Assessment of pulsed electromagnetic field therapy with Serum YKL-40 and ultrasonography in patients with knee osteoarthritis.

AIM: The use of biomarkers of osteoarthritis (OA) have potential for early diagnosis, evaluation of disease severity and monitoring treatment. Serum and synovial fluid YKL-40 levels are increased in severe knee OA. Pulsed electromagnetic field (PEMF) therapy is a novel treatment method for OA. However, studies evaluating the PEMF therapy in treatment of knee OA revealed conflicting results. This study was conducted to objectively assess the effect of PEMF therapy in patients with knee OA, by using ultrasonographic measurements and a novel biomarker, YKL-40. METHODS: Forty patients were randomized into two treatment groups. Both groups received conventional physical therapy, while Group 1 received additional PEMF therapy. The patients were asked to rate their pain on a visual analogue scale (VAS) and complete a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Serum YKL-40 levels were measured, and knee effusion and cartilage degeneration level were evaluated with ultrasonography before and after treatment. RESULTS: Pre-treatment YKL-40 level was correlated with WOMAC pain subscale (P = 0.032, r = 0.339). VAS and WOMAC scores significantly improved in both treatment groups (P < 0.05). The effusion in the right knee significantly decreased in Group 1. The change in YKL-40 level was not correlated with the change in VAS, WOMAC scores and knee effusion. CONCLUSION: This study revealed that adjuvant PEMF therapy has no additional effect on pain in patients with knee OA. Serum YKL-40 level seems to be unuseful for monitoring the treatment in knee OA.

Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review.

The identification of early biochemical predictors of osteoarthritis (OA) has been the focus of much research over the past few years. However, it still is unclear whether current biochemical markers can be used in prognostic risk assessment of OA. The aim of this systematic review is to evaluate the possible prognostic application of blood and urinary biochemical markers of knee and hip OA. Abstract and full text selection was done by two independent reviewers. A total of 25 relevant publications including 37 biochemical markers of bone and cartilage turnover and inflammation associated with some aspects of OA were reviewed. Most of those biomarkers were studied only once or twice. Due to heterogeneity of both OA-phenotype and determinant among the publications, meta-analysis of the studied biochemical markers was not possible. There was strong evidence for urinary C-terminal telopeptide of collagen type II (uCTX-II) as a prognostic marker for knee OA progression and serum cartilage oligomeric protein (COMP) level as prognostic marker for incidence of knee and hip OA. Evidence for prognostic value of C-reactive protein is still inconclusive. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.

Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency.

