Hip symptoms are associated with premature mortality: the Johnston County Osteoarthritis Project.

OBJECTIVE: To investigate the impact of hip osteoarthritis (OA) and/or hip symptoms on excess mortality. DESIGN: We analyzed data from 3,919 individuals in a community-based prospective cohort of African Americans and Caucasians age ≥45 years. Women ≥50 years of age and all men underwent supine anteroposterior pelvic radiography at baseline, with the participant's feet in 15 degrees of internal rotation. Hip radiographic (rOA) was defined as a Kellgren-Lawrence grade of ≥2 in at least one hip. Participants completed questionnaires at baseline to determine presence of hip symptoms and covariate status. Participants with symptomatic hip rOA (SxOA) are a subset of individuals with hip rOA and symptoms in the same hip. Multiple imputation was used to impute missing values of covariates. Mortality was determined through 2015 and follow-up time was calculated from baseline assessment until death or censoring which took place when a participant was lost to follow-up or reached the end of study period. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We carried out additional analyses stratified by sex, race, age and obesity. RESULTS: Mean follow-up time was 14.2 years during which 1762 deaths occurred. There were 29.9% participants in our population with hip rOA at baseline. Compared to those with neither hip rOA nor hip symptoms, we observed an increased risk of all-cause mortality in participants with hip symptoms alone (HR = 1.28, 95% CI = 1.13-1.46), but no association for hip rOA either with or without symptoms. In stratified analyses we observed increased associations for hip symptoms alone and hip sxOA in those <65 years (43% and 39% increase, respectively) and in Caucasians (34% and 21% increase, respectively). CONCLUSIONS: Individuals who had hip symptoms without hip rOA had an increased risk of mortality. These effects were particularly strong for those who were <65 years of age and Caucasians. Effective interventions to identify those with hip pain in order to lessen it could reduce premature mortality.

Incidence and progression of hand osteoarthritis in a large community-based cohort: the Johnston County Osteoarthritis Project.

OBJECTIVE: To describe the incidence and progression of radiographic and symptomatic hand osteoarthritis (rHOA and sxHOA) in a large community-based cohort. DESIGN: Data were from the Johnston County OA Project (1999-2015, 12 ± 1.2 years follow-up, age 45+). Participants had bilateral hand radiographs each visit, read for Kellgren-Lawrence grade (KLG) at 30 joints. We defined rHOA as KLG ≥2 in ≥1 joint. SxHOA was defined in a hand/joint with rHOA and self-reported symptoms or tenderness on exam. Incidence was assessed in those without, while progression was assessed in those with, baseline rHOA. Proportions or medians are reported; differences by sex and race were assessed using models appropriate for dichotomous or continuous definitions, additionally adjusted for age, education, body mass index (BMI), and weight change. RESULTS: Of 800 participants (68% women, 32% African American, mean age 60 years), 327 had baseline rHOA and were older, more often white and female, than those without rHOA (n = 473). The incidence of HOA was high, for rHOA (60%) and for sxHOA (13%). Women were more likely than men to have incident HOA, particularly for distal interphalangeal joint radiographic osteoarthritis (DIP rOA) (adjusted odds ratios (aOR) 1.60 95% confidence intervals (95% CI) [1.03, 2.49]) and sxHOA (aOR 2.98 [1.50, 5.91]). Progressive HOA was more similar by sex, although thumb base rOA progressed more frequently in women than in men (aOR 2.56 [1.44, 4.55]). Particularly HOA incidence, but also progression, was more frequent among whites compared with African Americans. CONCLUSION: This study provides much needed information about the natural history of HOA, a common and frequently debilitating condition, in the general population.

The impact of painful knee osteoarthritis on mortality: a community-based cohort study with over 24 years of follow-up.

OBJECTIVE: To investigate the impact of knee osteoarthritis (OA) and/or knee pain on excess mortality. METHOD: We analyzed data from 4,182 participants in a community-based prospective cohort study of African American and Caucasian men and women aged ≥45 years. Participants completed knee radiographs and questionnaires at baseline and at up to three follow-ups to determine knee OA (rOA), knee pain and covariate status. Mortality was determined through 2015. We used Cox proportional hazards regression with time-varying covariates (TVC) to estimate hazard ratios (HR) and 95% confidence intervals (CI). Additional analyses stratified by sex, race and age were carried out. RESULTS: Median follow-up time was 14.6 years during which 1822 deaths occurred. Baseline knee radiographic osteoarthritis (rOA) was 27.7%, 38.8% at first follow-up, 52.6% at second follow-up and 61.9% at the third follow-up. Knee rOA with pain and knee pain alone were both associated with a >15% increase in premature all-cause mortality. In analyses stratified by sex, race and age, associations between knee pain, with or without knee rOA, and all-cause death were found among women, Caucasians, those ≤65 years of age, and those with a body mass index (BMI)≥30, with observed increased risks of death between 21% and 65%. We observed similar, somewhat attenuated, results for cardiovascular disease (CVD) deaths. CONCLUSION: In models taking into account variables that change over time, individuals who had knee pain, alone or with knee rOA, had increased mortality. These effects were particularly strong among those obese. Effective interventions to reduce knee pain, particularly those including weight management and prevention of comorbidities, could reduce mortality.

Associations between the chemokine biomarker CCL2 and knee osteoarthritis outcomes: the Johnston County Osteoarthritis Project.

OBJECTIVE: Our study analyzes the association between chemokine-ligand-2 (CCL2) serum concentrations at baseline and knee radiographic osteoarthritis (OA) (knee-rOA), knee-rOA progression, individual radiographic features and knee symptomatic OA at 5-year follow-up. DESIGN: OA outcomes were analyzed in a community-based cohort including a baseline enrollment and a 5-year follow-up. Baseline CCL2 serum concentrations were assessed by multiplex assay and associated with presence or progression of individual radiographic features at 5-year follow-up. Separate multiple logistic regression models were used to examine adjusted associations between baseline CCL2 and each of the knee OA variables at follow-up. CCL2 at baseline was modeled as an explanatory variable, whereas each of the knee OA variables at follow-up served as the response variables. Models were adjusted for age, BMI, race, and sex. Trend tests were conducted to assess any linear effect on outcomes across CCL2 tertiles. RESULTS: Participants (n = 168) had a median age of 57-years and median BMI of 29 kg/m2. About 63% of all participants were women, and 58% Caucasian (42% African American). In adjusted logistic models, continuous log-CCL2 was significantly associated with knee-rOA. For each unit increase in log CCL2, the odds of having knee-rOA at follow-up was increased by 72%. CCL2 tertiles showed significant linear associations with presence and progression of knee-rOA and medial joint space narrowing (JSN), but not with presence or progression of osteophytes, bone sclerosis, knee symptoms, or symptomatic knee-rOA. CONCLUSIONS: Serum CCL2 may help to elucidate some mechanisms of joint destruction and identify individuals with higher odds of structural knee changes.

Population-based prevalence of multiple radiographically-defined hip morphologies: the Johnston County Osteoarthritis Project.

OBJECTIVE: To provide the first prevalence estimates of different radiographic hip morphologies relevant to dysplasia and femoroacetabular impingement in a well-characterized USA population-based cohort. METHODS: Cross-sectional data were from the baseline examination (1991-1997) of a large population-based prospective longitudinal cohort study (The Johnston County Osteoarthritis Project). HipMorf software (Oxford, UK) was used to assess hip morphology on anteroposterior (AP) pelvis radiographs. Weighted, sex-stratified prevalence estimates and 95% confidence intervals for four key hip morphologies (AP alpha angle, triangular index sign, lateral center edge angle (LCEA), and protrusio acetabula) were derived and further stratified by age, race and body mass index (BMI). RESULTS: A total of 5192 hips from 2596 individuals were included (31% African American, 43% male, mean age 63 years, mean BMI 29 kg/m2). Cam morphology was seen in more than 25% of men and 10% of women. Mild dysplasia was present in about 1/3 of men and women, while pincer morphology was identified in 7% of men and 10% of women. Femoral side (cam) morphologies were more common and more frequently bilateral among men, while pincer morphologies were more common in women; mixed morphologies were infrequent. African-Americans were more likely to have protrusio acetabula than whites. CONCLUSION: We report the first population-based prevalence estimates of radiographic hip morphologies relevant to femoroacetabular impingement (FAI) and dysplasia in the USA. These morphologies are very common, with » men and 1/10 women having cam morphology, 1/3 of all adults having mild dysplasia, and 1/15 men and 1/10 women having pincer morphology in at least one hip.

Biomarkers reflect differences in osteoarthritis phenotypes of the lumbar spine: the Johnston County Osteoarthritis Project.

OBJECTIVE: To determine differences in biomarker levels between radiographic phenotypes of facet joint osteoarthritis (FOA) only, spine OA only ((disc space narrowing (DSN) and vertebral osteophytes (OST)) or the combination of FOA and spine OA. DESIGN: A cross-sectional analysis of data from 555 participants in the Johnston County Osteoarthritis Project was performed. Lumbar spine levels were graded by severity (OST and DSN) and presence (FOA) of degeneration. Biomarkers included hyaluronan (HA) and type II collagen (CTX-II). Adjusted risk ratios (aRRR) were estimated using multinomial regression, with adjustment for age, race, sex, body mass index (BMI), and radiographic OA (knee, hip, hand). Interactions were tested between sex, race and low back symptoms. RESULTS: FOA only was present in 22.4%, 14.5% had spine OA only, and 34.6% had the combination of FOA and spine OA. Compared to the reference group of neither FOA or spine OA, a one unit higher ln HA level was associated with 31% higher relative risk ratio (RRR = 1.31 (95% 1.03, 1.67)) of having FOA only, while, a one unit higher lnuCTX-II level was associated with 84% higher relative risk ratio (RRR = 1.84 (95% CI 1.19, 2.84)) of having spine OA only. No significant interactions were identified. CONCLUSION: Interestingly, OA affecting the synovial facet joint was associated with a marker of inflammation (HA). Spine OA, affecting intervertebral discs that contain collagen type II, was associated with a marker reflecting collagen type II degradation (CTX-II). These findings suggest that biomarkers may reflect the different pathophysiologic processes of lumbar spine OA phenotypes.

Annual incidence rates of hip symptoms and three hip OA outcomes from a U.S. population-based cohort study: the Johnston County Osteoarthritis Project.

OBJECTIVE: Estimate annual incidence rates (IRs) of hip symptoms and three osteoarthritis (OA) outcomes (radiographic, symptomatic, and severe radiographic) overall and by race, sociodemographic characteristics, and hip OA risk factors. DESIGN: Analyze baseline (1991-1997) and first follow-up (1999-2003) data (n = 1446) from the Johnston County Osteoarthritis Project, a population-based, prospective study of adults ≥45 years in North Carolina. Hip symptoms were pain, aching, and/or stiffness on most days, or groin pain. Radiographic and severe radiographic OA were Kellgren-Lawrence (KL) grades ≥2 and ≥3, respectively. Symptomatic OA was radiographic OA with symptoms in the same hip. Sociodemographics were age, gender, race, highest attained education, and annual household income. Hip OA risk factors were self-reported body mass index (BMI) at age 18 years, clinically measured BMI at baseline, and history of hip injury. RESULTS: Annual IRs (median = 5.5 years follow-up) were 37, 23, 13, and 2.9 per 1000 person-years for hip symptoms, and radiographic, symptomatic, and severe radiographic hip OA, respectively. We found low IRs of radiographic and symptomatic hip OA among African Americans and high IRs of hip symptoms among the obese and the very poor. Across outcomes, IRs were highest for those with hip injury. CONCLUSION: No prior studies have reported IRs of hip symptoms; IRs of radiographic and severe radiographic hip OA were similar to, and the IR of symptomatic hip OA was higher than, previous estimates. Prevention efforts should target low socioeconomic status (SES) populations and obese adults; interventions for hip OA and hip symptoms are imperative for those with hip injuries.

Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women.

INTRODUCTION: Hip shape is a risk factor for the development of hip osteoarthritis (OA), and current methods to assess hip shape from radiographs are limited; therefore this study explored current and novel methods to assess hip shape. METHODS: Data from a prior case-control study nested in the Johnston County OA Project were used, including 382 hips (from 342 individuals). Hips were classified by radiographic hip OA (RHOA) status as RHOA cases (baseline Kellgren Lawrence grade [KLG] 0 or 1, follow-up [mean 6 years] KLG ≥ 2) or controls (KLG = 0 or 1 at both baseline and follow-up). Proximal femur shape was assessed using a 60-point model as previously described. The current analysis explored commonly used principal component analysis (PCA), as well as novel statistical methodologies suited to high dimension low sample size settings (Distance Weighted Discrimination [DWD] and Distance Projection Permutation [DiProPerm] hypothesis testing) to assess differences between cases and controls. RESULTS: Using these novel methodologies, we were able to better characterize morphologic differences by sex and race. In particular, the proximal femurs of African American women demonstrated significantly different shapes between cases and controls, implying an important role for sex and race in the development of RHOA. Notably, discrimination was improved with the use of DWD and DiProPerm compared to PCA. CONCLUSIONS: DWD with DiProPerm significance testing provides improved discrimination of variation in hip morphology between groups, and enables subgroup analyses even under small sample sizes.

Measures of hip morphology are related to development of worsening radiographic hip osteoarthritis over 6 to 13 year follow-up: the Johnston County Osteoarthritis Project.

OBJECTIVES: We sought to describe the effect of alterations in hip morphology with respect to worsening hip OA in a community-based sample including African American (AA) and white men and women. METHODS: This nested case-control study defined case hips as Kellgren Lawrence grade (KLG) <3 on baseline supine pelvis radiographs and KLG ≥3 or THR for OA at the 1st or 2nd follow-up visit (mean 6 and 13 years, respectively); control hips had KLG <3 at both visits, with gender/race distribution similar to cases. Hip morphology was assessed using HipMorf software (Oxford, UK). Descriptive means and standard errors were obtained from generalized estimating equation (GEE) models. Sex-stratified GEE regression models (accounting for within-person correlation), adjusted for age, race, BMI, and side were then employed. RESULTS: A total of 120 individuals (239 hips; 71 case/168 control) were included (25% male, 26% AA, mean age 62 years, BMI 30 kg/m(2)). Case hips tended to have greater baseline AP alpha angles, smaller minimum joint space width (mJSW) and more frequent triangular index signs. Adjusted results among men revealed that higher AP alpha angle, Gosvig ratio, and acetabular index were positively associated with case hips; coxa profunda was negatively associated. Among women, greater AP alpha angle, smaller mJSW, protrusio acetabuli, and triangular index sign were associated with case hips. CONCLUSIONS: We confirmed an increased risk of worsening hip OA due to baseline features of cam deformity among men and women, as well as protrusio acetabuli among women, and provide the first estimates of these measures in AAs.

Atlas of radiographic features of osteoarthritis of the ankle and hindfoot.

OBJECTIVE: To develop a radiographic atlas of osteoarthritis (OA) for use as a template and guide for standardized scoring of radiographic features of OA of the ankle and hindfoot joints. METHOD: Under Institutional Review Board approval, ankle and hindfoot images were selected from a cohort study and from among cases that underwent ankle radiography during a 6-month period at Duke University Medical Center. Missing OA pathology was obtained through supplementation of cases with the assistance of a foot and ankle specialist in Orthopaedic surgery and a musculoskeletal radiologist. Images were obtained and reviewed without patient identifying information. Images went through multiple rounds of review and final images were selected by consensus of the study team. For intra-rater and inter-rater reliability, the kappa statistic was calculated for two readings by three musculoskeletal radiologists, a minimum of two weeks apart, of ankle and hindfoot radiographs from 30 anonymized subjects. RESULTS: The atlas demonstrates individual radiographic features (osteophyte and joint space narrowing (JSN)) and Kellgren-Lawrence grade for all aspects of the talocrural (ankle joint proper) and talocalcaneal (subtalar) joints. Reliability of scoring based on the atlas was quite good to excellent for most features indicated. Additional examples of ankle joint findings are illustrated including sclerosis, os trigonum, subchondral cysts and talar tilt. CONCLUSIONS: It is anticipated that this atlas will assist with standardization of scoring of ankle and hindfoot OA by basic and clinical OA researchers.

Radiographic features of hand osteoarthritis in adult Kashin-Beck Disease (KBD): the Yongshou KBD study.

OBJECTIVE: Kashin-Beck Disease (KBD) is a rare and severe osteoarthropathy endemic to China. We evaluated the frequency and patterns of hand radiographic osteoarthritis (rOA) in adults with and without KBD. METHODS: Han Chinese (N = 438) from Yongshou County of central China underwent right hand radiography for determining case status. Presence of KBD was based on characteristic radiographic deformities of articular ends of bones including articular surface depression, carpal crowding, any subchondral bone deformities in the proximal end of phalanges or first metacarpal bone, or the distal ends of metacarpal bones 2-5, and any bony enlargement with deformity of the distal ends of phalanges. Hand rOA severity was determined by osteophyte (OST), joint space narrowing (JSN), and Kellgren and Lawrence (KL) grades. RESULTS: This study included 127 KBD and 311 non-KBD adults of similar mean age (39 years) and body mass index (BMI) (21 kg/m(2)). Inter- and intra-rater reliability for radiographic determination of case status and rOA features was high (kappa 0.72-0.96). Compared to non-KBD, KBD adults had significantly more severe hand rOA of the thumb, distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints. Only KBD adults had end-stage carpometacapal (CMC) disease. In KBD, DIPs and PIPs were more affected than MCPs and the frequency of OSTs was significantly higher in PIPs than DIPs. CONCLUSIONS: Compared with age-matched adults from the same area and farming occupation, KBD hand rOA was more widespread and severe, particularly of PIPs and CMCs. The ability to differentiate adult KBD from non-KBD hand rOA will facilitate genetic analyses of the vast majority of affected individuals.

Meeting physical activity guidelines and the risk of incident knee osteoarthritis: a population-based prospective cohort study.

OBJECTIVE: Knee osteoarthritis (OA) is a leading cause of disability and joint pain. Although other risk factors of knee OA have been identified, how physical activity affects incident knee OA remains unclear. METHODS: Using data from the first (1999-2004) and second (2005-2010) followup periods of the Johnston County Osteoarthritis Project study, we tested the association between meeting physical activity guidelines and incident knee outcomes among 1,522 adults ages ≥45 years. The median followup time was 6.5 years (range 4.0-10.2 years). Physical activity at baseline (moderate-equivalent physical activity minutes/week) was calculated using the Minnesota Leisure Time Physical Activity questionnaire. Incident knee radiographic OA (ROA) was defined as the development of Kellgren/Lawrence grade ≥2 in a knee at followup. Incident knee symptomatic ROA (sROA) was defined as the development of ROA and symptoms in at least 1 knee at followup. Weibull regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for interval-censored data. RESULTS: In multivariable models, meeting the 2008 Department of Health and Human Services (HHS) physical activity guidelines (≥150 minutes/week) was not significantly associated with ROA (HR 1.20 [95% CI 0.92-1.56]) or sROA (HR 1.24 [95% CI 0.87-1.76]). Adults in the highest level (≥300 minutes/week) of physical activity had a higher risk of knee ROA and sROA compared with inactive (0 to <10 minutes/week) participants; however, these associations were not statistically significant (HR 1.62 [95% CI 0.97-2.68] and HR 1.42 [95% CI 0.76-2.65], respectively). CONCLUSION: Meeting the HHS physical activity guidelines was not associated with incident knee ROA or sROA in a cohort of middle-aged and older adults.

High prevalence of contralateral ankle abnormalities in association with knee osteoarthritis and malalignment.

OBJECTIVE: To evaluate ankle joint abnormalities in a knee osteoarthritis (OA) cohort. METHODS: Participants (n = 159) with symptomatic and radiographic OA in at least one knee underwent technetium-99m methylene diphosphonate bone scan (scored 0-3) of the ankles and forefeet. Knee radiographs were graded for OA features of joint space narrowing (JSN) and osteophyte (OST). Ankle symptoms and history of ankle injury were assessed by self-report. Knee alignment was measured from a long-limb radiograph. Ankle radiographs were obtained on those who returned for follow-up (n = 138) and were graded for ankle tibiotalar JSN and OST. DESIGN: Ankle scintigraphic abnormalities were frequent (31% of individuals, one-third bilateral). Ankle symptoms were reported by 23% of individuals and history of ankle injury by 24%. Controlling for gender, age, body mass index (BMI), and contralateral predictor, ankle scintigraphic abnormalities were associated with: ipsilateral ankle symptoms (P = 0.005); contralateral knee JSN (P = 0.001), knee OST (P = 0.006) and knee malalignment (P = 0.08); and history of ankle injury or surgery of either ankle (P < 0.0001). At follow-up, scintigraphic abnormalities of the ankle were strongly associated with presence of tibiotalar radiographic OA (P < 0.0001). CONCLUSIONS: Although considered rare, we observed a high prevalence of radiographic features of ankle OA in this knee OA cohort. History of overt ankle injury did not appear to account for the majority of ankle abnormalities. These results are consistent with a probable kinematic association of knee OA pathology and contralateral ankle abnormalities and suggest that interventions targeting mechanical factors may be needed to prevent ankle OA in the setting of knee OA.

IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort.

OBJECTIVE: Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time. DESIGN: 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective. RESULTS: Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype. CONCLUSION: A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.

Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project.

OBJECTIVE: (1) To determine associations between radiographic features of lumbosacral (LS) spine disc space narrowing (DSN) and osteophytes (OST) and joint metabolism biomarkers (serum cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), collagen neoepitope (C2C), C-propeptide of type II procollagen (CP-II), urine C-terminal cross-linking telopeptide (CTX-II) and N-terminal telopeptide (NTX-I)). (2) To explore interactions with race, gender and low back symptoms. DESIGN: Cross-sectional analysis of 547 participants enrolled in the Johnston County (JoCo) Osteoarthritis Project from 2003 to 2004. Mean biomarker levels were estimated with linear regression. Proportional and partial-proportional odds models were used to estimate associations. Interactions were tested with likelihood ratio tests at a P-value < 0.10. Biomarkers were natural log (ln) transformed. RESULTS: Significant differences in mean biomarker levels were found across severity of DSN for lnHA and lnC2C and lnCTX-II across severity of both DSN and OST. Moderate-to-strong associations were found between biomarkers of type II collagen and DSN, whereas associations with OST were weak. An association between lnHA and DSN was seen in women (adjusted odds ratio [aOR] = 1.34 (95% confidence intervals (CI) 1.08, 1.65)) but no association among men (aOR = 0.90 (95% CI 0.63, 1.26)). In Caucasians there was a decreased association with NTX-I and OST (aOR = 0.67 (95% CI 0.49, 0.91)) and no association in African Americans (AAs) (aOR = 1.06 (95% CI 0.76, 1.47)). There was a positive association of lnCOMP with DSN among those with low back symptoms (aOR = 1.82 (95% CI 1.02, 3.27)), but no association in those without low back symptoms (aOR = 0.65 (95% CI 0.35, 1.20)). CONCLUSION: Joint metabolism biomarkers suggest biological differences in the pathologic process involved in DSN and OST that may be gender (HA) and ethnicity (NTX-I) specific.

Association of knee and ankle osteoarthritis with physical performance.

OBJECTIVE: The direct measurement of the ability to perform physical tasks yields information about factors contributing to poor function and insights into strategies for preventing disability. Our goal was to evaluate the relationship of walking speed and balance tests with specific radiographic features of knee and ankle osteoarthritis (OA). METHODS: A timed eight foot walk and a standing balance test were performed by 138 participants of a longitudinal observational study of knee OA progression. Radiographic features of OA severity, joint space narrowing (JSN), a surrogate for cartilage loss and osteophyte (OST) formation, were assessed for the knee and ankle. The association of these performance measures with radiographic OA was evaluated using correlation analysis, adjusted for age, gender, body mass index (BMI), and number of comorbidities. RESULTS: Knee and ankle JSN, but not OST, was negatively associated with specific performance tests: walking speed was associated with knee JSN (Spearman rho = -0.20, P = 0.02) and balance was associated with ankle (subtalar joint) JSN (Spearman rho = -0.22, P = 0.01). These relationships remained significant upon further control for knee and ankle pain. CONCLUSIONS: Structural joint damage due to OA (JSN in contrast to OST) negatively impacted specific domains of physical performance. These results indicate that targeting specific joints for specific functional outcomes may be indicated, and suggest that prevention of cartilage damage in these joints is a sensible target for OA disease modification to prevent disability.

Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women.

UNLABELLED: The association between follicle-stimulating hormone (FSH) and bone density was tested in 111 postmenopausal women aged 50-64 years. In the multivariable analysis, weight and race were important determinants of bone mineral density. FSH, bioavailable estradiol, and other hormonal variables did not show statistically significant associations with bone density at any site. INTRODUCTION: FSH has been associated with bone density loss in animal models and longitudinal studies of women. Most of these analyses have not considered the effect of weight or race. METHODS: We tested the association between FSH and bone density in younger postmenopausal women, adjusting for patient-related factors. In 111 postmenopausal women aged 50-64 years, areal bone mineral density (BMD) was measured at the lumbar spine, femoral neck, total hip, and distal radius using dual-energy X-ray absorptiometry, and volumetric BMD was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Height, weight, osteoporosis risk factors, and serum hormonal factors were assessed. RESULTS: FSH inversely correlated with weight, bioavailable estradiol, areal BMD at the lumbar spine and hip, and volumetric BMD at the ultradistal radius. In the multivariable analysis, no hormonal variable showed a statistically significant association with areal BMD at any site. Weight was independently associated with BMD at all central sites (p < 0.001), but not with BMD or pQCT measures at the distal radius. Race was independently associated with areal BMD at all sites (p ≤ 0.008) and with cortical area at the 33% distal radius (p = 0.004). CONCLUSIONS: Correlations between FSH and bioavailable estradiol and BMD did not persist after adjustment for weight and race in younger postmenopausal women. Weight and race were more important determinants of bone density and should be included in analyses of hormonal influences on bone.

One in four people may develop symptomatic hip osteoarthritis in his or her lifetime.

OBJECTIVE: To estimate the lifetime risk of symptomatic hip osteoarthritis (OA). DESIGN: We analyzed data from the Johnston County Osteoarthritis Project [a longitudinal population-based study of OA in North Carolina, United States (n=3068)]. The weighted baseline sample comprised 18% blacks and 54% women, and the mean age was 63 years (range=45-93). Symptomatic hip OA was defined as a Kellgren-Lawrence (K-L) radiographic score of ≥ 2 (anterior-posterior pelvis X-rays) and pain, aching or stiffness on most days, or groin pain, in the same hip. Lifetime risk, defined as the proportion who developed symptomatic hip OA in at least one hip by age 85, among people who live to age 85, was modeled using logistic regression with repeated measures (through generalized estimating equations). RESULTS: Lifetime risk of symptomatic hip OA was 25.3% [95% confidence interval (CI)=21.3-29.3]. Lifetime risk was similar by sex, race, highest educational attainment, and hip injury history. We studied lifetime risk by body mass index (BMI) in three forms: at age 18; at baseline and follow-up; and at age 18, baseline and follow-up and found no differences in estimates. CONCLUSION: The burden of symptomatic hip OA is substantial with one in four people developing this condition by age 85. The similar race-specific estimates suggest that racial disparities in total hip replacements are not attributable to differences in disease occurrence. Despite increasing evidence that obesity predicts an increased risk of both hip OA and joint replacement, we found no association between BMI and lifetime risk.

Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive radiographic osteoarthritis at the hip and knee: the Johnston County Osteoarthritis Project.

PURPOSE: To test whether serum transforming growth factor-beta 1 (TGF-beta1) predicts incident and progressive hip or knee radiographic OA (rOA). METHODS: Serum TGF-beta1 was measured for 330 participants aged 45 years and older in the Johnston County Osteoarthritis Project, with paired longitudinal films available for 618 hips and 658 knees. Incident and progressive rOA were defined using Kellgren-Lawrence (K-L) grade as well as osteophyte (OST) and joint space narrowing (JSN) scores. Natural logarithm transformation was used to produce near-normal distributions for continuous TGF-beta1 (lnTGF-beta1). Separate multivariable Weibull regression models were used to provide hazard ratios (HRs) for a 1-unit increase lnTGF-beta1 with each rOA outcome, accounting for variable follow-up times and clustering by individual, adjusted for age, race, gender, and body mass index (BMI). Interaction terms were considered statistically significant at P<0.10. RESULTS: The mean (+/-SD) age of the sample was 61.9+/-9.7 years, the mean BMI was 30.3+/-6.9 kg/m(2), with 60.6% women and 42.4% AA. The mean (+/-SD) TGF-beta1 was 17.8+/-6.1 ng/ml; follow-up time was 6.1+/-1.3 years. There were no significant interactions by race or gender. HRs showed no significant relationship between lnTGF-beta1 and incident or progressive rOA, OST, or JSN, at the knee or the hip. CONCLUSIONS: Levels of TGF-beta1 do not predict incident or progressive rOA, OST, or JSN at the hip or knee in this longitudinal, population-based study, making it unlikely that TGF-beta1 will be a robust biomarker for rOA in future studies.

Differences in radiographic features of knee osteoarthritis in African-Americans and Caucasians: the Johnston county osteoarthritis project.

OBJECTIVE: To examine racial differences in tibiofemoral joint (TFJ) and patellofemoral joint (PFJ) radiographic osteoarthritis in African-American (AA) and Caucasian men and women. METHOD: Multiple logistic regression was used to evaluate cross-sectional associations between race and tibiofemoral osteoarthritis (TF-OA) and the presence, severity and location of individual radiographic features of tibiofemoral joint osteoarthritis [TFJ-OA] (osteophytes, joint space narrowing [JSN], sclerosis and cysts) and patellofemoral joint osteoarthritis (PFJ-OA) (osteophytes, JSN and sclerosis), using data from the Johnston County Osteoarthritis Project. Proportional odds ratios (POR) assessed severity of TF-OA, TFJ and PFJ osteophytes, and JSN, adjusting for confounders. Generalized estimating equations accounted for auto-correlation of knees. RESULTS: Among 3187 participants (32.5% AAs; 62% women; mean age 62 years), 6300 TFJ and 1957 PFJ were included. Compared to Caucasians, AA men were more likely to have TF-OA (adjusted odds ratio [aOR]=1.36; 95% CI, 1.00-1.86); tri-compartmental TFJ and PFJ osteophytes (aOR=3.06; 95%CI=1.96-4.78), and TFJ and PFJ sclerosis. AA women were more likely than Caucasian to have medial TFJ and tri-compartmental osteophytes (aOR=2.13; 1.55-2.94), and lateral TFJ sclerosis. AAs had more severe TF-OA than Caucasians (adjusted cumulative odds ratio [aPOR]=2.08; 95% CI, 1.19-3.64 for men; aPOR=1.56; 95% CI, 1.06-2.29 for women) and were more likely to have lateral TFJ JSN. CONCLUSIONS: Compared to Caucasians, AAs were more likely to have more severe TF-OA; tri-compartmental disease; and lateral JSN. Further research to clarify the discrepancy between radiographic features in OA among races appears warranted.