Prevalence of Radiographic Osteoarthritis of the Knee and Its Relationship to Self-Reported Pain

Background and Aim

Osteoarthritis (OA) of the knee is one of the most common skeletal disorders, yet little data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic OA of the knee, and its relationship to self-reported pain in a Vietnamese population.

Methods

The study was based on a sample of 170 men and 488 women aged ≥40 years who were randomly sampled from the Ho Chi Minh City (Vietnam). Radiographs of the knee were graded from 0 to 4 according to the Kellgren and Lawrence scale. Osteoarthritis was defined as being present in a knee if radiographic grades of 2 or higher were detected. Knee pain and symptoms were ascertained by direct interview using a structured questionnaire.

Results

The point prevalence of radiographic OA of the knee was 34.2%, with women having higher rate than men (35.3% vs 31.2%). The prevalence of knee OA increased with advancing age: 8% among those aged 40–49 years, 30% in those aged 50–59 years, and 61.1% in those aged ≥60 years. Greater BMI was associated with higher risk of knee OA. Self-reported knee pain was found in 35% of men and 62% of women. There was a statistically significant association between self-reported knee pain and knee OA (prevalence ratio 3.1; 95% CI 2.0 to 4.6).

Conclusions

These data indicate that approximately a third of Vietnamese men and women have radiographic OA in the knee, and that self-reported knee pain may be used as an indicator of knee osteoarthritis.     

Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis

Introduction

The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA).

Methods

We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined.

Results

2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥25 kg/m²) individuals with the variant allele of single-nucleotide polymorphism (SNP) rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P <0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P <0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013).

Conclusion

TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.     

Cruciate Ligament Reconstruction and Risk of Knee Osteoarthritis: The Association between Cruciate Ligament Injury and Post-Traumatic Osteoarthritis. A Population Based Nationwide Study in Sweden, 1987–2009

Objective

To study the association between Cruciate Ligament (CL) injury and development of post-traumatic osteoarthritis in the knee in patients treated operatively with CL reconstruction compared with patients treated non-operatively.

Design

Population based cohort study; level of evidence II-2.

Setting

Sweden, 1987–2009.

Participants

All patients aged between 15–60 years being diagnosed and registered with a CL injury in The National Swedish Patient Register between 1987 and 2009.

Main Outcome Measures

Knee osteoarthritis.

Results

A total of 64,614 patients diagnosed with CL injury during 1987 to 2009 in Sweden were included in the study. Seven percent of the patients were diagnosed with knee OA in specialized healthcare during the follow-up (mean 9 years). Stratified analysis by follow-up showed that while those with shorter follow-up had a non-significant difference in risk (0.99, 95%CI 0.90–1.09 for follow-up less than five years compared with the non-operated cohort), those with longer follow-up had an increased risk of knee OA after CL reconstruction (HR = 1.42, 95%CI 1.27–1.58 for follow-up more than ten years compared with non-operated cohort). The risk to develop OA was not affected by sex.

Conclusion

CL reconstructive surgery does not seem to have a protective effect on long term OA in either men or women.     

Adiposity and hand osteoarthritis: the Netherlands Epidemiology of Obesity study

Introduction

Obesity, usually characterized by the body mass index (BMI), is a risk factor for hand osteoarthritis (OA). We investigated whether adipose tissue and abdominal fat distribution are associated with hand OA.

Methods

The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45 to 65 years, including 5315 participants (53% women, median BMI 29.9 kg/m²). Fat percentage and fat mass (FM) (kg) were estimated using bioelectrical impedance analysis. The waist-to-hip ratio (WHR) was calculated. In 1721 participants, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (cm²) were assessed using abdominal MR imaging. Hand OA was defined according to the ACR criteria.Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of fat percentage, FM, WHR, VAT and SAT with hand OA using logistic regression analyses per standard deviation, stratified by sex and adjusted for age.

Results

Hand OA was present in 8% of men and 20% of women. Fat percentage was associated with hand OA in men (OR 1.34 (95% CI 1.11 to 1.61)) and women (OR 1.26 (1.05 to 1.51)), as was FM. WHR was associated with hand OA in men (OR 1.45 (1.13 to 1.85)), and to a lesser extent in women (OR 1.17 (1.00 to 1.36)). Subgroup analysis revealed that VAT was associated with hand OA in men (OR1.33 (1.01 to 1.75)). This association increased after additional adjustment for FM (OR 1.51 (1.13 to 2.03)).

