Association Analysis of BMD‐associated SNPs with Knee Osteoarthritis

Osteoarthritis (OA) risk is widely recognized to be heritable but few loci have been identified. Observational studies have identified higher systemic bone mineral density (BMD) to be associated with an increased risk of radiographic knee osteoarthritis. With this in mind, we sought to evaluate whether well‐established genetic loci for variance in BMD are associated with risk for radiographic OA in the Osteoarthritis Initiative (OAI) and the Johnston County Osteoarthritis (JoCo) Project. Cases had at least one knee with definite radiographic OA, defined as the presence of definite osteophytes with or without joint space narrowing (Kellgren‐Lawrence [KL] grade ≥ 2) and controls were absent for definite radiographic OA in both knees (KL grade ≤ 1 bilaterally). There were 2014 and 658 Caucasian cases, respectively, in the OAI and JoCo Studies, and 953 and 823 controls. Single nucleotide polymorphisms (SNPs) were identified for association analysis from the literature. Genotyping was carried out on Illumina 2.5M and 1M arrays in Genetic Components of Knee OA (GeCKO) and JoCo, respectively and imputation was done. Association analyses were carried out separately in each cohort with adjustments for age, body mass index (BMI), and sex, and then parameter estimates were combined across the two cohorts by meta‐analysis. We identified four SNPs significantly associated with prevalent radiographic knee OA. The strongest signal (p = 0.0009; OR = 1.22; 95% CI, 1.08–1.37) maps to 12q3, which contains a gene coding for SP7. Additional loci map to 7p14.1 (TXNDC3), 11q13.2 (LRP5), and 11p14.1 (LIN7C). For all four loci the allele associated with higher BMD was associated with higher odds of OA. A BMD risk allele score was not significantly associated with OA risk. This meta‐analysis demonstrates that several genomewide association studies (GWAS)‐identified BMD SNPs are nominally associated with prevalent radiographic knee OA and further supports the hypothesis that BMD, or its determinants, may be a risk factor contributing to OA development. © 2014 American Society for Bone and Mineral Research.     

The Outcomes of Nonoperative Management of Patients With Hip and Knee Osteoarthritis Triaged to a Physiotherapy-Led Clinic at Minimum 5-Year Follow-Up and Factors Associated With Progression to Surgery

BackgroundThe purpose of this study is to determine outcomes of a nonoperative treatment service for hip and knee osteoarthritis (OA), the “Joint Clinic,” at minimum 5-year follow-up, and investigate factors that may influence progression to joint replacement surgery.MethodsThis is an observational cohort study of 337 patients with hip (n = 151, 45%) or knee OA (n = 186, 55%) seen at the Joint Clinic, at 5-7 years of follow-up. Kaplan-Meier survival curves were used to determine survivorship of the affected joint and Cox regression used to determine factors associated with time to surgery.ResultsAt mean 6-year follow up, 188 (56%) patients had undergone or were awaiting total joint arthroplasty, 127 (38%) were still being managed nonoperatively, and 22 (7%) had died without having surgery. Patients with hip OA were more likely to have required surgery (111/151, 74%) than patients with knee OA (77/186, 41%) (chi-square = 33.6, P < .001). The 7-year surgery-free survival for hip OA was 23.7% and knee OA 55.9% (P < .001). Factors associated with increased likelihood of surgery were joint affected (hip, hazard ratio [HR] 2.80), Kellgren-Lawrence (KL) grade (KL 3, HR 2.02; KL 4, 4.79), and Oxford Hip/Knee Score (HR 1.34 for each 5 points worse at baseline).ConclusionMore than 50% of the patients referred to secondary care with mild-moderate knee OA may not need surgery at 7 years. Patients with hip OA and those with severe radiographic changes are more likely to require surgery and should not be delayed if there is not an adequate response to conservative measures.     

