Associations of components of sarcopenia with risk of fracture in the Osteoporotic Fractures in Men (MrOS) study.

Our aim was to evaluate the associations between the individual components of sarcopenia and fracture types. In this cohort, the risk of experiencing any clinical, hip, or major osteoporotic fracture is greater in men with slow walking speed in comparison to normal walking speed. INTRODUCTION: The association between the components of sarcopenia and fractures has not been clearly elucidated and has hindered the development of appropriate therapeutic interventions. Our aim was to evaluate the associations between the individual components of sarcopenia, specifically lean mass, strength, and physical performance and fracture (any fracture, hip fracture, major osteoporotic fracture) in the Osteoporotic Fractures in Men (MrOS) study. METHODS: The Osteoporotic Fractures in Men study (MrOS) recruited 5995 men ≥ 65 years of age. We measured appendicular lean mass (ALM) by dual-energy X-ray absorptiometry (low as residual value < 20th percentile for the cohort), walking speed (fastest trial of usual pace, values < 0.8 m/s were low), and grip strength (max score of 2 trials, values < 30 kg were low). Information on fractures was assessed tri-annually over an average follow-up of 12 years and centrally adjudicated. Cox proportional hazard models estimated the hazard ratio (HR) (95% confidence intervals) for slow walking speed, low grip strength, and low lean mass. RESULTS: Overall, 1413 men had a fracture during follow-up. Slow walking speed was associated with an increased risk for any HR = 1.39, 1.05-1.84; hip HR = 2.37, 1.54-3.63; and major osteoporotic, HR = 1.89, 1.34-2.67 in multi-variate-adjusted models. Low lean mass and low grip strength were not significantly associated with fracture. CONCLUSIONS: In this cohort of older adult men, the risk of experiencing any, hip, or major osteoporotic fracture is greater in men with slow walking speed in comparison to men with normal walking speed, but low grip strength and low lean mass were not associated with fracture.

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints.

OBJECTIVE: Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up period. METHOD: Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren-Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5 mm; knee pain at worst 4-9 in the past 30 days on an 11-point scale, or 0-3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes. RESULTS: Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively). CONCLUSIONS: 2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.

Lack of evidence that beta blocker use reduces knee pain, areas of joint pain, or analgesic use among individuals with symptomatic knee osteoarthritis.

OBJECTIVE: The potential for beta blocker use to reduce joint pain and analgesic use in osteoarthritis (OA) patients has not been well established. The objective of this study was to estimate the association between beta blocker use and knee pain, areas of joint pain, and analgesic use among participants with symptomatic knee OA. DESIGN: We selected participants with symptomatic knee OA from the Osteoarthritis Initiative. Outcome measures included knee pain (e.g., WOMAC pain subscale), areas of joint pain (e.g., widespread joint pain), and analgesic use (e.g., use of strong pain prescriptions including opioids). We decomposed time-varying beta blocker use into within-person and between-person variation, and included these components in linear mixed effects models for repeated outcome measures of knee pain, joint pain, and analgesic use over 8 years. RESULTS: Among 1,168 participants, 15% reported beta blocker use at baseline. Beta blocker users (5.2, 95% CI [4.7, 5.8]) had similar estimated mean WOMAC pain scores as other anti-hypertensive users (4.9, 95% CI [4.6, 5.2]), with an estimated within-person difference of 0.1 (95% CI [-0.3, 0.4]). Proportion of participants reporting widespread joint pain was similar between beta blocker users and other anti-hypertensive users (40.1% vs 40.3%; within-person effect, odds ratio [OR] = 0.87, 95% CI [0.63, 1.22]). Reported use of strong prescription pain medication was also similar between beta blocker users and other anti-hypertensive users (7.7% vs 8.2%; within-person effect, OR = 1.39, 95% CI [0.75, 2.55]). CONCLUSIONS: We found no evidence that beta blockers confer a clinically meaningful reduction in knee pain severity, areas of joint pain, or analgesic use among participants with symptomatic knee OA.

The morphology of proximal tibiofibular joint (PTFJ) predicts incident radiographic osteoarthritis: data from Osteoarthritis Initiative.

OBJECTIVE: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. METHODS: A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. RESULTS: 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m2. Baseline PTFJ morphological parameters (S, Sτ and Sυ) were significantly associated with iROA over 4 years, and these associations remained unchanged after adjustment for BMI, number of knee bending activities, self-reported knee injury and surgery. S, Sτ and Sυ were also significantly associated with iROA at P1 and P0. In subgroup analysed, S, Sτ and Sυ were associated with risks of incident joint space narrowing in the medial, but not the lateral tibiofemoral compartment. CONCLUSION: Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.

Qualitative and quantitative measures of prefemoral and quadriceps fat pads are associated with incident radiographic osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine if qualitative and quantitative measures of prefemoral fat pad (PFP) and quadriceps fat pad (QFP) are associated with incident radiographic osteoarthritis (iROA) over 4 years in the Osteoarthritis Initiative (OAI) study. DESIGN: Participants in this nested case-control study were selected from the OAI study with knees that had Kellgren Lawrence grades (KLG) of 0 or 1 at baseline. Case knees were defined by iROA (KLG≥ 2) over 4 years. Control knees without iROA were matched 1:1 with case knees. Magnetic resonance images (MRIs) were read at P0 (time of onset of iROA), P-1 (1 year prior to P0) and baseline, and used to assess PFP (i.e., prefemoral hyperintensity alteration, patellofemoral hyperintensity alteration, maximum axial area) and QFP (i.e., hyperintensity alteration, mass effect, maximum axial area). Conditional logistic regression analyses were performed to study the associations between PFP/QFP measures and iROA, after adjustment for covariates. RESULTS: 354 case knees with iROA were matched to 354 control knees. 66.9% of the participants were female, with an average age of 60.1 years. PFP prefemoral hyperintensity alteration measured at three time points (OR [95%CI]: 1.46 [1.18-1.82], 1.50 [1.20-1.88], 1.52 [1.22-1.89] respectively), PFP maximum axial area (OR [95%CI]: 1.07 [1.01-1.14], 1.08 [1.01-1.15], 1.08 [1.02-1.15] respectively) and QFP hyperintensity alteration (OR [95%CI]: 1.59 [1.27-2.00], 1.44 [1.13-1.82], 1.38 [1.09-1.73] respectively) were significantly associated with iROA in multivariable conditional logistic analyses. QFP mass effect measured at BL and P-1 (OR [95%CI]: 1.42 [1.11-1.82], 1.33 [1.01-1.73] respectively) were significantly associated with iROA. CONCLUSIONS: Qualitative and quantitative measures of PFP and QFP are associated with increased iROA over 4 years.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

Diagnostic performance of knee physical exam and participant-reported symptoms for MRI-detected effusion-synovitis among participants with early or late stage knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: Evaluate the diagnostic performance of knee physical exam findings and participant-reported symptoms for MRI-detected effusion-synovitis (ES) among knees with early and late-stage osteoarthritis (OA). DESIGN: The Osteoarthritis Initiative (OAI) is a longitudinal study of participants with or at risk for knee OA. Two samples with MRI readings were available: 344 knees with early OA (312 participants) and 216 with late-stage OA (186 participants). Trained examiners performed bulge sign (BS) and patellar tap (PT) exams, and participants reported on knee swelling and pain with leg straightening. Effusion-synovitis on 3T non-contrast MRI was scored using the MRI Osteoarthritis Knee Score (MOAKS). Diagnostic performance of physical exam findings and symptoms was estimated with bootstrapped confidence intervals. RESULTS: For the early OA sample, the highest sensitivity for medium/large effusion-synovitis was achieved with a positive finding for any of the physical exam maneuvers and/or participant-reported symptoms (81.0 [95% CI: 70.0, 91.3]). Both knee symptoms in combination had a prevalence of 11.7% and yielded the highest estimated positive predictive value (PPV) (50.0 [95% CI: 34.2, 66.7]) and likelihood ratio positive (LR+) (5.2 [95% CI: 2.9, 9.7]). In late-stage OA knees, exam findings and symptoms provided minimal information beyond the prevalence. CONCLUSION: Patient report of both symptoms, or at least one positive exam finding and at least one symptom, could be used to identify knees at increased risk of effusion-synovitis in knees with early stage OA, either for screening purposes in clinical evaluation, or for study sample enrichment with an inflammatory phenotype; diagnostic performance was not sufficiently high for clinical diagnostic purposes.

Social & psychological factors associated with oral analgesic use in knee osteoarthritis management.

OBJECTIVE: Determine modifiable social and psychological health factors that are associated with use of oral opioid and non-opioid medications for OA. METHODS: Patients were categorized based on use of the following oral medications: opioids (with/without other oral analgesic treatments), non-opioid analgesics, and no oral analgesic treatment. We used multinomial logistic regression models to estimate adjusted relative risk ratios (RRRs) of using an opioid or a non-opioid analgesic (vs. no oral analgesic treatment), comparing patients by levels of social support (Medical Outcomes Study scale), health literacy ("How confident are you filling out medical forms by yourself?"), and depressive symptoms (Patient Health Questionnaire-8). Models were adjusted for demographic and clinical characteristics. RESULTS: In this sample (mean age 64.2 years, 23.6% women), 30.6% (n = 110) reported taking opioid analgesics for OA, 54.2% (n = 195) reported non-opioid use, and 15.3% (n = 55) reported no oral analgesic use. Opioid users had lower mean social support scores (10.0 vs 10.5 vs 11.9, P = 0.007) and were more likely to have moderate-severe depressive symptoms (42.7% vs 24.1% vs 14.5%, P < 0.001). Health literacy did not differ by treatment group type. Having moderate-severe depression was associated with higher risk of opioid analgesic use compared to no oral analgesic use (RRR 2.96, 95%CI 1.08-8.07) when adjusted for sociodemographic and clinical factors. Neither social support nor health literacy was associated with opioid or non-opioid oral analgesic use in fully adjusted models. CONCLUSIONS: Knee OA patients with more severe depression symptoms, compared to those without, were more likely to report using opioid analgesics for OA.

Natural history of pain and disability among African-Americans and Whites with or at risk for knee osteoarthritis: A longitudinal study.

OBJECTIVE: Compare knee pain and disability between African Americans (AAs) and Whites (WHs), with or at risk of knee osteoarthritis (KOA), over 9 years, and evaluate racial disparities in KOA-related symptoms across socioeconomic and clinical characteristics. DESIGN: Osteoarthritis Initiative (OAI) participants were evaluated annually over 9 years for pain and disability, assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a numerical rating scale (NRS) for knee pain severity. Mean annual WOMAC pain, NRS pain, and WOMAC disability levels were estimated by race using mixed effects models, adjusted for age, sex, education, marital status, body mass index (BMI), depression, and baseline Kellgren-Lawrence grade score. Race-specific mean WOMAC pain scores were also estimated in analyses stratified by socioeconomic and clinical characteristics. RESULTS: AAs reported worse mean WOMAC pain compared to WHs at baseline (3.69 vs 2.20; P ≤ 0.0001) and over 9 years of follow-up, with similar disparities reflected in NRS pain severity and WOMAC disability. Radiographic severity did not account for the differences in pain and disability, as substantial and significant racial disparities were observed after stratification by Kellgren-Lawrence grade. Depression and low income exacerbated differences in WOMAC pain between AAs and WHs by a substantial and significant magnitude. CONCLUSIONS: Over 9 years of follow-up, AAs reported persistently greater KOA symptoms than WHs. Socioeconomically and clinically disadvantaged AAs reported the most pronounced disparities in pain and disability.

A quantitative metric for knee osteoarthritis: reference values of joint space loss.

