Incident Radiographic Hip Osteoarthritis Research Articles

Femoroacetabular impingement syndrome in middle-aged individuals is strongly associated with the development of hip osteoarthritis within 10-year follow-up: a prospective cohort study (CHECK)

ObjectiveThe objective is to determine the association and absolute risk of femoroacetabular impingement syndrome (FAIS) for the development of radiographic hip osteoarthritis (RHOA).MethodsThis is a nationwide, multicentre prospective cohort study...

The different subtypes of cam morphology as defined by statistical shape modeling and their relationship with the development of hip osteoarthritis: A nationwide prospective cohort study (CHECK) with 10 years follow-up

ObjectiveTo determine if subtypes of cam morphology on anteroposterior (AP) radiographs exist using statistical shape modelling (SSM), and to assess their association with incident radiographic hip osteoarthritis (RHOA) within 10 years. DesignThe nationwide prospective Cohort Hip and Cohort Knee (CHECK) study included 1,002 participants aged 45-65 years with 10-year follow-up. Subtypes of cam morphology were defined as SSM-based shape variations of femoral head-neck junction that are associated with baseline cam morphology (alpha angle ≥60°). The association between each subtype in hips free of osteoarthritis at baseline (Kellgren & Lawrence (KL) grade <2) and incident RHOA (KL grade≥2, or a total hip replacement) was estimated using logistic regression at 10-year follow-up and stratified by sex. ResultsIn sex-combined group, but also for males and females separately, cam morphology subtypes were captured in modes 1, 3, 4, and 5 with odds ratios (ORs) ranging from 0.39(0.27-0.58) to 2.25(1.64-3.10). For sex-combined group, only mode 3, a flattened head-neck junction, was associated with incident RHOA (OR:1.14, 1.02-1.27). Males’ modes 1 and 3 and females’ modes 3 and 4 were associated with RHOA. Notably, the female mode 4, a slightly flattened neck but with subtle curvature, was significantly protective for RHOA (OR:0.88, 0.80-0.98). ConclusionsWe identified four distinct morphological subtypes of cam morphology defined by alpha angle. Only some subtypes were found acting as risk factors for RHOA at 10-year follow-up, which differed between males and females. This highlights the need to study cam morphology beyond the alpha angle alone.

Pincer Morphology Is Not Associated With Hip Osteoarthritis Unless Hip Pain Is Present: Follow-Up Data From a Prospective Cohort Study.

The objective of this study was to assess the relationship between pincer morphology and radiographic hip osteoarthritis (RHOA) over 2, 5, 8, and 10 years' follow-up and to study the interaction between pincer morphology and pain. Individuals from the prospective Cohort Hip and Cohort Knee study were drawn. Anteroposterior pelvic and false profile radiographs were obtained. Hips free of definite RHOA (Kellgren and Lawrence [KL] grade 0 or 1) at baseline were included. Pincer morphology was defined as a lateral or anterior center edge angle or both ≥40° at baseline. Incident RHOA was defined as KL ≥ 2 or total hip replacement at follow-up. Multivariable logistic regression with generalized estimating equations estimated the associations at follow-up. Associations were expressed as unadjusted odds ratios (ORs) and adjusted ORs with 95% confidence intervals (CIs). An interaction term was added to investigate whether pincer morphology had a different effect on symptomatic hips. Incident RHOA developed in 69 hips (5%) at2 years' follow-up, in 178 hips (14%) at 5 years' follow-up, in 279 hips (24%) at 8 years' follow-up, and in 495 hips (42%) at 10 years' follow-up. No significant associations were found between pincer morphology and incident RHOA (adjusted OR 0.35 [95% CI 0.06-2.15]; adjusted OR 1.50 [95% CI 0.94-2.38]). Significant interactions between pain and anterior pincer morphology in predicting incident RHOA were found at 5, 8, and 10 years' follow-up (OR 1.97 [95% CI 1.03-3.78]; OR 3.41 [95% CI 1.35-8.61]). No associations were found between radiographic pincer morphology and incident RHOA at any follow-up moment. Anteriorly located pincer morphology with hip pain, however, was significantly associated with incident RHOA. This highlights the importance of studying symptoms and hip morphology simultaneously.