Conclusions

Fat percentage, FM and WHR were associated with hand OA. VAT was associated with hand OA in men, suggesting involvement of visceral fat in hand OA.     

Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl/fl mice

Introduction

Previous observations implicate Indian hedgehog (Ihh) signaling in osteoarthritis (OA) development because it regulates chondrocyte hypertrophy and matrix metallopeptidase 13 (MMP-13) expression. However, there is no direct genetic evidence for the role of Ihh in OA, because mice with cartilage or other tissue-specific deletion of the Ihh gene die shortly after birth. We evaluated the role of Ihh in vivo via a Cre-loxP-mediated approach to circumvent the early death caused by Ihh deficiency.

Methods

To evaluate the role of Ihh in OA development, Ihh was specifically deleted in murine cartilage using an Ihh conditional deletion construct (Col2a1-CreER^T2; Ihh^fl/fl). The extent of cartilage degradation and OA progression after Ihh deletion was assessed by histological analysis, immunohistochemistry, real-time PCR and in vivo fluorescence molecular tomography (FMT) 2 months after OA was induced by partial medial meniscectomy. The effect of Ihh signaling on cartilage was compared between Ihh-deleted mice and their control littermates.

Results

Only mild OA changes were observed in Ihh-deleted mice, while control mice displayed significantly more cartilage damage. Typical OA markers such as type X collagen and MMP-13 were decreased in Ihh-deleted mice. In vivo FMT demonstrated decreased cathepsins and MMP activity in knee joints of animals with deletion of Ihh.

Conclusions

These findings support the protective role of Ihh deletion in surgically induced OA. Thus, our findings suggest the potential to develop new therapeutic strategies that can prevent and treat OA by inhibiting Ihh signaling in chondrocytes.     

Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

Background

Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.

Methods

We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.

Results

OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.

Conclusions

Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.     

Adults with Down syndrome have reduced cardiac response after light exercise testing

Objective

Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS.

Design

Case controlled before-after trial.

Setting

Residential centre for people with intellectual disabilities.

Participants

96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls.

Interventions

Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends.

Main outcome measure

Exercise testing

Results

At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m², p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m², p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response.

Conclusions

CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.     

MMP13 is a critical target gene during the progression of osteoarthritis

Introduction

Osteoarthritis (OA) is a degenerative joint disease affecting a large population of people. The mechanism of this highly prevalent disease is not fully understood. Currently there is no effective disease-modifying treatment for OA. The purpose of this study was two-fold: 1) to investigate the role of MMP13 in the development of OA; and 2) to evaluate the efficacy of the MMP13 inhibitor CL82198 as a pharmacologic treatment for preventing OA progression.

Methods

To investigate the role of the endogenous Mmp13 gene in OA development, tamoxifen was administered to two-week-old Col2CreER;Mmp13^fx/fx (Mmp13^Col2ER) and Cre-negative control mice for five days. OA was induced by meniscal-ligamentous injury (MLI) when the mice were 10 weeks old and MLI or sham-operated joints were harvested 4, 8, 12, or 16 weeks after surgery. To evaluate the efficacy of CL82198, MLI surgery was performed on 10-week-old wild type mice. CL82198 or saline was administered to the mice daily beginning immediately after the surgery for up to 16 weeks. The joint tissues collected from both experiments were evaluated by cartilage grading, histology/histomorphometry, immunohistochemistry (IHC), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The ability of CL82198 to inhibit MMP13 activity in vitro was confirmed by ELISA.

