Bone-strengthening supplement (BSP) promotes bone and cartilage repair, for the treatment of Osteonecrosis of Femoral Head: an MRI-based study.

Currently, no effective drug treatment is available for bone and joint disease, a disorder of the bone and cartilage cells. Osteonecrosis of the femoral head (ONFH) is an example of bone and joint disease. It is progressive, with femoral head collapse resulting from the death of osteocytes and the bone marrow, leading to a poor quality of life and surgical interventions. However, the mechanism of this disease is still unknown, and the effects of current therapy are not satisfactory. In our previous study, we showed, using an ONFH rat model, that a new Chinese medicine, "bone-strengthening supplement" (BSP), enhances bone growth, promotes bone density, and restores blood circulation in the femoral head, and can significantly relieve pain, improve hip joint function, and reduce claudication. In the present study, we evaluated the curative effect of BSP in patients with ONFH using MRI with a double-blind randomized protocol. BSP significantly relieved pain unlike the control treatment; in addition, this treatment could improve MRI signal in ONFH patients. These results suggest that, overall; BSP can restore blood circulation and promote bone and cartilage growth during restoration of bone necrosis and the treatment of bone and joint disease.

A Traditional Herbal Formula Xianlinggubao for Pain Control and Function Improvement in Patients with Knee and Hand Osteoarthritis: A Multicenter, Randomized, Open-Label, Controlled Trial.

Evidence of efficacy of a traditional herbal formula Xianlinggubao (XLGB) for treatment of osteoarthritis (OA) is limited. The present study was designed to evaluate the efficacy of XLGB in the management of patients with knee and hand OA. This was a multicenter, stratified, open-label, randomized controlled trial conducted at six centers in China. People aged 40 or above, diagnosed with OA of the knee or hand, were randomly assigned to the XLGB treatment group or watchful waiting control group. Main outcome measures were the changes in the numeric pain rating scales (NPRS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) or the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) scores, from baseline to 6 months. In total 534 patients (272 to XLGB and 262 to control group) received interventions. Participants in the XLGB group exhibited significant improvement in NPRS (P < 0.001) and WOMAC score (P < 0.001) or AUSCAN score (P < 0.001) compared to control group. Treatment with XLGB at current regime significantly reduced pain and improved function of the knee and hand in patients with OA over a 6-month period, implying that XLGB could be suggested as an alternative treatment for patients with knee or hand OA.

Bone-strengthening pill (BSP) promotes bone cell and chondrocyte repair, and the clinical and experimental study of BSP in the treatment of osteonecrosis of the femoral head.

About 1 in 3 people suffer from bone and joint disease, which is a disease of bone and cartilage cells. Osteonecrosis of the femoral head (ONFH) is a typical example of bone and joint disease involving bone cell necrosis. Osteonecrosis of the femoral head leads to the occurrence of premature osteoarthritis of the hip and collapse of the cartilage cells, and there is currently no effective drug treatment available. In order to study the effects of "bone-strengthening pill" (BSP) on the repair of bone and cartilage cells, we investigated the potential effects of the herbal mixture BSP in an animal model of avascular necrosis of the femoral head and in patients. Results showed that 90% of rats injected with prednisone developed ONFH, whereas BSP administration prevented ONFH development in 70% of prednisone-injected rats. We evaluated the constituents of BSP by HPLC fingerprinting. We also evaluated the clinical efficacy of BSP in a double-blind, randomized, controlled trial of 300 patients with ONFH. The response rate was found to be higher in the treatment group than in the control group, with a response rate of 82% in the treatment group. Treatment with BSP also significantly reduced pain, improved hip function, reduced lameness, and improved pathology by X-ray and MRI analysis, compared with patients who did not receive BSP. These results suggest that BSP treatment inhibits and reverses necrosis of the femoral head bone cells and cartilage cells to repair the femoral head, promote the repair of bone and cartilage diseases.

Variations in the PBEF1 gene are associated with body mass index: A population-based study in northern China.

OBJECTIVE: PBEF1 and its polymorphisms may be important in the physiopathology of obesity. We hypothesized that polymorphisms in PBEF1 gene may modify body mass index (BMI). METHODS: Thus, we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 gene and evaluated the association between the genetic variants and BMI in a population-based study including 442 subjects in northern China. RESULTS: We found that the SNP rs3801267 was significantly associated with decreased BMI (P = 0.026 in additive model), while the other 2 SNPs (rs4730153 and rs16872158) showed a borderline significant association with decreased BMI (P = 0.068 and 0.060 in additive models). Combined analysis of these 3 SNPs showed a significant allele-dosage association between the number of variant alleles and decreased BMI (P trend  = 0.007). CONCLUSIONS: These findings indicate that genetic variants in PBEF1 gene may modify individual BMI in the Chinese population.