OBJECTIVES: Knee osteoarthritis (OA) onset and progression has been defined with transitions in Kellgren-Lawrence (KL) grade or Osteoarthritis Research Society International (OARSI) Joint Space Narrowing (JSN) grade. We quantitatively describe one-year transitions in KL grade and JSN, using fixed joint space width (fJSW), among knees with or at risk of OA. METHODS: Radiographic assessments from the Osteoarthritis Initiative (OAI) were used to identify transitions in KLG and JSN grade between consecutive annual visits. The fJSW was measured in the medial and lateral compartments. The distribution of change in fJSW for KLG and JSN transitions were described, and mean change in fJSW was estimated using mixed models. RESULTS: KL grade and JSN scores were available for about 20,000 annual transitions from 6047 knees contributed by 3389 participants. Knees that remained stable in KL or OARSI-JSN over 1 year had mean medial fJSW loss between -0.06 and -0.19 mm/year. Transition from KL grade 0 to 1, 0 to 2, and KL 1 to 2 were similar with respect to mean medial fJSW loss (0.18-0.28 mm). Greatest annual changes in medial fJSW corresponded to KL 0 to 3 (1.62 mm), KL 2 to 4 (1.23 mm) and JSN 0 to 2 (1.85 mm). CONCLUSIONS: Anchoring quantitatively measured loss of joint space width to transitions in KL grade and JSN provides reference values based on traditional definitions of knee OA onset and progression.

Signal intensity alteration within infrapatellar fat pad predicts knee replacement within 5 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether infrapatellar fat pad (IPFP) signal intensity (SI) alteration predicts the occurrence of knee replacement (KR) in knee osteoarthritis (OA) patients over 5 years. DESIGN: The subjects were selected from Osteoarthritis Initiative (OAI) study. Case knees (n = 127) were defined as those who received KR during 5 years follow-up visit. They were matched by gender, age and radiographic status with control knees (n = 127). We used T2-weighted MR images to measure IPFP SI alteration using a newly developed algorithm in MATLAB. The measurements were assessed at baseline (BL), T0 (the visit just before KR) and 1 year before T0 (T-1). Conditional logistic regression was used to analyse the associations between IPFP SI alterations and the risk of KR. RESULTS: Participants were mostly female (57%), with an average age of 63.7 years old and a mean body mass index (BMI) of 29.5 kg/m2. In multivariable analysis, the standard deviation (SD) of IPFP SI [sDev (IPFP)] and the ratio of high SI region volume to whole IPFP volume [Percentage (H)] measured at BL were significantly associated with increased risks of KR after adjustment for covariates. IPFP SI alterations measured at T-1 including sDev (IPFP), Percentage (H) and clustering effect of high SI [Clustering factor (H)] were significantly associated with higher risks of KR. All measurements were significantly associated with higher risks of KR at T0. CONCLUSIONS: IPFP SI is associated with the occurrence of KR suggesting it may play a role in end-stage knee OA.

Mitochondrial DNA haplogroups associated with MRI-detected structural damage in early knee osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI)-detected structural features are associated with increased risk of radiographic osteoarthritis (ROA). Specific mitochondrial DNA (mtDNA) haplogroups have been associated with incident ROA. Our objective was to compare the presence of MRI-detected structural features across mtDNA haplogroups among knees that developed incident ROA. DESIGN: Knees from the Osteoarthritis Initiative (OAI) that developed incident ROA during 48 months follow-up were identified from Caucasian participants. mtDNA haplogroups were assigned based on a single base extension assay. MRIs were obtained annually between baseline and 4-year follow-up and scored using the MRI Osteoarthritis Knee Score (MOAKS). The association between mtDNA haplogroups and MRI-detected structural features was estimated using log-binomial regression. Participants who carried haplogroup H served as the reference group. RESULTS: The sample included 255 participants contributing 277 knees that developed ROA. Haplogroups included H (116, 45%), J (17, 7%), T (26, 10%), Uk (61, 24%), and the remaining less common haplogroups ("others") (35, 14%). Knees of participants with haplogroup J had significantly lower risk of medium/large bone marrow lesions (BMLs) in the medial compartment [3.2%, relative risks (RR) = 0.17; 95%CI: 0.05, 0.64; P = 0.009] compared to knees of participants who carried haplogroup H [16.3%], as did knees from participants within the "others" group [2.8%, RR = 0.20; 95%CI: 0.08, 0.55; P = 0.002], over the 4 year follow-up period. CONCLUSIONS: mtDNA haplogroup J was associated with lower risk of BMLs in the medial compartment among knees that developed ROA. Our results offer a potential hypothesis to explain the mechanism underlying the previously reported protective association between haplogroup J and ROA.

