Hussain Ijaz Khan

The clinical significance, natural history and predictors of bone marrow lesion change over eight years

IntroductionThere is increasing evidence to suggest that bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA). However, there is a lack of long term data. The aim of this study was to describe the natural history of knee BMLs, their association with knee pain and examine predictors of BML change over eight years.MethodsA total of 198 subjects (109 adult offspring of subjects who had a knee replacement and 89 community-based controls) were studied. Knee pain and BML size were assessed at two and ten year visits.ResultsAt the two year visit, 64% of participants (n = 127) had 229 BMLs (34% patella, 26% femoral and 40% tibial). Over eight years, 24% (55/229) increased in size, 55% (125/229) remained stable and 21% (49/229) decreased in size or resolved completely. Of the participants without BMLs at baseline, 52% (37/71) developed incident BMLs.After adjusting for confounders, eight year change in total BML size was associated with change in knee pain in offspring (β = 2.50, 95% confidence interval (CI) 0.96 to 4.05) but not controls. This association was stronger in males. Incident BMLs were associated with increase in pain (β = 3.60, 95% CI 1.14 to 6.05). Body mass index (BMI) and strenuous activity (but not radiographic osteoarthritis or smoking) were associated with an increase in BML size.ConclusionIn this midlife cohort, the proportion of BMLs increasing in size was similar to those decreasing in size with the majority remaining stable. Change in BMLs was predicted by BMI and strenuous activity. An increase in BML size or a new BML resulted in an increase in pain especially in males and those with a family history of OA.

A family history of knee joint replacement increases the progression of knee radiographic osteoarthritis and medial tibial cartilage volume loss over 10 years

OBJECTIVES Osteoarthritis (OA) has a genetic component but it is uncertain if the offspring of those with knee OA are at a greater risk. The aim of this study was to describe radiographic OA (ROA) progression and cartilage loss over 10 years in a midlife cohort with some having a family history of OA and some community based controls. METHODS 220 participants [mean-age 45 (26-61); 57% female] were studied at baseline and 10 years. Half were adult offspring of subjects who underwent knee replacement for OA and the remainder were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed on radiographs and cartilage volume (tibial, femoral and patellar), cartilage defects, bone marrow lesions (BMLs) and meniscal tears were assessed on Magnetic resonance imaging (MRI). RESULTS For ROA, there was a significant difference between offspring and controls in unadjusted analysis for change in total ROA, medial JSN, total medial, total lateral and total osteophyte scores. This difference persisted for medial JSN (difference in ratios = +1.93 (+1.04, +3.51)) only, after adjustment for confounders and baseline differences. In unadjusted analysis for cartilage loss, offspring lost more cartilage at the medial tibial (difference in means = -79.13 (-161.92, +3.71)) site only. This difference became of borderline significance after adjustment for baseline differences (P = 0.055). CONCLUSION The offspring of subjects having a total knee replacement have a greater worsening of ROA (both JSN and osteophytes) and higher medial tibial cartilage volume loss over 10 years. Most of these changes are mediated by differences in baseline characteristics of offspring and controls except for increase in medial JSN.

The offspring of people with a total knee replacement for severe primary knee osteoarthritis have a higher risk of worsening knee pain over 8 years

Objective To investigate whether offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) have an increased risk of worsening knee pain over 8 years as compared with controls with no family history of knee OA. Methods A total of 219 participants (mean age 48 years, range 29–61 years) with 115 offspring and 104 controls participated in this study. Knee pain was respectively assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2 years and 10 years. T1-weighted or T2-weighted fat saturated MRI of the right knee was performed to assess knee cartilage defects, bone marrow lesions, effusion, meniscal extrusion and tears. Results Compared with controls, the prevalence of knee pain for offspring was similar at 2 years (56% vs 54%, p=0.764) and higher at 10 years (74% vs 54%, p=0.002). Over 8 years, offspring more frequently had an increase in total knee pain (66% vs 41% ≥1 point increase, p=0.003) and in all subscales apart from walking (all p<0.05). In multivariable analysis, after adjustment for confounders and structural factors, offspring had an elevated risk of worsening total knee pain (OR=2.16, 95% CI 1.14 to 4.12), as well as each subscale except for walking and standing (OR=1.95 to 3.30, all p<0.05). Conclusions Offspring with a family history of knee OA have an increased risk of worsening knee pain, which is independent of structural factors, suggesting that genetic factors may be involved in the pathogenesis of knee pain.

Familial effects on structural changes relevant to knee osteoarthritis: a prospective cohort study

OBJECTIVE Genetic factors play an important role in the pathogenesis of knee osteoarthritis (OA), but which knee structural changes mediate this is unclear. This study aimed to describe the differences in knee structural changes over 8-10 years between offspring having at least one parent with total knee replacement (TKR) for severe primary knee OA and controls with no family history of knee OA. DESIGN 115 offspring (mean age 45 years) with a family history of TKR for severe knee OA were compared with 104 (mean age 46 years) controls. T1 or T2-weighted fat saturated magnetic resonance imaging (MRI) was performed respectively to evaluate knee cartilage defects, bone marrow lesions (BMLs), meniscal extrusion and tears at baseline and 10 years. Multivariate logistic regression model was used to adjust for potential confounders. RESULTS Offspring had a greater increase in cartilage defect score (1.03 vs 0.52, P = 0.007) and meniscal extrusion score (0.28 vs 0.10, P = 0.027) over 10 years, and a greater increase in meniscal tear score (0.40 vs 0.10, P = 0.012) over 8 years in the medial but not the lateral tibiofemoral compartment. Changes in BMLs over 8-years were not different between the two groups. These associations were independent of potential confounders, and strengthened after further adjustment for each other. CONCLUSION With the exception of BMLs, offspring with a family history of knee OA have a greater risk of increases in multiple knee structural abnormalities in the medial tibiofemoral compartment suggesting pleiotropic familial effects.

