Within‐subregion relationship between bone marrow lesions and subsequent cartilage loss in knee osteoarthritis

Objective

Bone marrow lesions are believed to increase risk of knee osteoarthritis (OA) progression. Whether their effect is local and whether it can be explained by other types of bone lesions concomitantly present in the same subregion is unclear. We evaluated bone lesion frequency in subregions without cartilage lesions and cartilage lesion frequency in subregions without bone lesions, and investigated the within‐subregion bone marrow lesion/subsequent cartilage loss relationship after adjusting for other types of bone lesions at baseline.

Methods

Individuals with knee OA had magnetic resonance imaging at baseline and 2 years later. Cartilage integrity and bone marrow lesions, cysts, and attrition were scored within tibiofemoral subregions. Logistic regression, with generalized estimating equations to account for correlation among multiple subregions within a knee, was used to estimate odds ratios (ORs) for cartilage loss associated with bone marrow lesions, adjusting for age, sex, body mass index, and bone attrition and cysts in the same subregion.

Results

Analyzing 1,953 subregions among 177 knees, 90% of subregions had no bone lesions at baseline. Only 0–3% of subregions without cartilage lesions had bone lesions in the same subregion; in contrast, 5–33% of subregions without bone lesions had cartilage lesions. Bone marrow lesions at baseline were associated with cartilage loss in the same subregion at 2 years, adjusting for other types of bone lesions at baseline (adjusted OR 3.74, 95% confidence interval 1.59–8.82).

Conclusion

In subjects with knee OA, bone marrow lesions were rare at early disease stages but predicted subregional cartilage loss after accounting for the presence of other types of bone lesions in the same subregion.     

Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies

OBJECTIVE: To confirm reports that 25-hydroxyvitamin D (25[OH]D) deficiency is associated with an increased risk of joint space narrowing or cartilage loss in osteoarthritis (OA). METHODS: We measured 25(OH)D levels in subjects from 2 longitudinal cohort studies, the Framingham Osteoarthritis Study and the Boston Osteoarthritis of the Knee Study (BOKS). In the first, weight-bearing anteroposterior (AP) and lateral knee radiographs were obtained on subjects in 1993-1994 and again in 2002-2005 (mean interval 9 years); blood was drawn for measurement of vitamin D status in 1996-2000. In the second, subjects with symptomatic knee OA participating in a natural history study had fluoroscopically positioned semiflexed posteroanterior (PA) and lateral radiography of both knees and magnetic resonance imaging (MRI) of the more symptomatic knee performed at baseline and at 15 and 30 months. Blood was drawn at all visits, and the baseline specimen was used when available. In both studies, we defined radiographic worsening based on joint space loss in the tibiofemoral joint on either AP/PA or lateral weight-bearing views, using a semiquantitative scale (worsening defined as increase by > or =1 on a 0-3 scale). In the BOKS, we evaluated cartilage loss semiquantitatively, using the Whole-Organ Magnetic Resonance Imaging Score. In both studies, 25(OH)D levels were measured by radioimmunoassay. Analyses focused on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D <20 ng/ml) versus nondeficient, predicted worsening of OA. Logistic regression analysis adjusted for age, body mass index, sex, and baseline OA level was used. RESULTS: The 715 subjects in the Framingham Study had a mean 25(OH)D level of 20 ng/ml at baseline, and 20.3% of the knees showed worsening, during the course of the study, with most knees having had no evidence of OA at baseline. The 277 subjects with OA in the BOKS had a mean 25(OH)D level of 20 ng/ml at baseline with 23.6% of knees showing radiographic worsening. We found no association of baseline 25(OH)D levels with radiographic worsening in either cohort, and confidence limits in the analyses of vitamin D deficiency were narrow, suggesting that results were not based on insufficient power. In fact, the risk of worsening was slightly, but not significantly, lower in persons with low levels of vitamin D than in persons with higher levels. In the BOKS, vitamin D levels were unrelated to cartilage loss seen on MRI. CONCLUSION: The findings indicate that vitamin D status is unrelated to the risk of joint space or cartilage loss in knee OA.     

