First Qualification Study of Serum Biomarkers as Indicators of Total Body Burden of Osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a debilitating chronic multijoint disease of global proportions. OA presence and severity is usually documented by x-ray imaging but whole body imaging is impractical due to radiation exposure, time and cost. Systemic (serum or urine) biomarkers offer a potential alternative method of quantifying total body burden of disease but no OA-related biomarker has ever been stringently qualified to determine the feasibility of this approach. The goal of this study was to evaluate the ability of three OA-related biomarkers to predict various forms or subspecies of OA and total body burden of disease. METHODOLOGY/PRINCIPAL FINDINGS: Female participants (461) with clinical hand OA underwent radiography of hands, hips, knees and lumbar spine; x-rays were comprehensively scored for OA features of osteophyte and joint space narrowing. Three OA-related biomarkers, serum hyaluronan (sHA), cartilage oligomeric matrix protein (sCOMP), and urinary C-telopeptide of type II collagen (uCTX2), were measured by ELISA. sHA, sCOMP and uCTX2 correlated positively with total osteophyte burden in models accounting for demographics (age, weight, height): R(2) = 0.60, R(2) = 0.47, R(2) = 0.51 (all p<10(-6)); sCOMP correlated negatively with total joint space narrowing burden: R(2) = 0.69 (p<10(-6)). Biomarkers and demographics predicted 35-38% of variance in total burden of OA (total joint space narrowing or osteophyte). Joint size did not determine the contribution to the systemic biomarker concentration. Biomarker correlation with disease in the lumbar spine resembled that in the rest of the skeleton. CONCLUSIONS/SIGNIFICANCE: We have suspected that the correlation of systemic biomarkers with disease has been hampered by the inability to fully phenotype the burden of OA in a patient. These results confirm the hypothesis, revealed upon adequate patient phenotyping, that systemic joint tissue concentrations of several biomarkers can be quantitative indicators of specific subspecies of OA and of total body burden of disease

Cross-sectional associations between variations in ankle shape by statistical shape modeling, injury history, and race : the Johnston County Osteoarthritis Project

Rheumatology Research Foundation Medical Student Preceptorship Award (Lateef/Nelson), NIAMS K23 AR061406 (Nelson); NIH/NIAMS P60AR064166 and U01DP003206 (Jordan/Renner), NIH/NIAMS R01AR067743 (Golightly). The funders had no role in study design; collection, analysis, or interpretation of data; writing the manuscript or the decision to submit for publication.Peer reviewedPublisher PD

Serum N-propeptide of collagen IIA (PIIANP) as a marker of radiographic osteoarthritis burden

Cartilage homeostasis relies on a balance of catabolism and anabolism of cartilage matrix. Our goal was to evaluate the burden of radiographic osteoarthritis and serum levels of type IIA procollagen amino terminal propeptide (sPIIANP), a biomarker representing type II collagen synthesis, in osteoarthritis

Quantification of the whole-body burden of radiographic osteoarthritis using factor analysis

INTRODUCTION: Although osteoarthritis (OA) commonly involves multiple joints, no widely accepted method for quantifying whole-body OA burden exists. Therefore, our aim was to apply factor analytic methods to radiographic OA (rOA) grades across multiple joint sites, representing both presence and severity, to quantify the burden of rOA. METHODS: We used cross-sectional data from the Johnston County Osteoarthritis Project. The sample (n = 2092) had a mean age of 65 ± 11 years, body mass index (BMI) 31 ± 7 kg/m2, with 33% men and 34% African Americans. A single expert reader (intra-rater κ = 0.89) provided radiographic grades based on standard atlases for the hands (30 joints, including bilateral distal and proximal interphalangeal [IP], thumb IP, metacarpophalangeal [MCP] and carpometacarpal [CMC] joints), knees (patellofemoral and tibiofemoral, 4 joints), hips (2 joints), and spine (5 levels [L1/2 to L5/S1]). All grades were entered into an exploratory common factor analysis as continuous variables. Stratified factor analyses were used to look for differences by gender, race, age, and cohort subgroups. RESULTS: Four factors were identified as follows: IP/CMC factor (20 joints), MCP factor (8 joints), Knee factor (4 joints), Spine factor (5 levels). These factors had high internal consistency reliability (Cronbach's α range 0.80 to 0.95), were not collapsible into a single factor, and had moderate between-factor correlations (Pearson correlation coefficient r = 0.24 to 0.44). There were no major differences in factor structure when stratified by subgroup. CONCLUSIONS: The 4 factors obtained in this analysis indicate that the variables contained within each factor share an underlying cause, but the 4 factors are distinct, suggesting that combining these joint sites into one overall measure is not appropriate. Using such factors to reflect multi-joint rOA in statistical models can reduce the number of variables needed and increase precision

Lumbar spine radiographic features and demographic, clinical, and radiographic knee, hip and hand osteoarthritis: The Johnston County Osteoarthritis Project