Results

The OA progression was decelerated in Mmp13^Col2ER mice 8, 12, and 16 weeks post-surgery. Cartilage grading by blinded observers confirmed decreased articular cartilage degeneration in Mmp13^Col2ER mice at 8, 12 and 16 weeks compared to Cre-negative mice. Histomorphometric analysis demonstrated that Mmp13^Col2ER mice had a higher articular cartilage area and thickness at 12 and 16 weeks post-surgery compared to the control mice. Results of IHC revealed greater type II collagen and proteoglycan expression in Mmp13^Col2ER mice. Chondrocyte apoptosis, as determined by TUNEL staining, was higher in control mice compared to Mmp13^Col2ER mice. CL82198 inhibited MMP13 activity in conditioned media from vehicle (> 85%) or bone morphogenetic protein 2 (BMP2)-treated (> 90%) primary murine sternal chondrocytes. Intraperitoneal injection of CL82198 decelerated MLI-induced OA progression, increased type II collagen and proteoglycan levels, and inhibited chondrocyte apoptosis compared to saline treatment as determined by OA grading, histology, histomorphometry, IHC, and TUNEL staining, respectively.

Conclusions

Mmp13 is critical for OA progression and pharmacologic inhibition of MMP13 is an effective strategy to decelerate articular cartilage loss in a murine model of injury-induced knee OA.     

Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis

Background

Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ. We therefore studied the role of endogenous BMP signaling in bleomycin induced lung fibrosis.

Methods

Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog^+/LacZ) mice by intratracheal instillation of bleomycin, or phosphate buffered saline as a control. Invasive pulmonary function tests were performed using the flexiVent® SCIREQ system. The mice were sacrificed and lung tissue was collected for analysis using histopathology, collagen quantification, immunohistochemistry and gene expression analysis.

Results

Nog^+/LacZ mice are a known model of increased BMP signaling and were partially protected from bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen content and preservation of pulmonary compliance. In bleomycin-induced lung fibrosis, TGFβ and BMP signaling followed an inverse course, with dynamic activation of TGFβ signaling and repression of BMP signaling activity.

Conclusions

Upon bleomycin exposure, active BMP signaling is decreased. Derepression of BMP signaling in Nog^+/LacZ mice protects against bleomycin-induced pulmonary fibrosis. Modulating the balance between BMP and TGFβ, in particular increasing endogenous BMP signals, may therefore be a therapeutic target in fibrotic lung disease.     

Adipokine Hormones and Hand Osteoarthritis: Radiographic Severity and Pain

Introduction

Obesity''s association with hand osteoarthritis cannot be fully explained by mechanical loading. We examined the relationship between adipokines and radiographic hand osteoarthritis severity and pain.

Methods

In a pilot study of 44 hand osteoarthritis patients (39 women and 5 men), serum adipokine concentrations and hand x-ray Kallman-scores were analyzed using linear regression models. Secondary analyses examined correlates of hand pain.

Results

The cohort had a mean age of 63.5 years for women and 72.6 for men; mean (standard deviation) Kallman-scores were 43.3(17.4) for women and 46.2(10.8) for men. Mean body-mass-index was 30 kg/m² for women and men. Mean leptin concentration was 32.2 ng/ml (women) and 18.5 ng/ml (men); mean adiponectin-total was 7.9 ng/ml (women) and 5.3 ng/ml (men); mean resistin was 7.3 ng/ml (women) and 9.4 ng/ml (men). No association was found between Kallman-scores and adipokine concentrations (R² = 0.00–0.04 unadjusted analysis, all p-values>0.22). Secondary analyses showed mean visual-analog-scale pain of 4.8(2.4) for women and 6.6(0.9) for men. Leptin, BMI, and history of coronary artery disease were found to be associated with visual-analog-scale scores for chronic hand pain (R² = 0.36 unadjusted analysis, p-values≤0.04).

Conclusion

In this pilot study, we found that adipokine serum concentrations were not associated with hand osteoarthritis radiographic severity; the most important correlates of joint damage were age and disease duration. Leptin serum concentration, BMI, and coronary artery disease were associated with the intensity of chronic hand OA pain.     

Kinematic and dynamic gait compensations resulting from knee instability in a rat model of osteoarthritis

Introduction

Osteoarthritis (OA) results in pain and disability; however, preclinical OA models often focus on joint-level changes. Gait analysis is one method used to evaluate both preclinical OA models and OA patients. The objective of this study is to describe spatiotemporal and ground reaction force changes in a rat medial meniscus transection (MMT) model of knee OA and to compare these gait measures with assays of weight bearing and tactile allodynia.

