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.     

Patients with Severe Radiographic Osteoarthritis Have a Better Prognosis in Physical Functioning after Hip and Knee Replacement: A Cohort-Study

Introduction

Although Total Hip and Knee Replacements (THR/TKR) improve Health-Related Quality of Life (HRQoL) at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA) is related to the improvement in HRQoL after THR or TKR, both at the population and individual level.

Methods

In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2–5 years follow-up, using the Short-Form 36 (SF36). Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS). The radiographic severity of OA was classified according to Kellgren and Lawrence (KL) by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score≥Minimal Clinically Important Difference) between patients with mild OA (KL Grade 0–2) and severe OA (KL Grade 3+4), whilst adjusting for confounders.

Results

Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients.

Discussion

Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.     

Clinical features of symptomatic patellofemoral joint osteoarthritis

Introduction

Patellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting.

Methods

This was a population-based cross-sectional study of 745 adults aged ≥50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: ''any OA'' and ''moderate to severe OA''. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets.

Results

Distinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA.

Conclusions

Early isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.     

Genetic Influences on Hand Osteoarthritis in Finnish Women – A Replication Study of Candidate Genes

Objectives

Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs) in five genes (A2BP1, COG5, GDF5, HFE, ESR1) with hand osteoarthritis (OA), and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1) associated with OA at other joint sites were associated with hand OA among Finnish women.

Design

We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA) and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression.

Results

Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5–0.9) and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2–2.9). We found an interaction between ESR1 (rs9340799) and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3–6.5). We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1–6.1). There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3–2.5).

Conclusions

Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.     

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.     

SMAD3 Is Associated with the Total Burden of Radiographic Osteoarthritis: The Chingford Study

Background

A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.

Methods

Study participants were derived from the Chingford study. Kellgren-Lawrence (KL) grades and the individual features of osteophytes and joint space narrowing (JSN) were scored from radiographs of hands, knees, hips, and lumbar spines. The total KL score, osteophyte score, and JSN score were calculated and used as indicators of the total burden of radiographic OA. Forty-one common SNPs within SMAD3 were genotyped using the Illumina HumanHap610Q array. Linear regression modelling was used to test the association between the total KL score, osteophyte score, and JSN score and each of the 41 SNPs, with adjustment for patient age and BMI. Permutation testing was used to control the false positive rate.

Results

A total of 609 individuals were included in the analysis. All were Caucasian females with a mean age of 60.9±5.8. We found that rs3825977, with a minor allele (T) frequency of 20%, in the last intron of SMAD3, was significantly associated with total KL score (β = 0.14, P_permutation = 0.002). This association was stronger for the total JSN score (β = 0.19, P_permutation = 0.002) than for total osteophyte score (β = 0.11, P_permutation = 0.02). The T allele is associated with a 1.47-fold increased odds for people with 5 or more joints to be affected by radiographic OA (P_permutation = 0.046).

Conclusion

We found that SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association.     

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.     

Association of a BMP5 microsatellite with knee osteoarthritis: case-control study

Introduction

We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.

Methods

OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls.

Results

Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10^-4 to 4.1 x10^-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with those previously reported for hip OA.

Conclusions

We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joints. This result also shows the interest of analysing other multiallelic polymorphisms.     

Differences in self-reported health in the Osteoarthritis Initiative (OAI) and Third National Health and Nutrition Examination Survey (NHANES-III)

Objective

To assess self-reported health status (SRHS) in two cohorts of participants with radiographic knee osteoarthritis (OA) and examine the extent that differences in SRHS are due to study design.

Method

We used data from the Third National Health and Nutritional Examination Survey (NHANES-III; population-based national survey) and the Osteoarthritis Initiative (OAI; prospective cohort study). Inclusion criteria for this analysis were age 60–79 and presence of radiographic knee OA. SRHS, elicited as a five-item domain (excellent, very good, good, fair, poor), was analyzed by dichotomizing the general health status measure as “fair/poor” versus all other states. We estimated the proportion of participants in fair/poor health from each study. Propensity score methodology was used to adjust for the differences in sampling strategies between the two studies.

Results

Thirty-four percent (N = 1,608) of OAI and 29% (N = 756) of NHANES-III participants satisfied inclusion criteria. The proportion in fair/poor health was higher in NHANES-III (28%) than in OAI (5%). After adjusting for the propensity score, the proportion in fair/poor health was four times higher in NHANES-III than in OAI.

Conclusion

SRHS was substantially better in OAI than in NHANES-III. Self-selection bias may contribute to overestimation of SRHS in prospective cohort studies such as OAI.     

Simple Scoring System and Artificial Neural Network for Knee Osteoarthritis Risk Prediction: A Cross-Sectional Study

Background

Knee osteoarthritis (OA) is the most common joint disease of adults worldwide. Since the treatments for advanced radiographic knee OA are limited, clinicians face a significant challenge of identifying patients who are at high risk of OA in a timely and appropriate way. Therefore, we developed a simple self-assessment scoring system and an improved artificial neural network (ANN) model for knee OA.

Methods

The Fifth Korea National Health and Nutrition Examination Surveys (KNHANES V-1) data were used to develop a scoring system and ANN for radiographic knee OA. A logistic regression analysis was used to determine the predictors of the scoring system. The ANN was constructed using 1777 participants and validated internally on 888 participants in the KNHANES V-1. The predictors of the scoring system were selected as the inputs of the ANN. External validation was performed using 4731 participants in the Osteoarthritis Initiative (OAI). Area under the curve (AUC) of the receiver operating characteristic was calculated to compare the prediction models.

Results

The scoring system and ANN were built using the independent predictors including sex, age, body mass index, educational status, hypertension, moderate physical activity, and knee pain. In the internal validation, both scoring system and ANN predicted radiographic knee OA (AUC 0.73 versus 0.81, p<0.001) and symptomatic knee OA (AUC 0.88 versus 0.94, p<0.001) with good discriminative ability. In the external validation, both scoring system and ANN showed lower discriminative ability in predicting radiographic knee OA (AUC 0.62 versus 0.67, p<0.001) and symptomatic knee OA (AUC 0.70 versus 0.76, p<0.001).

Conclusions

The self-assessment scoring system may be useful for identifying the adults at high risk for knee OA. The performance of the scoring system is improved significantly by the ANN. We provided an ANN calculator to simply predict the knee OA risk.     

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.     

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.     

Infrapatellar fat pad in the knee: is local fat good or bad for knee osteoarthritis?

Introduction

Recent studies regarding the infrapatellar fat pad (IPFP) mainly focus on the roles of the cells derived from the IPFP. There have been few clinical or epidemiological studies reporting on the association between the IPFP and knee osteoarthritis (OA). Our objective is to generate hypotheses regarding the associations between IPFP maximum area and knee OA measures in older adults.

Methods

A total of 977 subjects between 50 and 80 years of age (mean, 62.4 years) participated in the study. Radiographic knee osteophyte and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was utilized to assess IPFP maximum area, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire.

Results

After adjustment for potential confounders, IPFP maximum area was significantly associated with joint space narrowing (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.62 to 0.91 (medial), 0.77, 95% CI: 0.62 to 0.96 (lateral)) and medial osteophytes (OR: 0.52, 95% CI: 0.35 to 0.76), knee tibial and patellar cartilage volume (β: 56.9 to 164.9 mm³/cm², all P <0.001), tibial cartilage defects (OR: 0.58, 95% CI: 0.41 to 0.81 (medial), 0.53, 95% CI: 0.40-0.71 (lateral)), any BMLs (OR: 0.77, 95% CI: 0.63 to 0.94), and knee pain on a flat surface (OR: 0.79, 95% CI: 0.63 to 0.98). IPFP maximum area was negatively, but not significantly, associated with femoral cartilage defects, lateral tibiofemoral BMLs, and total knee pain or other knee pain subscales.

Conclusion

IPFP maximum area is beneficially associated with radiographic OA, MRI structural pathology and knee pain on a flat surface suggesting a protective role for IPFP possibly through shock absorption. Consequently, we must pay special attention to IPFP in the clinical settings, avoiding resection of normal IPFP in knee surgery.     

Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer

Background

Colorectal cancer (CRC) risk is partly conferred by common, low-penetrance single nucleotide polymorphisms (SNPs). We hypothesized that these SNPs are associated with outcomes in metastatic CRC.

Methods

Six candidate SNPs from 8q24, 10p14, 15q13, 18q21 were investigated for their association with response rate (RR), time to progression (TTP) and overall survival (OS) among 524 patients treated on a phase III clinical trial of first-line chemotherapy for metastatic CRC.

Results

rs10795668 was weakly associated with TTP (p = 0.02), but not RR or OS. No other SNPs carried statistically significant HRs for any of the primary outcomes (RR, TTP or OS).

Conclusion

Common low-penetrance CRC risk SNPs were not associated with outcomes among patients with metastatic CRC.     

Biomechanical factors and physical examination findings in osteoarthritis of the knee: associations with tissue abnormalities assessed by conventional radiography and high-resolution 3.0 Tesla magnetic resonance imaging

Introduction

We aimed to explore the associations between knee osteoarthritis (OA)-related tissue abnormalities assessed by conventional radiography (CR) and by high-resolution 3.0 Tesla magnetic resonance imaging (MRI), as well as biomechanical factors and findings from physical examination in patients with knee OA.

Methods

This was an explorative cross-sectional study of 105 patients with knee OA. Index knees were imaged using CR and MRI. Multiple features from CR and MRI (cartilage, osteophytes, bone marrow lesions, effusion and synovitis) were related to biomechanical factors (quadriceps and hamstrings muscle strength, proprioceptive accuracy and varus-valgus laxity) and physical examination findings (bony tenderness, crepitus, bony enlargement and palpable warmth), using multivariable regression analyses.

Results

Quadriceps weakness was associated with cartilage integrity, effusion, synovitis (all detected by MRI) and CR-detected joint space narrowing. Knee joint laxity was associated with MRI-detected cartilage integrity, CR-detected joint space narrowing and osteophyte formation. Multiple tissue abnormalities including cartilage integrity, osteophytes and effusion, but only those detected by MRI, were found to be associated with physical examination findings such as crepitus.

Conclusion

We observed clinically relevant findings, including a significant association between quadriceps weakness and both effusion and synovitis, detected by MRI. Inflammation was detected in over one-third of the participants, emphasizing the inflammatory component of OA and a possible important role for anti-inflammatory therapies in knee OA. In general, OA-related tissue abnormalities of the knee, even those detected by MRI, were found to be discordant with biomechanical and physical examination features.     

Development and Validation of a Questionnaire Assessing Fears and Beliefs of Patients with Knee Osteoarthritis: The Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ)

Objective

We aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA.

Design

We sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique.

Results

137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend.

Conclusions

We propose an 11-item questionnaire assessing patients'' fears and beliefs concerning knee OA with good content and construct validity.     

Periarticular Osteophytes as an Appendicular Joint Stress Marker (JSM): Analysis in a Contemporary Japanese Skeletal Collection

Objective

The aim of this study was to investigate the possibility that periarticular osteophytes plays a role as a appendicular joint stress marker (JSM) which reflects the biomechanical stresses on individuals and populations.

Methods

A total of 366 contemporary Japanese skeletons (231 males, 135 females) were examined closely to evaluate the periarticular osteophytes of six major joints, the shoulder, elbow, wrist, hip, knee, and ankle and osteophyte scores (OS) were determined using an original grading system. These scores were aggregated and analyzed statistically from some viewpoints.

Results

All of the OS for the respective joints were correlated logarithmically with the age-at-death of the individuals. For 70 individuals, in whom both sides of all six joints were evaluated without missing values, the age-standardized OS were calculated. A right side dominancy was recognized in the joints of the upper extremities, shoulder and wrist joints, and the bilateral correlations were large in the three joints on the lower extremity. For the shoulder joint and the hip joint, it was inferred by some distinctions that systemic factors were relatively large. All of these six joints could be assorted by the extent of systemic and local factors on osteophytes formation. Moreover, when the age-standardized OS of all the joints was summed up, some individuals had significantly high total scores, and others had significantly low total scores; namely, all of the individuals varied greatly in their systemic predisposition for osteophytes formation.

Conclusions

This study demonstrated the significance of periarticular osteophytes; the evaluating system for OS could be used to detect differences among joints and individuals. Periarticular osteophytes could be applied as an appendicular joint stress marker (JSM); by applying OS evaluating system for skeletal populations, intra-skeletal and inter-skeletal variations in biomechanical stresses throughout the lives could be clarified.     

Linked decreases in liver kinase B1 and AMP-activated protein kinase activity modulate matrix catabolic responses to biomechanical injury in chondrocytes

Introduction

AMP-activated protein kinase (AMPK) maintains cultured chondrocyte matrix homeostasis in response to inflammatory cytokines. AMPK activity is decreased in human knee osteoarthritis (OA) chondrocytes. Liver kinase B1 (LKB1) is one of the upstream activators of AMPK. Hence, we examined the relationship between LKB1 and AMPK activity in OA and aging cartilages, and in chondrocytes subjected to inflammatory cytokine treatment and biomechanical compression injury, and performed translational studies of AMPK pharmacologic activation.

Methods

We assessed activity (phosphorylation) of LKB1 and AMPKα in mouse knee OA cartilage, in aging mouse cartilage (6 to 24 months), and in chondrocytes after mechanical injury by dynamic compression, via immunohistochemistry or western blot. We knocked down LKB1 by siRNA transfection. Nitric oxide, matrix metalloproteinase (MMP)-3, and MMP-13 release were measured by Griess reaction and ELISA, respectively.

Results

Knockdown of LKB1 attenuated chondrocyte AMPK activity, and increased nitric oxide, MMP-3 and MMP-13 release (P <0.05) in response to IL-1β and TNFα. Both LKB1 and AMPK activity were decreased in mouse knee OA and aged knee cartilage, and in bovine chondrocytes after biomechanical injury. Pretreatment of bovine chondrocytes with AMPK activators AICAR and A-769662 inhibited both AMPKα dephosphorylation and catabolic responses after biomechanical injury.

Conclusion

LKB1 is required for chondrocyte AMPK activity, thereby inhibiting matrix catabolic responses to inflammatory cytokines. Concurrent loss of LKB1 and AMPK activity in articular chondrocytes is associated with OA, aging and biomechanical injury. Conversely, pharmacologic AMPK activation attenuates catabolic responses to biomechanical injury, suggesting a potentially novel approach to inhibit OA development and progression.     

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.