Hip dysplasia as risk factor for clinically relevant and radiographic hip osteoarthritis: 10-year results from the CHECK cohort.

To investigate hip dysplasia as a risk factor for clinically relevant and incident radiographic hip osteoarthritis. From a prospective cohort (CHECK) of 1002 middle-aged, new consulters for hip and/or knee pain, 468 hips (251 individuals) were selected based on hip pain, available lateral center edge angle (LCEA) and absence of definite radiographic hip OA (Kellgren and Lawrence grade (KL) <2) at baseline, as well as available follow-up measures. Clinically relevant hip OA was defined by an expert diagnosis based on clinical and radiographic data obtained between year 5-10 from baseline. Incident radiographic hip OA was defined by KL grade ≥2 or a total hip replacement at the 10-year follow-up. Associations between hip dysplasia (LCEA ≤20°) and outcomes were expressed in odds ratios (OR) adjusted for age, sex and BMI. At baseline, participants had a mean age of 55.5 years (SD 5.4), 88% were female and, on hip level, the prevalence of hip dysplasia was 3.6% (n = 17). After 10 years, hip dysplasia was associated with an increased risk for clinically relevant hip OA (OR 2.80 (95% CI 1.15, 6.79), but not for incident radiographic hip OA (OR 0.78 (95% CI 0.26, 2.30)). In the long term, baseline hip dysplasia was associated with an increased risk for clinically relevant hip OA, but not for incident radiographic hip OA. With this in mind, we suggest that future research investigating the link between hip dysplasia and OA strive to include a definition for OA that is clinically relevant.

Risk Factors and Population-Attributable Fractions for Incident Hip Osteoarthritis.

Despite the huge burden of hip osteoarthritis (OA) and the lack of effective treatment, research into the primary prevention of hip OA is in its infancy. We sought to evaluate risk factors for incident clinical and incident radiographic hip OA among middle-aged and older adults, to evaluate the importance of risk factors from a preventive perspective, and to estimate the percentage of new cases attributable to these risk factors. We retrospectively reviewed data from the Rotterdam study, an open-population cohort study of individuals aged 55 years or older. Data including baseline age, sex, body mass index, smoking status, education level, diagnosis of diabetes, C-reactive protein (CRP), cam morphology, acetabular dysplasia, radiographic thumb OA, radiographic hip OA, and hip pain were assessed for their association with incident clinical hip OA and incident radiographic hip OA separately, after 11 years of follow-up. The population-attributable fractions (PAFs) of statistically significant modifiable risk factors were calculated, as well. New onset of clinical hip OA was seen in 19.9% (544 of 2729) and incident radiographic hip OA in 9.9% (329 of 3309). Female sex, education level below average (PAF 21.4%), and radiographic hip OA (PAF 3.4%) were statistically significantly associated with incident clinical hip OA. Female sex, age, overweight (PAF 20.0%), cam morphology (PAF 7.9%), acetabular dysplasia (PAF 3.6%), and radiographic thumb OA (PAF 4.7%) were statistically significantly associated with radiographic hip OA. Our retrospective analysis suggests that, from a primary prevention perspective, the most important modifiable risk factors among middle-aged and older individuals may be low educational level for incident clinical hip OA and overweight for incident radiographic hip OA. Further study is warranted.

We Challenged the Kellgren and Lawrence Radiographic Scoring Method and Came Up With Some Interesting Epidemiology for Osteoarthritis of the Hip.

The study of hip osteoarthritis (OA) was slowed due to a lack of a good definition of radiographic hip OA (RHOA). The radiographic changes that occur in hip OA include both joint space narrowing and femoral head osteophytes in the early stages of the disease. This differs from OA of the knee, in which radiographic OA changes initially include osteophytes and only much later is joint space narrowing considered. The modified Croft Score is a novel scoring method for the hip that includes an equal weighting of femoral osteophytes and joint space narrowing. It is used to evaluate the epidemiology of prevalent, incident, and progressive RHOA. Use of the Croft Score found that mild changes in the femoral head or acetabulum could increase the risk of incident RHOA. Pioneering research on active shape modeling was undertaken to provide a more comprehensive assessment of hip shape and define actual femoral head shapes that increased the risk of RHOA. After defining RHOA, investigators found several risk factors, which included higher total hip bone mineral density and polymorphisms of the wnt/β-catenin signaling pathway, to be significant predictors of RHOA in elderly white women. Recently, it was found that RHOA was a strong risk factor for both all-cause mortality and cardiovascular disease mortality in elderly women.

Cam morphology is strongly and consistently associated with development of radiographic hip osteoarthritis throughout 4 follow-up visits within 10 years

To determine the association between cam morphology and the development of radiographic hip osteoarthritis (RHOA) at four time points within 10-year follow-up. The nationwide prospective Cohort Hip and Cohort Knee study includes 1002 participants aged 45-65 years with 2-, 5-, 8-, and 10-year follow-ups. The associations of cam morphology (alpha angle >60°) and large cam morphology (alpha angle >78°) in hips free of osteoarthritis at baseline (Kellgren & Lawrence (KL) grade <2) with the development of both incident RHOA (KL grade≥2) and end-stage RHOA (KL grade≥3) were estimated using logistic regression with generalized estimating equation at each follow-up and using Cox regression over 10 years, adjusted for age, sex, and body mass index. Both cam morphology and large cam morphology were associated with the development of incident RHOA at all follow-ups with adjusted Odd Ratios (aORs) ranging from 2.7 (95% Confidence interval 1.8-4.1) to 2.9 (95% CI 2.0-4.4) for cam morphology and ranging from 2.5 (95% CI 1.5-4.3) to 4.2 (95% CI 2.2-8.3) for large cam morphology. For end-stage RHOA, cam morphology resulted in aORs ranging from 4.9 (95% CI 1.8-13.2) to 8.5 (95% CI 1.1-64.4), and aORs for large cam morphology ranged from 6.7 (95% CI 3.1-14.7) to 12.7 (95% CI 1.9-84.4). Cam morphology poses the hip at 2-13 times increased odds for developing RHOA within a 10-year follow-up. The association was particularly strong for large cam morphology and end-stage RHOA, while the strength of association was consistent over time.

Acetabular dysplasia and the risk of developing hip osteoarthritis at 2,5,8, and 10 years follow-up in a prospective nationwide cohort study (CHECK).

ObjectiveTo assess the relationship between acetabular dysplasia (AD) and the risk of incident and end-stage radiographic hip osteoarthritis (RHOA) over 2,5,8 and 10 years. DesignIndividuals (n = 1002) aged between 45 and 65 from the prospective Cohort Hip and Cohort Knee (CHECK) were studied. Anteroposterior pelvic radiographs were obtained at baseline and 2,5,8, and 10-years follow-up. False profile radiographs were obtained at baseline. AD was defined as a lateral center edge angle, an anterior center edge angle, or both <25° at baseline. The risk of developing RHOA was determined at each follow-up moment. Incident RHOA was defined by Kellgren & Lawrence (KL) grade ≥2 or total hip replacement (THR), end-stage RHOA by a KL grade ≥3 or THR. Associations were expressed in odds ratios (OR) using logistic regression with generalized estimating equations. ResultsAD was associated with the development of incident RHOA at 2 years follow-up (OR 2.46, 95% CI 1.00–6.04), 5 years follow-up (OR 2.28, 95% CI 1.20–4.31), and 8 years follow-up (OR 1.86, 95%CI 1.22–2.83). AD was only associated with end-stage RHOA at 5 years follow-up (OR 3.75, 95% CI 1.02–13.77). No statistically significant associations were observed between AD and RHOA at 10-years follow-up. ConclusionBaseline AD in individuals between 45 and 65 years is associated with an increased risk of developing RHOA within 2- and 5 years. However, this association seems to weaken after 8 years and disappears after 10 years.