Methods

Sixteen rats were used in the study. The medial collateral ligament (MCL) was transected in twelve Lewis rats (male, 200 to 250 g); in six rats, the medial meniscus was transected, and the remaining six rats served as sham controls. The remaining four rats served as naïve controls. Gait, weight-bearing as measured by an incapacitance meter, and tactile allodynia were assessed on postoperative days 9 to 24. On day 28, knee joints were collected for histology. Cytokine concentrations in the serum were assessed with a 10-plex cytokine panel.

Results

Weight bearing was not affected by sham or MMT surgery; however, the MMT group had decreased mechanical paw-withdrawal thresholds in the operated limb relative to the contralateral limb (P = 0.017). The gait of the MMT group became increasingly asymmetric from postoperative days 9 to 24 (P = 0.020); moreover, MMT animals tended to spend more time on their contralateral limb than their operated limb while walking (P < 0.1). Ground reaction forces confirmed temporal shifts in symmetry and stance time, as the MMT group had lower vertical and propulsive ground reaction forces in their operated limb relative to the contralateral limb, naïve, and sham controls (P < 0.05). Levels of interleukin 6 in the MMT group tended to be higher than naïve controls (P = 0.072). Histology confirmed increased cartilage damage in the MMT group, consistent with OA initiation. Post hoc analysis revealed that gait symmetry, stance time imbalance, peak propulsive force, and serum interleukin 6 concentrations had significant correlations to the severity of cartilage lesion formation.

Conclusion

These data indicate significant gait compensations were present in the MMT group relative to medial collateral ligament (MCL) injury (sham) alone and naïve controls. Moreover, these data suggest that gait compensations are likely driven by meniscal instability and/or cartilage damage, and not by MCL injury alone.     

Cholesterol accumulation caused by low density lipoprotein receptor deficiency or a cholesterol-rich diet results in ectopic bone formation during experimental osteoarthritis

Introduction

Osteoarthritis (OA) is associated with the metabolic syndrome, however the underlying mechanisms remain unclear. We investigated whether low density lipoprotein (LDL) accumulation leads to increased LDL uptake by synovial macrophages and affects synovial activation, cartilage destruction and enthesophyte/osteophyte formation during experimental OA in mice.

Methods

LDL receptor deficient (LDLr^−/−) mice and wild type (WT) controls received a cholesterol-rich or control diet for 120 days. Experimental OA was induced by intra-articular injection of collagenase twelve weeks after start of the diet. OA knee joints and synovial wash-outs were analyzed for OA-related changes. Murine bone marrow derived macrophages were stimulated with oxidized LDL (oxLDL), whereupon growth factor presence and gene expression were analyzed.

Results

A cholesterol-rich diet increased apolipoprotein B (ApoB) accumulation in synovial macrophages. Although increased LDL levels did not enhance thickening of the synovial lining, S100A8 expression within macrophages was increased in WT mice after receiving a cholesterol-rich diet, reflecting an elevated activation status. Both a cholesterol-rich diet and LDLr deficiency had no effect on cartilage damage; in contrast, ectopic bone formation was increased within joint ligaments (fold increase 6.7 and 6.1, respectively). Moreover, increased osteophyte size was found at the margins of the tibial plateau (4.4 fold increase after a cholesterol-rich diet and 5.3 fold increase in LDLr^−/− mice). Synovial wash-outs of LDLr^−/− mice and supernatants of macrophages stimulated with oxLDL led to increased transforming growth factor-beta (TGF-β) signaling compared to controls.

Conclusions

LDL accumulation within synovial lining cells leads to increased activation of synovium and osteophyte formation in experimental OA. OxLDL uptake by macrophages activates growth factors of the TGF-superfamily.     

Sex Differences in Monocyte Activation in Systemic Lupus Erythematosus (SLE)

Introduction

TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis.

Methods

Human blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine.

Results

Monocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine.

Conclusion

Monocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility.     

Asymmetries and relationships between dynamic loading,muscle strength,and proprioceptive acuity at the knees in symptomatic unilateral hip osteoarthritis

Introduction

High joint loading, knee muscle weakness, and poor proprioceptive acuity are important factors that have been linked to knee osteoarthritis (OA). We previously reported that those with unilateral hip OA and bilateral asymptomatic knees are more predisposed to develop progressive OA in the contralateral knee relative to the ipsilateral knee. In the present study, we evaluate asymmetries in muscle strength and proprioception between the limbs and also evaluate relationships between these factors and joint loading that may be associated with the asymmetric evolution of OA in this group.