Five Questions to Identify Patients With Osteoarthritis of the Knee

BackgroundTo treat the increasing number of patients with osteoarthritis (OA) of the knee, high-volume institutions rely on central referral services as first contact point. Depending on the grading of arthritis, patients will be referred to a nonoperative or operative care provider. The present study reports on a simple 5-step questionnaire to identify patients with OA (Kellgren/Lawrence [KL] grade ≥2) of the knee to improve efficiency of referrals.MethodsWe included 998 patients who contacted the physician referral service at the author’s institution complaining of knee pain and divided them into 2 groups. The study group included patients with an appointment and consisted of 646 patients (345 women [53.4%] and 301 men [46.6%]). X-rays of the knee were graded according to the KL classification system. The control group of patients who did not make an appointment consisted of 352 patients (187 women [53.1%] and 165 men [46.9%]). These patients were contacted to evaluate whether they had been diagnosed with OA of the knee since their initial call, to assure that the study group was not exposed to a selection bias.ResultsLogistic regression revealed 5 questions as significant predictors for OA of the knee (KL grade ≥2). When combining both groups, an 86.9% sensitivity, a 73.3% specificity, and an 84.3% overall accuracy were reached, when patients answered 3 or more questions positively.ConclusionThe present study revealed a simple 5-step questionnaire to identify patients with OA of the knee. Implementation of the questionnaire has the potential to improve the accuracy of referral processes and streamline organization before the first appointment.     

Risk factors for the incidence and progression of radiographic osteoarthritis of the knee among Japanese

This longitudinal study aimed to identify risk factors for the incidence and progression of radiographic knee osteoarthritis (OA). We examined the inhabitants of Miyagawa village aged ≥65 years every two years between 1997 and 2007. Anteroposterior radiographs of both knees were graded for OA using the Kellgren-Lawrence (K/L) grading system. Knee OA was defined as grade ≥2. We recorded the incidence of knee OA among participants in whom both knees changed from K/L grades 0 or 1 to ≥2 over a four-year follow-up period. We also recorded the progression of knee OA using this threshold among patients in whom one or both knees changed from K/L grades 2 or 3 to any higher grade over the follow-up period. Baseline data obtained from standard questionnaires, physical findings and X-rays included age, gender, body mass index (BMI), osteoporosis, Heberden’s nodes, knee range of motion (ROM), knee pain and cigarette smoking. The rates of incidence and progression of knee OA among 360 participants (241 women, 119 men) who fulfilled the study criteria were 4.0 and 6.0% per year, respectively. Female gender (odds ratio [OR] 2.849, 95% confidence interval [CI] 1.170–6.944) and high BMI (OR 1.243, 95% CI 1.095–1.411) were significantly associated with the incidence of knee OA, and restricted knee ROM (OR 0.941, 95% CI 0.892–0.992) was significantly associated with knee OA progression. Patients with a low knee ROM relative to grade of radiographic knee OA require more careful follow-up than those with a higher ROM.     

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration.MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%).ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration.ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.     

Role of Triple Injection Platelet-Rich Plasma for Osteoarthritis Knees: A 2 Years Follow-Up Study

PurposeTo assess the clinical outcomes of intra-articular Platelet-rich plasma (PRP) injection in knee osteoarthritis (OA) at 2 year follow-up.MethodsThis was a prospective interventional study. 68 cases (105 knees) with Kellgren-Lawrence (KL) grades I, II and III knee OA received 3 intra-articular injections of PRP 1 month apart. The cases were followed up for 2-years. Outcomes were measured using Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and Visual analog scale (VAS) scores.ResultsThe mean age was 51.7 years. 18 knees had KL grade I, 55 had grade II and 32 had grade III OA. The mean pre-treatment VAS score decreased significantly at 1 year (mean difference − 5.3, p = 0.003) and 2 year follow-up (mean difference − 6, p = 0.007). The mean pre-treatment WOMAC score decreased significantly at 1 year (mean difference − 45.9, p = 0.011) and at 2 year (mean difference − 52.4, p = 0.009). The WOMAC and VAS scores improved significantly from baseline to final follow-up across all KL grades (p = 0.001 and 0.001, 0.009 and 0.007, 0.021 and 0.017 for WOMAC and VAS across KL grade I, II and III, respectively). There was no significant differences in WOMAC and VAS scores between three KL grades at final follow-up (p = 0.17 and 0.09, respectively), although the baseline scores had significant difference (p = 0.001 for both VAS and WOMAC) with worse scores in higher KL grades. The variables like age, sex, BMI, KL grade, baseline VAS and baseline WOMAC did not predict the final VAS and WOMAC scores.ConclusionTriple injection of intra-articular PRP given one month apart significantly relieves the symptoms of knee OA till 2 years in KL grade I, II and III. The improvement in symptoms at 2-year follow-up did not differ across different KL grades.     

