fractures， and the effect on microcirculation， osteogenic differentiation factor and bone metabolism index. Method:A total of 70 patients were randomly divided into control group and observation group by random number table， with 35 cases in each group. Patients in both groups received LCP. Patients in control group got Dieda Shenggu granule， 10 g/time， 1 time/day. Patients in observation group got Bushen Huoxuetang， 1 dose/day. The course of treatment lasted for 3 months， and 3-month follow-up data were recorded. On a weekly basis， the main symptoms， such as pain， tenderness， longitudinal percussion pain and swelling were checked， and the time of disappearing of main symptoms and signs were compared. On a weekly basis， a X-ray examination was performed for callus formation and fracture line， and the fracture healing time was recorded. Before and after treatment， Fugl-Meyer （FMA） was scored， and levels of fibrinogen （FIB）， whole blood viscosity （BV） （high shear， low shear）， plasma viscosity （PV）， platelet aggregation rate （PAR）， <italic>D</italic>-Dimer （<italic>D</italic>-D）， bone morphogenetic protein-2 （BMP-2）， BMP-7， insulin-like growth factor-1 （IGF-1）， vascular endothelial growth factor （VEGF）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， osteocalcin （BGP）， osteoprotegerin （OPG）， procollagen type Ⅰ N-terminal propeptideserum amino pro peptide （PINP）， serum type 1 collagen cross-linked C-terminal peptide （S-CTX） and serum tartrate resistant acid phosphatase （TRACP） of type I procollagen were detected， and the safety was evaluated. Result:Disappearance time of symptoms and signs and fracture healing time in observation group were all lower than those in control group （<italic>P</italic><0.01）. At the third month after treatment， and during the three-month follow-up， scores of callus and FMA （upper and lower limbs） in observation group were all higher than those in control group （<italic>P</italic><0.01）. Levels of <italic>D</italic>-D， FIB， PAR， BV and PV （high-cut and low-cut）， BMP-2， BMP-7， IGF-1， VEGF， TGF-<italic>β</italic>₁， S-CTX and TRACP were all lower than those in control group （<italic>P</italic><0.01）， whereas levels of BGP， OPG and PINP were higher than those in control group （<italic>P</italic><0.01）. The curative effect of fracture healing was better than that of control group （<italic>Z</italic>=1.977， <italic>P</italic><0.05）. And the limb function recovery was superior to that in control group （<italic>Z</italic>=1.970， <italic>P</italic><0.05）. Conclusion:Based on autogenous bone and LCP， modified Bushen Huoxuetang can promote the fracture healing， shorten the course of disease， and promote the recovery of limb function， with a good clinical efficacy. It can improve microcirculation， promote the expression of osteogenic differentiation factor， regulate bone metabolism， and play a role in promoting fracture healing， with a safety in clinical use.

Bone Metabolism Biochemical Markers for Spinal Cord Injury: A Retrospective Study of 135 Patients / 中国康复理论与实践

Objective:To observe the relationship between bone metabolism biochemical markers and clinic features in patients with spinal cord injury. Methods:From July, 2018 to December, 2019, totally 135 patients with spinal cord injury were enrolled. They were assessed with American Spinal Injury Association Impairment Scale (AIS). β-collagen type I C-terminal telopeptide (β-CTX), total N-terminal propeptide of type I precollagen (TP1NP), 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), serum calcium and serum phosphorus were measured. The level of TP1NP, β-CTX, 25(OH)D and PTH among clinical characteristics (gender, age, disease course, AIS grade and so on) were analyzed. Results:The levels of β-CTX and 25(OH)D were lower in women than in men (|t| > 2.044, P < 0.01). There was difference in the level of 25(OH)D among different ages (F = 3.156, P < 0.05). The levels of β-CTX and TP1NP increased in the first four months after spinal cord injury, and decreased then; while the level of PTH decreased in the first four months, and increased then (P < 0.001). The level of β-CTX was lower in patients of AIS D than in patients of AIS A and C (t >2.679, P < 0.05). The level of TP1NP was higher in paraplegics than in quadriplegics (Z = -2.035, P < 0.05). The level of β-CTX was higher in patients with fractures or surgeries involving bone than in patients without fractures or surgeries involving bone (t = 2.169, P < 0.05). There was no difference in all the bone metabolism markers between patients with and without lower extremity motor function (t < 0.839, Z < 1.822, P > 0.05). The ratio of 25(OH)D deficience was 85.19%. Conclusion:Bone conversion was active in the first four months after spinal cord injury, and decreased gradually then, which may be related to fractures of spine or surgeries involving spine after injury. The effect of spinal cord injury on bone metabolism markers is not clear. Most of patients with spinal cord injury were lack of vitamin D.