Mingmin Shi

Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis

The aim of this study was to perform a head‐to‐head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of ‘Cochrane Handbook for systematic Reviews of Interventions 5.0.2’, we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW.

Effects of cartilage oligomeric matrix protein on bone morphogenetic protein-2-induced differentiation of mesenchymal stem cells.

To investigate the effect of overexpression of cartilage oligomeric matrix protein (COMP) on bone morphogenetic protein‐2 (BMP‐2) induced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we used liposomes to transfect MSCs with plasmid encoding COMP and then induced the transfected MSCs to differentiate in osteogenic and chondrogenic differentiation media containing BMP‐2.

In vitro and in vivo evaluation of vancomycin-loaded PMMA cement in combination with ultrasound and microbubbles-mediated ultrasound.

Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic against Staphylococcus aureus (S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated with S. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonic S. aureus was significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders against S. aureus was significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.

Effectiveness of corticosteroid injections in adhesive capsulitis of shoulder: A meta-analysis.

Background: Primary adhesive capsulitis is mainly characterized by spontaneous chronic shoulder pain and the gradual loss of shoulder motion. The main treatment for adhesive capsulitis is a trial of conservative therapies, including analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs, and intra-articular corticosteroid injections. Previously, it was reported that intra-articular corticosteroid lead to fast pain relief and improvement of range of motion (ROM). The objective of this study was to determine whether corticosteroid injections would lead to better pain relief and greater improvement in ROM. Methods: We searched PubMed, Medline, and the Cochrane library. We included 5 articles of the 1166 articles identified. Totally injection group included 115 patients and placebo group included 110 patients. We calculated the weighted mean differences to evaluate the pain relief as the primary outcome. We determined the ROM as the secondary outcome. Study quality was evaluated using the 12-item scale. We also used the criteria of the Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of evidence. Results: In total, 5 studies were included, 4 of which were randomized clinical trials, with a sample size of 225 patients with adhesive capsulitis of the shoulders. The overall pooled data demonstrated that, compared with placebo as control treatment, intra-articular corticosteroid injections were more effective in reducing the pain score at 0 to 8 weeks, but there was no difference between the injection group and the control group at 9 to 24 weeks. Improvement of ROM in the injection group was greater than that of the control group both at 0 to 8 and 9 to 24 weeks. Conclusions: Intra-articular corticosteroid injections were more effective in pain relief in the short term, but this pain relief did not sustain in the long term. Intra-articular corticosteroid injection resulted in greater improvement in passive ROM both in the short and the long terms.

Cartilage oligomeric matrix protein gene multilayers inhibit osteogenic differentiation and promote chondrogenic differentiation of mesenchymal stem cells

There are still many challenges to acquire the optimal integration of biomedical materials with the surrounding tissues. Gene coatings on the surface of biomaterials may offer an effective approach to solve the problem. In order to investigate the gene multilayers mediated differentiation of mesenchymal stem cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were constructed in this study via the layer-by-layer self-assembly technique. Characterizations of the HA/DNA multilayered films indicated the successful build-up process. Cells could be directly transfected by gene films and a higher expression could be obtained with the increasing bilayer number. The multilayered films were stable for a long period and DNA could be easily released in an enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented significantly higher (p < 0.01) COMP expression of MSCs cultured with HA/COMP multilayered films. Compared with control groups, the osteogenic gene expression levels of MSCs with HA/COMP multilayered films were down-regulated while the chondrogenic gene expression levels were up-regulated. Similarly, the alkaline phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films were weakened while the alcian blue staining was enhanced. These results demonstrated that HA/COMP multilayered films could inhibit osteogenic differentiation and promote chondrogenic differentiation of MSCs, which might provide new insight for physiological ligament-bone healing.