Cartilage loss occurs in the same subregions as subchondral bone attrition: A within‐knee subregion‐matched approach from the multicenter osteoarthritis study

Objective

By magnetic resonance imaging (MRI), subchondral bone attrition (SBA) can be seen in early osteoarthritis (OA), but the significance of this is unknown. We therefore evaluated whether SBA was associated with cartilage loss within the same subregion of the knee.

Methods

The Multicenter Osteoarthritis Study is a cohort of individuals who have or are at high risk for knee OA. At baseline and 30 months, participants' knee MRIs were graded using the Whole‐Organ Magnetic Resonance Imaging Score in the 10 subregions of the tibiofemoral joint for cartilage morphology and SBA. We conducted analyses within a knee to eliminate between‐person confounding, using an M:N (cases:controls) matched case–control approach with the 10 subregions of a person's knee forming a matched set. Cases within a knee were defined as subregions with cartilage loss, while controls were subregions in that same knee without cartilage loss. We evaluated the association of cartilage loss over 30 months with the presence of baseline SBA in the same subregion within that knee using conditional logistic regression.

Results

SBA was associated with an odds ratio of 7.5 (95% confidence interval 5.6–9.9, P < 0.0001) for cartilage loss in the same subregion compared with subregions without any baseline SBA in our sample of 459 knees from participants, 64% of whom were women, with a mean age of 63 years and a mean body mass index of 30.5 kg/m².

Conclusion

SBA is strongly associated with cartilage loss within the same subregion of a knee. SBA may directly influence overlying cartilage loss or serve as a marker of an area undergoing great compressive stress and in which cartilage loss is inevitable.     

Varus–valgus alignment: Reduced risk of subsequent cartilage loss in the less loaded compartment

Objective

Varus–valgus alignment has been linked to subsequent progression of osteoarthritis (OA) within the mechanically stressed (medial for varus, lateral for valgus) tibiofemoral compartment. Cartilage data from the off‐loaded compartment are sparse. The purpose of this study was to examine our hypotheses that neutral and valgus (versus varus) knees each have reduced odds of cartilage loss in the medial subregions and that neutral and varus (versus valgus) knees each have reduced odds of cartilage loss in the lateral subregions.

Methods

Patients with knee OA underwent knee magnetic resonance imaging at baseline and 2 years. The mean cartilage thickness was quantified within 5 tibial and 3 femoral subregions. We used logistic regression with generalized estimating equations to analyze the relationship between baseline alignment and subregional cartilage loss at 2 years, adjusting for age, sex, body mass index, and disease severity.

Results

A reduced risk of cartilage loss in the medial subregions was associated with neutral (versus varus) alignment (external tibial, central femoral, external femoral) and with valgus (versus varus) alignment (central tibial, external tibial, central femoral, external femoral). A reduced risk of cartilage loss in the lateral subregions was associated with neutral (versus valgus) alignment (central tibial, internal tibial, posterior tibial) and with varus (versus valgus) alignment (central tibial, external tibial, posterior tibial, external femoral).

Conclusion

Neutral and valgus alignment were each associated with a reduction in the risk of subsequent cartilage loss in certain medial subregions and neutral and varus alignment with a reduction in the risk of cartilage loss in certain lateral subregions. These results support load redistribution as an in vivo mechanism of the long‐term alignment effects on cartilage loss in knee OA.

     

Association of cartilage defects with loss of knee cartilage in healthy, middle-age adults: a prospective study

OBJECTIVE: The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross-sectionally and longitudinally in healthy, middle-age adults. METHODS: Eighty-six healthy men and women (mean +/- SD age 53.8 +/- 8.8 years) underwent T1-weighted fat-suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2-year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0-4) and as present (a defect score of > or = 2) or absent in the medial and lateral tibiofemoral compartments. RESULTS: Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross-sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA). CONCLUSION: These data suggest that the presence of asymptomatic, non-full-thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.     

Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?