Bone texture analysis for prediction of incident radiographic hip osteoarthritis using machine learning: data from the Cohort Hip and Cohort Knee (CHECK) study

To assess the ability of radiography-based bone texture variables in proximal femur and acetabulum to predict incident radiographic hip osteoarthritis (rHOA) over a 10 years period. Pelvic radiographs from CHECKat baseline (987 hips) were analyzed for bone texture using fractal signature analysis (FSA) in proximal femur and acetabulum. Elastic net (machine learning) was used to predict the incidence of rHOA (including Kellgren-Lawrence grade (KL)≥2 or total hip replacement (THR)), joint space narrowing score (JSN, range 0-3), and osteophyte score (OST, range 0-3) after 10 years. Performance of prediction models was assessed using the area under the receiver operating characteristic curve (ROC AUC). Of the 987 hips without rHOA at baseline, 435 (44%) had rHOA at 10-year follow-up. Of the 667 hips with JSN grade 0at baseline, 471 (71%) had JSN grade≥1at 10-year follow-up. Of the 613 hips with OST grade 0at baseline, 526 (86%) had OST grade≥1at 10-year follow-up. AUCs for the models including age, gender, and body mass index (BMI) to predict incident rHOA, JSN, and OST were 0.59, 0.54, and 0.51, respectively. The inclusion of bone texture variables in the models improved the prediction of incident rHOA (ROC AUC 0.68 and 0.71 when baseline KL was also included in the model) and JSN (ROC AUC 0.62), but not incident OST (ROC AUC 0.52). Bone texture analysis provides additional information for predicting incident rHOA or THR over 10 years.

Variation of radius of curvature around the femoral head and its associations with gender and incident radiographic hip osteoarthritis: Data from the Osteoarthritis Initiative

Author(s): Lynch, JA; Liu, F; Tolstykh, I; Wise, B; Lane, NE; McCulloch, CE; Link, TM; Nevitt, MC

The shape of the hip joint as a risk factor for osteoarthritis

Purpose: Cam-type femoroacetabular impingement characterized by extra bone formation at the anterolateral head-neck junction of the hip creates a non-spherical femoral head, known as a cam deformity. The cam deformity is forced into the acetabulum during flexion and internal rotation of the hip, leading to structural damage as acetabular labrum tears and cartilage delamination. This damage might gradually lead to osteoarthritis. Cam deformity and subtle acetabular dysplasia are recently recognized as relevant risk factors for hip osteoarthritis (HOA). In subtle acetabular dysplasia, the femoral head has contact with a small area of the shallowacetabulum. Therefore, more focal stress is put on this small area, which provides insufficient coverage for the femur. Cumulative articular surface contact stress above a critical threshold in dysplastic joints causes joint degeneration. However, the influence of these deformities on HOA incidence compared with other risk factors including age, gender, and body mass index (BMI) and the effect modification of other known determinants on these associations are not yet known. Methods: Participants of Rotterdam Study (RS-I: n = 2960, RS-II: n = 1470) including men and women aged >55 years with a Kellgren and Lawrence (K/L) grade ≥1 at baseline and mean follow-up of 9.2 years were included in the study. Incident radiographic HOA was defined as a K/L grade of ≥2 or a total joint replacement at follow-up. The shape of the proximal femur and the acetabulumwere outlined by a set of points (23 points, Figure 1) that were positioned on pre-defined anatomical landmarks on the anteroposterior pelvic radiographs using statistical shape modeling software. Using this point set, alpha and center-edge (CE) angles, parameters that quantify these deformities were calculated. Acetabular dysplasia and cam deformity were defined as the presence of a CE angle 60°, respectively (Figure 1). Using generalized estimating equation models, odds ratios were calculated to assess the associations between both hip deformities and the development of HOA. Results: At the follow-up times, 234 and 179 cases of HOAwere identified for RS-I and RS-II, respectively. Incident OA was defined in 281 hips within RS-I among that 12.2% (n = 34) had cam deformity and 8.3% (n = 23) had acetabular dysplasia, while out of 218 hips with incident OA in RS-II,16.1% (n = 35) had cam deformity and 7.3% (n = 16) had dysplasia. In pooled data analyses (Table 1), individuals with cam deformity had a two-fold increased risk for developing osteoarthritis (OR = 2.0, 95% CI= 1.48-2.71, p = 0.00001) compared with individuals without cam deformity. Moreover, subtle acetabular dysplasia was significantly associated with increased risk of HOA (OR = 1.96, 95% CI = 1.35-2.84, p = 0.0004). Both associations were independent of known risk factors of HOA such as age, sex, and BMI and were only significantly associated with development of OA in younger individuals. These bony deformities were independently related to the outcomewhen included in the samemodel (camdeformity: OR (95% CI) = 2.03 (1.50-2.76), hip dysplasia: OR (95% CI) = 2.03 (1.41-2.92)). The results were almost consistent in both cohorts. Conclusions: Individuals with cam deformity and acetabular dysplasia are strongly predisposed to progression to HOA independently from other well known risk factors of age, sex, and BMI. Interestingly, both deformities were only predisposing to OA in relatively young individuals. Therefore, early identification of these conditions is important and might provide an opportunity to prevent hip osteoarthritis. (Figure Presented).

