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.

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.

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.

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.

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.

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.