Objective. Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. We hypothesized that increased intake of antioxidant micronutrients might be associated with decreased rates of osteoarthritis (OA) in the knees, a common age-related disorder. Methods. Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography at examinations 18 (1983–1985) and 22 (1992–1993). Usual dietary intake was assessed using the Food Frequency Questionnaire, administered at examination 20 (1988–1989). Knees without OA at baseline (Kellgren and Lawrence [K&L] grade ⩾1) were classified as having incident OA if they had a K&L grade ⩽2 at followup. Knees with OA at baseline were classified as having progressive OA if their score increased by ⩽1 at followup. Knees were also classified as having cartilage loss or osteophyte growth if their maximal joint space narrowing or osteophyte growth score increased by ⩽1 (range 0–3). The association of vitamin C, beta carotene, and vitamin E intake, ranked in sex-specific tertiles, with incidence and progression of OA was compared with that of a panel of nonantioxidant vitamins, B₁, B₆, niacin, and folate, using logistic regression and generalized estimation equations to adjust for correlation between fellow knees. The lowest tertile for each dietary exposure was used as the referent category. Odds ratios (OR) were adjusted for age, sex, body mass index, weight change, knee injury, physical activity, energy intake, and health status. Results. Six hundred forty participants received complete assessments. Incident and progressive OA occurred in 81 and 68 knees, respectively. We found no significant association of incident OA with any nutrient. A 3-fold reduction in risk of OA progression was found for both the middle tertile (adjusted OR = 0.3, 95% confidence interval [95% CI] 0.1–0.8) and highest tertile (adjusted OR = 0.3, 95% CI 0.1–0.6) of vitamin C intake. This related predominantly to a reduced risk of cartilage loss (adjusted OR = 0.3, 95% CI 0.1–0.8). Those with high vitamin C intake also had a reduced risk of developing knee pain (adjusted OR = 0.3, 95% CI 0.1–0.8). A reduction in risk of OA progression was seen for beta carotene (adjusted OR = 0.4, 95% CI 0.2–0.9) and vitamin E intake (adjusted OR = 0.7, 95% CI 0.3–1.6), but was less consistent. No significant associations were observed for the nonantioxidant nutrients. Conclusion. High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effect of antioxidant nutrients on incident OA. These preliminary findings warrant confirmation.     

The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study

OBJECTIVES: To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS: One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. RESULTS: Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. CONCLUSIONS: Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.     

The relationship between cartilage loss on magnetic resonance imaging and radiographic progression in men and women with knee osteoarthritis

OBJECTIVE: To determine the relationship between radiographic progression of joint space narrowing and cartilage loss on magnetic resonance imaging (MRI) in patients with symptomatic knee osteoarthritis (OA), and to investigate the location of MRI-based cartilage loss in the knee and its relation to radiographic progression. METHODS: Two hundred twenty-four men and women (mean age 66 years) were studied. Radiographs and MRI of the more symptomatic knee were obtained at baseline and at 15- and 30-month followup. Radiographs of the knee (with weight-bearing) were read for joint space narrowing (scale 0-3), with progression defined as any worsening in score. We used a semiquantitative method to score cartilage morphology in all 5 regions of the tibiofemoral joint, and defined cartilage loss as an increase in score (scale 0-4) at any region. We examined the relationship between progression of joint space narrowing on radiographic images and cartilage loss on MRI, using a generalized estimating equation proportional odds logistic regression, adjusted for baseline cartilage score, age, body mass index, and sex. The medial and lateral compartments were analyzed separately. RESULTS: In the medial compartment, 104 knees (46%) had cartilage loss detected by MRI. The adjusted odds ratio was 3.7 (95% confidence interval 2.2-6.3) for radiographic progression being predictive of cartilage loss on MRI. However, there was still a substantial proportion of knees (80 of 189 [42%]) with cartilage loss visible on MRI when no radiographic progression was apparent. Cartilage loss occurred frequently in the central regions of the femur and tibia as well as the posterior femur region, but radiographic progression was less likely to be observed when posterior femur regions showed cartilage loss. Radiographic progression appeared specific (91%) but not sensitive (23%) for cartilage loss. Overall findings were similar for the lateral compartment. CONCLUSION: While our results provide longitudinal evidence that radiographic progression of joint space narrowing is predictive of cartilage loss assessed on MRI, radiography is not a sensitive measure, and if used alone, will miss a substantial proportion of knees with cartilage loss.     

