As the incidence of osteoporosis (OP) is increasing year by year, high morbidity and mortality caused by osteoporotic fractures have become major problems of health in China and over the world. Quantitative measurement of bone using 99mTc-methylene diphosphonate (99mTc-MDP) provides global or local information of skeletal metabolism or transformation. In this paper, we make a brief review on the quantitative measurement of bone using 99mTc-MDP and expect to provide guidance for clinical diagnosis and treatment.
Objective To study the changes of receptor activator of nuclear factor-κB ligand (RANKL, an osteoclastogenesis-promoting factor) and osteoprotegerin (OPG, the decoy receptor for RANKL), oxidative stress and bone turnover markers in obstructive sleep apnea-hypopnea syndrome (OSAHS), in order to understand the potential mechanisms underlying bone loss in OSAHS patients. Methods Ninety-eight male patients with OSAHS, confirmed by polysomnography (PSG) study, were enrolled. The patients were divided into mild-moderate groups and severe groups. Forty-two male subjects who were confirmed as not having OSAHS served as the controls. The subjects’ bone mineral density (BMD) and T-score were assessed in lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Blood samples were collected from all subjects for measurement of RANKL, OPG, the bone formation marker bone-specific alkaline phosphatase (BAP), the bone resorption marker tartrate-resistant acid phosphatase-5b (TRAP-5b), total antioxidant capacity (TAOC). Twenty-eight severe OSAHS patients accepted continuous positive airway pressure (CPAP) treatment voluntarily. After 6 months, PSG was conducted, and serum RANKL, OPG, TAOC, TRAP-5b, BAP was measured after six months treatment. Results The BMD, T-score of the femoral neck and the lumbar spine were significantly lower in OSAHS patients as compared to the control group. The level of BAP was significantly decreased in the OSAHS group as compared to the control group, and there was no significant difference in TRAP-5b level between two groups. As compared with the control group, levels of OPG, TAOC and the OPG/RANKL ratio decreased significantly. None of these parameters (BMD, T-score, RANKL, OPG, TRAP-5b, BAP) showed significant difference between patients with mild-moderate and severe OSAHS group. Correlation analysis showed that the apnea hypopnea index and oxygen desaturation index were correlated with TAOC. BAP level was positively correlated with TAOC and lowest pulse oxygen saturation. The serum level of TAOC was lower in the OSAHS group after CPAP therapy, but the levels of RANKL, OPG, TRAP-5b, BAP were not different. As compared with the OSAHS group before CPAP therapy, the BMD of the femoral neck and the lumbar spine were not significant difference. Conclusions In patients with OSAHS, the oxidative stress response is enhanced, and imbalance of OPG/RANKL is shifted, which participates in the occurrence of osteoporosis. The oxidative stress injury of severe OSAHS patients was relieved after non-invasive ventilation treatment, but the effect of oxidative stress response on bone metabolism still needs further evaluation.
Objective To explore the relationship between periodontitis and postmenopausal osteoporosis.Methods Databases were electronically searched from PubMed (1966 to December, 2010), EMbase (1974 to December, 2010), CBM (1978 to December, 2010), VIP (1989 to December, 2010), CNKI (1979 to December, 2010) and WanFang Data (January, 2007 to December, 2010), and the references listed in all papers were also retrieved. The literature was screened according to the inclusion and exclusion criteria by two reviewers independently; the methodology quality was evaluated after data abstraction; and then the RevMan 5.0 software was used for meta-analyses. Results Four trials were included. Among the total 678 patients involved, 263 were postmenopausal osteoporosis patients, while the other 415 were non-osteoporosis patients. The results of meta-analyses showed that: a) Clinical attachment loss (CAL) of the postmenopausal osteoporosis patients was significantly higher than that of the non-osteoporosis patients (WMD=0.60, 95%CI 0.23 to 0.96); b) The level of gingival recession of the postmenopausal osteoporosis patients was significantly higher than that of the non-osteoporosis patients (WMD=0.78, 95%CI 0.41 to 1.14); c) There were no significant differences in plaque index (PI), gingival index (GI) and periodontal probing depth (PPD) between the two groups (WMD=0.17, 95%CI 0.00 to 0.35; WMD=0.05, 95%CI –0.09 to 0.19; and WMD=–0.08, 95%CI –0.24 to 0.09); d) The results of one study indicated that the rate of periodontitis in the postmenopausal osteoporosis patients was higher than that of the non-osteoporosis patients (OR=2.45, 95%CI 1.38 to 4.34, Plt;0.01); the severe alveolar crest height loss was related to osteoporosis (OR=4.20, 95%CI 1.57 to 11.22, Plt;0.01). Conclusion Postmenopausal osteoporosis patients are more prone to suffer from periodontitis or turn to the worse stage of periodontitis. In consideration of the factors such as small scales and incomplete measure indexes of the included studies, which have influences on the intensity and comprehensiveness of this conclusion, more high-quality studies are required.
