Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
(1) To test whether single nucleotide polymorphisms (SNPs) of the FRZB gene are associated with hip shape. (2) To determine whether FRZB variant alleles affect the relationship between hip shape and radiographic hip osteoarthritis (RHOA).
A nested case-control study of Caucasian women aged ≥ 65 years in the Study of Osteoporotic Fractures (SOF) was performed. Cases (n = 451) demonstrated incident RHOA during follow-up (mean 8.0 ± 0.4 years). Controls (n = 601) had no RHOA at baseline or follow-up. Statistical shape modeling (SSM) of digitized hip radiographs was used to assess proximal femur shape, and center-edge angle and acetabular depth were used to assess 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 RHOA was analyzed using logistic regression with and without interaction terms.
The rs288326 and rs7775 alleles were associated with shape of the proximal femur (SSM Mode 2). There was a significant interaction between the rs288326 SNP and proximal femur shape (Mode 2) in predicting RHOA (p for interaction = 0.022). Among subjects with the rs288326 variant allele, there were increasing odds of RHOA with increasing quartiles of proximal femur shape Mode 2 (OR for 4th quartile of Mode 2 = 2.5, 95% confidence interval 1.2–5.3; 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 RHOA. Together, these findings suggest that FRZB may serve an important role in determining hip shape and may modify the relationship between hip shape and OA.
FRZB; WNT pathway; osteoarthritis; joint shape; active shape modeling; bone
Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a sub-study of BMD conducted at 5 of 16 clinical centers, hip, spine and whole body dual x-ray absorptiometry scans were obtained at baseline and one year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2 kg/m2. Total hip BMD T-score was <−2.5 in 1% and <−1.0 in 8%. At one year, weight loss was greater in ILI than DSE (−8.6% versus −0.7%), and glycemic control and fitness were also improved. Bone loss over one year was greater in ILI at the total hip (−1.4% versus −0.4%; p<0.001) and femoral neck (−1.5% versus −0.8%; p=0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control.
bone mineral density; weight loss; type 2 diabetes; obesity; glycemic control; physical fitness
To examine the changes in knee cartilage T2 values over 24 months in subjects with and without risk factors for knee osteoarthritis (OA) and their association with focal knee lesions at baseline.
Materials and Methods
Forty-one subjects without, and 101 subjects with OA risk factors (such as history of knee injury or surgery) were selected from the Osteoarthritis Initiative database (age: 45-55 years, no radiographic OA in the right knee). Baseline MR images of the right knee were assessed for prevalence and grade of focal knee lesions. Right knee cartilage T2 measurements were performed in five compartments (patella, medial/lateral femur/tibia) at baseline and 24 month follow-up.
Compared to subjects without OA risk factors, those with OA risk factors showed no significant differences in baseline prevalence and grade of focal knee lesions (p>0.05), but had significantly higher T2 values in the medial femur compartment at both time points (p<0.05). T2 values averaged over all five compartments increased significantly over 24 months in both groups, but differences in T2 increase between the groups were not significant. Subjects with cartilage lesions showed significantly higher T2 values compared to subjects without cartilage lesions at both time points, but no accelerated T2 increase over 24 months (p>0.05).
Cartilage T2 values significantly increased over 24 months in subjects with and without OA risk factors, but neither the presence of OA risk factors nor the presence of cartilage lesions at baseline were associated with these T2 increases.
Osteoarthritis; OAI; MRI; WORMS; T2 relaxation time; T2 laminar analysis
To evaluate the association of MRI-based knee cartilage T2 measurements and focal knee lesions with knee pain in knees without radiographic osteoarthritis (OA) among subjects with OA risk factors.
We studied the right knees of 126 subjects from the Osteoarthritis Initiative database. We randomly selected 42 subjects aged 45–55 years with OA risk factors, right knee pain (WOMAC pain score ≥5), no left knee pain (WOMAC pain score =0) and no radiographic OA (KL-score ≤1) in the right knee. We also selected two comparison groups: 42 subjects without knee pain in either knee and 42 with bilateral knee pain. Both groups were frequency matched to subjects with right knee only pain by gender, age, BMI and KL-score. All subjects underwent 3T MRI of the right knee. Focal knee lesions were assessed and cartilage T2 measurements were performed.