Relationship of limb length inequality with radiographic knee and hip osteoarthritis

OBJECTIVE: This study examined the relationship of limb length inequality (LLI) with radiographic hip and knee osteoarthritis (OA) in a large, community-based sample. METHODS: The total study group comprised 926 participants with radiographic knee OA, 796 with radiographic hip OA, and 210 (6.6%) with LLI >or=2cm. The presence of radiographic OA was defined as Kellgren/Lawrence (K/L) grade >or=2. Multiple logistic regression models were used to examine the relationship of LLI with hip and knee OA, while controlling for age, gender, race, body mass index, and history of hip or knee problems (joint injury, fracture, surgery, or congenital anomalies). RESULTS: In unadjusted analyses, participants with LLI were more likely than those without LLI to have radiographic knee OA (45.1% vs 28.3%, P<0.001) and radiographic hip OA (35.2% vs 28.7%, P=0.063). In multiple logistic regression models, knee OA was significantly associated with presence of LLI (adjusted Odds Ratio [aOR]=1.80, 95% Confidence Interval [95% CI] 1.29-2.52), but there was no significant relationship between hip OA and LLI (aOR=1.20, 95% CI 0.86-1.67). Among participants with LLI, right hip OA was more common when the contralateral limb was longer than when the ipsilateral limb was longer (30.3% vs 17.5%, P=0.070). CONCLUSION: LLI was associated with radiographic knee OA, controlling for other important variables. Future research should examine the relationship of LLI with hip or knee OA incidence, progression, and symptom severity, as well as the efficacy for LLI corrective treatments in OA.     

T2 analysis of the entire osteoarthritis initiative dataset

While substantial work has been done to understand the relationships between cartilage T₂ relaxation times and osteoarthritis (OA), diagnostic and prognostic abilities of T₂ on a large population yet need to be established. Using 3921 manually annotated 2D multi‐slice multi‐echo spin‐echo magnetic resonance imaging volume, a segmentation model for automatic knee cartilage segmentation was built and evaluated. The optimized model was then used to calculate T₂ values on the entire osteoarthritis initiative (OAI) dataset composed of longitudinal acquisitions of 4796 unique patients, 25 729 magnetic resonance imaging studies in total. Cross‐sectional relationships between T₂ values, OA risk factors, radiographic OA, and pain were analyzed in the entire OAI dataset. The performance of T₂ values in predicting the future incidence of radiographic OA as well as total knee replacement (TKR) were also explored. Automatic T₂ values were comparable with manual ones. Significant associations between T₂ relaxation times and demographic and clinical variables were found. Subjects in the highest 25% quartile of tibio‐femoral T₂ values had a five times higher risk of radiographic OA incidence 2 years later. Elevation of medial femur T₂ values was significantly associated with TKR after 5 years (coeff = 0.10; P = .036; CI = [0.01,0.20]). Our investigation reinforces the predictive value of T₂ for future incidence OA and TKR. The inclusion of T₂ averages from the automatic segmentation model improved several evaluation metrics when compared to only using demographic and clinical variables.     

What Are the Prognostic Factors for Radiographic Progression of Knee Osteoarthritis? A Meta-analysis

Background

A previous systematic review on prognostic factors for knee osteoarthritis (OA) progression showed associations for generalized OA and hyaluronic acid levels. Knee pain, radiographic severity, sex, quadriceps strength, knee injury, and regular sport activities were not associated. It has been a decade since the literature search of that review and many studies have been performed since then investigating prognostic factors for radiographic knee OA progression.

Questions/purposes

The purpose of this study is to provide an updated systematic review of available evidence regarding prognostic factors for radiographic knee OA progression.

Methods

We searched for observational studies in MEDLINE and EMBASE. Key words were: knee, osteoarthritis (or arthritis, or arthrosis, or degenerative joint disease), progression (or prognosis, or precipitate, or predictive), and case-control (or cohort, or longitudinal, or follow-up). Studies fulfilling the inclusion criteria were assessed for methodologic quality according to established criteria for reviews on prognostic factors in musculoskeletal disorders. Data were extracted and results were pooled if possible or summarized according to a best-evidence synthesis. A total of 1912 additional articles were identified; 43 met our inclusion criteria. The previous review contained 36 articles, thus providing a new total of 79 articles. Seventy-two of the included articles were scored high quality, the remaining seven were low quality.

Results

The pooled odds ratio (OR) of two determinants showed associations with knee OA progression: baseline knee pain (OR, 2.38 [95% CI, 1.74–3.27) and Heberden nodes (OR, 2.66 [95% CI, 1.46–8.84]). Our best-evidence synthesis showed strong evidence that varus alignment, serum hyaluronic acid, and tumor necrosis factor-α are associated with knee OA progression. There is strong evidence that sex, former knee injury, quadriceps strength, smoking, running, and regular performance of sports are not associated with knee OA progression. Evidence for the majority of determined associations, however, was limited, conflicting, or inconclusive.

Conclusions

Baseline knee pain, presence of Heberden nodes, varus alignment, and high levels of serum markers hyaluronic acid and tumor necrosis factor-α predict knee OA progression. Sex, knee injury, and quadriceps strength, among others, did not predict knee OA progression. Large variation remains in definitions of knee OA and knee OA progression. Clinical studies should use more consistent definitions of these factors to facilitate data pooling by future meta-analyses.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4349-z) contains supplementary material, which is available to authorized users.     

Morphological evaluation and diagnosis of medial type osteoarthritis of the knee using ultrasound

Objective

The aim of this study was to diagnose osteoarthritis (OA) of the knee joint using ultrasound (US).

Methods

The study subjects included 27 males and 54 females (131 knees), who had a mean age of 62.8 years. US was used to evaluate the medial joint space of both knees in complete extension with and without weight-bearing. In each patient, the medial radial displacement of the medial meniscus (MRD), the peripheral joint space (PJS) and the number of osteophytes were evaluated. The subjects were divided into five groups based on the KL grade (0–4), and then each value was compared. Additionally, the subjects were divided into two groups: KL grade 0 and 1 (non-OA group) and KL grade 2–4 (OA group). We classified patients who met the following criteria as having OA on the US assessment: <5 mm of PJS during weight-bearing, >5 mm of MRD during weight-bearing, and >2 mm of osteophytes. Then we examined the diagnostic accuracy of the radiographic diagnosis (non-OA or OA of the knee) using US assessment.

Results

The PJS was significantly decreased and the MRD was significantly increased in the OA group compared to the non-OA group (p < 0.001). The percentage of radiographic OA of the knee that was correctly diagnosed by ultrasound was 90.8 % (sensitivity), with a specificity of 95.5 %. The positive predictive value was 97.5 % and the negative predictive value was 84.0 %.

Conclusions

Our study therefore showed that US has both a high reliability and excellent diagnostic accuracy.     

Association of serum carotenoids, retinol, and tocopherols with radiographic knee osteoarthritis: possible risk factors in rural Japanese inhabitants

Background

The consumption of antioxidant nutrients may influence the development and progression of osteoarthritis (OA). To determine the association between serum antioxidants and radiographic knee osteoarthritis, we undertook a cross-sectional investigation in a community-based study in Japan.

Methods

A total of 562 subjects (224 male, 338 female) ≥40 years of age were enrolled in the Comprehensive Health Examination Program (CHEP, Yakumo Study) from 2003 to 2005. Subjects were categorized to the OA group (n = 140) if either knee was graded as Kellgren-Lawrence (K-L) grade ≥2. The no-OA group was defined as showing radiographic findings of K-L 0 or 1 in either knee (n = 422). The serum levels of retinol, β-/γ-tocopherols, α-tocopherol, zeaxanthin/lutein, canthaxanthin, cryptoxanthin, lycopene, α-carotene, and β-carotene were measured by high-performance liquid chromatography. The values of these antioxidants were divided into tertiles, and a logistic regression analysis was performed to analyze the association between them and radiographic knee OA, adjusting for potential confounders.

Results

Logistic regression analysis showed that compared to the lowest tertile of β-/γ-tocopherols the adjusted odds ratio (OR) was 0.52 [95% confidence interval (CI) 0.29–0.93] in the highest tertile; it also indicated a linear trend across tertiles. Furthermore, the adjusted OR was significantly decreased only in the middle tertile of α-tocopherol (OR 0.51, 95% CI 0.29–0.90). We reevaluated any independent association for these tocopherols after adjustment by entering them into the model simultaneously. The significance of β-/γ-tocopherols was maintained. In contrast, no associations were found with any carotenoids or retinol.

Conclusions

High serum values of β-/γ-tocopherols were found to be significantly associated with a low OR for radiographic knee osteoarthritis. The decreasing risk with a high serum value of β-/γ-tocopherols may support the possible protective effects against knee OA.     

More Severe Radiographic Osteoarthritis Is Associated With Increased Improvement in Patients’ Health State Following a Total Knee Arthroplasty

BackgroundTo assess whether preoperative radiological severity of osteoarthritis (OA) is related to the level of improvement in patients’ health state measured 1 year after total knee arthroplasty (TKA).MethodsRadiographic severity of OA was graded using the Kellgren-Lawrence (KL) classification. Two independent observers were blinded to patients’ outcome scores. Health-related quality of life was measured using EQ-5D-3L preoperatively and at 12-month follow-up. The 5 dimensions of the EQ-5D were converted into a health state index score. The association between KL grade and improvement in health state score was analyzed using multiple linear regression.ResultsAmong 156 consecutive patients (68% females, mean age 69 years) who underwent primary TKA, 3 knees (2%) were classified as KL grade 2, 115 as KL grade 3 (74%), and 38 as KL grade 4 (24%). Follow-up rate was 77%. There was substantial intra-rater and inter-rater agreement (Cohen’s kappa = 0.80 and 0.79). Most patients (64%) had clinically significant improvement in their health state score 1 year after TKA. However, after adjusting for relevant covariates, patients with severe OA (KL grade 4) were found to have significantly more improvement in their health state score than patients with mild or moderate OA (KL grade 2 or 3, respectively). Separate analysis of the 5 EQ-5D dimensions showed that the KL group differences were most evident in the “usual activities” and “pain/discomfort” dimensions.ConclusionPatients with severe OA have significantly more improvement in their usual activities and pain/discomfort 1 year after TKA than patients with less severe OA.     

Relationship of Bone Mineral Density and Knee Osteoarthritis (Kellgren-Lawrence Grade): Fifth Korea National Health and Nutrition Examination Survey

BackgroundOsteoarthritis (OA) and osteoporosis (OP) are the 2 most common bone disorders associated with aging. We can simply assume that older patients have a higher incidence of OA and OP with more severity. Although several papers have conducted studies on the relationship between OA and OP, none of them has demonstrated a conclusive link. In this study, we used radiological knee OA and bone mineral density (BMD; T-score of the total hip and lumbar spine) to analyze the incidence of OA and OP in a large population. We aimed to determine the relationship between OA and OP and investigate the associated risk factorsMethodsThis cross-sectional study used data extracted from the 2010–2012 Korea National Health and Nutrition Examination Survey. We evaluated a total of 4,250 participants aged ≥ 50 years who underwent knee radiography and dual-energy X-ray absorptiometry and their laboratory results. The relationship between radiological knee OA and BMD was assessed. The generalized linear model was used to evaluate the relationship between BMD and Kellgren-Lawrence (KL) grade.ResultsThe higher KL grade was associated with older age, higher body mass index (BMI), female sex, and lower hemoglobin level (p < 0.001). No significant association was found between OA and the following variables: white blood cell, platelet, total cholesterol, vitamin D, alkaline phosphatase, parathyroid hormone, hypertension, diabetes, asthma, dyslipidemia, smoking status, alcohol consumption, and regular exercise (p > 0.05). After adjusting for confounding factors (age, BMI, diabetes, hypertension, smoking, and alcohol consumption), the average T-scores of total hip and lumbar spine were the highest in the mild OA group with KL grade 2 (−0.22 ± 1.08 and −0.89 ± 1.46, respectively, p < 0.001). The average T-scores of the total hip and lumbar spine significantly decreased as OA progressed from moderate (KL grade 3; −0.49 ± 1.05 and −1.33 ± 1.38, respectively, p < 0.001) to severe (KL grade 4; −0.73 ± 1.13 and −1.74 ± 1.75, respectively, p < 0.001). T-scores of the moderate-to-severe OA group were significantly lower than those of the non-OA group (KL grades 0 and 1, p < 0.001).ConclusionsCompared with the non-OA group, BMD (T-scores of the total hip and lumbar spine) was higher in the mild OA group and lower in the moderate-to-severe OA group.     