Objective To systematically review the efficacy and adverse events of alendronate on bone mineral density and fractures in men with osteoporosis. Methods We electronically searched MEDLINE (1990 to 2005), EMBASE (1990 to 2005), The Cochrane Library (Issue 3, 2005), Controlled Trials Register and The National Research Register, CBM disc, VIP, and CNKI. We also handsearched some related journals. The search was conducted in Nov., 2005. The quality of included randomized controlled trials (RCTs) was evaluated and meta-analysis was conducted by RevMan 4.2.8. Results We identified 7 studies including 817 patients. Sufficient evidence showed that alendronate plus calcium was superior as preventive treatment to calcium in increasing the bone mineral density (SMD 0.59, 95% CI 0.15 to 1.03, P=0.009) of the lumbar spine. The incidence of withdrawal and lost to follow-up due to adverse events of the alendronate plus calcium was lower than that of calcium (RR 0.32, 95% CI 0.11 to 0.87). Two studies showed that alendronate was superior to placebo in increasing the bone mineral density in men with osteoporosis but with no significantly statistical difference in reducing fractures. Two studies showed alendronate was superior to alfacalcidol in increasing the bone mineral density and reducing the vertebral fractures in men with osteoporosis. One study showed alendronate was not superior to calcitonin or alfacalcidol in increasing the bone mineral density in men at high risk of osteoporosis. One study comparing anledronate or parathyroid hormone with combination of these drugs in men with osteoporosis suggested that anledronate wasn’t superior to parathyroid hormone in increasing the bone mineral density, and the combination did not show any difference compared to parathyroid hormone alone. Conclusions Alendronate is more effective in prevention and treatment of men with osteoporosis compared to placebo. Alendronate is more effective than alfacalcidol in increasing bone mineral density and reducingvertebral fractures in men with osteoporosis. Alendronate is not superior to alfacalcidol or calcitonin in increasing the bone mineral density in preventing men osteoporosis. Alendronate compared to combination of parathyroid hormone does not show more effectiveness in increasing the bone mineral density in men with osteoporosis. More RCTs of high quality, especially multiple center trials are needed to generate ber evidence.