Predictive and concurrent validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate the predictive and concurrent validity of magnetic resonance imaging (MRI)-based cartilage thickness change between baseline (BL) and year-two (Y2) follow-up (predictive validity) and between Y2 and Y4 follow-up (concurrent validity) for symptomatic and radiographic knee osteoarthritis (OA) progression during Y2→Y4. METHODS: 777 knees from 777 Osteoarthritis Initiative (OAI) participants (age: 61.3 ± 9.0 years, BMI: 30.1 ± 4.8 kg/m2) with Kellgren Lawrence (KL) grade 1-3 at Y2 (visit before progression interval) had cartilage thickness measurements from 3T MRI at BL, Y2 (n = 777), and Y4 (n = 708). Analysis of covariance and logistic regression were used to assess the association of pain progression (≥9 WOMAC units [scale 0-100], n = 205/572 with/without progression) and radiographic progression (≥0.7 mm minimum joint space width (mJSW) loss, n = 166/611 with/without progression) between Y2 and Y4 with preceding (BL→Y2) and concurrent (Y2→Y4) change in central medial femorotibial (cMFTC) compartment cartilage thickness. RESULTS: Symptomatic progression was associated with concurrent (Y2→Y4: -305 ± 470 µm vs -155 ± 346 µm, Odds ratios (OR) = 1.5 [1.2, 1.7]) but not with preceding cartilage thickness loss in cMFTC (-150 ± 276 µm vs -151 ± 299 µm, OR = 0.9 95% CI: [0.8, 1.1]). Radiographic progression, in contrast, was significantly associated with both concurrent (-542 ± 550 µm vs -98 ± 255 µm, OR = 3.4 [2.6, 4.3]) and preceding cMFTC thickness loss (-229 ± 355 µm vs -130 ± 270 µm, OR = 1.3 [1.1, 1.5]). CONCLUSIONS: These results extend previous reports that did not discern predictive vs concurrent associations of cartilage thickness loss with OA progression. The observed predictive and concurrent validity of cartilage thickness loss for radiographic progression and observed concurrent validity for symptomatic progression provide an important step in qualifying cartilage thickness loss as a biomarker of knee OA progression. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

Magnetic resonance imaging lesions are more severe and cartilage T2 relaxation time measurements are higher in isolated lateral compartment radiographic knee osteoarthritis than in isolated medial compartment disease - data from the Osteoarthritis Initiative.

OBJECTIVE: Isolated lateral compartment tibiofemoral radiographic osteoarthritis (IL-ROA) is an understudied form of knee osteoarthritis (OA). The objective of the present study was to characterize Magnetic Resonance Imaging (MRI) abnormalities and MR-T2 relaxation time measurements associated with IL-ROA and with isolated medial compartment ROA (IM-ROA) compared with knees without OA. METHOD: 200 case subjects with IL-ROA (Kellgren/Lawrence (K/L) grade≥2 and joint space narrowing (JSN) > 0 in the lateral compartment but JSN = 0 in the medial compartment) were randomly selected from the Osteoarthritis Initiative baseline visit. 200 cases with IM-ROA and 200 controls were frequency matched to the IL-ROA cases. Cases and controls were analyzed for odds of having a subregion with >10% cartilage area affected, with ≥25% bone marrow lesions (BML), with meniscal tear or maceration, and for association with cartilage T2 values. RESULTS: IL-ROA was more strongly associated with ipsilateral MRI knee pathologies than IM-ROA (IL-ROA: OR = 135.2 for size of cartilage lesion, 95% CI 42.7-427.4; OR = 145.4 for large size BML, 95% CI 41.5-509.5; OR = 176 for meniscal tears, 95% CI 59.8-517.7; IM-ROA: OR = 28.4 for size of cartilage lesion, 95% CI 14.7-54.7; OR = 38.1 for size of BML, 95% CI 12.7-114; OR = 37.0 for meniscal tears, 95% CI 12-113.6). Cartilage T2 values were higher in both tibial and medial femoral compartments in IL-ROA, but in IM-ROA were only significantly different from controls in the medial femur. CONCLUSION: IL-ROA knees show a greater prevalence and severity of MRI lesions and higher cartilage T2 values than IM-ROA knees compared with controls.

Analgesic use and risk of recurrent falls in participants with or at risk of knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: Few studies have compared the risk of recurrent falls across different types of analgesic use, and with limited adjustment for potential confounders (e.g., pain/depression severity). We assessed analgesic use and the subsequent risk of recurrent falls, among participants with or at risk of knee osteoarthritis (OA). METHODS: A longitudinal analysis included 4231 participants aged 45-79 years at baseline with 4-year follow-up from the Osteoarthritis Initiative (OAI) cohort study. We grouped participants into six mutually exclusive subgroups based on annually assessed analgesic use in the following hierarchical order of analgesic/central nervous system (CNS) potency: use of (1) opioids, (2) antidepressants, (3) other prescription pain medications, (4) over-the-counter (OTC) pain medications, (5) nutraceuticals, and (6) no analgesics. We used multivariable modified Poisson regression models with a robust error variance to estimate the effect of analgesic use on the risk of recurrent falls (≥2) in the following year, adjusted for demographics and health status/behavior factors. RESULTS: Opioid use increased from 2.7% at baseline to 3.6% at the 36-month visit (>80% using other analgesics/nutraceuticals), while other prescription pain medication use decreased from 16.7% to 11.9% over this time period. Approximately 15% of participants reported recurrent falls. Compared to those not using analgesics, participants who used opioids and/or antidepressants had a 22-25% increased risk of recurrent falls (opioids: RRadjusted = 1.22, 95% CI = 1.04-1.45; antidepressants: RRadjusted = 1.25, 95% CI = 1.10-1.41). CONCLUSION: Participants with or at risk of knee OA who used opioids and antidepressants with/without other analgesics/nutraceuticals may have an increased risk of recurrent falls after adjusting for potential confounders. Use of opioids and antidepressants warrants caution.

Synovitis in knee osteoarthritis: a precursor of disease?

OBJECTIVES: It is unknown whether joint inflammation precedes other articular tissue damage in osteoarthritis. Therefore, this study aims to determine if synovitis precedes the development of radiographic knee osteoarthritis (ROA). METHODS: The participants in this nested case-control study were selected from persons in the Osteoarthritis Initiative with knees that had a Kellgren Lawrence grading (KLG)=0 at baseline (BL). These knees were evaluated annually with radiography and non-contrast-enhanced MRI over 4 years. MRIs were assessed for effusion-synovitis and Hoffa-synovitis. Case knees were defined by ROA (KLG≥2) on the postero-anterior knee radiographs at any assessment after BL. Radiographs were assessed at P0 (time of onset of ROA), 1 year prior to P0 (P-1) and at BL. Controls were participants who did not develop incident ROA (iROA) from BL to 48 months). RESULTS: 133 knees of 120 persons with ROA (83 women) were matched to 133 control knees (83 women). ORs for occurrence of iROA associated with the presence of effusion-synovitis at BL, P-1 and P0 were 1.56 (95% CI 0.86 to 2.81), 3.23 (1.72 to 6.06) and 4.7 (1.10 to 2.95), respectively. The ORs for the occurrence of iROA associated with the presence of Hoffa-synovitis at BL, P-1 and P0 were 1.80 (1.1 to 2.95), 2.47 (1.45 to 4.23) and 2.40 (1.43 to 4.04), respectively. CONCLUSIONS: Effusion-synovitis and Hoffa-synovitis strongly predicted the development of iROA.

An illustrative overview of semi-quantitative MRI scoring of knee osteoarthritis: lessons learned from longitudinal observational studies.