Prevalence of meniscal, bone marrow and ligamentous lesions and joint effusion were not significantly different between the groups (p>0.05), while cartilage lesions were more frequent in subjects with right only knee pain compared to subjects without knee pain (p<0.05). T2 values averaged over all compartments were similar in subjects with right only knee pain (34.4±1.8ms) and with bilateral knee pain (34.7±4.7ms), but significantly higher compared to subjects without knee pain (32.4±1.8ms) (p<0.05).
These results suggest that elevated cartilage T2 values are associated with findings of pain in the early phase of OA, while among morphological knee abnormalities only knee cartilage lesions are significantly associated with knee pain status.
Osteoarthritis; WOMAC; MRI; T2 relaxation time; WORMS
To examine the relationships between knee osteoarthritis (OA) and muscle parameters in a biracial cohort of older adults.
858 participants in the Health, Aging and Body Composition Study were included in this cross-sectional analysis. Computed tomography (CT) was used to measure muscle area and quadriceps strength was measured isokinetically. Muscle quality (specific torque) was defined as strength per unit of muscle area for both total thigh and quadriceps. Knee OA was assessed based on radiographic features and knee pain. We compared muscle parameters between those with and without radiographic knee OA (+RKOA, −RKOA) and among four groups defined by +/− RKOA with and without pain.
The mean age was 73.5 (2.9) years and mean BMI was 27.9 (4.8) kg/m2. 58% of participants were women and 44% were Black. Compared to − RKOA, +RKOA participants had a higher BMI (30.2 vs. 26.8 kg/m2), larger thigh muscles (117.9 vs. 108.9 cm2), and a greater amount of intermuscular fat (12.5 vs. 9.9 cm2) (all p<0.0001). In adjusted models, +RKOA subjects had significantly lower specific torque (p<0.001), indicating poorer muscle quality, than −RKOA subjects, but there was no difference between groups in quadriceps specific torque. +RKOA/−pain (p<0.05) and +RKOA/+pain (p<0.001) subjects had lower specific torque compared to −RKOA/−pain group. There were no significant differences in quadriceps specific torque among RKOA/pain groups.
Muscle quality was significantly poorer in participants with RKOA regardless of pain status. Future studies should address how lifestyle interventions might affect muscle quality and progression of knee OA.
Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteoporotic Fractures (SOF) between 1986 and 1998. SOF participants were women ≥65 years at baseline who were recruited from four regions in the U.S. DM was ascertained by self-report. BMD was measured with dual-energy x-ray absorptiometry (DXA) at baseline and at least one follow-up visit at the hip (N = 6624) and calcaneus (N = 6700) and, on a subset of women, at the spine (N = 396) and distal radius (N = 306). Annualized percent change in BMD was compared by DM status, using random effects models. Of 6,867 women with at least one follow-up DXA scan, 409 had DM at baseline. Mean age was 70.8 (SD 4.7) years. Baseline BMD was higher in women with DM at all measured sites. In models adjusted for age and clinic, women with prevalent DM lost bone more rapidly than those without DM at the femoral neck (−0.96 vs. −0.59%/year, p < 0.001), total hip (−0.98 vs. −0.70%/year, p < 0.001), calcaneus (−1.64 vs. −1.40%/year, p = 0.005), and spine (−0.33 vs. +0.33%/year, p = 0.033), but not at the distal radius (−0.97 vs. −0.90%/year, p = 0.91). These findings suggest that despite higher baseline BMD, older women with DM experience more rapid bone loss than those without DM at the hip, spine, and calcaneus, but not the radius. Higher rates of bone loss may partially explain higher fracture rates in older women with DM.
type 2 diabetes mellitus; bone mineral density; women; older adults; longitudinal studies
To evaluate if two different measures of synovial activation, baseline Hoffa-synovitis and effusion-synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis (OA) of the knee.
Non-contrast enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a STIR sequence in the coronal plane. Hoffa-synovitis, effusion-synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic OA nor MRI-detected tibio-femoral cartilage damage at the baseline visit. Presence of Hoffa-synovitis was defined as any grade ≥2 (range from 0–3) and effusion-synovitis as any grade ≥2 (range from 0–3). We performed logistic regression to examine the relation of presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders of cartilage loss.
Of 514 knees included in the analysis, prevalence of Hoffa-synovitis and effusion-synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion-synovitis was associated with an increased risk for cartilage loss (odds ratio (OR) = 2.7, 95% confidence intervals 1.4–5.1, p=0.002); however, no such an association was observed for baseline Hoffa-synovitis (OR =1.0, 95% confidence intervals 0.5–2.0).
Baseline effusion-synovitis, but not Hoffa-synovitis, predicted cartilage loss. Our findings suggest that effusion-synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in future development of cartilage lesions in knees without OA.
Osteoarthritis; magnetic resonance imaging; effusion; synovitis; cartilage loss
To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs.
Subjects from the Multicenter Osteoarthritis Study aged 50–79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month MRI of knees (n=1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form ‘more loaded’ compartment, while lateral compartment in valgus and medial compartment in varus were combined to form ‘less loaded’ compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline.
Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment (adjusted RRs [95%CI]: 1.5 [1.2–1.9]) and valgus alignment in the lateral compartment (1.4 [1.0–2.1]). Increase in BML score was more likely in the more loaded compartments (1.7 [1.4–2.0]) in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees (0.8, [0.7–1.0]).
Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.
bone marrow lesion; malalignment; osteoarthritis; knee; MRI
Osteoarthritis (OA) clinical practice guidelines identify a substantial therapeutic role for physical activity but objective information about the physical activity of this population is lacking. We objectively measured physical activity levels of adults with knee OA and report the prevalence of meeting public health physical activity guidelines.
Cross-sectional accelerometer data from 1111 adults with radiographic knee OA aged 49 to 84 years participating in Osteoarthritis Initiative accelerometer monitoring ancillary study were assessed for meeting the aerobic component of the 2008 Physical Activity Guidelines for Americans (≥150 minutes/week in episodes≥10 minutes). Quantile regression was used to test median gender differences in physical activity levels.
Aerobic physical activity guidelines were met by 12.9% of men and 7.7% of women with knee OA. A substantial 40.1% of men and 56.5% of women were inactive, doing no moderate-to-vigorous (MV) activity over 7 days that lasted 10 minutes or more. Although men engaged in significantly more MV intensity activity (20.7 vs. 12.3 average daily minutes) they also spent more time in no or very light intensity activity (608.2 vs. 585.8 average daily minutes) than women.
Despite substantial health benefits from physical activity, adults with knee OA were particularly inactive based on objective accelerometer monitoring. The percentages of men and women who met public health physical activity guidelines were substantially less than previous reports based on self-reported activity in arthritis populations. These findings support intensified public health efforts to increase physical activity levels among persons with knee OA.
Recent findings suggest that contact stress is a potent predictor of subsequent symptomatic osteoarthritis development in the knee. However, much larger numbers of knees (likely on the order of hundreds, if not thousands) need to be reliably analyzed to achieve the statistical power necessary to clarify this relationship. This study assessed the reliability of new semiautomated computational methods for estimating contact stress in knees from large population-based cohorts. Ten knees of subjects from the Multicenter Osteoarthritis Study were included. Bone surfaces were manually segmented from sequential 1.0 Tesla magnetic resonance imaging slices by three individuals on two nonconsecutive days. Four individuals then registered the resulting bone surfaces to corresponding bone edges on weight-bearing radiographs, using a semi-automated algorithm. Discrete element analysis methods were used to estimate contact stress distributions for each knee. Segmentation and registration reliabilities (day-to-day and interrater) for peak and mean medial and lateral tibiofemoral contact stress were assessed with Shrout-Fleiss intraclass correlation coefficients (ICCs). The segmentation and registration steps of the modeling approach were found to have excellent day-to-day (ICC 0.93–0.99) and good inter-rater reliability (0.84–0.97). This approach for estimating compartment-specific tibiofemoral contact stress appears to be sufficiently reliable for use in large population-based cohorts.
Hip osteoarthritis (OA) is a common disabling disease, which has a much higher prevalence in Caucasians than Asians. The reasons for this ethnic difference in prevalence are unknown. Hip OA often is thought to be secondary to morphologic abnormalities. If particular abnormalities predisposing to hip OA occur more frequently in Caucasians, these differences in hip shape could account for prevalence differences.
A morphometric study was performed using 400 non-osteoarthritic hips of 200 women participants from 2 studies: the Beijing OA study and the SOF study from the U.S. We focused on measures of hip dysplasia and impingement (Lateral Center Edge Angle, Impingement Angle, Acetabular Slope, Femoral Head Neck Ratio and the Cross Over Sign) and compared data from Chinese and Caucasian hips.
Compared with their Chinese counterparts, Caucasian women had a lower mean impingement angle (83.6° vs. 87.0°’ p=.03) and were more likely to have center edge angles suggestive of impingement (for center edge angle >35°, 11% of Chinese vs. 23% of Caucasian hips, p = .008). On the other hand, low center edge angles suggesting dysplasia were found more often in Chinese women (for <20°, 22% of Chinese vs. 7% of Caucasian hips, p = .005).
In a study of elderly women without signs of OA, the morphometry of impingement and asphericity were more common in Caucasian than Chinese hips. Our findings suggest that Caucasians may be at higher risk of hip OA than Chinese because of morphologic findings that predispose them to femoro-acetabular impingement.
The objective of this study was to evaluate right proximal femur shape as a risk factor for incident hip fracture using active shape modeling (ASM). A nested case-control study of white women 65 years of age and older enrolled in the Study of Osteoporotic Fractures (SOF) was performed. Subjects (n = 168) were randomly selected from study participants who experienced hip fracture during the follow-up period (mean 8.3 years). Controls (n = 231) had no fracture during follow-up. Subjects with baseline radiographic hip osteoarthritis were excluded. ASM of digitized right hip radiographs generated 10 independent modes of variation in proximal femur shape that together accounted for 95% of the variance in proximal femur shape. The association of ASM modes with incident hip fracture was analyzed by logistic regression. Together, the 10 ASM modes demonstrated good discrimination of incident hip fracture. In models controlling for age and body mass index (BMI), the area under receiver operating characteristic (AUROC) curve for hip shape was 0.813, 95% confidence interval (CI) 0.771–0.854 compared with models containing femoral neck bone mineral density (AUROC = 0.675, 95% CI 0.620–0.730), intertrochanteric bone mineral density (AUROC = 0.645, 95% CI 0.589–0.701), femoral neck length (AUROC = 0.631, 95% CI 0.573–0.690), or femoral neck width (AUROC = 0.633, 95% CI 0.574–0.691). The accuracy of fracture discrimination was improved by combining ASM modes with femoral neck bone mineral density (AUROC = 0.835, 95% CI 0.795–0.875) or with intertrochanteric bone mineral density (AUROC = 0.834, 95% CI 0.794–0.875). Hips with positive standard deviations of ASM mode 4 had the highest risk of incident hip fracture (odds ratio = 2.48, 95% CI 1.68–3.31, p < .001). We conclude that variations in the relative size of the femoral head and neck are important determinants of incident hip fracture. The addition of hip shape to fracture-prediction tools may improve the risk assessment for osteoporotic hip fractures. © 2011 American Society for Bone and Mineral Research.
ACTIVE SHAPE MODELING; HIP SHAPE; HIP FRACTURE; OSTEOPOROSIS; BONE
To determine the extent to which disease-related symptoms and impairments, which constitute measures of disease severity or targets of therapy, account for the associations between chronic diseases and universal health outcomes.
Cardiovascular Health Study (CHS) and Health ABC.
5,654 CHS, and 2,706 Health ABC, members.
Diseases included heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, and cognitive impairment. The universal health outcomes included self-rated health, basic and instrumental activities of daily living (BADLs-IADLs), and death. Disease-related symptoms/impairments included HF symptoms and ejection fraction (EF) for HF; Dyspnea Scale and FEV1 for COPD; joint pain for osteoarthritis, and executive function for cognitive impairment.
The diseases were associated with the universal health outcomes (p<0.001) except osteoarthritis with death (both cohorts) and cognitive impairment with self-rated health (Health ABC). Symptoms/impairments accounted for ≥30% of each disease’s effect on the universal health outcomes. In CHS, for example, HF, compared with no HF, was associated with one fewer (0.918) BADLs-IADL performed without difficulty; 27% of this effect was accounted for by HF symptoms, only 5% by EF. The hazard ratio for death with HF was 6.5 (95% CI, 4.7, 8.9) with 40% accounted for by EF and only 14% by HF symptoms.
Disease-related symptoms/impairments accounted for much of the significant associations between the 4 chronic diseases and the universal health outcomes. Results support considering universal health outcomes as common metrics across diseases in clinical decision-making, perhaps by targeting the disease-related symptoms/impairments that contribute most strongly to the effect of the disease on the universal health outcomes.
chronic diseases; universal health outcomes; patient-reported outcomes; clinical decision-making
To study the role of vastus lateralis/vastus medialis cross-sectional area ratio (VL/VM CSA ratio) in preclinical knee osteoarthritis (OA) using MRI-based cartilage T2 mapping technique and morphological analysis at 3.0T in non-symptomatic, middle-aged subjects.
Material and Methods
174 non-symptomatic individuals aged 45–55 years with OA risk factors were selected from the Osteoarthritis Initiative incidence cohort. OA-related knee abnormalities were analyzed using the whole-organ MR imaging score (WORMS). Knee cartilage T2 maps were generated using sagittal 2D multiecho spin echo images of the right knee. Cross-sectional area (CSA) of thigh muscles was measured using axial T1W images of the right mid thigh. Spline-based segmentation of cartilage and muscles was performed on a SUN/SPARC workstation. Muscle measurements were normalized to body size using body surface area. Statistical significance was determined using Student’s t-test, Pearson correlation test, and multiple regression models. To correct for multiple testing, Bonferroni adjustments were applied across all tests within each of the primary results tables (Tables 3 – 7).
Higher T2 values were associated with increased prevalence and severity of cartilage degeneration. In our study, male and female subjects with higher VL/VM CSA ratio demonstrated significantly lower mean cartilage T2 values (all compartments combined) (mean 44.10 versus 45.17, p = 0.0017), and significantly lower WORMS scores (mean 14.12 versus 18.68, p = 0.0316). Regression analyses of combined mean cartilage T2 using VL/VM CSA ratio as a continuous predictor showed a significant curvilinear relationship between these two variables (p = 0. 0.0082).
Our results suggested that higher VL/VM CSA ratio is associated with lower T2 values and decreased presence and severity of OA-related morphological changes. Additional studies will be needed to determine causality.
osteoarthritis; OAI; cartilage T2; WORMS; vastus lateralis; vastus medialis
To determine whether intra- and periarticular cyst-like lesions of the knee are associated with incident knee pain and incident radiographic knee osteoarthritis (OA).
The Multicenter Osteoarthritis (MOST) Study is a cohort of individuals who have or are at high risk for knee OA. Using a nested case-control study design, we investigated the associations of cyst-like lesions (Baker’s, meniscal and proximal tibiofibular joint (PTFJ) cysts, and prepatellar and anserine bursitides) with (a) incident pain at 15- or 30-month follow-up and (b) incident radiographic OA at 30-month follow-up. Baseline cyst-like lesions were scored semiquantitatively using the Whole Organ Magnetic Resonance Imaging Score (WORMS). Conditional logistic regression models were used to assess the relation between these lesions and the outcomes, adjusting for potential confounding factors (i.e. cartilage loss, meniscal damage, bone marrow lesions, synovitis and joint effusion, which were also scored using WORMS).
Incident knee pain study included 157 cases and 336 controls. Prevalence of meniscal and PTFJ cysts in the case group was twice that in the control group (9 (6%) vs. 9 (3%) and 9 (6%) vs. 10 (3%), respectively). Incident radiographic OA study included 149 cases and 298 controls. Prevalence of grade 2 Baker’s cysts and PTFJ cysts in the case group was approximately 4 times that in the control group (16 [11%] vs. 9 [3%] and 6 [4%] vs. 3 [1%], respectively). However, none of the cyst-like lesions was associated with incident pain or radiographic OA after fully adjusted logistic regression analyses and correction of p-values for multiple comparisons.
None of the analyzed lesions was an independent predictor of incident knee pain or radiographic OA. Intra- and periarticular cyst-like lesions are likely to be a secondary phenomenon seen in painful or OA-affected knees, rather than a primary trigger for incident knee pain or radiographic OA.
Cysts; Bursitis; Magnetic Resonance Imaging; Osteoarthritis; Knee; Pain
There are two widely used scoring systems for knee MRI in OA and the strengths and weaknesses of each system in terms of ease of use and association with known risk factors and outcomes are unknown..
To compare WORMS and BLOKS scales using longitudinal MRI and x-ray data
In the Osteoarthritis Initiative (OAI), knee radiographs, long limb films for alignment and MRI's were acquired in the interval from 0 to 24 months follow-up. OAI MRI's from baseline and 24 months were read separately using BLOKS and WORMS scales. X-rays were scored semiquantitatively for joint space loss and long limb films were measured for alignment angle. We evaluated which of the WORMS or BLOKS cartilage loss scores best correlated with joint space loss on the x-ray and which was best predicted by varus malalignment on long limb film. To examine the validity of BML and meniscal scales, we tested which of WORMS or BLOKS baseline scores for BML or meniscus best predicted cartilage loss from baseline to 24 months. We critically evaluated strengths and weaknesses of each scoring system also.
Of 113 knees read longitudinally, 33 showed any cartilage loss using BLOKS and 30 using WORMS with high agreement between the scales. In the medial compartment, both BLOKS and WORMS picked up only 42% of the knees with x-ray joint space loss with similar specificity (88 vs. 86%). Varus knees were more likely to be a risk factor for medial cartilage loss in BLOKS (adj OR 5.9 (95% CI1.5, 24.0)) than in WORMS (adj OR 2.1 (95% CI 0.7,6.3)). WORMS BML scores predicted cartilage loss more strongly than any BLOKS BML variables and some BLOKS BML measures did not affect risk of cartilage loss at all. However, across the range of scores, meniscal tear scores in BLOKS predicted cartilage loss better for each abnormality than did WORMS meniscal tear scores and the meniscal signal abnormality scored in BLOKS but not in WORMS, predicted cartilage loss. BLOKS took longer and was more difficult to score longitudinally especially for bone marrow lesion scores.
In a comparison of instruments limited by small numbers of knees compared, BLOKS meniscal score was preferable to WORMS meniscal scale in predicting cartilage loss most likely because it includes potentially important pathology missed by WORMS. On the other hand, BML scoring in WORMS was preferable in that it better predicted later cartilage loss,was easier to score and did not include potentially extraneous measures. Neither method was definitively better for cartilage scoring.
Osteoarthritis; Knee; Magnetic Resonance Imaging; longitudinal studies
To compare two semiquantitative scoring systems for assessing the prevalence and severity of morphologic cartilage lesions, meniscal damage and bone marrow lesions from MRIs of knees with OA.
From participants in the Osteoarthritis Initiative, a sample of 115 knees with radiographic OA at high risk of cartilage loss, were selected based on risk factors for progression. Knee MRIs were read separately using both WORMS and BLOKS, and a subset was fed back to readers for reliability. Baseline readings were used for comparison of the two methods for inter-reader reliability as well as agreement on presence/absence and severity of MRI features at both the compartment level and finer anatomical subregion levels.
Both methods had high inter-reader agreement for all features studied (kappa for WORMS 0.69 to 1.0 and for BLOKS 0.65 to 1.0). . Although the methods agreed well on presence and severity of morphological cartilage lesions (inter-method kappas from 0.66 to 0.95), BLOKS was more sensitive for full thickness defects. The two methods gave equivalent results for extent (kappa 0.74 to 0.80) and number (Spearman’s Rho = 0.85) of BMLs, and little extra information was obtained using the more complex BLOKS BML scoring. Similar results were also obtained for the common types of meniscal damage and extrusion (inter-method kappa 0.85 to 0.94), but the inclusion in BLOKS of meniscal signal abnormality and uncommon types of tear may be an advantage if these prove clinically meaningful.
In conclusion, both WORMS and BLOKS had high reliability. The two methods gave similar results in this sample for prevalence and severity of cartilage loss, bone marrow lesions and meniscal damage. Selecting between, or combining, the two methods should be based on factors such as reader effort, appropriateness for the goals of a study, and longitudinal performance.
osteoarthritis; knee; magnetic resonance imaging; articular cartilage; bone marrow lesions; meniscus
Development of functional limitation is thought to be unrelated to changes in severity of radiographic knee osteoarthritis (ROA). We evaluated the relation of change in ROA to the incidence of severe functional limitation.