Objective To investigate the effects of R-spondin 2 (Rspo2) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone mineral content in ovariectomized mice. Methods BMSCs were extracted from the bone marrow of the long bones of 7 4-week-old female C57BL/6 mice using whole bone marrow culture and passaged. After the cell phenotype was identified by flow cytometry, the 3rd generation cells were co-cultured with 10, 20, 40, 80, and 100 nmol/L Rspo2. Then, the cell activity and proliferative capacity were determined by cell counting kit 8 (CCK-8), and the intervention concentration of Rspo2 was screened for the subsequent experiments. The osteogenic differentiation ability of BMSCs was detected by alkaline phosphatase (ALP) staining, and the mRNA levels of osteogenesis-related genes [RUNX family transcription factor 2 (Runx2), collagen type Ⅰ alpha 1 (Col1), osteocalcin (OCN)] were detected by real-time fluorescence quantitative PCR (RT-qPCR). In addition, 18 10-week-old female C57BL/6 mice were randomly divided into sham operation group (sham group), ovariectomy group (OVX group), and OVX+Rspo2-intervention group (OVX+Rspo2 group), with 6 mice in each group. The sham group only underwent bilateral back incision and suturing, while the other two groups established osteoporosis mouse models by bilateral ovarian castration. Then, the mice were given a weekly intraperitoneal Rspo2 (1 mg/kg) treatment in OVX+Rspo2 group and saline at the same dosage in sham group and OVX group. After 12 weeks of treatment, the body mass and uterus mass of the mice were weighed in the 3 groups to assess whether the OVX model was successfully prepared; the tibia bones were stained with HE and immunohistochemistry staining to observe the changes in tibial bone mass and the expression level of Runx2 protein in the bone tissues. Blood was collected to detect the expressions of bone metabolism markers [ALP, OCN, type Ⅰ procollagen amino-terminal peptide (PINP)] and bone resorption marker [β-collagen degradation product (β-CTX)] by ELISA assay. Micro-CT was used to detect the bone microstructure changes in the tibia, and three-dimensional histomorphometric analyses were performed to analyze the trabeculae thickness (Tb.Th), trabeculae number (Tb.N), trabeculae separation (Tb.Sp), and bone volume fraction (BV/TV). Results CCK-8 assay showed that Rspo2 concentrations below 80 nmol/L were not cytotoxic (P>0.05), and the cell viability of 20 nmol/L Rspo2 group was significantly higher than that of the control group (P<0.05). Based on the above results, 10, 20, and 40 nmol/L Rspo2 were selected for subsequent experiments. ALP staining showed that the positive cell area of each concentration of Rspo2 group was significantly larger than that of the control group (P<0.05), with the highest showed in the 20 nmol/L Rspo2 group. The expression levels of the osteogenesis-related genes (Runx2, Col1, OCN) significantly increased, and the differences were significant between Rspo2 groups and control group (P<0.05) except for Runx2 in the 40 nmol/L Rspo2 group. In animal experiments, all groups of mice survived until the completion of the experiment, and the results of the body mass and uterus mass after 12 weeks of treatment showed that the OVX model was successfully prepared. Histological and immunohistochemical staining showed that the sparseness and connectivity of bone trabecula and the expression of Runx2 in the OVX group were lower than those in the sham group, whereas they were reversed in the OVX+Rspo2 group after treatment with Rspo2, and the differences were significant (P<0.05). ELISA assay showed that compared with the sham group, the serum bone metabolism markers in OVX group had an increase in ALP and a decrease in PINP (P<0.05). After Rspo2 intervention, PINP expression significantly reversed and increased, with significant differences compared to the sham group and OVX group (P<0.05). The bone resorption marker (β-CTX) was significantly higher in the OVX group than in the sham group (P<0.05), and it was significantly decreased in the OVX+Rspo2 group when compared with the OVX group (P<0.05). Compared with the sham group, Tb.Th, Tb.N, and BV/TV significantly decreased in the OVX group, while Tb.Sp significantly increased (P<0.05); after Rspo2 intervention, all of the above indexes significantly improved in the OVX+Rspo2 group (P<0.05) except Tb.Th. Conclusion Rspo2 promotes differentiation of BMSCs to osteoblasts, ameliorates osteoporosis due to estrogen deficiency, and promotes bone formation in mice.