Methods

Sixty-two participants with symptomatic unilateral hip OA and asymptomatic knees were evaluated for muscle strength, joint position sense and dynamic joint loads at the knees. Muscle strength and proprioception were compared between limbs and correlations between these factors and dynamic joint loading were evaluated. Subgroup analyses were also performed in only those participants that fulfilled criteria for severe hip OA.

Results

Quadriceps muscle strength was 15% greater, and in the severe subgroup, proprioceptive acuity was 25% worse at the contralateral compared to ipsilateral knee of participants with unilateral hip OA (P <0.05). In addition, at the affected limb, there was an association between decreased proprioceptive acuity and higher knee loading (Spearman’s rho = 0.377, P = 0.007) and between decreased proprioceptive acuity and decreased muscle strength (Spearman’s rho = −0.328, P = 0.016).

Conclusions

This study demonstrated asymmetries in muscle strength and proprioception between the limbs in a unilateral hip OA population. Early alterations in these factors suggest their possible role in the future development of OA at the contralateral ‘OA-predisposed knee’ in this group. Furthermore, the significant association observed between proprioception, loading, and muscle strength at the affected hip limb suggests that these factors may be interrelated.     

Elevated C-reactive protein is associated with lower increase in knee muscle strength in patients with knee osteoarthritis: a 2-year follow-up study in the Amsterdam Osteoarthritis (AMS-OA) cohort

Introduction

The aim of this study was to examine the associations of elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with change in muscle strength in patients with established knee osteoarthritis (OA), at 2 years.

Methods

Data from 186 patients with knee OA were gathered at baseline and at 2-year follow-up. CRP (in milligrams per liter) and ESR (in millimeters per hour) were measured in serum from patients’ blood. Strength of quadriceps and hamstrings muscles was assessed by using an isokinetic dynamometer. The association of inflammatory markers with change in knee muscle strength was analyzed by using uni- and multi-variate linear regression models.

Results

Patients with elevated CRP values at both baseline and 2-year follow-up exhibited a lower increase in knee muscle strength for a period of 2 years (β = -0.22; P = 0.01) compared with the group with non-elevated levels at both times of assessment. The association persisted after adjustment for relevant confounders. Elevated ESR values at both times of assessment were not significantly associated with change in knee muscle strength (β = -0.05; P = 0.49).

Conclusions

Our results indicate that elevated CRP values are related to a lower gain in muscle strength over time in patients with established knee OA. Although the mechanism to explain this relationship is not fully elucidated, these results suggest inflammation as a relevant factor influencing muscle strength in this group of patients.     

Intra-articular hyaluronic acid injection versus oral non-steroidal anti-inflammatory drug for the treatment of knee osteoarthritis: a multi-center,randomized, open-label,non-inferiority trial

Introduction

While many of the commonly used conservative treatments for knee osteoarthritis (OA) have been recognized to be effective, there is still insufficient evidence available. Among the pharmacological treatments for knee OA, oral non-steroidal anti-inflammatory drugs (NSAIDs) act rapidly and are recommended for the management of OA. However, frequent and serious adverse effects of NSAIDs have been recognized. Intra-articular injections of hyaluronic acid (IA-HA) for the treatment of knee OA have been shown to reduce pain and improve joint function. However, there has been no qualified direct comparison study of the efficacy and safety between IA-HA and NSAIDs for patients with knee OA. The aim of this study was to clarify the efficacy and safety of early-phase IA-HA in comparison to those of NSAIDs for patients with knee OA.

Methods

This multicenter, randomized, open-label, parallel-group, non-inferiority comparison study with an oral NSAID involved a total of 200 patients with knee OA. An independent, computer-generated randomization sequence was used to randomly assign patients in a 1:1 ratio to NSAIDs three times per day for five weeks (n = 100) or IA-HA once a week for five weeks (n = 100). The primary endpoint was the percentage change in the patient-oriented outcome measure for knee OA, the Japanese Knee Osteoarthritis Measure (JKOM) score. All patients were questioned regarding any adverse events during treatment. The full analysis set (FAS) was used for analysis. The margin of non-inferiority was 10%.

