Author Correction: Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study.

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Knee osteoarthritis patients with more subchondral cysts have altered tibial subchondral bone mineral density.

BACKGROUND: Subchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA. METHODS: The preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters. RESULTS: At both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region. CONCLUSION: Cyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study.

Our objective was to identify precise mechanical metrics of the proximal tibia which differentiated OA and normal knees. We developed subject-specific FE models for 14 participants (7 OA, 7 normal) who were imaged three times each for assessing precision (repeatability). We assessed various mechanical metrics (minimum principal and von Mises stress and strain as well as structural stiffness) across the proximal tibia for each subject. In vivo precision of these mechanical metrics was assessed using CV%RMS. We performed parametric and non-parametric statistical analyses and determined Cohen's d effect sizes to explore differences between OA and normal knees. For all FE-based mechanical metrics, average CV%RMS was less than 6%. Minimum principal stress was, on average, 75% higher in OA versus normal knees while minimum principal strain values did not differ. No difference was observed in structural stiffness. FE modeling could precisely quantify and differentiate mechanical metrics variations in normal and OA knees, in vivo. This study suggests that bone stress patterns may be important for understanding OA pathogenesis at the knee.

Proximal tibial trabecular bone mineral density is related to pain in patients with osteoarthritis.

BACKGROUND: Our objective was to examine the relationships between proximal tibial trabecular (epiphyseal and metaphyseal) bone mineral density (BMD) and osteoarthritis (OA)-related pain in patients with severe knee OA. METHODS: The knee was scanned preoperatively using quantitative computed tomography (QCT) in 42 patients undergoing knee arthroplasty. OA severity was classified using radiographic Kellgren-Lawrence scoring and pain was measured using the pain subsection of the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We used three-dimensional image processing techniques to assess tibial epiphyseal trabecular BMD between the epiphyseal line and 7.5 mm from the subchondral surface and tibial metaphyseal trabecular BMD 10 mm distal from the epiphyseal line. Regional analysis included the total epiphyseal and metaphyseal region, and the medial and lateral epiphyseal compartments. The association between total WOMAC pain scores and BMD measurements was assessed using hierarchical multiple regression with age, sex, and body mass index (BMI) as covariates. Statistical significance was set at p < 0.05. RESULTS: Total WOMAC pain was associated with total epiphyseal BMD adjusted for age, sex, and BMI (p = 0.013) and total metaphyseal BMD (p = 0.017). Regionally, total WOMAC pain was associated with medial epiphyseal BMD adjusted for age, sex, and BMI (p = 0.006). CONCLUSION: These findings suggest that low proximal tibial trabecular BMD may have a role in OA-related pain pathogenesis.

Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study).

OBJECTIVE: To examine use of magnetic resonance imaging (MRI) of knees with no radiographic evidence of osteoarthritis to determine the prevalence of structural lesions associated with osteoarthritis and their relation to age, sex, and obesity. DESIGN: Population based observational study. SETTING: Community cohort in Framingham, MA, United States (Framingham osteoarthritis study). PARTICIPANTS: 710 people aged >50 who had no radiographic evidence of knee osteoarthritis (Kellgren-Lawrence grade 0) and who underwent MRI of the knee. MAIN OUTCOME MEASURES: Prevalence of MRI findings that are suggestive of knee osteoarthritis (osteophytes, cartilage damage, bone marrow lesions, subchondral cysts, meniscal lesions, synovitis, attrition, and ligamentous lesions) in all participants and after stratification by age, sex, body mass index (BMI), and the presence or absence of knee pain. Pain was assessed by three different questions and also by WOMAC questionnaire. RESULTS: Of the 710 participants, 393 (55%) were women, 660 (93%) were white, and 206 (29%) had knee pain in the past month. The mean age was 62.3 years and mean BMI was 27.9. Prevalence of "any abnormality" was 89% (631/710) overall. Osteophytes were the most common abnormality among all participants (74%, 524/710), followed by cartilage damage (69%, 492/710) and bone marrow lesions (52%, 371/710). The higher the age, the higher the prevalence of all types of abnormalities detectable by MRI. There were no significant differences in the prevalence of any of the features between BMI groups. The prevalence of at least one type of pathology ("any abnormality") was high in both painful (90-97%, depending on pain definition) and painless (86-88%) knees. CONCLUSIONS: MRI shows lesions in the tibiofemoral joint in most middle aged and elderly people in whom knee radiographs do not show any features of osteoarthritis, regardless of pain.

In vivo precision of a depth-specific topographic mapping technique in the CT analysis of osteoarthritic and normal proximal tibial subchondral bone density.

OBJECTIVE: To test the in vivo precision of a depth-specific topographic mapping technique (CT-TOMASD, computed tomography topographic mapping of subchondral density) for the 3D assessment of subchondral cortical and trabecular bone density in normal and osteoarthritic (OA) human tibiae. METHODS: Fourteen participants were recruited (3 men:11 women; mean age: 49.9, SD: 11.9 years) and categorized as normal (n = 7) or OA (n = 7). Each participant was scanned using clinical quantitative CT (QCT) three times over 2 days. We assessed average subchondral bone mineral density (BMD) across three layers (0-2.5 mm, 2.5-5 mm and 5-10 mm) measured in relation to depth from the subchondral surface. Regional analyses included: medial plateau BMD; lateral plateau BMD; anterior/central/posterior compartment BMD; medial:lateral (M:L) BMD ratio; and average BMD of a 10-mm diameter "focal spot," which searched each medial and lateral plateau for the highest focal densities present within each plateau. Precision was assessed using root mean square coefficients of variation (CV%(RMS)) and intraclass correlation coefficients (ICC). RESULTS: Average CV%(RMS) precision errors for BMD measures were 2.3%, reaching a maximum CV%(RMS) of 3.9%. ICC showed high repeatability above 0.98. CONCLUSIONS: CT-TOMASD offered precise 3D measures of subchondral BMD. This method has the potential to identify and quantify changes in subchondral BMD associated with OA in vivo.

Serum 25-hydroxyvitamin D and bone mineral density in a racially and ethnically diverse group of men.

CONTEXT: Although racial and ethnic differences in vitamin D status and bone mineral density (BMD) are recognized, less is known about how differences in vitamin D status impact BMD, especially among men. OBJECTIVE: Our objective was to examine the relation between serum 25-hydroxyvitamin D [25(OH)D] and BMD by race and ethnic group. DESIGN: We conducted a population-based, observational survey. PARTICIPANTS: PARTICIPANTS included 1114 Black, Hispanic, and White men, 30-79 yr of age. OUTCOMES: We assessed 25(OH)D by a competitive protein binding assay and BMD by dual-energy x-ray absorptiometry. RESULTS: Mean age +/- SD of the 331 Black, 362 Hispanic, and 421 White men was 48 +/- 12.8 yr. Mean 25(OH)D was lower among Black (25.0 +/- 14.7 ng/ml) and Hispanic (32.9 +/- 13.9 ng/ml) men compared with White men (37.4 +/- 14.0 ng/ml, P < 0.01). A higher percentage of both Black (44%) and Hispanic (23%) men had levels of 25(OH)D in the lowest quartile, compared with 11% of White men (P < 0.001). After adjusting for age, height, and weight, only White men showed significant positive correlation between 25(OH)D and BMD (range of correlations, 0.00-0.14). Serum 25(OH)D was not associated with BMD in Black or Hispanic men at any bone site. Results were similar when adjusted for age only. CONCLUSIONS: Our findings confirm substantial racial and ethnic group differences in BMD and serum 25(OH)D in men. Serum 25(OH)D and BMD are significantly related to one another in White men only. This may have implications for evaluation of bone health and supplementation in men with low levels of 25(OH)D. Further understanding of the biological mechanisms for these differences between race and ethnic groups is needed.

Bone marrow lesions in the knee are associated with increased local bone density.

OBJECTIVE: Bone marrow lesions are associated with pain and compartment-specific progression of joint space narrowing in patients with knee osteoarthritis (OA). Bone marrow lesions occur in regions under increased loading, and excess loading produces increased bone mineral density (BMD). The ratio of BMD in the medial tibial plateau compared with that in the lateral tibial plateau (M:L BMD ratio) reflects loading in the knee. Therefore, we hypothesized that a higher M:L BMD ratio would be associated with medial bone marrow lesions, and that lower ratios would be associated with lateral bone marrow lesions. METHODS: Participants in the Framingham Osteoarthritis Study underwent magnetic resonance imaging (MRI), measurement of bone mineral density (BMD), and knee radiography between 2002 and 2004. MRI was used to define medial and lateral bone marrow lesions in the medial and lateral tibiofemoral compartments, respectively. We performed a logistic regression analysis with medial bone marrow lesions as the outcome, testing M:L BMD ratio groups as predictor variables. We adjusted for age, sex, body mass index, and systemic BMD, using generalized estimating equations to adjust for correlations between knees. An identical analysis evaluating lateral bone marrow lesions was performed. RESULTS: Medial bone marrow lesions were strongly associated with a high M:L BMD ratio. The odds ratios (ORs) for prevalent medial bone marrow lesions, for the lowest to the highest quartile of M:L BMD ratios, were 1.0 (referent), 1.3, 5.0, and infinity (P for trend < 0.0001). Lateral bone marrow lesions were strongly associated with low M:L BMD ratios (the ORs for prevalent lateral bone marrow lesions, for the highest to the lowest quartile, were 1.0 [referent], 3.0, 26.8, and 54.0 [P for trend < 0.0001]). CONCLUSION: Medial bone marrow lesions occur in knees with relatively higher local medial tibial bone density, and lateral bone marrow lesions occur in knees with relatively higher lateral tibial bone density, supporting the hypothesis that local BMD reflects loading within the knee. Our findings emphasize the importance of loading in the pathophysiology of OA.