Objective To evaluate and select essential medicine for middle-aged and elderly women with primary osteoporosis using evidence-based methods based on the burden of disease. Methods By means of the approaches, criteria, and workflow set up in the second article of this series, we referred to the recommendations of evidence-based or authority guidelines from inside and outside China, collected relevant evidence from domestic clinical studies, and recommended essential medicine based on evidence-based evaluation. Data were analyzed by Review Manager (RevMan) 5.1 and GRADE profiler 3.6 to evaluate quality of evidence. Results (1) 18 guidelines were included, 14 of which were evidence-based or based on expert consensus. Recommended medicines included bisphosphonates, calcitonin, estrogen, parathyroid hormone, selective estrogen receptor modulator, strontium and Chinese patent drug. (2) A result of one quasi-RCT (very low quality) indicated that caltrate D had a better effect on elderly women with primary osteoporosis than calcium gluconate in improving bone mineral density (BMD) (MD=0.04, 95%CI 0.02 to 0.06) and ameliorating bone ache ( RR=2.64, 95%CI 1.40 to 4.96). A few cases treated by caltrate D presented with adverse reaction such as gastrointestinal discomfort, poor appetite, constipation and nausea which disappeared later. Caltrate D (calcium carbonate D3) with good applicability cost 1.00 yuan daily. (3) A result of one RCT (low quality) indicated that alendronate had a better effect than caltrate D in improving L2-L4 BMD (MD=0.06, 95%CI 0.017 to 0.10) and ameliorating bone ache (RR=1.8, 95%CI 1.40 to 2.52). A result of two RCTs (moderate quality) indicated that alendronate plus calcium carbonate plus vitamin D6 had a better effect than calcium carbonate plus vitamin D in improving L2-L4 BMD (MD=0.05, 95%CI 0.02 to 0.08) and reducing blood alkaline phosphatase (MD=–31.9, 95%CI –54.99 to –8.81). There were slight adverse effects mainly including gastrointestinal reaction. Alendronate with fairly poor applicability cost 2.67 yuan daily. (4) A result of one RCT (moderate quality) indicated that after a 3-month treatment, Xian Ling Gu Bao Jiao Nang (name of a Chinese patent drug, abbreviated as XLGB) plus calcium preparation had a better effect than calcium preparation alone (MD=10, 95%CI 0.05 to 0.15). A result of one RCT (moderate quality) indicated that given for 3 to 6 months, XLGB plus calcium preparation was superior to calcium preparation alone in increasing the density of Ward’s triangle and the great femoral trochanter. A result of one RCT (low quality) indicated that XLGB plus calcitriol had a better effect than calcitriol alone in pain relief (RR=1.26, 95%CI 1.04 to 1.52). There were slight adverse effects mainly including reaction in the digestive system, the circulatory system and the skin. XLGB with good applicability cost 4.58 yuan daily. Conclusion We offer a weak recommendation for alendronate applied to middle-aged and elderly women with primary osteoporosis and pain and fracture caused by primary osteoporosis. We also offer a b recommendation for caltrate D and XLGB applied to middle-aged and elderly women with primary osteoporosis and pain and fracture caused by primary osteoporosis. In addition, we propose that the census on elder people with osteoporosis in rural areas should be carried out. More clinical and pharmacoeconomic studies of large-sample, high-quality on alendronate and its calcium preparation for adult osteoporosis are needed in China.
ObjectiveTo compare the effectiveness of short-segment and long-segment bone cement-augmented fixation combined with vertebroplasty in treatment of stage Ⅲ Kümmell disease.MethodsA clinical data of 44 patients with stage Ⅲ Kümmell disease met the selection criteria between January 2014 and December 2017 was retrospectively analyzed. Eighteen cases were treated with short-segment bone cement-augmented fixation combined with vertebroplasty (short-segment group) and 26 cases were treated with long-segment bone cement-augmented fixation combined with vertebroplasty (long-segment group). There was no significant difference in gender, age, disease duration, fracture segment, bone mineral density (T value), Frankle grading, and preoperative pain visual analogue scale (VAS) score, Oswestry disability index (ODI), anterior edge height of injured vertebrae, kyphosis Cobb angle, and thoracolumbar kyphosis (TLK) between the two groups (P>0.05). The operation time, intraoperative blood loss, bone cement injection volume, bone cement leakage rate, VAS score, ODI, anterior edge height of injured vertebrae, kyphosis Cobb angle, and TLK were compared between the two groups.ResultsThe operation time and the intraoperative blood loss in the short- segment group were significant lower than those in the long-segment group (P<0.05). There was no significant difference in bone cement injection volume and bone cement leakage rate between the two groups (P>0.05). All patients were followed up 12-36 months, with an average of 24.4 months. The VAS score, ODI, anterior edge height of injured vertebrae, kyphosis Cobb angle, and TLK significantly improved at 1 week after operation and last follow-up in the two groups (P<0.05), there was no significant difference between the two groups (P>0.05). At last follow-up, the neurological function of the two groups recovered, and there was no significant difference in Frankle grading between the two groups (P>0.05). There were 3 cases (16.67%) of non-surgical vertebral fractures in the short-segment group and 6 cases (23.08%) in the long-segment group, showing no significant difference between the two groups (P>0.05). Bone rejection occurred in 1 case in the short-segment group, and neither internal fixation failure nor collapse of the injured vertebrae occurred during follow-up.ConclusionBoth short-segment and long-segment bone cement-augmented fixation combined with vertebroplasty can achieve good effectiveness in treatment of stage Ⅲ Kümmell disease, and can maintain the height of the injured vertebra and prevent the collapse of the injured vertebra. Compared with long-segment fixation, short-segment fixation has the advantages of shorter operation time and less intraoperative bleeding.