Cartilage thickening in early radiographic knee osteoarthritis: A within‐person,between‐knee comparison

Objective

To determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within‐person, between‐knee cross‐sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight‐bearing medial femoral condyle (ecMF) and external weight‐bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.

Methods

Both knees of 61 Osteoarthritis Initiative participants (n = 4,796) displayed definite tibial or femoral marginal osteophytes and no JSN in 1 knee, and no signs of radiographic osteoarthritis (OA) in the contralateral knee; this was confirmed by an expert central reader. In these participants, cartilage thickness was measured in 16 femorotibial subregions of each knee, based on sagittal double‐echo steady‐state with water excitation magnetic resonance images. Location‐specific joint space width from fixed‐flexion radiographs was determined using dedicated software. Location‐specific associations of osteophytes with cartilage thickness were evaluated using paired t‐tests and mixed‐effects models.

Results

Of the 61 participants, 48% had only medial osteophytes, 36% only lateral osteophytes, and 16% bicompartmental osteophytes. The knees with osteophytes had significantly thicker cartilage than contralateral knees without osteophytes in the ecMF (mean ± SD +71 ± 223 μmoles, equivalent to an increase of +5.5%; P = 0.015) and ecLF (mean ± SD +64 ± 195 μmoles, +4.1%; P = 0.013). No significant differences between knees were noted in other subregions or in joint space width. Cartilage thickness in the ecMF and ecLF was significantly associated with tibial osteophytes in the same (medial or lateral) compartment (P = 0.003).

Conclusion

The knees with early radiographic OA display thicker cartilage than (contralateral) knees without radiographic findings of OA, specifically in the external femoral subregions of compartments with marginal osteophytes.     

The relationship between chondrocalcinosis and osteoarthritis in Saudi Arabia

The association between articular chondrocalcinosis and osteoarthritis was sought by studying 92 patients over the age of 60. Anteroposterior and lateral X-ray projections of knees, hands and wrists were studied for the presence of chondrocalcinosis and osteoarthritis. Of the 92 patients (60 males, 32 females), six had chondrocalcinosis of the knees; two of them also had it in the wrist. The six cases with chondrocalcinosis were compared to the 86 cases without, for the presence of osteoarthritis in the different compartments of the knees, intercarpal joints (IC) and metacarpophalangeal joints (MCP). We found an association between chondrocalcinosis and osteoarthritis of the lateral knee compartment (odd ratio (OR) 10.59, 95% CI 3.47–34.9), second MCP joint (OR 3.27 95% CI 1.44–8.93), third MCP joints (OR 6.92, 95% CI 1.99–25.54) and IC joint (OR 5.69, 95% CI 1.14–29.7). No association was found with overall knee OA, medial knee compartment OA or patellofemoral OA. In conclusion, chondrocalcinosis was associated with OA of the lateral knee compartment, second MCP, third MCP and IC joints. Received: 25 January 2002 / Accepted: 10 June 2002 Correspondence and offprint requests to: Dr Abdurhman S. Al-Arfaj, PO Box 34471, Riyadh 11468, Saudi Arabia. E-mail: asarfaj@ksu.edu.sa     

Analysis of the association between chondrocalcinosis and osteoarthritis: a community based study.

OBJECTIVES--To analyse the association between chondrocalcinosis and osteoarthritis (OA) of the hands and knees in an unselected elderly rural population. METHODS--A community based cross sectional study was performed in individuals randomly selected from a previous epidemiological survey on the prevalence of chondrocalcinosis in people older than 60 years from Osona county, Catalonia, northeastern Spain. Radiological OA (grade 2 or more of Kellgren's classification) was evaluated in 26 individuals with chondrocalcinosis and in 104 controls. A total of 18 articular areas of both knees (medial and lateral tibiofemoral compartments) and hands (first, second and third metacarpophalangeal (MCP), first carpometacarpal, trapezium-scaphoid, radiocarpal and distal radioulnar joints) were studied. RESULTS--Radiological changes of OA in the knees were more common in subjects with chondrocalcinosis than in those without it, with an odds ratio adjusted for age and gender (aOR) of 4.3 (95% confidence interval (CI) 1.6 to 11.8, p = 0.005). OA was also more frequent in almost all areas of the hands in individuals with chondrocalcinosis, though the difference reached statistical significance only in the MCP joints (aOR 3.1; 95% CI 1.1 to 8.8; p = 0.033). However, taking into account the side and the different joint compartments analysed, the association between chondrocalcinosis and OA was significant only in the lateral tibiofemoral compartment and the left MCP joints. CONCLUSIONS--In an elderly population unselected for their rheumatic complaints, there was a real association between OA and chondrocalcinosis. This association was particularly relevant in the lateral tibiofemoral compartment of the knee and in the first three left MCP joints.     

Association of cartilage defects with loss of knee cartilage in healthy,middle‐age adults: A prospective study

Objective

The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross‐sectionally and longitudinally in healthy, middle‐age adults.

Methods

Eighty‐six healthy men and women (mean ± SD age 53.8 ± 8.8 years) underwent T1‐weighted fat‐suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2‐year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0–4) and as present (a defect score of ≥2) or absent in the medial and lateral tibiofemoral compartments.

Results

Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross‐sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA).

Conclusion

These data suggest that the presence of asymptomatic, non–full‐thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.

     

Risk factors for progressive cartilage loss in the knee: a longitudinal magnetic resonance imaging study in forty-three patients

OBJECTIVE: To evaluate the rate of progression of cartilage loss in the knee joint using magnetic resonance imaging (MRI) and to evaluate potential risk factors for more rapid cartilage loss. METHODS: We evaluated baseline and followup MRIs of the knees in 43 patients (minimum time interval of 1 year, mean 1.8 years, range 52-285 weeks). Cartilage loss was graded in the anterior, central, and posterior regions of the medial and lateral knee compartments. Knee joints were also evaluated for other pathology. Data were analyzed using analysis of variance models. RESULTS: Patients who had sustained meniscal tears showed a higher average rate of progression of cartilage loss (22%) than that seen in those who had intact menisci (14.9%) (P 相似文献   

A 12 year follow up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee.

The natural history and prognostic factors of cartilage loss in osteoarthritis of the knee were studied in subjects from a general population survey on rheumatic diseases in 1975-8. Baseline data were collected by questionnaire, physical examination, and weightbearing anteroposterior knee radiographs. Follow up of the subjects aged 46-68 years with radiological osteoarthritis grade 2-4 (Kellgren) took place in 1988-9. Cartilage loss was assessed by two observers who scored the change in joint space width between two radiographs. Thirty four per cent had cartilage loss. Prognostic factors and adjusted odds ratios (ORs) (95% confidence intervals) were: body mass index OR = 11.1 (3.3 to 37.3) fourth v first quartile; body weight OR = 7.9 (2.6 to 24.0) third v first tertile; age OR = 3.8 (1.1 to 13.4) > 60 v < or = 49 years; Heberden's nodes OR = 6.0 (1.5 to 23.1); clinical diagnosis of generalised osteoarthritis OR = 3.3 (1.3 to 8.3); and previous bow legs or knock knees OR = 5.1 (1.1 to 23.1). The relation of age with cartilage loss was also confounded by the presence of Heberden's nodes or a diagnosis of generalised osteoarthritis. There was no statistically significant relation for gender, meniscectomy, injury, uric acid concentration, chondrocalcinosis, smoking, and occupation related factors, except possibly standing.     

Self‐reported knee and foot alignments in early adult life and risk of osteoarthritis

Objective

To determine whether self‐reported early adult life malalignment of knees or feet are risk factors for knee or hip osteoarthritis (OA).