OBJECTIVE: To introduce the most popular magnetic resonance imaging (MRI) osteoarthritis (OA) semi-quantitative (SQ) scoring systems to a broader audience with a focus on the most commonly applied scores, i.e., the MOAKS and WORMS system and illustrate similarities and differences. DESIGN: While the main structure and methodology of each scoring system are publicly available, the core of this overview will be an illustrative imaging atlas section including image examples from multiple OA studies applying MRI in regard to different features assessed, show specific examples of different grades and point out pitfalls and specifics of SQ assessment including artifacts, blinding to time point of acquisition and within-grade evaluation. RESULTS: Similarities and differences between different scoring systems are presented. Technical considerations are followed by a brief description of the most commonly utilized SQ scoring systems including their responsiveness and reliability. The second part is comprised of the atlas section presenting illustrative image examples. CONCLUSIONS: Evidence suggests that SQ assessment of OA by expert MRI readers is valid, reliable and responsive, which helps investigators to understand the natural history of this complex disease and to evaluate potential new drugs in OA clinical trials. Researchers have to be aware of the differences and specifics of the different systems to be able to engage in imaging assessment and interpretation of imaging-based data. SQ scoring has enabled us to explain associations of structural tissue damage with clinical manifestations of the disease and with morphological alterations thought to represent disease progression.

Loss of anterior cruciate ligament integrity and the development of radiographic knee osteoarthritis: a sub-study of the osteoarthritis initiative.

INTRODUCTION: The aim of this study was to determine whether loss of ACL integrity in an older cohort precedes the onset of radiographic OA (ROA). METHODS: Participants in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study who had risk factors for OA development but did not have ROA (Kellgren-Lawrence grading (KLG) of 0 or 1) in both knees at baseline. The MRIs were assessed for the presence of ACL tears. Case knees were defined by the development of ROA on knee radiographs between the 12 and 48 month visits. Their radiographs were assessed at P0 (time of onset of radiographic knee OA), 1 year prior to P0 (P-1) and at baseline. Controls were selected from amongst those who did not develop incident ROA and were matched to cases. RESULTS: 355 persons who developed ROA were matched to 355 controls. No relationship between loss of ACL integrity and incident ROA was found at any assessment time point. Odds ratios (OR) for baseline, 1 year prior to incident ROA (P1) and at point of occurrence of incident ROA (P0) were 2.00 (0.66-6.06), 2.5 (0.76-8.24) and 2.75 (0.85-8.88) respectively. A significant risk of incident ROA was found in participants who had a history of knee injury with an OR of 1.51 (1.05-2.16). CONCLUSION: Loss of ACL integrity does not confer a significantly increased risk of incident ROA in an older adult cohort. In contrast, a history of knee injury was associated with an increased risk of incident ROA.

Brief report: symmetricity of radiographic and MRI-detected structural joint damage in persons with knee pain--the Joints on Glucosamine (JOG) Study.

OBJECTIVE: Most MRI-based osteoarthritis (OA) studies have focused on a single knee per person and thus, data on bilaterality is sparse. Study aim was to describe symmetricity of MRI-detected OA features in a cohort of subjects with knee pain. DESIGN: Participants were 169 subjects with chronic knee pain who had 3 T MRI of both knees using the same protocol as in the Osteoarthritis Initiative. Knees were read for cartilage damage, bone marrow lesions (BMLs), and meniscal damage according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Chi(2) tests were used to compare the proportion of knees with unilateral tissue pathology to the proportion what would be expected if both knees were independent. We further used percent agreement and linear weighted kappa statistics to describe agreement of cartilage damage and BMLs in the same articular plates. RESULTS: 51.2% of participants were men, mean age was 52.1 (±6.2), mean BMI was 29.0 kg/m(2) (±4.1). All plates showed a significant higher degree of symmetricity for cartilage damage as evidenced by weighted kappas ranging from 0.32 to 0.59. For BMLs the degree of symmetricity was higher for the patella, trochlea, medial tibia, lateral femur, and medial femur; for meniscal damage the degree of unilaterality was lower for all medial meniscal subregions but not all lateral. Kappas ranged between 0.52 and 0.68 for cartilage and 0.30 and 0.55 for BMLs for the four subregions with highest agreement. CONCLUSION: A higher degree of symmetricity of tissue damage than expected by chance was observed in this cohort of subjects with knee pain.

The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study.

BACKGROUND: Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. OBJECTIVE: To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI). METHODS: Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders. RESULTS: Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]. CONCLUSION: Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA.