Search

ObjectiveTo determine the optimal combination of imaging and biochemical biomarkers for use in the prediction of knee osteoarthritis (OA) progression.MethodsThe present study was a nested case-control trial from the Foundation of the National Institutes of Health OA Biomarkers Consortium that assessed study participants with a Kellgren/Lawrence grade of 1-3 who had complete biomarker data available (n = 539 to 550). Cases were participants' knees that had radiographic and pain progression between 24 and 48 months compared to baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) that had a P value of

Additional file 8.

Additional file 9.

Additional file 10.

Additional file 6.

Additional file 1.

Additional file 2.

Additional file 4.

Additional file 7.

Additional file 3.

Additional file 5.

Objective: Diabetes mellitus (DM) appears to increase osteoarthritic knee pain, which may be related to greater adiposity and more advanced disease status often observed in individuals with osteoarthritis (OA) and DM. We aimed to assess whether OA knee pain and health status are worse in individuals with OA and DM, independent of these potential confounders. Methods: We included 202 OA participants with DM and 2,279 without DM from the Osteoarthritis Initiative. Knee pain was evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a numeric rating scale (NRS). Physical and mental status were assessed by the Medical Outcomes Study Short Form 12 (SF-12) questionnaire, physical component summary (PCS) score and mental component summary (MCS) score, and by the Center for Epidemiologic Studies Depression Scale (CES-D). Linear regression models assessed the influence of DM, adjusted for age, sex, body mass index (BMI), and radiographic severity. Results: OA participants with DM reported worse knee pain and greater physical and mental issues compared with participants without DM. Individuals with DM had worse KOOS pain (β = –4.72 [95% confidence interval (95% CI) –7.22, –2.23]) and worse NRS pain (β = 0.42 [95% CI 0.04, 0.80]) independent of BMI, OA severity, age, and sex. The negative influence of DM was also apparent for SF-12 PCS (β = –3.49 [95% CI –4.73, –2.25]), SF-12 MCS (β = –1.42 [95% CI –2.57, –0.26]), and CES-D (β = 1.08 [95% CI 0.08, 2.08]). Conclusion: Individuals with knee OA experience on average higher pain intensity and a worse physical and mental health status if they have DM. Linear regression models show that DM is a risk factor for higher pain, in addition to and independent of greater BMI and radiographic OA severity.

Background and purpose — Knee extensor (KE) muscle weakness is a modifiable feature commonly observed in individuals with knee osteoarthritis (KOA) and constitutes a potential target for patient-specific interventions. Therefore, in this study, we explored whether KE weakness is associated with radiographic (medial and/or lateral) KOA progression and how this relationship differs depending on frontal plane knee alignment and sex. Patients and methods — We studied 3,075 knees (1,961 participants, 58% female) from the Osteoarthritis Initiative with radiographic Kellgren–Lawrence grade 1–3. Peak KE torque (Nm/kg) was assessed at baseline, and progression defined as fixed-location joint space width loss (≥ 0.7mm) in medial and lateral tibiofemoral compartments from baseline to 4-year follow-up. Knee-based generalized estimating equations, stratified by alignment (malaligned vs. neutral), estimated the relative risk (RR) of progression for those in the lowest (and middle) vs. highest KE torque group (split by tertiles). Secondary analyses explored whether this relationship was compartmental- or sex-specific. Results — Being in the lowest (or middle) compared with the highest torque group increased the risk of progression in neutrally aligned knees (relative risk [RR] 1.2 [95% CI 1.0–1.4]; and 1.2 [CI 1.0–1.4], respectively), but not after adjusting for age, sex, BMI, pain, and radiographic severity. In secondary analyses, women with neutral alignment in the lowest compared with the highest torque group had significantly increased risk of lateral compartment progression independent of age, BMI, disease severity, and pain (RR 1.3 [CI 1.0–1.8]). No association was observed between KE torque and KOA progression in men, irrespective of alignment. Interpretation — These results identify a potentially important clinical phenotype: KE weakness may be a more important risk factor for radiographic KOA progression in women without knee malalignment.

ObjectiveTo explore whether baseline to 12-month followup change in femorotibial cartilage thickness differs between subjects who received a total knee arthroplasty (TKA) between 24 and 60 months from those without TKA (non-TKA).MethodsIn this prospective cohort study, 531 right knees from Osteoarthritis Initiative participants with definite radiographic knee osteoarthritis (Kellgren/Lawrence [K/L] grades 2-4) were studied. Segmentation was applied to coronal fast low-angle shot magnetic resonance images, to quantitatively determine cartilage thickness in 16 femorotibial subregions. Unadjusted P values (t-tests) and P values adjusted for age, baseline body mass index (BMI), K/L grade, and sex (generalized estimating equation models) were used to evaluate differences in longitudinal 1-year rates of cartilage thickness between TKAs and non-TKAs, with total knee arthroplasty status as fixed effect.ResultsOf the 531 participants (mean ± SD ages 63 ± 9 years, BMI 30 ± 4.8 kg/m(2)), 40 received a femorotibial TKA within 4 years. At baseline, TKAs had thinner medial and lateral femorotibial cartilage (-15%; P < 0.001) than non-TKAs. Longitudinal cartilage thickness change was significantly greater in TKAs than in non-TKAs in the total femorotibial joint (area under the curve [AUC] 0.64), the lateral compartment (AUC 0.66), both tibiae (AUC ≥ 0.61), and the first 9 (of 16) ordered values of subregion change (AUC 0.64-0.69). Discrimination was stronger for TKAs that occurred at 24 and 36 months (n = 18) than for those at 48 and 60 months (n = 22).ConclusionKnees with incident TKA displayed smaller baseline cartilage thickness and greater lateral as well as location-independent ordered value femorotibial cartilage loss than non-TKAs. Discrimination of cartilage loss was greater for TKAs occurring within 2 years after the measurement than for those occurring later.

ObjectiveTo determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within-person, between-knee cross-sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight-bearing medial femoral condyle (ecMF) and external weight-bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.MethodsBoth knees of 61 Osteoarthritis Initiative participants (n = 4,796) displayed definite tibial or femoral marginal osteophytes and no JSN in 1 knee, and no signs of radiographic osteoarthritis (OA) in the contralateral knee; this was confirmed by an expert central reader. In these participants, cartilage thickness was measured in 16 femorotibial subregions of each knee, based on sagittal double-echo steady-state with water excitation magnetic resonance images. Location-specific joint space width from fixed-flexion radiographs was determined using dedicated software. Location-specific associations of osteophytes with cartilage thickness were evaluated using paired t-tests and mixed-effects models.ResultsOf the 61 participants, 48% had only medial osteophytes, 36% only lateral osteophytes, and 16% bicompartmental osteophytes. The knees with osteophytes had significantly thicker cartilage than contralateral knees without osteophytes in the ecMF (mean ± SD +71 ± 223 μmoles, equivalent to an increase of +5.5%; P = 0.015) and ecLF (mean ± SD +64 ± 195 μmoles, +4.1%; P = 0.013). No significant differences between knees were noted in other subregions or in joint space width. Cartilage thickness in the ecMF and ecLF was significantly associated with tibial osteophytes in the same (medial or lateral) compartment (P = 0.003).ConclusionThe knees with early radiographic OA display thicker cartilage than (contralateral) knees without radiographic findings of OA, specifically in the external femoral subregions of compartments with marginal osteophytes.

Osteoarthritis (OA) is the most common joint disorder. The osteoarthritis initiative (OAI) is a multicentre, longitudinal, prospective observational cohort study of knee OA that aims to provide publicly accessible clinical datasets, images and biospecimens, to enable researchers to investigate factors that influence the onset and development of OA, and evaluate biomarkers that predict and track the course of the disease. In this Perspectives, we describe the rationale and design of the OAI and its cohort, discuss imaging protocols and summarize image analyses completed to date. We include descriptive analyses of publicly available longitudinal (2-year) data of changes in cartilage thickness in a core sample of 600 knees from 590 participants in the OAI progression subcohort. Furthermore, we describe published methodological and applied imaging research that has emerged from OAI pilot studies and OAI data releases, and how these studies might contribute to clinical development of biomarkers for assessing the efficacy of intervention trials.