Objective—1) To determine the prevalence of lumbar spine individual radiographic features (IRF) of disc space narrowing (DSN), osteophytes (OST) and facet joint osteoarthritis (FOA). 2) To describe the frequencies of demographic, clinic and radiographic knee, hip and hand osteoarthritis (OA) across lumbar spine IRF. 3) To determine factors associated with lumbar spine IRF. Methods—A cross-sectional study of 840 participants enrolled in the Johnston County OA Project (2003-4). Sample-based prevalence estimates were generated for each lumbar spine IRF. Associations between lumbar spine IRF and demographic, clinical and peripheral joint OA were determined with logistic regression models. Results—Sample-based prevalence estimates were similar for DSN (57.6%) and FOA (57.9%) but higher for OST (88.1%) with significant differences across race and gender. Hand and knee OA frequencies increased across IRF whereas the effect was absent for hip OA. African Americans had lower odds of FOA (adjusted odds ratio [aOR]=0.45 (95% CI 0.32, 0.62)) while there was no racial association with DSN and OST. Low back symptoms were associated with DSN (aOR=1.37 (95% CI 1.04, 1.80)) but not OST or FOA. Knee OA was associated with OST (aOR=1.62 (95% CI 1.16, 2.27)) and FOA (aOR=1.69 (95% CI 1.15, 2.49)) but not DSN. Hand OA was associated with FOA (aOR=1.67 (95% CI 1.20, 2.28)) but not with DSN or OST. No associations were found with hip OA. Conclusion—These findings underscore the importance of analyzing lumbar spine IRF separately as the associations with demographic, clinic and radiographic knee, hip and hand OA differ widely

Performance of global assessments of hip, knee, and back symptom change

To compare patients’ global assessments of change in knee, hip, and back symptoms with actual changes over time in pain, function, and radiographic severity

Associations of educational attainment, occupation and community poverty with knee osteoarthritis in the Johnston County (North Carolina) osteoarthritis project

Abstract: Introduction: The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA. Methods: A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34% African American). Educational attainment ( 25%) were examined separately and together in logistic models adjusting for covariates of age, gender, race, body mass index (BMI), smoking, knee injury and occupational activity score. Outcomes were presence of radiographic knee OA (rOA), symptomatic knee OA (sxOA), bilateral rOA and bilateral sxOA. Results: When all three socioeconomic status (SES) variables were analyzed simultaneously, low educational attainment was significantly associated with rOA (odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.20, 1.73), bilateral rOA (OR = 1.43, 95% CI 1.13, 1.81), and sxOA (OR = 1.66, 95% CI 1.34, 2.06), after adjusting for covariates. Independently, living in a community of high household poverty rate was associated with rOA (OR = 1.83, 95% CI 1.43, 2.36), bilateral rOA (OR = 1.56, 95% CI 1.12, 2.16), and sxOA (OR = 1.36, 95% CI 1.00, 1.83). Occupation had no significant independent association beyond educational attainment and community poverty. Conclusions: Both educational attainment and community SES were independently associated with knee OA after adjusting for primary risk factors for knee OA

Racial differences in associations between baseline patterns of radiographic osteoarthritis and multiple definitions of progression of hip osteoarthritis: the Johnston County Osteoarthritis Project

Abstract Background To identify baseline radiographic features that predict hip osteoarthritis (HOA) progression, and to explore differences in these associations by race. Methods Radiographs from the community-based Johnston County OA Project were scored using Kellgren-Lawrence (KL) grade and for presence and location of joint space narrowing (JSN), osteophytes, and subchondral changes. Associations between these features and HOA progression (increase of at least 1 KL grade, interval hip replacement, range of motion [ROM, a reduction of ≥10° in internal rotation], or disability [increase of ≥0.2 in Health Assessment Questionnaire scores], or Any of these) were assessed using logistic regression, adjusting for age, gender, race, hip injury, BMI, education, smoking and follow-up time, accounting for multiple comparisons. Race interactions were assessed and analyses stratified as indicated. Results The sample (n = 1,422) included 40 % men and 26 % African American (AA) participants, with mean age 61 years and BMI 29 kg/m2. The baseline frequency of radiographic hip OA (RHOA) between Caucasians and AAs was similar (23 %), although some radiographic features differed. AAs were more likely to have progression defined by ROM or disability or Any progression; Caucasians were more likely to have RHOA progression. JSN, subchondral sclerosis, and medial osteophytes were associated with increased RHOA progression overall; JSN was associated with disability progression only in AAs, while lateral osteophytes were associated with ROM progression only in Caucasians. Conclusions AAs and Caucasians exhibited differences in the radiographic presentation and progression patterns of HOA, with AAs reporting progressive pain and disability, while Caucasians had more RHOA progression

Follicle-stimulating Hormone is Independently Associated with Lean Mass but not BMD in Younger Postmenopausal Women

PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT).RESULTS: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD.CONCLUSIONS: After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight