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.     

Association between several clinical and radiological determinants with long-term clinical progression and good prognosis of lower limb osteoarthritis

Objective

To investigate the factors associated with clinical progression and good prognosis in patients with lower limb osteoarthritis (OA).

Methods

Cohort study of 145 patients with OA in either knee, hip or both. Progression was defined as 1) new joint prosthesis or 2) increase in WOMAC pain or function score during 6-years follow-up above pre-defined thresholds. Patients without progression with decrease in WOMAC pain or function score lower than pre-defined thresholds were categorized as good prognosis. Relative risks (RRs) for progression and good prognosis with 95% confidence interval (95% CI) were calculated by comparing the highest tertile or category to the lowest tertile, for baseline determinants (age, sex, BMI, WOMAC pain and function scores, pain on physical examination, total range of motion (tROM), osteophytes and joint space narrowing (JSN) scores), and for worsening in WOMAC pain and function score in 1-year. Adjustments were performed for age, sex, and BMI.

Results

Follow-up was completed by 117 patients (81%, median age 60 years, 84% female); 62 (53%) and 31 patients (26%) showed progression and good prognosis, respectively. These following determinants were associated with progression: pain on physical examination (RR 1.2 (1.0 to 1.5)); tROM (1.4 (1.1 to 1.6); worsening in WOMAC pain (1.9 (1.2 to 2.3)); worsening in WOMAC function (2.4 (1.7 to 2.6)); osteophytes 1.5 (1.0 to 1.8); and JSN scores (2.3 (1.5 to 2.7)). Worsening in WOMAC pain (0.1 (0.1 to 0.8)) and function score (0.1 (0.1 to 0.7)), were negatively associated with good prognosis.

Conclusion

Worsening of self-reported pain and function in one year, limited tROM and higher osteophytes and JSN scores were associated with clinical progression. Worsening in WOMAC pain and function score in 1- year were associated with lower risk to have good prognosis. These findings help to inform patients with regard to their OA prognosis.     

Do early life factors affect the development of knee osteoarthritis in later life: a narrative review

Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life.     

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

Introduction  

Subchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA.     

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-derived mesenchymal stromal cell product for treatment of knee osteoarthritis: a first-in-human study with evaluation of the potency marker

Background aimsInfrapatellar fat pad-derived mesenchymal stromal cells (IFP-MSCs) have not yet been used in a human clinical trial. In this open-label phase 1 study, patients with knee osteoarthritis (OA) received a single intra-articular injection of autologous IFP-MSCs. Safety was assessed through physical examination of the knee joint, vital signs, laboratory tests and adverse events. Efficacy was evaluated with regard to pain and function using questionnaires, x-ray and magnetic resonance imaging (MRI). Indoleamine-2,3-dioxygenase (IDO) expression in IFP-MSCs primed with interferon gamma was used as an in vitro potency measurement in investigating the correlations of clinical outcomes.MethodsTwelve patients with symptomatic knee OA were recruited. IFP adipose tissue was harvested from each patient's knee through surgical excision for IFP-MSC manufacturing. Cryopreserved IFP-MSCs (5 × 10⁷ cells) were injected into the knee joint immediately after thawing.ResultsNo significant adverse events were observed. Patients who received IFP-MSCs exhibited clinically significant pain and functional improvement at 48-week follow-up. The MRI Osteoarthritis Knee Score average was also significantly reduced from 100.2 before injection to 85.0 at 48 weeks after injection. The IDO expression of the primed IFP-MSCs of the 12 patients was correlated with clinical outcomes after injection.ConclusionsA single intra-articular injection of IFP-MSCs appears to be a safe therapy for treating knee OA and may improve disease symptoms. IDO measurement of primed IFP-MSCs has potential as a potency marker of MSC products for immunomodulatory therapy.     

Obesity profiles with knee osteoarthritis: correlation with pain, disability, disease progression

Objectives: To identify the prevalence of overweight among community‐dwelling adults diagnosed as having knee osteoarthritis (OA) and the relationship between the weight status of these individuals, selected disease‐related outcomes, and disease progression. Research Methods and Procedures: The BMIs of 82 women and 18 men with unilateral or bilateral knee OA were examined on a single occasion along with data on physical comorbidities, pain, and function and subjected to correlation analyses. BMIs from two additional samples, one that included 16 women with and without knee OA and one that included 24 women and 6 men with knee joint OA that required surgery for the subsequent onset of hip OA, were also assessed. Results: At least 80% of all present cohorts were overweight or obese. Those with higher BMIs reported more pain than those with lower BMIs (p < 0.05) and pain was related to perceived physical exertion (p < 0.05). Body mass indices were not significantly correlated with generic gait measures, but an inverse trend toward the time spent in the gait cycle (r = ?0.63; p = 0.097) that may impact the disease process was identified. Those with comorbidities had the same body mass, on average, as those with no comorbidities, and those with bilateral disease were heavier than those with unilateral disease. Discussion: A high body mass is present in most adults with knee OA. Moreover, being overweight may affect knee joint impact rates and pain incrementally. Having high body weights may heighten the risk for bilateral knee joint, as well as hip joint, OA.     

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis

Introduction

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.

Methods

Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).

Results

sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.

Conclusions

These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.     

Association between Dietary Magnesium Intake and Radiographic Knee Osteoarthritis

ObjectiveTo examine the cross-sectional associations between dietary magnesium (Mg) intake and radiographic knee osteoarthritis (OA), joint space narrowing (JSN), and osteophytes (OST) respectively.MethodsA total of 1626 subjects were included in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade 2 in at least one leg. JSN and OST were assessed individually according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the various associations after adjusting for potentially confounding factors.ResultsThe relative odds of radiographic knee OA were decreased by 0.53 times in the third quintile of Mg intake [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.28–1.01], 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.17–0.94) and 0.34 times in the fifth quintile (OR 0.34, 95% CI 0.11–1.00) compared with those in the lowest quintile, while P for trend was 0.111. The relative odds of JSN were decreased by 0.49 times in the third quintile of Mg intake (OR 0.49, 95% CI 0.28–0.88) and 0.37 times in the fifth quintile (OR 0.37, 95% CI 0.14–0.98) compared with those in the lowest quintile, while P for trend was 0.088. There was no significant relationship between dietary Mg intake and the presence of OST.ConclusionsThe findings of this cross-sectional study indicate that Mg intake is inversely associated with radiographic knee OA and JSN. It supports potential role of Mg in the prevention of knee OA.

Level of Evidence

LevelIII, cross-sectional study.     

Gait and neuromuscular pattern changes are associated with differences in knee osteoarthritis severity levels

Knee osteoarthritis (OA) is a multifactoral, progressive disease process of the musculoskeletal system. Mechanical factors have been implicated in the progression of knee OA, but the role of altered joint mechanics and neuromuscular control strategies in progressive mechanisms of the disease have not been fully explored. Previous biomechanical studies of knee OA have characterized changes in joint kinematics and kinetics with the disease, but it has been difficult to determine if these biomechanical changes are involved in the development of disease, are in response to degenerative changes in the joint, or are compensatory mechanisms in response to these degenerative changes or other related factors as joint pain. The goal of this study was to explore the association between biomechanical changes and knee OA severity in an effort to understand the changing role of biomechanical factors in the progression of knee OA. A three-group cross-sectional model was used that included asymptomatic subjects, subjects clinically diagnosed with moderate knee OA and severe knee OA subjects just prior to total joint replacement surgery. Principal component analysis and discriminant analysis were used to determine the combinations of electromyography, kinematic and kinetic waveform pattern changes at the knee, hip and ankle joints during gait that optimally separated the three levels of severity. Different biomechanical mechanisms were important in discriminating between severity levels. Changes in knee and hip kinetic patterns and rectus femoris activation were important in separating the asymptomatic and moderate OA gait patterns. In contrast, changes in knee kinematics, hip and ankle kinetics and medial gastrocnemius activity were important in discriminating between the moderate and severe OA gait patterns.     

Changes in knee joint muscle activation patterns during walking associated with increased structural severity in knee osteoarthritis

PurposeTo determine whether alterations in knee joint muscle activation patterns during gait were related to structural severity determined by Kellgren–Lawrence (KL) radiographic grades, for those with a moderate knee OA classification.ScopeEighty-two individuals with knee OA, classified as moderate using a functional and clinical criterion were stratified on KL-grade (KL II, KL III and KL IV). Thirty-five asymptomatic individuals were matched for age and walking velocity. Lower limb motion and surface electromyograms from rectus femoris plus lateral and medial sites for the gastrocnemii, vastii and hamstring muscles were recorded during self-selected walking. Gait velocity and characteristics from sagittal plane knee angular displacement waveforms were calculated. Principal component analysis extracted amplitude and temporal features from electromyographic waveform. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05) for these features. No differences in anthropometrics, velocity, knee muscle strength and symptoms were found among the three OA groups (p > 0.05). Specific features from medial gastrocnemius, lateral hamstring and quadriceps amplitude and temporal patterns were significantly different among OA groups (p < 0.05).ConclusionsSystematic alterations in specific knee joint muscle activation patterns were associated with increasing structural severity based on KL-grades whereas other alterations were associated with the presence of OA.     

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.     

Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.Inhibitory cannabinoid 2 (CB₂) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB₂ receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB₂ receptor mRNA and protein expression in an OA pain model. The expression of CB₂ receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB₂ receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB₂ receptor mRNA and macroscopic knee chondropathy.These data provide new clinically relevant evidence that joint damage and spinal CB₂ receptor expression are correlated combined with converging pre-clinical evidence that activation of CB₂ receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB₂ receptors may have therapeutic potential for treating OA pain.     

Vitamin D attenuates inflammation,fatty infiltration,and cartilage loss in the knee of hyperlipidemic microswine

BackgroundOsteoarthritis (OA) of the knee joint is a degenerative process resulting in cartilage loss. Recent evidence suggests that OA is not merely a disease of cartilage but a disease of the entire knee joint and that inflammation may play an important role. OA has been associated with vitamin D deficiency. Vitamin D as an immunomodulator and anti-inflammatory agent may attenuate inflammation in the knee. The aim of this study was to assess the anti-inflammatory effect of vitamin D on inflammation in the knee.MethodsThis study was conducted with 13 microswine on a high cholesterol diet categorized into three groups of vitamin D-deficient, vitamin D-sufficient, and vitamin D supplementation. After 1 year, microswine were killed, and their knee joint tissues were harvested. Histological and immunofluorescence studies were carried out on the tissue specimens to evaluate the effect of vitamin D status.ResultsHistological and immunofluorescence studies of the knee joint tissues showed (1) increased inflammation in the knee joint tissues, (2) fatty infiltration in quadriceps muscle, patellar tendon, and collateral ligaments, and (3) chondrocyte clustering in the vitamin D-deficient and vitamin D-sufficient groups compared with the vitamin D supplementation group. Architectural distortion of the quadriceps muscle, patellar tendon, and collateral ligaments was also seen in the areas of inflammatory foci and fatty infiltration in the vitamin D-deficient group.ConclusionsDecreased inflammation and fatty infiltration in the vitamin D supplementation group suggest the potential role of vitamin D in attenuating inflammation and fatty infiltration as well as in protecting the architecture of the tissue in the knee joint.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-016-1099-6) contains supplementary material, which is available to authorized users.     

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.     

Animal models of osteoarthritis

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA - and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease - is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.     

Beer and wine consumption and risk of knee or hip osteoarthritis: a case control study

IntroductionThe aim of this study was to investigate the association between alcoholic and non-alcoholic beverages and knee or hip osteoarthritis (OA).MethodsWe conducted a case–control study of Caucasian men and women aged 45 to 86 years of age from Nottingham, UK. Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee or hip OA. Exposure information was sought using interview-based questionnaires and a semi-quantitative food frequency questionnaire to assess beverage consumption at ages 21 to 50 years. Odds ratios (ORs), adjusted ORs (aORs), 95% confidence intervals (CI) and P values were estimated using logistic regression models.ResultsA total of 1,001 knee OA, 993 hip OA and 933 control participants were included in the study. Increasing beer consumption was associated with an increasing risk of OA (P for trend ≤0.001). Compared to those who did not consume beer, aORs for people who consumed 20 or more servings of beer were 1.93 (95% CI 1.26 to 2.94) and 2.15 (95% CI 1.45 to 3.19) for knee OA and hip OA, respectively. In contrast, increasing levels of wine consumption were associated with decreased likelihood of knee OA (P for trend <0.001). Compared to those who did not consume wine, aOR for knee OA among those who consumed 4 to 6 glasses of wine per week and ≥7 glasses of wine per week was 0.55 (95% CI 0.34 to 0.87) and 0.48 (95% CI 0.29 to 0.80), respectively. No association was identified between non-alcoholic beverages and knee or hip OA.ConclusionsBeer consumption appears to be a risk factor for knee and hip OA whereas consumption of wine has a negative association with knee OA. The mechanism behind these findings is speculative but warrants further study.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0534-4) contains supplementary material, which is available to authorized users.     

Genetic,clinical and radiographic signs in knee osteoarthritis susceptibility

Introduction

Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals.

Methods

In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis.

Results

In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features.

Conclusions

This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.     

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.