Participants of the Multicenter Osteoarthritis (MOST) Study, a cohort study of persons with or at high risk of knee OA were evaluated at 0 and 30 months. Subjects were classified as having no, incident, stable, or worsening ROA. Incidence of severe functional limitation was defined as 1) WOMAC physical function scores (≥ 36/68) and 2) walking speed (≤ 1.0 m/s) at 30 months. The relation of change in ROA to the incidence of severe functional limitation was evaluated by calculating risk ratios adjusted for potential confounders.
Of the 2110 subjects included (mean age 62, mean BMI 30 kg/m2, female 60%), 53% had no, 6% incident, 14% stable, and 27% worsening ROA. Persons with incident ROA had 1.9 and 1.8 times the risk by WOMAC physical function and walking speed, respectively, to have incident severe functional limitation compared with those with no ROA over 30 months. Compared with those with stable ROA, persons with worsening ROA had 2.2 and 2.5 times the risk of incident severe functional limitation, respectively.
Changes in structural disease are associated with the development of severe functional limitations in persons with or even those at high risk of knee OA.
The extent and factors associated with knee pain fluctuation are not well-known. We evaluated the prevalence, correlates, and association with function of consistency of knee pain.
Participants of The Multicenter Osteoarthritis (MOST) Study, a cohort of individuals with or at high risk of knee osteoarthritis (OA) had baseline knee x-rays, questionnaires, and a question about frequent knee pain (FKnP) (pain on most of the past 30 days) at two time points: a telephone screen and a later clinic visit. We computed the prevalence of inconsistent knee pain (positive answer to FKnP question at only one time point) and consistent knee pain (positive answer to FKnP question at both time points). We evaluated the association of consistency of FKnP with a number of sociodemographic factors, pain severity, and function.
There were 2940 participants with complete data (5867 knees) (mean age 62, mean BMI 30.7, 60% female). Of those, 2977 knees had pain, with 43% having inconsistent and 57% having consistent knee pain. Those with radiographic OA (OR 0.46), depressive symptoms (OR 0.73), and widespread pain (OR 0.68) (all p<0.05) were less likely to have inconsistent compared with consistent knee pain. Pain, function, and strength were significantly better in persons with 2 knees that had inconsistent compared with consistent pain.
A substantial proportion of persons with knee pain have inconsistent knee pain, associated with better physical function and strength (adjusting for pain severity). Such pain may be suggestive of an earlier stage of disease.
Osteoarthritis; Knee pain; Temporal pattern; function
To investigate the association between meniscal pathology and incident or enlarging bone marrow lesions (BMLs) in knee osteoarthritis (OA)
We studied subjects from the Multicenter Osteoarthritis Study (MOST) aged 50 to 79 either with knee OA or at high risk of the disease. Baseline and 30-months magnetic resonance images of knees (n=1344) were scored for subchondral BMLs. Outcome was defined as an increase in BML score in either the tibial or femoral condyle in medial and lateral compartments, respectively. We defined meniscal pathology at baseline as the presence of either meniscal lesions or meniscal extrusion. We estimated the risk of an increase in BML score in relation to meniscal status in the same compartment using a log linear regression model adjusted for age, sex, body mass index, physical activity level, and mechanical axis. In secondary analyses we stratified by ipsilateral tibiofemoral cartilage status at baseline and compartments with pre-existing BMLs.
The adjusted relative risk of incident or enlarging BMLs ranged from 1.8; 95% confidence interval (95% CI) 1.3, 2.3 for mild medial meniscal pathology to 5.0; 95% CI 3.2, 7.7 for major lateral meniscal pathology (using no meniscal pathology in the same compartment as reference). Stratification by cartilage or BML status at baseline had essentially no effect on these estimates.
Knee compartments with meniscal pathology have a substantially increased risk of incident or enlarging subchondral BMLs over 30 months. Higher relative risks were seen in those with more severe and with lateral meniscal pathology.