Predicting early symptomatic osteoarthritis in the human knee using machine learning classification of magnetic resonance images from the osteoarthritis initiative

The purpose of this study is to evaluate the ability of a machine learning algorithm to classify in vivo magnetic resonance images (MRI) of human articular cartilage for development of osteoarthritis (OA). Sixty‐eight subjects were selected from the osteoarthritis initiative (OAI) control and incidence cohorts. Progression to clinical OA was defined by the development of symptoms as quantified by the Western Ontario and McMaster Universities Arthritis (WOMAC) questionnaire 3 years after baseline evaluation. Multi‐slice T₂‐weighted knee images, obtained through the OAI, of these subjects were registered using a nonlinear image registration algorithm. T ₂ maps of cartilage from the central weight bearing slices of the medial femoral condyle were derived from the registered images using the multiple available echo times and were classified for “progression to symptomatic OA” using the machine learning tool, weighted neighbor distance using compound hierarchy of algorithms representing morphology (WND‐CHRM). WND‐CHRM classified the isolated T ₂ maps for the progression to symptomatic OA with 75% accuracy. Clinical significance: Machine learning algorithms applied to T ₂ maps have the potential to provide important prognostic information for the development of OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2243–2250, 2017.

     

Prevalence and Risk Factors of Spine,Shoulder, Hand,Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years

Background

Osteoarthritis (OA) is common and disabling among older patients around the world. Data exploring the prevalence and risk factors of OA are of paramount importance in establishing healthcare policies. However, few studies have evaluated these topics among Asian populations.

Questions/purposes

This study was conducted to determine the prevalence and risk factors of radiographic OA in the spine, shoulder, hand, hip, and knee in Koreans older than age 65 years.

Methods

A simple random sample (N = 1118) was drawn from a roster of elderly individuals older than age 65 years in Seongnam. Of the 1118 invited subjects, 696 (males = 298, females = 398) participated in this study (a response rate of 62%). The mean age of respondents was 72 ± 5 years (range, 65–91 years). Radiographs of the lumbar spine, shoulder, hand, hip, and knee were taken and afterward evaluated for radiographic OA. The Kellgren-Lawrence grading system was used for all mentioned joints, and radiographic OA was defined as Grade 2 changes or higher. The association of sex, aging, and obesity with OA in each of the mentioned joints was determined with the help of multivariate logistic regression.

Results

The highest prevalence of radiographic OA was seen in the spine (number of subjects with OA/number of whole population = 462 of 696 [66%]) followed by the hand (415 of 692 [60%]), knee (265 of 696 [38%]), shoulder (36 of 696 [5%]), and hip (15 of 686 [2%]). Female sex was associated with knee OA (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.9–8.4; p < 0.001) and hand OA (OR, 2.3; 95% CI, 1.6–3.1; p < 0.001), and male sex was associated with spine OA (OR, 0.7; 95% CI, 0.5–1.0; p = 0.025). Aging was associated with radiographic OA in the spine, knee, and hand (OR per 5-year increments, 1.3 [95% CI, 1.1–1.6; p = 0.001], 1.6 [95% CI, 1.4–1.9; p < 0.001], and 1.4 [95% CI, 1.2–1.7; p < 0.001]), respectively) but not associated with OA in the hip and shoulder. Obesity was associated with knee OA (OR, 3.4; 95% CI, 2.4–5.0; p < 0.001) and spine OA (OR, 1.5; 95% CI, 1.1–2.2; p = 0.014) but not with OA in other joints.

Conclusions

OA of the spine, hand, and knee is likely to become a major public health problem rather than shoulder and hip OA in Korea. Associations of demographic factors with radiographic OA differed among each joint, and that would be valuable information to assess the role and influence of risk factors of OA in various joints.

Level of Evidence

Level III, prognostic study.     

Factors associated with rapid progression to knee arthroplasty: complete analysis of three-year data from the osteoarthritis initiative

ObjectivesOnly a few studies have identified prognostic factors indicating risk of future knee arthroplasty in patients with osteoarthritis (OA) of the knee. The Osteoarthritis Initiative (OAI) is a National Institutes of Health and privately funded cohort study of 4796 persons with or at high risk of knee OA. The OAI is ideally suited to a more extensive study of knee arthroplasty prognostic factors than has been undertaken. The purpose of our study was to identify patient factors which predict rapid progression to knee arthroplasty, defined as arthroplasty within three years of baseline data collection.MethodsWe used alternating logistic regression models to analyze complete three year follow-up data from the OAI on 4670 persons with, or at risk for knee OA, aged 45 to 79 years during the years 2004 to 2008.ResultsA total of 128 knees (116 persons) underwent knee arthroplasty during the study period. After adjusting for known prognostic factors, several previously unidentified predictors of future knee arthroplasty were found including past history of knee surgery (RR = 2.04, 95% CI = 1.33, 3.13), knee flexion contracture in degrees (RR = 1.06, 95% CI = 1.02, 1.11) and pain, on a 0 to 10 scale, with active knee flexion (RR = 1.58, 95% CI = 1.04, 2.39).Discussion/ConclusionsThis study identifies new and easily measured clinical variables that are associated with more rapid progression to arthroplasty. The data may help to inform both physicians and patients of medical history and clinical examination findings most highly associated with short-term arthroplasty.     