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

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

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

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. 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 1at 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. 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. DWD with DiProPerm significance testing provides improved discrimination of variation in hip morphology between groups, and enables subgroup analyses even under small sample sizes.

Association of Incident Symptomatic Hip Osteoarthritis With Differences in Hip Shape by Active Shape Modeling: The Johnston County Osteoarthritis Project

To investigate hip shape by active shape modeling (ASM) as a potential predictor of incident radiographic hip osteoarthritis (RHOA) and symptomatic hip osteoarthritis (SRHOA). All hips developing RHOA from baseline (Kellgren/Lawrence [K/L] grade 0/1) to mean 6-year followup (K/L grade ≥2, 190 hips) and 1:1 control hips (K/L grade 0/1 at both times, 192 hips) were included. Proximal femur shape was defined on baseline anteroposterior pelvis radiographs and submitted to ASM, producing a mean shape and continuous variables representing independent modes of shape variation. Mode scores (n = 14, explaining 95% of shape variance) were simultaneously included in logistic regression models with incident RHOA and SRHOA as dependent variables, adjusted for intraperson correlations, sex, race, body mass index (BMI), baseline K/L grade, and/or symptoms. We evaluated 382 hips from 342 individuals: 61% women and 83% white, with mean age 62 years and mean BMI 29 kg/m(2) . Several modes differed by sex and race, but no modes were associated with incident RHOA overall. Among men only, modes 1 and 2 were significantly associated (for a 1-SD decrease in mode 1 score: odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.1-2.5] and for a 1-SD increase in mode 2 score: OR 1.5 [95% CI 1.0-2.2]) with incident RHOA. A 1-SD decrease in mode 2 or 3 score increased the odds of SRHOA by 50%. This study confirms other reports that variations in proximal femur shape have a modest association with incident hip OA. The observation of proximal femur shape associations with hip symptoms requires further investigation.

Variant alleles of the Wnt antagonist FRZB are determinants of hip shape and modify the relationship between hip shape and osteoarthritis

To test whether single-nucleotide polymorphisms (SNPs) of the FRZB gene are associated with hip shape, and to determine whether FRZB variant alleles affect the relationship between hip shape and radiographic osteoarthritis (OA) of the hip. A nested case-control study of Caucasian women, age ≥65 years, from the Study of Osteoporotic Fractures cohort was performed. Cases (n = 451) were defined as subjects with radiographic evidence of incident hip OA during followup, while controls (n = 601) were subjects in whom no radiographic hip OA was identified at baseline or followup. Statistical shape modeling (SSM) of the digitized hip radiographs was performed to assess the shape of the proximal femur, using 10 independent modes of shape variation generated by principal components analysis. In addition, center-edge angle and acetabular depth were assessed as geometric measurements of acetabular shape. The association of the rs288326 and rs7775 FRZB variant alleles with hip shape was analyzed using linear regression. The effect of these alleles on the relationship between hip shape and radiographic hip OA was analyzed using a logistic regression model with or without inclusion of interaction terms. The rs288326 and rs7775 alleles were associated with the shape of the proximal femur (SSM mode 2). There was a significant interaction between the rs288326 SNP and proximal femur shape (SSM mode 2) in predicting radiographic hip OA (P for interaction = 0.022). Among subjects with the rs288326 variant allele, there was an increased likelihood of radiographic hip OA in association with increasing quartiles of proximal femur shape mode 2 (for the fourth quartile of mode 2, odds ratio 2.5, 95% confidence interval 1.15, 5.25; P for linear trend = 0.02). The rs288326 and rs7775 FRZB SNPs are associated with the shape of the proximal femur. The presence of the rs288326 SNP alters the relationship between proximal femur shape and incident radiographic hip OA. These findings suggest that FRZB may serve an important role in determining hip shape and may modify the relationship between hip shape and OA.

Changes in proximal femoral mineral geometry precede the onset of radiographic hip osteoarthritis: The study of osteoporotic fractures.

Radiographic hip osteoarthritis (RHOA) is associated with increased hip areal bone mineral density (aBMD). This study was undertaken to examine whether femoral geometry is associated with RHOA independent of aBMD. Participants in the Study of Osteoporotic Fractures in whom pelvic radiographs had been obtained at visits 1 and 5 (mean 8.3 years apart) and hip dual x-ray absorptiometry (DXA) had been performed (2 years after baseline) were included. Prevalent and incident RHOA phenotypes were defined as composite (osteophytes and joint space narrowing [JSN]), atrophic (JSN without osteophytes), or osteophytic (femoral osteophytes without JSN). Analogous definitions of progression were based on minimum joint space and total osteophyte score. Hip DXA scans were assessed using the Hip Structural Analysis program to derive geometric measures, including femoral neck length, width, and centroid position. Relative risks and 95% confidence intervals for prevalent, incident, and progressive RHOA per SD increase in geometric measure were estimated in a hip-based analysis using multinomial logistic regression with adjustment for age, body mass index, knee height, and total hip aBMD. In 5,245 women (mean age 72.6 years), a wider femoral neck with a more medial centroid position was associated with prevalent and incident osteophytic and composite RHOA phenotypes (P < 0.05). Increased neck width and centroid position were associated with osteophyte progression (both P < 0.05). No significant geometric associations with atrophic RHOA were found. Differences in proximal femoral bone geometry and spatial distribution of bone mass occur early in hip OA and predict prevalent, incident, and progressive osteophytic and composite phenotypes, but not the atrophic phenotype. These bone differences may reflect responses to loading occurring early in the natural history of RHOA.

The association of proximal femoral shape and incident radiographic hip OA in elderly women

Variations in femoral head shape are reported to predict incident hip osteoarthritis (OA). This study evaluated if proximal femur shape at baseline was a risk factor for incident radiographic hip OA (RHOA) after 8.3 years of follow-up in a cohort of elderly Caucasian women. Supine pelvic radiographs were obtained as part of the Study of Osteoporotic Fractures (SOF) at baseline and Visit 5 (8.3 years later), and were scored for RHOA. A nested case-control study was performed: hips were eligible for inclusion if they had no prevalent RHOA in either hip at baseline. Cases of incident RHOA were defined as no RHOA at baseline and RHOA in their right hip present at Visit 5 [or right total hip replacement (THR) for OA between baseline for follow-up] and a random selection of one half of all incident RHOA cases plus right THR cases (n=102) were chosen. A random selection (n=249) of control subjects who had no RHOA in their right hip at both baseline and follow-up visit were included for comparison. The shape of the right proximal femur was outlined on a digitized baseline radiograph and a statistical image analysis technique, Active Shape Modeling (ASM), was used to generate 10 unique and independent "modes" or variations in shape, which explained 95% of the variance in the shape of the proximal femurs studied. Any hip shape was therefore described as the average shape plus a linear combination of these 10 independent modes of variation. The values for each of these 10 modes for each hip analyzed were entered into a logistic regression model as independent predictors of incident RHOA adjusting for covariates. The incident RHOA cases were slightly taller, heavier and had higher total hip bone mineral density (BMD) than control subjects (P<0.05), but were otherwise similar demographically. Results of ASM showed that Modes 1, 2 and 3 together explained 81% of the variance in proximal femur shape among all subjects analyzed. Modes 3, 5, 9 which accounted for 8.9%, 3.3% and 0.8% of the variance respectively, were significant predictors of incident RHOA with adjusted odds-ratios ranging from 1.61 to 1.99 (P<0.001) for every 1 standard deviation (SD) increase in the mode score. These results suggest that variations in the relative sizes of the femoral head and neck at baseline are modest determinants of incident RHOA in elderly Caucasian women.

