Patricia A. Berry

Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review

OBJECTIVE To systematically review the evidence for a relationship between malalignment of the knee joint and progression and/or development of knee osteoarthritis (OA). METHODS Electronic searches of Medline, EMBase, and CINAHL were performed up to July 2008 using medical subject headings and free-text words. We included radiographic or magnetic resonance imaging (MRI) studies that met a set of predefined criteria. Two independent reviewers extracted the data and assessed the methodologic quality of the selected studies. Due to both heterogeneity and a limited number of studies, the results were summarized using a best evidence synthesis. RESULTS Fourteen studies met our inclusion criteria and 8 were considered high quality. We found limited evidence for an association between knee malalignment and incident knee OA, because only 1 cohort study examined this relationship. However, there was strong evidence based on 4 high-quality cohort studies that knee malalignment is an independent risk factor for progression of radiographic knee OA. This finding was further supported by 2 high-quality MRI cohort studies that found a relationship between varus and valgus alignment and structural progression of knee OA. CONCLUSION Malalignment of the knee joint was found to be an independent risk factor for the progression of knee OA. Given the paucity of investigation into the relationship between knee malalignment and risk of incident OA, further high-quality cohort studies are needed, and these may have important implications for the prevention of knee OA.

Bone marrow lesions in people with knee osteoarthritis predict progression of disease and joint replacement: a longitudinal study

OBJECTIVES The presence of bone marrow lesions (BMLs) has been linked to pain and progression of knee OA. The aim of this study was to determine the relationship between BMLs and longitudinal change in tibial cartilage volume and risk of knee joint replacement in subjects with knee OA. METHODS One hundred and nine men and women with symptomatic knee OA were recruited. The same knee was imaged using MRI at baseline and ∼2 years later. Tibial cartilage volume and BMLs were measured. Knee joint replacement over 4 years was determined. RESULTS The mean age of the subjects at baseline was 63.2 (s.d. 10.3) years. BMLs were present in 66% of the subjects. Cross-sectionally, BMLs were negatively associated with both medial (regression coefficient -121.4; 95% CI -183.8, -859.1; P<0.001) and lateral (regression coefficient -142.1; 95% CI -241.8, -42.4; P=0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase in baseline BML severity (range 0-4), the annual total tibial cartilage loss was increased by 1.14% (95% CI 0.29%, 1.87%; P=0.01). The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P=0.03). CONCLUSION The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty.

Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis

OBJECTIVE The association of obesity with both hand and knee osteoarthritis (OA) is suggestive of a link between dysfunctional metabolism and joint integrity. Given the role of adipokines in mediating bone and cartilage homeostasis, we undertook this study to examine the relationship between adipokines and bone and cartilage biomarkers in a population of subjects with OA, and to determine whether adipokine levels predicted 2-year cartilage integrity. METHODS One hundred seventeen subjects underwent magnetic resonance imaging at baseline and at 2-year followup. Cartilage volume was assessed from these images. Serum adipokine levels were measured at baseline. Bone and cartilage biomarker levels were measured at baseline and at 2-year followup. Linear regression was used to examine the relationship between baseline levels of adipokines and adipokine receptors (leptin, soluble leptin receptor [sOB-Rb], resistin, and adiponectin) and changes in levels of bone biomarkers (osteocalcin, N-terminal type I procollagen propeptide [PINP], C-terminal crosslinking telopeptide of type I collagen, N-terminal crosslinking telopeptide of type I collagen, or C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases), levels of cartilage biomarkers (cartilage oligomeric matrix protein, N-terminal type IIA procollagen propeptide [PIIANP], or C2C), cartilage defects score, and cartilage volume over 2 years. RESULTS Baseline leptin was associated with increased levels of bone formation biomarkers (osteocalcin and PINP) over 2 years, while sOB-Rb was associated with reduced levels of osteocalcin. Baseline sOB-Rb was associated with reduced levels of the cartilage formation biomarker PIIANP, an increased cartilage defects score, and increased cartilage volume loss over 2 years. All results were independent of age, sex, and body mass index. CONCLUSION The findings of this study support the concept that serum adipokines may provide a nonmechanical link between obesity and joint integrity (which may be mediated by bone and cartilage turnover) that subsequently results in changes to the cartilage defects score and cartilage volume loss. This may facilitate our understanding of the mechanisms by which obesity is involved in the pathogenesis of OA.

What Is the Effect of Physical Activity on the Knee Joint? A Systematic Review

PURPOSE Although several studies have examined the relationship between physical activity and knee osteoarthritis, the effect of physical activity on knee joint health is unclear. The aim of this systematic review was to examine the relationships between physical activity and individual joint structures at the knee. METHODS Computer-aided searches were conducted up until November 2008, and the reference lists of key articles were examined. The methodological quality of selected studies was assessed based on established criteria, and a best-evidence synthesis was used to summarize the results. RESULTS We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects. CONCLUSIONS This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health.

Relationship between obesity and foot pain and its association with fat mass, fat distribution, and muscle mass

To examine the relationship between obesity, body composition, and foot pain as assessed by the Manchester Foot Pain and Disability Index (MFPDI).

The relationship between body composition and structural changes at the knee

OBJECTIVE Obesity is an important risk factor for knee OA. Evidence suggests that fat and muscle have differential effects on the pathogenesis of disease. The aim of this study was to examine the relationship between body composition and knee structure, including knee cartilage volume, defects and bone marrow lesions (BMLs). METHODS A total of 153 subjects aged 25-60 years, 81% females, were recruited across a range of BMI (18-55 kg/m2) for a study examining the relationship between obesity and musculoskeletal disease. MRI was performed of the dominant knee. Cartilage volume, defects and BMLs were measured using validated methods. Body composition was measured using dual X-ray absorptiometry. RESULTS There was an 81 (95% CI: 69, 94) mm3 increase in cartilage volume for every 1 kg increase in skeletal muscle mass. Fat mass was not significantly associated with cartilage volume. Fat mass, but not skeletal muscle mass, was a risk factor for cartilage defects and BMLs. For every 1 kg increase in total body fat there was an increased risk of cartilage defects (OR=1.31, 95% CI: 1.04, 1.64) and BMLs (OR=1.09, 95% CI: 1.01, 1.18). CONCLUSIONS In this relatively healthy population, fat mass was associated with increased cartilage defects and BMLs, which are features of early knee OA. In contrast, skeletal muscle mass was positively associated with cartilage volume, which may be due to coinheritance, a commonality of environmental factors associated with cartilage accrual or a protective effect of increased muscle.

Increase in vastus medialis cross-sectional area is associated with reduced pain, cartilage loss, and joint replacement risk in knee osteoarthritis

OBJECTIVE Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). RESULTS After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = -0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient -10.9 [95% CI -19.5, -2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient -16.8 [95% CI -28.9, -4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). CONCLUSION In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

Variation in rates of hip and knee joint replacement in Australia based on socio‐economic status, geographical locality, birthplace and indigenous status

Background:  Our understanding of the incidence of joint replacement across different subgroups of the Australian population is limited. This study investigated whether rates of hip and knee joint replacement vary according to socio‐economic status, geographical locality, birthplace and indigenous status.

Relationship of serum markers of cartilage metabolism to imaging and clinical outcome measures of knee joint structure

Background Biomarkers of cartilage metabolism have prognostic potential. Objective To examine whether serum cartilage biomarkers, cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA procollagen (PIIANP), type II collagen breakdown product (collagen type-II cleavage (C2C)) predict cartilage volume loss and knee joint replacement. Methods 117 subjects with knee osteoarthritis (OA) had MRI at baseline and 2 years. Cartilage biomarkers were measured at baseline. Change in knee cartilage volume over 2 years and knee joint replacement over 4 years was determined. The population was divided into subgroups with high or low cartilage biomarkers (based on biomarker levels greater than or equal to, or less than, the mean, respectively). The relationships between biomarkers and outcome measures were examined in the whole population, and separately in marker subgroups. Results The relationship between cartilage biomarkers and cartilage volume loss was not linear across the whole population. In the low (regression coefficient B=–9.7, 95% CI –0.01 to 0.003, p=0.01), but not high (B=–0.46, 95% CI –8.9 to 8.0, p=0.92) COMP subgroup, COMP was significantly associated with a reduced rate of medial cartilage volume loss (p for difference between groups=0.05). Similarly, in the low (B=–8.2, 95% CI –12.9 to –3.5, p=0.001) but not high (B=2.6, 95% CI –3.3 to 8.5, p=0.38) PIIANP subgroup, PIIANP was associated with a significantly reduced rate of medial volume cartilage loss (p for difference=0.003). C2C was not significantly associated with rate of cartilage volume loss. PIIANP was associated with a reduced risk of joint replacement (odds ratio (OR)=0.28, 95% CI 0.10 to 0.93, p=0.04). Conclusion Cartilage biomarkers may be used to identify subgroups among those with clinical knee OA in whom disease progresses at different rates. This may facilitate our understanding of the pathogenesis of disease and allow us to differentiate phenotypes of disease within a heterogeneous knee OA population.

Markers of Bone Formation and Resorption Identify Subgroups of Patients with Clinical Knee Osteoarthritis Who Have Reduced Rates of Cartilage Loss

Objective. To determine whether serum markers of bone formation and resorption, used individually or in combination, can be used to identify subgroups who lose cartilage volume at different rates over 2 years within a knee osteoarthritis (OA) population. Methods. Changes in cartilage volume over 2 years were measured in 117 subjects with knee OA using magnetic resonance imaging. We examined relationships between change in cartilage volume and baseline serum markers of bone formation [intact N-terminal propeptide of type I procollagen (PINP) and osteocalcin] and resorption [N-telopeptide of type I collagen (NTX-I), C-telopeptide of type I collagen (CTX-I), and C-telopeptide of type I collagen (ICTP). Results. The baseline markers of bone formation, PINP and osteocalcin (p = 0.02, p = 0.01, respectively), and the baseline markers of bone resorption, CTX-I and NTX-I (p = 0.02 for both), were significantly associated with reduced cartilage loss. There were no significant associations between baseline ratios of bone formation to resorption markers and cartilage loss. However, when subjects were divided into subgroups with high or low bone formation markers (based on levels of marker ≥ mean or < mean for the population, respectively), in the subgroup with high PINP there was a significant association between increasing bone resorption markers CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.001, respectively). Similarly, in the subgroup with high osteocalcin, there was a significant association between increasing CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.003, respectively). In contrast, in subgroups with low bone formation markers, no significant associations were obtained between markers of bone resorption and cartilage loss. Conclusion. Overall, the results suggest that higher bone remodeling (i.e., higher serum levels of bone formation and resorption) is associated with reduced cartilage loss. Considering markers of bone formation and resorption together, it is possible to identify subgroups within the OA population who have reduced rates of cartilage loss.