Methods

Participants in the Genetics of Osteoarthritis and Lifestyle case–control database were sent a questionnaire (n = 3,022) containing line‐drawing instruments for self‐reported knee and foot alignment at ages 20–29 years. Respondents were categorized as having straight, valgus, or varus knee, and straight, toe‐in, or toe‐out feet. Radiographic criteria were used to define current isolated knee or hip OA, combined knee and hip OA, or non‐OA controls. Odds ratios (ORs), adjusted ORs, and 95% confidence intervals (95% CIs) were calculated and logistic regression was performed.

Results

The response rate was 72%; 87.5% of responders (n = 1,901) completed the alignment questions. Increased risk of isolated knee OA occurred with early adult varus (adjusted OR 5.16, 95% CI 2.87–9.41) and valgus knees (adjusted OR 3.16, 95% CI 1.04–9.64). The positive association between knee OA and toe‐in foot was explained by varus knee. There was an increased risk of combined knee/hip OA from varus (adjusted OR 4.52, 95% CI 2.39–8.53) and valgus knees (adjusted OR 3.07, 95% CI 0.99–9.54). Varus knee was associated with risk of medial tibiofemoral OA, whereas valgus knee was associated with risk of lateral tibiofemoral and lateral patellofemoral OA. Toe‐out foot was associated with reduced medial patellofemoral OA. For knee OA, a multiplicative interaction analysis between occupational risks and varus/valgus yielded an OR_int of 3.20 (95% CI 1.08–9.49).

Conclusion

Constitutional alignment of the leg in terms of varus or valgus knee or foot rotation may be a significant factor in determining development and distribution of knee but not hip OA.     

Rates of change and sensitivity to change in cartilage morphology in healthy knees and in knees with mild, moderate, and end-stage radiographic osteoarthritis: results from 831 participants from the Osteoarthritis Initiative

Objective

To study the longitudinal rate of (and sensitivity to) change of knee cartilage thickness across defined stages of radiographic osteoarthritis (OA), specifically healthy knees and knees with end‐stage radiographic OA.

Methods

One knee of 831 Osteoarthritis Initiative participants was examined: 112 healthy knees, without radiographic OA or risk factors for knee OA, and 719 radiographic OA knees (310 calculated Kellgren/Lawrence [K/L] grade 2, 300 calculated K/L grade 3, and 109 calculated K/L grade 4). Subregional change in thickness was assessed after segmentation of weight‐bearing femorotibial cartilage at baseline and 1 year from coronal magnetic resonance imaging (MRI). Regional and ordered values (OVs) of change were compared by baseline radiographic OA status.

Results

Healthy knees displayed small changes in plates and subregions (±0.7%; standardized response mean [SRM] ±0.15), with OVs being symmetrically distributed close to zero. In calculated K/L grade 2 knees, changes in cartilage thickness were small (<1%; minimal SRM ?0.22) and not significantly different from healthy knees. Knees with calculated K/L grade 3 showed substantial loss of cartilage thickness (up to ?2.5%; minimal SRM ?0.35), with OV1 changes being significantly (P < 0.05) greater than those in healthy knees. Calculated K/L grade 4 knees displayed the largest rate of loss across radiographic OA grades (up to ?3.9%; minimal SRM ?0.51), with OV1 changes also significantly (P < 0.05) greater than in healthy knees.

Conclusion

MRI‐based cartilage thickness showed high rates of loss in knees with moderate and end‐stage radiographic OA, and small rates (indistinguishable from healthy knees) in mild radiographic OA. From the perspective of sensitivity to change, end‐stage radiographic OA knees need not be excluded from longitudinal studies using MRI cartilage morphology as an end point.