Results

The analyses of primary endpoint included 98 patients in the IA-HA group and 86 patients in the NSAID group. The difference in the percentage changes of the JKOM score between the two intervention arms (IA-HA; -34.7% (P<0.001), NSAID; -32.2% (P<0.001)) was -2.5% (95% confidence interval (CI): -14.0 to 9.1), indicating IA-HA was not inferior to NSAID. The frequency of both withdrawal and adverse events in the IA-HA group were significantly lower than those in the NSAID group (P = 0.026 and 0.004, respectively).

Conclusions

The early efficacy of IA-HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA-HA is superior to that of NSAIDs for patients with knee OA.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR), UMIN000001026.     

Comparative,double-blind,controlled study of intra-articular hyaluronic acid (Hyalubrix?) injections versus local anesthetic in osteoarthritis of the hip

Introduction

Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix^®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.

Methods

A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne''s algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.

Results

Patients in the HA group exhibited a significantly reduced Lequesne''s algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.

Conclusions

This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.

Trial registration number

ISRCTN39397064.     

Patients' and practitioners' views of knee osteoarthritis and its management: a qualitative interview study

Purpose

To identify the views of patients and care providers regarding the management of knee osteoarthritis (OA) and to reveal potential obstacles to improving health care strategies.

Methods

We performed a qualitative study based on semi-structured interviews of a stratified sample of 81 patients (59 women) and 29 practitioners (8 women, 11 general practitioners [GPs], 6 rheumatologists, 4 orthopedic surgeons, and 8 [4 GPs] delivering alternative medicine).

Results

Two main domains of patient views were identified: one about the patient–physician relationship and the other about treatments. Patients feel that their complaints are not taken seriously. They also feel that practitioners act as technicians, paying more attention to the knee than to the individual, and they consider that not enough time is spent on information and counseling. They have negative perceptions of drugs and a feeling of medical uncertainty about OA, which leads to less compliance with treatment and a switch to alternative medicine. Patients believe that knee OA is an inevitable illness associated with age, that not much can be done to modify its evolution, that treatments are of little help, and that practitioners have not much to propose. They express unrealistic fears about the impact of knee OA on daily and social life. Practitioners'' views differ from those of patients. Physicians emphasize the difficulty in elaborating treatment strategies and the need for a tool to help in treatment choice.

Conclusions

This qualitative study suggests several ways to improve the patient–practitioner relationship and the efficacy of treatment strategies, by increasing their acceptability and compliance. Providing adapted and formalized information to patients, adopting more global assessment and therapeutic approaches, and dealing more accurately with patients'' paradoxal representation of drug therapy are main factors of improvement that should be addressed.     

OPN gene polymorphisms influence the risk of knee OA and OPN levels in synovial fluid in a Chinese population

Introduction

A body of studies suggests the role of osteopontin (OPN) in onset and development of osteoarthritis (OA), however, the association between OPN polymorphisms and OA susceptibility as well as its clinical features has not been reported.

Methods

A total of 750 patients with primary knee OA and 794 healthy volunteer were enrolled as controls. Both OA and control groups were interviewed to obtain demographic and clinical data. Three polymorphisms of OPN gene, namely, -156GG/G, -443C/T and -66T/G were determined. The levels of the full length and the thrombin-cleaved OPN in synovial fluid (SF) from OA subjects were measured.

Results

We found the polymorphisms of the -443C/T and the -66/T/G were significantly associated with the OA risk and the radiographic severity. The -443TT and -66GG showed protective effect against developing OA and were associated with lower Kellgren-Lawrence grade. Besides, the polymorphisms of -443C/T and -66T/G significantly affected the thrombin-cleaved OPN levels in SF from OA subjects. Subjects with -443TT and -66GG genotypes had lower thrombin-cleaved OPN levels in SF. The thrombin-cleaved OPN levels in SF were positively correlated to the radiographic severity of OA.

Conclusions

Our findings suggest that certain OPN gene polymorphisms may be used as molecular markers for the susceptibility and severity of OA.