Objective
To investigate the effect of collagen peptides from walleye pollock skin on the microstructure of osteoporosis model in ovariectomized rats, and to explore the feasibility of preventing and treating oste- oporosis.
Methods
Sixty adult Wistar female rats, weighing (250±10) g, were randomly divided into 5 groups (12 rats each group): normal group (group A), osteoporosis model group (group B), osteoporosis model+collagen peptides from walleye pollock skin prevention group (group C), osteoporosis model+low concentration of collagen peptides from walleye pollock skin treatment group (group D), and osteoporosis model+high concentration of collagen peptides from walleye pollock skin treatment group (group E). The rats in groups B, C, D, and E were removed bilateral ovarian to establish osteoporosis model. The rats in group C were treated with stomach perfusion of the collagen peptides from walleye pollock skin (1.0 g/kg) from 4 weeks after operation for 6 weeks; and the rats in groups D and E were treated with stomach perfusion of the collagen peptides from walleye pollock skin (0.5, 1.0 g/kg respectively) at 6 weeks after operation for 6 weeks. The rats in groups A and B were given equal volume of normal saline at the same time after operation. At 24 hours after the last administration, the femoral gray value of rats in groups A and B were measured by X-ray film; HE staining was performed on the proximal tibial bone of the left side in 4 groups; the histopathological changes of the bone were observed and the trabecular number (TN), mean trabecular plate thickness (MTPT), mean trabecular plate spacing (MTPS), trabecular bone volume (TBV), mean bone cortical thickness (MBCT) were measured; immunohistochemical staining was performed to observe the expression levels of caltitonin receptor (CTR) and interleukin 1 (IL-1).
Results
The femoral gray value of group B was significantly lower than that of group A (t=45.130, P=0.000), which indicated that the ovariectomized rat model was successfully prepared. Histological observation showed that TN, MTPS, TBV, and MBCT in groups A, C, and E were significantly different from those in group B (P<0.05). The histological parameters of bone tissue in group C were significantly different from those in groups D and E (P<0.05). TN, MTPS, TBV, and MBCT in group D were significantly different from those in group A (P<0.05); only MTPS in group E was significantly different from that in group A (P<0.05). MTPS, TBV, and MBCT in group E were significantly different from those in group D (P<0.05). The immunohistochemical staining showed that the levels of CTR and IL-1 in groups A, C, D, and E were lower than those in group B, in groups C and E were lower than in group D, showing significant differences (P<0.05).
Conclusion
Collagen peptides from walleye pollock skin can improve the bone microstructure of osteoporotic rats, and its mechanism may be related to the inhibition of CTR and IL-1 expression in bone tissue, but it has not been found to prevent osteoporosis.
ObjectiveTo explore the protective effects of sodium valproic acid (VPA) on oxidative stress injury of osteoblasts induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and its mechanism. Methods Osteoblasts were isolated from the skulls of 10 newborn Sprague Dawley rats and cultured by tissue block method, and the 1st generation cells were identified by alkaline phosphatase (ALP) and alizarin red staining. The 3rd generation osteoblasts were cultured with 2-18 μmol/L CCCP for 2-18 minutes, and cell counting kit 8 (CCK-8) was used to detect the cell survival rate. An appropriate inhibitory concentration and culture time were selected for the preparation of osteoblasts oxidative stress injury model based on half maximal concentration principle. The cells were cultured with 0.2- 2.0 mmol/mL VPA for 12-72 hours, and CCK-8 was used to detect cell activity, and appropriate concentration was selected for further treatment. The 3rd generation cells were randomly divided into 4 groups, including blank control group (normal cultured cells), CCCP group (the cells were cultured according to the selected appropriate CCCP concentration and culture time), VPA+CCCP group (the cells were pretreated according to the appropriate VAP concentration and culture time, and then cultured with CCCP), VPA+CCCP+ML385 group (the cells were pretreated with 10 μmol/L Nrf inhibitor ML385 for 2 hours before VPA treatment, and other treatments were the same as VPA+CCCP group). After the above treatment was complete, the cells of 4 groups were taken to detect oxidative stress indicators [reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA)], cell apoptosis rate, ALP/alizarin red staining, and the relative expressions of osteogenic related proteins [bone morphogenetic protein 2 (BMP-2), RUNX2], anti-apoptotic family protein (Bcl2), apoptotic core protein (Cleaved-Caspase-3, Bax), channel protein (Nrf2) by Western blot. Results The osteoblasts were successfully extracted. According to the results of CCK-8 assay, the oxidative stress injury model was established by 10 μmol/L CCCP cultured for 10 minutes and 0.8 mmol/mL VPA cultured for 24 hours was selected for subsequent experiments. Compared with blank control group, the activity and mineralization capacity of osteoblasts in CCCP group decreased, the contents of ROS and MDA increased, the activity of SOD decreased, and the apoptosis rate increased. Meanwhile, the relative expressions of BMP-2, RUNX2, and Bcl2 decreased, and the relative expressions of Cleaved-Caspase-3, Nrf2, and Bax increased. The differences were significant (P<0.05). After further VPA treatment, the oxidative stress damage of osteoblasts in VPA+CCCP group was relieved, and the above indexes showed a recovery trend (P<0.05). In VPA+CCCP+ML385 group, the above indexes showed an opposite trend (P<0.05), and the protective effects of VPA were reversed. Conclusion VPA can inhibit the CCCP-induced oxidative stress injury of osteoblasts and promote osteogenesis via Keap1/Nrf2/Are pathway.
This study aimed to comprehensively evaluate the biological activity in different passage populations of mesenchymal stem cells (BMSCs) derived from bone marrow in ovariectomy osteoporotic rats (named OVX-rBMSCs), providing experimental basis for new osteoporotic drug development and research. OVX-rBMSCs were isolated and cultured in vitro by the whole bone marrow adherent screening method. The morphological observation, cell surface markers (CD29, CD45, CD90) detection, cell proliferation, induced differentiation experimental detection were performed to evaluate the biological activity of Passage 1, 2, 3, 4 populations (P1, P2, P3, P4) OVX-rBMSCs. The results showed that whole bone marrow adherent culture method isolated and differentially subcultured OVX-The morphology of P4 OVX-rBMSCs was identical fibroblast-like and had the characteristics of ultrastructure of stem cells. The CD29 positive cells rate, CD90 positive cells rate, cell proliferation index, and the osteogenic, adipogenic, chondrogenic differentiation capacities of P4 OVX-rBMSCs were significantly better than those of other populations (P < 0.05). OVX-rBMSCs purity and biological activity were gradually optimized with the passaged, and among them P4 cells were superior to all the other populations. Based on these results, we report that the P4 OVX-rBMSCs model developed in this study can be used to develop a new and effective medical method for osteoporotic drug screening.