Reply to Letter to the Editor: Is There Really No Benefit of Vertebroplasty for Osteoporotic Vertebral Fractures? A Meta-analysis

We appreciate the interest in our meta-analysis by the American Academy of Orthopaedic Surgeons (AAOS). Some of the points in the letter addressed limitations of our meta-analysis [7]. We included four trials which were not included in the AAOS guideline 2010 [1, 4, 6, 8], of which two were randomized controlled trials and the other two were prospective nonrandomized controlled trails. In addition to two Level I trials, there were three Level II trials in the AAOS guideline that had the same quality as these four trials. Dr. Jevsevar and his colleagues commented in their letter that “A study is not the best available evidence if there are at least two studies of higher quality that measure the same outcomes”, a point with which we concur. However, these two sham-control trials [3, 5] had some limitations: (1) Although both trials questioned the effect of PVP, there was still a trend toward a better outcome with PVP. (2) There was a large proportion of patients declining to enroll and high crossover rate raising the question of whether they had enough subjects. (3) These two trials included acute and chronic fractures; is there no difference between acute and chronic fractures? Our analysis suggested the difference might influence the results. Further, our meta-analysis added other outcomes. For example, PVP did not increase the risk of recurrent fractures and some inclusion criteria might influence the result (eg, bone edema of vertebral fracture observed on MR images). Our review attempted to include all the available prospective evidence and was comprehensive. The AAOS guideline was based on more stringent selection criteria but eliminated some evidence. In addition, one new RCT has been published comparing PVP and conservative therapy [2] that concluded PVP achieved faster pain relief. We believe the AAOS guideline on treatment of symptomatic osteoporotic spinal compression fractures will face more challenges and we look forward to the findings of further investigations.

Effect of a 12-hour natural drainage technique on decreasing blood loss after total knee arthroplasty: a case-control study

Background Different methods of drainage have been used in patients with osteoarthritis after total knee arthroplasty (TKA), but the ideal strategy is controversial. This retrospective case-control study reported a technique of 12-hour natural drainage and aimed to confirm its efficacy and safety in the treatment for blood loss following TKA. Methods There were 231 patients divided into three groups who underwent TKA from January 2014 to July 2017: 76 patients underwent 12-hour natural drainage in Group A, 80 patients underwent 4-hour clamping drainage in Group B, and 75 patients underwent continuous drainage in Group C. All perioperative clinical data were reviewed for statistical analysis. Results The drainage volume and total blood loss after TKA were significantly lower in Group A than that in the other two groups (P<0.05), and serum level of hemoglobin was significantly higher in Group A than that in the other two groups (P<0.05). The maximum of active motion of the knee was greater in Group C at 2 days (P<0.05). Significantly more patients in Group C required blood transfusions (P<0.05). No difference was found in the complication rate among the three groups. Conclusion The 12-hour natural drainage is an effective technique for reducing blood loss for patients following TKA. Compared with temporary clamping drainage and continuous negative pressure drainage, 12-hour natural drainage decreases blood loss, reduces post-operative transfusion requirements, and does not increase the risk of complications. Therefore, this technique of 12-hour natural drainage is recommended to be used in patients after TKA.

Low-intensity pulsed ultrasound enhances antibiotic release of gentamicin-loaded, self-setting calcium phosphate cement

Objective This study aimed to investigate the effect of low-intensity pulsed ultrasound on antibiotic release from gentamicin-loaded, self-setting calcium phosphate cement. Methods A gentamicin-loaded calcium phosphate cement cylinder was eluted in stimulated body fluid. Low-intensity pulsed ultrasound (46.5 kHz, 200 mW/cm2) was used to produce a sinusoidal wave in the experimental group. Non-gentamicin calcium phosphate cement was used in the control group. Results The transient concentration and cumulatively released percentage of gentamicin in the ultrasound group were higher than those in control group at every time point. The duration of gentamicin concentrations over the level of the minimum inhibitory concentration was significantly prolonged in the ultrasound group compared with the control group. Antibacterial efficacy of gentamicin in the ultrasound group was significantly better than that in the control group with the same concentration of gentamicin. Conclusion Low-intensity pulsed ultrasound enhances antibiotic release, providing sustained antibiotic release at high concentrations. This increases the antibacterial effect of gentamicin.