Defining incident radiographic hip osteoarthritis for epidemiologic studies in women

To evaluate definitions of radiographic hip osteoarthritis (RHOA) for use in longitudinal epidemiologic studies of disease incidence in women. We studied 5,839 women from the Study of Osteoporotic Fractures who had had serial pelvic radiographs obtained (mean of 8.3 years apart) and who were followed up (mean followup 7.1 years from the time of the second radiograph) for evaluation of clinical outcomes. Definitions of RHOA were assessed for construct validity (association with symptoms and signs at the time of the second radiograph) and predictive validity (association with total hip replacement [THR] and signs and symptoms a mean of 7.1 years later). Odds ratios (ORs) and 95% confidence intervals were calculated to assess the strength of association using logistic regression. The cumulative incidence of RHOA ranged from 2.2% to 11.7%. All definitions displayed significant construct validity; the most consistent was found for composite definitions that required the concurrent presence of 2 or more individual radiographic features and definitions based on stringent criteria for joint space narrowing. All definitions except minimum joint space < or =2.5 mm displayed consistent predictive validity. Composite definitions had the strongest associations with THR (OR 10.5-18.5) and hip pain (OR 2.6-2.9). The hips identified as having OA by each definition varied, with especially small overlap between findings using definitions based on osteophytes and those using definitions based on joint space narrowing alone. Most definitions of incident RHOA display good construct and predictive validity. Composite definitions have the best overall performance, and definitions requiring the presence of both osteophytes (in particular, femoral osteophytes) and joint space narrowing would be recommended for most epidemiologic and genetic studies.

Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women

To determine whether serum levels of 2 Wnt signaling antagonists, Frizzled-related protein (FRP) and Dkk-1, are associated with the development and progression of radiographic hip osteoarthritis (RHOA). Pelvic radiographs were obtained a mean of 8.3 years apart in 5,928 Caucasian women >or=65 years of age who were enrolled in the Study of Osteoporotic Fractures. Random sampling of this cohort was performed, with approximately 180 subjects per group assigned to 2 nested case-control studies on RHOA incidence and progression. Baseline serum levels of FRP and Dkk-1 were measured by capture enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analyses with adjustment for potential covariates. There were no differences in serum levels of FRP and Dkk-1 between case subjects with incidence or progression of RHOA and their respective control subjects. There was a trend for higher baseline serum levels of FRP to be associated with a reduced risk of incident RHOA (age-adjusted OR 0.59 [95% CI 0.32-1.09], P = 0.09 for women in the highest quartile versus women in the lowest quartile). There was no association of serum levels of FRP with progression of RHOA. Serum levels of Dkk-1 did not correlate with incident RHOA. However, higher serum levels of Dkk-1 were associated with diminished risk of RHOA progression (age-adjusted OR 0.43 [95% CI 0.23-0.79], P = 0.007 for women in the highest quartile compared with women in the lowest quartile). Elevated circulating levels of Dkk-1 appeared to be associated with reduced progression of RHOA in elderly women, whereas the highest quartile of serum FRP levels tended to be associated with a modest reduction in risk of incident RHOA.

Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women

This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms. RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score > or =3 and 130 had an osteophyte score > or =2 and JSN score > or =2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P=0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P=0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P=0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P=0.19) compared to women with A/A genotype. We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.