C. Zeng

Effectiveness of continuous and pulsed ultrasound for the management of knee osteoarthritis: a systematic review and network meta-analysis

BACKGROUNDnTo investigate the efficacy of continuous and pulsed ultrasound (US) in the management of knee osteoarthritis (OA).nnnDESIGNnThis systematic review and network meta-analysis covered 12 trials in total. Electronic databases including MEDLINE, Embase and Cochrane Library were searched through to identify randomized controlled trials comparing the two modes of US with control interventions (sham or blank) or with each other. Bayesian network meta-analysis was used to integrate both the direct and indirect evidences on treatment effectiveness.nnnRESULTSnPulsed US (PUS) is more effective in both pain relief and function improvement when compared with the control group; but for continuous US (CUS), there is only a significant difference in pain relief in comparison with the control group. In addition, no matter in terms of pain intensity or function at the last follow-up time point, PUS always exhibited a greater probability of being the preferred mode. However, the evidence of heterogeneity and the limitation in sample size of some studies could be a potential threat to the validity of results.nnnCONCLUSIONSnOur findings indicated that PUS, with a greater probability of being the preferred mode, is more effective in both pain relief and function improvement when compared with the control group. However, CUS could only be considered as a pain relief treatment in the management of knee OA. The findings also confirmed that none of these modes is dangerous.nnnLEVEL OF EVIDENCEnLevel II, systematic review and network meta-analysis of randomized controlled trials.

Electrical stimulation for pain relief in knee osteoarthritis: systematic review and network meta-analysis

OBJECTIVEnTo investigate the efficacy of different electrical stimulation (ES) therapies in pain relief of patients with knee osteoarthritis (OA).nnnMETHODnElectronic databases including MEDLINE, Embase and Cochrane Library were searched through for randomized controlled trials (RCTs) comparing any ES therapies with control interventions (sham or blank) or with each other. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment effectiveness.nnnRESULTSn27 trials and six kinds of ES therapies, including high-frequency transcutaneous electrical nerve stimulation (h-TENS), low-frequency transcutaneous electrical nerve stimulation (l-TENS), neuromuscular electrical stimulation (NMES), interferential current (IFC), pulsed electrical stimulation (PES), and noninvasive interactive neurostimulation (NIN), were included. IFC is the only significantly effective treatment in terms of both pain intensity and change pain score at last follow-up time point when compared with the control group. Meanwhile, IFC showed the greatest probability of being the best option among the six treatment methods in pain relief. These estimates barely changed in sensitivity analysis. However, the evidence of heterogeneity and the limitation in sample size of some studies could be a potential threat to the validity of results.nnnCONCLUSIONnIFC seems to be the most promising pain relief treatment for the management of knee OA. However, evidence was limited due to the heterogeneity and small number of included trials. Although the recommendation level of the other ES therapies is either uncertain (h-TENS) or not appropriate (l-TENS, NMES, PES and NIN) for pain relief, it is likely that none of the interventions is dangerous.nnnLEVEL OF EVIDENCEnLevelⅡ, systematic review and network meta-analysis of RCTs.

Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis

ObjectivesTo investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease.MethodsAll 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods.ResultsCD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (Pxa0<xa00.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρxa0=xa0−0.848, Pxa0<xa00.01).ConclusionsCD44 in articular cartilage is associated with progressive knee OA joint damage.

Expression of synovial fluid and articular cartilage VIP in human osteoarthritic knee: a new indicator of disease severity?

OBJECTIVESnVasoactive intestinal peptide (VIP) is a molecule shared by the neuroendocrine immune network and is considered to be a potential candidate for treatment of inflammatory and autoimmune diseases. Although some recent studies demonstrate that VIP has a protective role in animal RA models, its variant in different disease grade of OA remains uncertain.nnnDESIGN AND METHODSnFifty patients with primary knee OA and ten controls with severe trauma were enrolled. Synovial fluid and articular cartilage samples were collected from specimens of total knee arthroplasty (TKA) or knee above amputation. VIP levels in these samples were assessed by ELISA and immunohistochemistry. Kellgren-Lawrence criteria and Mankin score were taken to determine the disease severity.nnnRESULTSnCompared to the controls, OA patients have lower VIP concentration in synovial fluid (659.70±112.79, 95%CI 579.01-740.38 vs 470.83±156.40, 95%CI 426.38-515.28 pg/mL, P<0.001) and articular cartilage (0.26±0.02, 95%CI 0.24-0.28 vs 0.20±0.04, 95%CI 0.18-0.21, P<0.001). Subsequent analysis show that the VIP expression in synovial fluid is markedly correlated with its OD in articular cartilage (Pearsons r=0.580, P<0.001). Furthermore, the synovial fluid and articular cartilage levels of VIP both demonstrated to be negatively correlated with severity of disease (Spearmans ρ=0.838, P<0.001; Spearmans ρ=0.814, P<0.001).nnnCONCLUSIONSnVIP in synovial fluid and articular cartilage is negatively associated with progressive joint damage in OA and is a potential indictor of disease severity.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke

BackgroundEpimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke.MethodsFifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined.ResultsSmoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover.ConclusionThe results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Usefulness of specific OA biomarkers, thrombin-cleaved osteopontin, in the posterior cruciate ligament OA rabbit model

OBJECTIVEnWe undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model.nnnMETHODnPCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay.nnnRESULTSnThe macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P < 0.001) and were elevated peaking at 24 weeks (P < 0.00001) after PCLT compared to baseline. A positive significant correlation was found between thrombin-cleaved OPN levels and the macroscopic scores (8 weeks: ρ = 0.695, P = 0.012; 16 weeks: ρ = 0.751, P = 0.005; 24 weeks: ρ = 0.660, P = 0.020). Furthermore, the same correlation was noted between thrombin-cleaved OPN levels and the histological scores (4 weeks: ρ = 0.609, P = 0.036; 8 weeks: ρ = 0.662, P = 0.019; 16 weeks: ρ = 0.827, P = 0.001; 24 weeks: ρ = 0.813, P = 0.001).nnnCONCLUSIONnIn this rabbit model of PCLT, thrombin-cleaved OPN levels in SF appear to provide a useful marker of OA disease severity and progression.

Food frequency questionnaire is an effective method for measuring micronutrient intake

We read the research of Chaganti et al.1 with great interest. We believe this is a well-conducted nested caseecontrol study which provided evidence that higher level of circulating vitamin C and E did not have a protection effect against incident radiographic knee OA, and it may be even associated with an increased risk of knee OA. Such findings were quite impressive and totally overturned our conventional notions. We sincerely appreciated the tremendous effort made by the authors for presenting this extremely valuable outcome. However, there are also some worthwhile issues need to be explored. First of all, in the third paragraph of the introduction, the authors cited reference 12 to support their point of view that food frequency questionnaires (FFQ) is a method prone to misclassification of micronutrient intake and dietary vitamin C intake data shows great variability, and plasma levels may better reflect the long term vitamin C status2. However, the study conducted by Brand et al.2 is a randomized controlled trial which assessed the effect of vitamin E for symptomatic knee osteoarthritis (OA). It is basically unrelated to this point. Maybe the authors mistook reference 12 for 13, but anyway, this judgment appeared too subjective. In addition, Tangney et al.3 (reference 13) concluded that FFQ provides reasonably valid estimates for vitamin C intakes, which covered both dietary intake and supplementation. There is actually no criticism. Furthermore, the study conducted by Tangney et al.3 did not prove that plasma levels may better reflect the long term vitamin C status as the authors claimed. On the other hand, the authors expressed their negative views again on the use of FFQ to assess dietary vitamin intake, especially for vitamin C in the third and fifth paragraphs of the discussion respectively. In the third paragraph, they stated that FFQ is a method restricted by weak correlations with objective micronutrient biomarkers and misclassification of nutrient intake, especially for vitamin C. However, according to the reference paper, Dehghan et al.4 suggested that FFQ had a moderate relationship, rather than a weak correlation, with plasma vitamin C. In addition, this study is only a systematic review and meta-analysis assessing the relationship between plasma vitamin C and vitamin C intake4, which could not reach a conclusion that blood levels can better

Comment on Laufer et al. entitled “Effectiveness of thermal and athermal short-wave diathermy for the management of knee osteoarthritis: a systematic review and meta-analysis”

We read with deep interest the article by Laufer et al.1. And we believe this is a well-conducted meta-analysis which attempted to assess the effectiveness of short-wave diathermy (SWD) treatment in the management of knee osteoarthritis (OA) and to assess whether the effects are related to the induction of a thermal effect. However, there are some worthwhile issues needs to explore. First, this systematic review and meta-analysis1 included seven studies in the final analysis. Unfortunately, in according to their specific inclusion and exclusion criteria, the authors missed one randomized controlled trial2 probably. The authors indicated that two studies were excluded due to a PEDro score of 4/10 without citing references clearly. The methodological quality of this missing study2 from our evaluation showed a good level (7/11) based on the PEDro classification scale. This was not against their pre-set minimum score of 6/10. By the way, the total points of PEDro classification scale was 11, not 10. In addition, the missing study2 reported that their short wave diathermy group followed the standardized schedules illustrated by another study3. In other words, it would also not be excluded for providing insufficient information regarding short wave diathermy. Second, one of the seven final randomized controlled trials included 46 patients with knee OA and 46 patients with hip OA3. Then 75 individuals with both hip and knee OA were included at the end of the follow-up. However, this meta-analysis was aimed to appraise the effect of SWD only for knee OA. The authors didn’t point out how to deal with these data explicitly. Third, the meta-analysis indicated that one study4 did not specify whether they used a continuous or pulsed mode nor were any other dosage parameters identified that could help them determinemean power of energy. Nevertheless, Akyol et al.4 didmention the treatment protocol in detail (continuous SWD, session the frequency of 27.12 MHz, session the duration of 15e20 min, three times weekly), even the place was unusual (the second paragraph from bottom of the discussion section). Fourth, as for the summary of treatment effects in Table IV, Rattanachaiyano et al.5 didn’t report any effect size. Furthermore, the result from this study was also out of the final meta-analysis base on the forest plots presented. From the outcomes of treatment at the end of week 3 of the original study5, standard deviation was not reported indeed. However, confidence interval also could be

[Meta-analysis of proximal femoral nail anti-rotation versus dynamic hip screw in the treatment of trochanteric fractures].

OBJECTIVEnTo compare the efficacy of proximal femoral nail anti-rotation (PFNA) versus dynamic hip screw (DHS) in the treatment of trochanteric fractures in adults.nnnMETHODSnReports of studies using randomized controlled trials (RCT) to compare PFNA with DHS in the management of intertrochanteric fractures were retrieved (up to December 5, 2011) from the Cochrane Library, MEDLINE, Elsevier, the Chinese Biomedical Database, Wanfang Data,and manually. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software Revman? 5.0 was used for data-analysis.nnnRESULTSnThirteen RCTs involving 958 cases were included in the Meta-analysis. The results showed that, compared with DHS, PFNA significantly decreased the duration of surgery [WMD = -21.38, 95%CI (-33.05,-9.26), P<0.05], intra-operative blood loss [WMD = -176.36, 95%CI (-232.20, -120.52), P<0.05], the rate of post-operative complication [RR=0.46, 95%CI (0.31, 0.70), P<0.05], the rate of post-operative fixation failure[RR=0.27, 95%CI(0.11,0.62), P<0.05].nnnCONCLUSIONnPFNA for intertrochanteric fractures is superior to DHS in regards to the mean duration of surgery, mean intra-operative blood loss, the rate of post-operative complication, and the rate of post-operative fixation failure. But there is not enough evidence to show any difference between PFNA and DHS in regards to the mean duration of hospital, the mean duration of fracture healing, the rate of post-operative fracture, the rate of post-operative coxa vara, the rate of postoperative superficial wound infection, the rate of other post-operative complications or the Harris score after surgery.