Decreased proliferation ability and differentiation potential of mesenchymal stem cells of osteoporosis rat.

OBJECTIVE: To explore decreased proliferation ability and differentiation potential of mesenchymal stem cells (MSCs) of osteoporosis rat. METHODS: MSCs were obtained from osteoporosis rat, and proliferation potency and impaired osteogenic differentiation potential were determined. RESULTS: The result showed a significant downregulation of MSCs pluripotency related gene (Oct 4) and osteogenic genes (BSP, OCN) expression in OVX MSCs compared with Sham MSCs (P<0.05). CONCLUSIONS: These data suggest that MSCs are aging in osteoporosis body, and autologous OVX MSCs transplantation is not appropriate to treat osteoporosis if necessary. There will be a possibility in establishing a new clinical application of MSCs autologous transplantation to treat osteoporosis, if OVX MSCs have stronger proliferation and differentiation.

Association of farnesyl diphosphate synthase polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis.

BACKGROUND: Genetic factors are important in the pathogenesis of osteoporosis, but less is known about the genetic determinants of osteoporosis treatment. We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase (FDPS) in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China. METHODS: The study group comprised 639 postmenopausal women aged (62.2 ± 7.0) years with osteoporosis or osteopenia who had been randomly assigned to low dose group (70 mg/2 w) or standard dose group (70 mg/w) of alendronate in this 1-year study. We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul. Before and after treatment, serum levels of calcium, phosphate, alkaline phosphatase (ALP), cross linked C-telopeptide of type I collagen (ß-CTX) were detected. Bone mineral density (BMD) at lumbar spine and proximal femur was measured. The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD, bone turnover biomarkers after the treatment. RESULTS: The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck, and patients with CC genotype had significantly higher baseline femoral neck BMD ((733.6 ± 84.1) mg/cm(2)) than those with AC genotypes ((703.0 ± 86.9) mg/cm(2)) and AA genotypes ((649.8 ± 62.4) mg/cm(2)) (P < 0.01). No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS. The percentage change of serum ALP level was significantly lower in patients with CC genotype (-22.9%) than that in those with AC genotype (-24.1%) and AA genotype (-29.8%) of FDPS after 12 months of alendronate treatment (P < 0.05). Neither percentage change of BMD nor ß-CTX level after alendronate treatment had association with FDPS genotype. CONCLUSIONS: FDPS gene was probably a candidate gene to predict femoral neck BMD at baseline. FDPS gene alleles could predict change percentage of ALP after treatment of alendronate, but possibly had no significant relationship with the responsiveness of BMD to alendronate therapy.

The in vitro and in vivo treatment effects of overexpressed lentiviral vector-mediated human BMP2 gene in the femoral bone marrow stromal cells of osteoporotic rats.

This study aimed to compare the treatment effects of lentiviral vector-mediated hBMP2 which was overexpressed in the femoral bone marrow stromal cells of osteoporotic rats through genetic infection in vitro and in vivo. Comparison of the two transgenic effects may be crucial to determining the lentivirus infection method to be used. Following a comparison of the rat bone marrow stromal cells (rBMSCs) in osteoporotic (MSCs OVX) and normal (MSCs CON) groups, the lentiviral vector-mediated human bone morphogenetic protein 2 (hBMP2), which overexpressed the BMSCs of osteoporotic rats in vitro (rBMSCs in OE group), was constructed. The osteogenic ability in the overexpressed (OE) group was then compared to that of the MSCs CON. The rBMSCs in the OE group (transplants of genetic infection in vitro) and the lentivirus-containing solution (injected material of genetic infection in vivo) were injected into the femurs. The treatment effect of each group was compared via bone mineral density (BMD) and bone histomorphometry. The hBMP2-modified osteoporosis rBMSCs formed by genetic infection in vitro (n=7) had an ameliorated treatment effect on the femur as compared to that of the in vivo (n=7) (BMD: 0.315 vs. 0.19 g/cm2, P<0.01; bone histomorphometry: For bone trabeculars (Tb.Ar/T.Ar): 0.301 vs. 0.114, P<0.01; for trabecular thickness (Tb.Th): 43.54 vs. 21.39 µm, P<0.01; for trabecular separation (Tb.Sp): 115.7 vs. 304.87 µm, P<0.01). The results showed that the treatment effects of osteoporotic rBMSCs on local osteoporosis performed by genetic infection were improved in vitro as compared to those in vivo.

Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-dose alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis. METHODS: This study was a large-sample, randomized, open-label, prospective, multicenter, clinical trial with a 12-month follow-up. A total of 639 postmenopausal women (aged 62.2 ± 7.0 y) with osteopenia or osteoporosis were randomized into two groups: low-dose ALN (70 mg every two weeks) and standard-dose ALN (70 mg weekly). All patients were also supplemented with calcium (600 mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12 months of treatment. BMD and bone turnover markers were compared between the baseline and the end of treatment, and the changes in BMD and bone turnover markers were also compared between the low-dose ALN group and the standard-dose ALN group. RESULTS: No significant differences in age, years since menopause, body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers were found at baseline between the two dose groups. A total of 558 (87.3%) and 540 (84.5%) women completed the treatment at the 6th and 12th months, respectively. After the 12-month treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly in both of the treatment groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%, and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%, respectively; P > 0.05). However, levels of serum alkaline phosphatase and carboxy-telopeptide of type I collagen in the standard-dose group decreased moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The women tolerated the two doses of ALN quite well. Adverse effects were similar in the two groups. CONCLUSIONS: Treatment with low-dose ALN (70 mg every two weeks) in women with postmenopausal osteopenia or osteoporosis effectively increases lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose ALN may be a cost-effective and safe protocol for treating osteopenia or osteoporosis in Chinese women.

Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han population: a community-based case-control study.

Aggrecanase-2 (ADAMTS5) is reported to play essential roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between ADAMTS5 gene polymorphisms and primary OA, we conducted a community-based case-control study. A total of 732 community residents aged 40-84 years participated in the community-based study in Northeast China. After taking physical examination and radiographic examination, 420 persons of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of patients and control group, genotypes of the ADAMTS5 gene polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction enzyme digestion (HAEIII for P692L in exon 7 and BSRBI for R614H in exon 5). The numbers of patients with different OA subtypes were also calculated. The genotype and allele frequency of for the exon 5C/T BSRBI polymorphism was significantly different between OA patients and control individuals (P = 0.001, OR = 0.701, 95% CI = 0.569-0.863). This difference was more obvious in cervical OA patients (P = 0.001, OR = 0.664, 95% CI = 0.521-0.847). The mutation type of exon 5C/T BSRBI polymorphism would be a protective factor for OA especially for cervical OA. Our results suggest that the ADAMTS5 gene polymorphisms may contribute to the susceptibility of osteoarthritis in the Chinese Han population.

MATN3 gene polymorphism is associated with osteoarthritis in Chinese Han population: a community-based case-control study.

BACKGROUND: The matrilin, especially matrilin-3 (MATN3), are reported to play important roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between MATN3 SNP6 (rs8176070) and primary OA, we conducted a community-based case-control study. METHODS: A total of 732 community residents aged 40-84 years participated in the community-based study in Northeast China. After taking physical and radiographic examinations, 420 of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of case and control groups, genotypes of the MATN3 SNP6 were determined by polymerase chain reaction followed by restriction enzyme digestion. The numbers of patients with different OA subtypes were also calculated. RESULTS: The distribution of genotypes and alleles of the MATN3 SNP6 between OA patients and controls was different significantly. The BB carrier tends to be associated with the increased osteoarthritis (P = 0.025, OR = 1.724, 95% CI = 1.071-2.77), especially the knee osteoarthritis (P = 0.021, OR = 2.402, 95% CI = 1.141-5.060) and lumber osteoarthritis (P = 0.020, OR = 1.880, 95% CI = 1.103-3.204). Bb carrier increased hand osteoarthritis risk (P = 0.002, OR = 5.380, 95% CI = 1.828-15.835). The B allele might have an effect on the increased knee osteoarthritis (P = 0.000, OR = 3.143, 95% CI = 2.283-4.328). CONCLUSION: These findings suggest that the MATN3 gene polymorphism might be associated with osteoarthritis in the Chinese Han population.

Prevalence and associated factors of knee osteoarthritis in a community-based population in Heilongjiang, Northeast China.

Few data exist concerning the prevalence of knee OA and associated factors in Northeast China. This study was undertaken to estimate the prevalence of radiographic and symptomatic knee OA among community residents and to elucidate relevant risk factors. Unmatched case-control study was adopted to study risk factors of knee OA. Radiographic OA was evaluated according to the Kellgren and Lawrence grading scheme. Statistical analyses included tests and logistic model regressions. A total of 1,196 people aged 40-84 years participated in the community-based health survey in Northeast China in 2005. Survey participants completed an interviewer-based questionnaire. The standardized prevalence of symptomatic knee OA was 16.05% and it was significantly higher in women than in men (19.87% vs. 11.91%, = 13.76, P < 0.001). There was also an increased tendency with age in both sex (men: x (2) = 29.67, P (trend) < 0.001; women: x (2) = 40.26, P (trend) < 0.001). The prevalence of symptomatic knee OA was significantly higher than that in Beijing and Shantou, while lower than that in Wuchuan county of inner Mongolia with nonsignificant difference. Logistic regressions revealed that age, sex, BMI, and work status might be risk factors for knee OA in urban residents, whereas age, BMI, and smoking habits might be risk factors in rural dwellers. Symptomatic knee OA is extremely common with preponderance for elderly women and constitutes a major public health problem. The findings will be useful to guide the distribution of future health care resources and preventive strategies.

[A comparative study on the prevalence of osteoarthritis in middle and old-aged people from the urban and the rural area in Heilongjiang province].

OBJECTIVE: To investigate the prevalence of osteoarthritis in inhabitants aged 40 years old and above from urban and rural areas in Heilongjiang province. METHODS: Through multistage stratified cluster random sampling methods, residents aged 40 years and above were selected. All subjects were given a standardized questionnaire and were conducted a radiographic examination on hands, knees, neck spine and lumbar spine after informed consent. All statistics were performed by SPSS13.0. RESULTS: A total of 1196 residents were surveyed, which including 573 males and 623 female subjects. The prevalence of osteoarthritis in cervical spine, lumbar spine, knee and hand for men were 26.00%, 31.20%, 11.87%, 15.53%, respectively and that were 34.80%, 30.20%, 20.06%, 27.93% for women respectively. The prevalence of osteoarthritis increased with aging both in men and women. Prevalence in 60 - 70 age group achieved the peak. The prevalence rates became relatively low among those over the 70 years old than expected. The most common sites of osteoarthritis were knees and hands (16.10%), followed by cervical and lumbar spine (12.40%). CONCLUSION: The prevalence of osteoarthritis was generally high in middle and old-aged people in Heilongjiang province.

Effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro.

OBJECTIVE: To observe the effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro. METHODS: Iliac trabecular bone specimens were obtained from adult patients undergoing necessary surgery. After the bone pieces were digested with collagenase-trypsin, osteoblasts were released and incubated at 37 degrees C in a relative humidity of 95% and 5% CO2. Then, the cells were purified, and their passages were given DMEM-F12 and fetal bovine serum medium. Subsequently, 10(-8) mol/L dexamethasone was added into the culture medium to incubate the osteoblasts for three days, and the cells from control groups were incubated without any drugs. All cells were observed continually with phase contrast microscope and transmission electron microscope. Finally, apoptosis was detected by the use of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and biochemical indices, alkaline phosphatase (ALP) and osteocalcin (OCN) were used to determine the effects of dexamethasone on proliferation, differentiation and apoptosis of adult osteoblasts in vitro. RESULTS: In the adult osteoblasts obtained by collagenase-trypsin digestion, it achieved high survival, stable biochemical indices and excellent purification. Under the condition of dexamethasone 10(-8) mol/L and osteoblasts 10,000/ml, there was significant promotion of ALP and OCN secretion without cell apoptosis. CONCLUSIONS: Dexamethasone has a significant effect on the proliferation and differentiation of adult osteoblasts in vitro without apoptosis, and dexamethasone at the suggested concentration can be used as positive control in drug studies for osteoporosis treatment.

[Effect of superoxide dismutase on adhesion molecules expression in skeletal muscle ischemia/reperfusion injury in rats].

OBJECTIVE: To study the effect of SOD on the expression of CD11b/CD18 and ICAM-1 after skeletal muscle ischemia / reperfusion injury in rats. METHODS: Establish the rat model of hind limb ischemia / reperfusion. One hundred and two rats were divided into 5 groups: sham operation group (Group I n = 6), ischemia group (GroupII n = 6), ischemia / reperfusion injury group (Group III n = 30), normal saline treatment group (Group IV n = 30), superoxide dismutase treatment group (Group V n = 30). Flow cytometric analysis and immunohistochemistry were used to assess the expression of CD11b/CD18 on the leukocytes, ICAM-1 in skeletal muscle at the end of ischemia and 1h, 2h, 4h,8h,12h after reperfusion. The changes of MDA in the plasma,MPO in the skeletal muscle and the tissue morphology were studied too. RESULTS: In group III,the expression of CD11b/CD18, ICAM-1,MDA,MPO were increased evidently. The longer time of reperfusion,the more serious the skeletal muscle's injury was. In group V, the changes were ameliorated as compared with group III (P < 0.05), group IV has no difference with group III. CONCLUSION: These data indicate that the expression of CD11b/CD18 and ICAM-1 were significantly correlated with skeletal muscle ischemia/reperfusion injury. SOD can inhibit the expression of free radicals and the adhesion molecules,consequently skeletal muscle ischemia/reperfusion injury is prevented.