Glucose homeostasis influences the risk of incident knee osteoarthritis: Data from the osteoarthritis initiative

We aimed to determine if serum measures of impaired glucose homeostasis (glucose concentrations or glycated serum protein, GSP) or systemic inflammation (high‐sensitivity C‐reactive protein, CRP) are related to incident typical knee osteoarthritis (KOA) or incident accelerated KOA. We conducted a case‐control study using the Osteoarthritis Initiative's baseline and first four annual visits. All participants had no radiographic KOA at baseline (Kellgren‐Lawrence [KL] < 2). We classified three groups: (i) incident accelerated KOA: > 1 knee developed advance‐stage KOA (KL Grade 3 or 4) within 48 months; (ii) incident typical KOA: > 1 knee increased in radiographic scoring within 48 months (excluding those with accelerated KOA); and (iii) No KOA: no change in KL grade by 48 months. We matched on sex. A laboratory blinded to group assignment used baseline serum samples to conduct assays for CRP, GSP, and glucose. Due to nonlinear relationships, we used three piece‐wise multinomial logistic regression models to determine if baseline CRP, GSP, or glucose were associated with incident typical KOA or accelerated KOA compared with no KOA. We adjusted for age, body mass index, and sex. We analyzed 54 adults/group. Lower and higher GSP concentrations were associated with incident typical KOA compared with adults with concentrations (log) closer to 5.7 (lnGSp < 5.7: OR = 0.28, 95%CI = 0.08–0.93; lnGSp > 5.7: OR = 3.21, 95%CI = 1.07–9.62). Glucose, GSP, and CRP were not significantly associated with incident accelerated KOA. Glucose homeostasis may predict individuals at risk of incident typical KOA but not accelerated KOA, which may indicate accelerated KOA is a distinct disorder from typical KOA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2282–2287, 2017.

     

Electromyographic patterns suggest changes in motor unit physiology associated with early osteoarthritis of the knee

OBJECTIVE: To assess characteristics of active motor units (MUs) during volitional vastus medialis (VM) activation in adults with symptomatic knee osteoarthritis (OA) across the spectrum of radiographic severity and age-comparable healthy control volunteers. METHODS: We evaluated 39 participants (age 65+/-3 years) in whom weight-bearing knee X-rays were assigned a Kellgren & Lawrence (KL) grade (18 with KL grade=0; four each with KL grades=1, 2 and 4; nine with grade 3). Electromyography (EMG) signals were simultaneously acquired using surface [surface EMG (S-EMG)] and intramuscular needle electrodes, and analyzed by decomposition-enhanced spike-triggered averaging to obtain estimates of size [surface-represented MU action potentials (S-MUAP) area], number [MU recruitment index (MURI)] and firing rates [MU firing rates (mFR)] of active MUs at 10%, 20%, 30% and 50% effort relative to maximum voluntary force [maximal voluntary isometric contraction (MVIC)] during isometric knee extension. RESULTS: Knee extensor MVIC was lower in OA participants, especially at higher KL grades (P=0.05). Taking the observed force differences into account, OA was also associated with activation of larger MUs (S-MUAP area/MVICx%effort; P<0.0001). In contrast, the estimated number of active units (MURI/MVICx%effort) changed differently as effort increased from 10% to 50% and was higher with advanced OA (KL=3, 4) than controls (P=0.0002). CONCLUSION: VM activation changes at the level of the MU with symptomatic knee OA, and this change is influenced by radiographic severity. Poor muscle quality may explain the pattern observed with higher KL grades, but alternative factors (e.g., nerve or joint injury, physical inactivity or muscle composition changes) should be examined in early OA.     

Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial

OBJECTIVE: To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate. DESIGN: Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed. RESULTS: Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between NTX-I levels and radiological progression was observed. CONCLUSION: CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.