Bone marrow lesion; Menisci; Tibial; Knee; Osteoarthritis; Magnetic Resonance Imaging
To identify determinants of different patterns of knee pain with a focus on risk factors for knee osteoarthritis
The Knee Pain Map is an interviewer-administered assessment that asks subjects to characterize their knee pain as localized, regional, or diffuse. A total of 2277 participants from the Osteoarthritis Initiative were studied.
We used multinomial logistic regression to examine the relationship between risk factors for OA and knee pain patterns. We examined the bivariate and multivariate relationships of knee pain pattern with age, BMI, sex, race, family history of total joint replacement, knee injury, knee surgery, and hand OA.
We compared 2462 knees with pain to 1805 knees without pain. In the bivariate analysis, age, sex, BMI, injury, surgery, and hand OA were associated with at least one pain pattern. In the multivariate model, all of these variables remained significantly associated with at least one pattern. When compared to knees without pain, higher BMI, injury, and surgery were associated with all patterns. BMI had its strongest association with diffuse pain. Older age was less likely to be associated with localized pain while female sex was associated with regional pain.
We have shown that specific OA risk factors are associated with different knee pain patterns. Better understanding of the relationship between OA risk factors and knee pain patterns may help to characterize the heterogeneous subsets of knee OA.
Knee osteoarthritis; pain localization; risk factors; knee pain
To calculate the frequency of clinically important improvement in function over 30 months and identify risk factors in people who have or are at risk of knee OA. Subjects were from MOST, a longitudinal study of persons with or at high risk of knee OA. We defined Minimal Clinically Important Improvement (MCII) with WOMAC physical function using three different methods. Baseline risk factors tested for improvement included age, gender, educational attainment, presence of radiographic knee OA (ROA), the number of comorbidities, Body Mass Index (BMI), knee pain, walking speed, isokinetic knee extensor strength, depressive symptoms, physical activity, and medication usage. We used logistic regression to evaluate the association of baseline risk factors with MCII. Of the 1801 subjects (age= 63, BMI= 31, 63% female), most had mild limitations in baseline function (WOMAC = 19 +/− 11). Regardless how defined, a substantial percentage of subjects (24%–39%) reached MCII at 30 months. Compared to their counterparts, people with MCII were less likely to have ROA and to use medications, and were more likely to have a lower BMI, less knee pain, a faster walking speed, more knee strength, and fewer depressive symptoms. After adjustment, MCII was 40% to 50% less likely in those with ROA, and 1.9 to 2.0 times more likely in those walking 1.0 m/s faster than counterparts. Clinically important improvement is frequent in people with or at high risk of knee OA. The absence of ROA and a faster walking speed appear to be associated with clinically important improvements.
Osteoarthritis; Functional limitation; Rehabilitation
To examine the accuracy and validity of self report of hip replacement (HR) for osteoarthritis.
We compared self-reported HR and the reason for surgery in elderly white women aged ≥ 65 years from the Study for Osteoporotic Fractures cohort to medical records and pelvis radiographs. Women, followed up for an average of 8 years at the fifth clinic visit were asked about any HRs since baseline.
Among 7421 women attending the fifth clinic visit, 347 reported 387 HRs. Radiographs and/or medical records were available for 316 self-reported HRs. Participants accurately reported that HRs were for arthritis or fracture, with 94.5% and 97.2% of these self-reported diagnoses, respectively, confirmed from medical records. However, 1 in 8 self-reported HRs were not attributed by participants to either arthritis or a fracture; of these, medical records indicated that 88% were for osteoarthritis. Overall, 302 (95.6%) of self-reported HRs were confirmed as HRs (kappa for agreement with self-report = 0.95, 95% CI: 0.92–.96). Under-reporting of HRs compared to HRs seen on radiographs was minimal (0.28%).
Elderly women accurately report HRs and whether the surgery is for arthritis or a hip fracture, though a small number of HRs for arthritis are not attributed to this diagnosis by women. Since hip osteoarthritis and hip fracture have very different determinants, epidemiologic studies that use self-reported HR as an indicator for the presence of hip osteoarthritis or as an outcome of hip osteoarthritis should verify the underlying cause by asking about reason for surgery.
There is limited evidence supporting the hypothesized environment–disability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations.
Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF.
Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2–3.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.3–0.8) but not with DAF in adjusted models.
People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently.
Activities of daily living; Environment; Residential characteristics