OBJECTIVES: Opioid-induced androgen deficiency (OPIAD) affects patients treated with opioid analgesics. The norepinephrine reuptake inhibitor (NRI) and µ-opioid receptor (MOR) agonist activities of tapentadol may result in tapentadol having less effect on serum androgen concentrations than analgesics acting through the MOR alone, such as morphine and oxycodone. The objectives of this publication are to 1) evaluate the effects of tapentadol (NUCYNTA and NUCYNTA extended release [ER]) on sex hormone concentrations in healthy male volunteers (vs placebo and morphine) and patients with osteoarthritis (vs placebo and oxycodone), and 2) present a mechanistic hypothesis explaining how the combined MOR agonist and NRI activities of tapentadol may result in less impact on androgen concentrations. METHODS: Three clinical studies were conducted: study 1 (single-dose comparison study vs morphine in healthy volunteers), study 2 (single-dose-escalation study in healthy volunteers without an active comparator), and study 3 (multiple-dose study vs oxycodone in patients with osteoarthritis). Studies 1 and 2 were conducted at medical research centers in Germany and the United Kingdom; study 3 was conducted at primary and secondary care centers and medical research centers in the United States. All three studies were randomized, double blind, and placebo controlled. Concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH; study 3 only) were evaluated at 6 and 24 hours postdose in studies 1 and 2, respectively, and at varying time points postdose in study 3. RESULTS: In study 1, mean serum total testosterone concentrations in healthy male volunteers were similar at baseline for all treatment periods; 6 hours after dosing, mean concentrations were comparable between placebo (8.6 nmol/L) and tapentadol immediate release (IR; 43 mg, 8.8 nmol/L; 86 mg, 9.3 nmol/L), but were lower following administration of morphine IR 30 mg (5.4 nmol/L). In study 2, there were no or minimal changes in testosterone in the therapeutic dose range with tapentadol IR (75-100 mg), and there was a modest decrease that appeared to level off in the supratherapeutic range (125-175 mg); mean testosterone and LH concentrations with all doses remained within normal ranges (testosterone, 4.56-28.2 nmol/L; LH, 2.9-4.6 U/L). In study 3, the decrease in the mean [standard deviation] testosterone concentration from baseline to endpoint for male patients receiving tapentadol ER (100 mg, -1.9 [0.71] nmol/L; 200 mg, -2.1 [0.93] nmol/L) was numerically smaller compared to oxycodone CR (20 mg, -2.7 [0.93] nmol/L), but higher compared to placebo (-0.3 [1.62] nmol/L). CONCLUSIONS: These results suggest that tapentadol, which has combined MOR and NRI activities, may have a lower impact on sex hormone concentrations than pure opioid analgesics, such as morphine or oxycodone. The data and mechanistic rationale presented herein provide a justification for conducting additional hypothesis testing studies, and are not intended to be used as a basis for clinical decision making. Future studies may help elucidate whether the observed trends are clinically significant and would translate into a reduced incidence of OPIAD.

Plasma adipokine levels and their association with overall burden of painful joints among individuals with hip and knee osteoarthritis.

OBJECTIVE: To investigate the association between plasma adipokine levels and the burden of painful joints among individuals with hip and knee osteoarthritis (OA). METHODS: Adipokines (leptin, adiponectin, adipsin, resistin) were determined by ELISA (n = 78). Individuals reported painful joints on a homunculus. Associations were examined by sex-stratified Poisson analyses. RESULTS: Adjusted for age, body mass index, and hip/knee OA, higher leptin and adiponectin and lower adipsin levels were associated with greater painful joint burden (i.e., counts) among women (p < 0.01). Among men, higher resistin levels were associated with lower counts (p = 0.03). CONCLUSION: Findings support the likelihood of a systemic-dependent sex-specific pain burden among individuals with OA.

Assessment of knee function and biochemical parameters of articular fluid and peripheral blood in gonarthrosis patients following intra-articular administration of hyaluronic acid.

BACKGROUND: The development of gonarthrosis (GA) involves inflammatory processes; the role of reactive oxygen species (ROS) is being increasingly mentioned. The body is protected from oxidative damage by the antioxidative barrier with fundamental role being played by antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT) and enzymes involved in glutathione transformations, particularly glutathione peroxidase (GPx). The methods of treatment of cartilage depend on the disease advancement, patient's reactions to pain, disease-related impairment in daily activities, as well as the age and overall health of the patient. Viscosupplementation involving intra-articular injection of agents that increase the viscosity of the articular fluid is aimed at reducing the friction between articular surfaces and thus at reducing pain and excessive wear of the remaining articular cartilage. The objective of the study was to examine whether intra-articular administration of a hyaluronic acid agent has any effect on the function of the knee and on the selected biochemical parameters of the articular fluid and blood in gonarthrosis, as well as to demonstrate of correlation or no correlation between the effects of viscosupplementation and administration of hyaluronic acid into a knee containing articular fluid or a "dry" knee. MATERIAL AND METHODS: The study group consisted of 22 gonarthrosis patients who received hyaluronic acid into the knee containing the articular fluid (group PS) as per the study protocol and 27 gonarthrosis patients who received hyaluronic acid into the "dry" knee (group PPI). The study lasted about 40 weeks and involved 10 visits at the study site. Hyaluronic acid was administered intra-articularly upon the first three visits held in one-week intervals, as well as on visit 4 (12 weeks after visit 3). The study knee was assessed clinically at all visits using the osteoarthritis WOMAC scale, visual assessment scale (0-10) for the assessment of pain intensity and HHS questionnaire for clinical assessment of the knee function. Blood for study-related analyses was collected at study start and 12 weeks after administration of the third dose of hyaluronic acid. The activity of superoxide dismutase (SOD) within the articular fluid and plasma and plasma levels of MDA were determined. Results Worse WOMAC-scale quality of life was observed in patients with osteoarthrosis and "dry" knee, mostly due to higher joint stiffness. Following viscosupplementation treatment, improvement in all tested WOMAC scores was observed in both groups, and no significant differences between groups was observed. The SOD activity and the MDA levels in plasma did not differ between the study groups, both before the study and after viscosupplementation. No statistically significant changes were observed in the biochemical parameters following viscosupplementation in both groups other than for reduced articular fluid MDA levels in the PS group. CONCLUSIONS: Viscosupplementation with hyaluronic acid administration is an effective method of conservative treatment in patients with gonarthrosis. Its beneficial effect consists mostly of pain reduction and knee function improvement both in patients with articular fluid present within the knee joints as in patients with "dry" knee joints.

Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study.

OBJECTIVE: To investigate the use of tanezumab, a humanized monoclonal antibody that inhibits nerve growth factor, for the treatment of moderate to severe osteoarthritis in Japanese patients. DESIGN: Patients received tanezumab 10, 25, 50, 100, 200 µg/kg, or placebo and were followed for 92 or 120 days. Endpoints included the incidence of adverse events (AEs) and the change from baseline to week 8 in pain intensity and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales. RESULTS: Patients (n = 83) were 69% female, age 44-73 years, with a Kellgren-Lawrence X-ray grade of 2-4. At week 8, compared with placebo, tanezumab 25, 100, and 200 µg/kg improved index knee pain during walking (-18.5, -14.3, and -27.6, respectively), index knee pain in the past 24 h (-19.1, -14.6, and -24.2, respectively), current index knee pain (-16.5, -10.9, and -22.8, respectively), and the WOMAC pain (-11.5, -9.6, and -18.8, respectively), physical function (-8.7, -9.5, and -17.6, respectively), and stiffness (-20.4, -11.2, and -10.2, respectively) subscales. Overall, seven patients reported AEs of abnormal peripheral sensation: allodynia (two in the tanezumab 200 µg/kg group); paresthesia (two in the tanezumab 200 µg/kg group), dysesthesia (one in the tanezumab 200 µg/kg group); thermohypoesthesia (one in the tanezumab 100 µg/kg group), and decreased vibratory sense (one in the placebo group). All of these AEs were mild to moderate in severity and transient in nature. CONCLUSIONS: Tanezumab was safe and generally well tolerated and may improve pain symptoms in Japanese patients with moderate to severe osteoarthritis of the knee. CLINICALTRIALS.GOV IDENTIFIER: NCT00669409.

Use of the blood transfusion service in total knee replacement arthroplasty. The cost implications.

In view of the rising costs of blood transfusion and reports of inappropriate transfusions an audit of the local practice was organised. The aim was to investigate whether blood transfusion in primary unilateral Total Knee replacement Arthroplasty (TKA) operations was being used inappropriately locally, the resultant cost implications and suggest ways of reducing these. A 1-year retrospective survey of blood transfusion practice was conducted for all consecutive elective, primary, unilateral TKA operations at a District-General Hospital. 169 operations were performed and 58 (34%) patients were transfused. A retrospective Haemoglobin concentration (Hb) analysis was performed for all the transfused patients to identify the number of transfusions that satisfied the suggested transfusion criteria of a threshold Hb of 8 g/dl and when indicated, a minimum transfusion of 2 units. Complete transfusion data was available on 49/58 (84%) patients transfused. When applying the above criteria to this sample, the potential annual saving for the department was estimated at approximately 8000 pounds Sterling; only 9 of these patients were deemed to be appropriately transfused.