     

Central bone marrow lesions in symptomatic knee osteoarthritis and their relationship to anterior cruciate ligament tears and cartilage loss

OBJECTIVE: Medial and lateral compartment bone marrow lesions (BMLs) have been tied to cartilage loss. We undertook this study to assess 2 types of BMLs in the central region of the knee (type 1 BMLs, which are related anatomically to anterior cruciate ligament [ACL]/posterior cruciate ligament [PCL] insertions, and type 2 BMLs, which encompass both the central region and either the medial or the lateral compartment) and determine their relationship to cartilage loss and ACL tears. METHODS: Magnetic resonance imaging (MRI) of the knee was performed at baseline and at followup (15 and/or 30 months) in 258 subjects with symptomatic osteoarthritis (OA). At baseline, we assessed ACL tears and central BMLs located at or between the tibial spines or adjacent to the femoral notch. Cartilage loss was present if the score in any region of the tibiofemoral joint increased by >or= 1 units at the last available followup, using a modified Whole-Organ MRI Score. We used logistic regression adjusted for alignment, body mass index, Kellgren/Lawrence score, sex, and age. RESULTS: One hundred thirty-nine knees (53.8%) had central BMLs, of which 129 had type 1 BMLs (96 abutted the ACL and had no coexistent type 2 features) and 25 had type 2 BMLs (often overlapped with type 1). Type 1 lesions were associated with ACL tears (odds ratio [OR] 5.9, 95% confidence interval [95% CI] 2.2-16.2) but not with cartilage loss (OR 1.6, 95% CI 0.8-3.1), while medial type 2 BMLs were related to medial cartilage loss (OR 6.1, 95% CI 1.0-35.2). CONCLUSION: Central BMLs that abutted the ACL were highly prevalent and strongly related to ACL pathology, suggesting a role of enthesopathy in OA. Only BMLs with medial extension were related to ipsilateral cartilage loss.     

The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis

OBJECTIVE: To explore the role of meniscal tears and meniscal malposition as risk factors for subsequent cartilage loss in subjects with symptomatic osteoarthritis (OA). METHODS: Study subjects were patients with symptomatic knee OA from the Boston Osteoarthritis of the Knee Study. Baseline assessments included knee magnetic resonance imaging (MRI) with followup MRI at 15 and 30 months. Cartilage and meniscal damage were scored on MRI in the medial and lateral tibiofemoral joints using the semiquantitative whole-organ magnetic resonance imaging score. Tibiofemoral cartilage was scored on MR images of all 5 plates of each tibiofemoral joint, and the meniscal position was measured using eFilm Workstation software. A proportional odds logistic regression model with generalized estimating equations was used to assess the effect of each predictor (meniscal position factor and meniscal damage as dichotomous predictors in each model) on cartilage loss in each of the 5 plates within a compartment. Models were adjusted for age, body mass index (BMI), tibial width, and sex. RESULTS: We assessed 257 subjects whose mean +/- SD age was 66.6 +/- 9.2 years and BMI was 31.5 +/- 5.7 kg/m2; 42% of subjects were female, and 77% of knees had a Kellgren/Lawrence radiographic severity grade > or = 2. In the medial tibiofemoral joint, each measure of meniscal malposition was associated with an increased risk of cartilage loss. There was also a strong association between meniscal damage and cartilage loss. Since meniscal coverage and meniscal height diminished with subluxation, less coverage and reduced height also increased the risk of cartilage loss. CONCLUSION: This study highlights the importance of an intact and functioning meniscus in patients with symptomatic knee OA, since the findings demonstrate that loss of this function has important consequences for cartilage loss.     

The effect of body weight on progression of knee osteoarthritis is dependent on alignment

OBJECTIVE: Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment. METHODS: The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations. RESULTS: Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45). CONCLUSION: Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.     

Longitudinal performance evaluation and validation of fixed-flexion radiography of the knee for detection of joint space loss

OBJECTIVE: The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed-flexion radiography protocol to detect knee joint space loss over 3 years. METHODS: We assessed the same-day test-retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23-47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70-79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions. RESULTS: A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean +/- SD joint space loss for all knees over 3 years was 0.24 +/- 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean +/- SD joint space loss over 3 years was 0.43 +/- 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 +/- 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup. CONCLUSION: Radiography of the knee in the fixed-flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.