Correlation Between Changes in Global Knee Structures Assessed by Magnetic Resonance Imaging and Radiographic Osteoarthritis Changes Over Ten Years in a Midlife Cohort

The aim of this study was to describe the correlation between changes in structural abnormalities assessed on magnetic resonance imaging (MRI) and change in radiographic osteoarthritis (OA) over 10 years in a midlife cohort.

Correlation between changes in global knee structures assessed on MRI and radiographic osteoarthritis changes over 10 years in a mid‐life cohort

The aim of this study was to describe the correlation between changes in structural abnormalities assessed on magnetic resonance imaging (MRI) and change in radiographic osteoarthritis (OA) over 10 years in a midlife cohort.

Correlation Between Changes in Global Knee Structures Assessed by Magnetic Resonance Imaging and Radiographic Osteoarthritis Changes Over Ten Years in a Midlife Cohort: MRI and Radiographic Knee Structures Assessment Correlation

The aim of this study was to describe the correlation between changes in structural abnormalities assessed on magnetic resonance imaging (MRI) and change in radiographic osteoarthritis (OA) over 10 years in a midlife cohort.

FRI0419 Association between Objectively Assessed Physical Activity and Disease Progression in A Population Based Sample of Ankylosing Spondylitis Patients

Background Ankylosing spondylitis (AS) is a chronic, systemic disease that is characterized by inflammation, especially at the spinal column. Chronic inflammation of the spinal and extraspinal joints and enthesis frequently lead to limitation of spinal and joint mobility. Although AS results in decreased physical and functional capacity, recent studies have suggested that physical activity (PA)/exercise is as crucial as drug treatment in the management of AS [1,2]. However the relationship between PA and AS disease activity remain s uncertain as the studies conducted thus far have used non-objective measures to assess PA. Objectives The aim of this study was to examine the association between PA at baseline and AS disease progression over 2 years especially in male participants. Methods 113 participants, initially recruited if they had inflammatory back pain or extra-articular features of AS for 10 years or less, were studied at baseline and 2 years. PA was assessed at the baseline visit only using a pedometer (steps/day) over 10 days. MRI scans of the spine were performed to assess inflammation at baseline and 2 years. Images were scored, using the Spondyloarthritis Research Consortium of Canada method. Disease activity, functional limitations and mobility were assessed at both time points using the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) respectively. Results 113 participants [mean-age (years) 41 (range 17–72); 64% male, BMI 27 (18–54)] were studied at baseline and two years. 62% of the participants had radiographic evidence of AS according to the modified New York criteria. 100 participants showed some evidence of spinal inflammation (mean 9.86 (0–60)). Mean steps/day were 4665 (1666–9711). Higher number of steps/day at the baseline visit showed an independent negative association with change in spinal MRI inflammation (β (per 1000 steps) = -0.49 (-0.91, -0.07) over 2 years. Further analysis (figure-1) showed a dose response relation between PA and change in spinal inflammation. Participants who had an increase in severity of inflammation had on average least number of steps/day, whereas participants who had a decrease in severity of inflammation had the highest number of steps/day at the baseline visit. Higher number of steps/day at the baseline visit were negatively associated with change in BASDAI (β (per 1000 steps) = -0.33 (-0.66, -0.04) score over 2 years. However we did not see any significant associations between PA and changes in BASFI and BASMI scores. We further explored sex interactions for the associations between PA and changes in spinal inflammation and BASDAI scores, and found that higher number of steps/day resulted in a significantly higher decrease in the severity of MRI inflammation and BASDAI scores (p<0.05) in the male participants. Conclusions Higher PA was associated with a decrease in disease activity both clinically and on imaging. References Heikkila S, Viitanen JV, Kautiainen H, Kauppi M. Sensitivity to change of mobility tests; effect of short term intensive physiotherapy and exercise on spinal, hip, and shoulder measurements in spondyloarthropathy. J Rheumatol. 2000; 27:1251–6. Ince G, Sarpel T, Durgun B, Erdogan S. Effects of a multimodal exercise program for people with ankylosing spondylitis. Phys Ther. 2006; 86:924–35. Disclosure of Interest None declared

Reply Letter to the Editor: Knee joint replacement and individual susceptibility for progression of knee osteoarthritis and tibial cartilage volume loss: not only genes run in the family.

We thank Kuijer et al. for their interest in our study and appreciate the opportunity to respond. We concluded in our study1 that the offspring of subjects having a total knee replacement (TKR) have a greater worsening of radiographic osteoarthritis (OA) and higher medial tibial cartilage volume loss over 10 years compared to community based controls, and most of these changes were mediated by baseline differences (including BMI) between the two groups. Kuijer et al. have raised an interesting and valid point that individuals with a lower socioeconomic position (SEP) are more likely to perform physically demanding work resulting in knee bending/lifting2,3. Hence they are more prone to develop OA at an earlier age due to increased knee-demanding work and this non-genetic factor might have also accounted for the associations we described in our study. Occupational knee bending/lifting was assessed in the Offspring study through a self-administered questionnaire at the baseline and 10-year follow-up visits. Participants were asked, “If employed, does your occupation involve significant knee bending and carrying heavy objects? e.g., Delivery work.” There was no significant difference in the distribution of occupational knee bending between the two groups (offspring 1⁄4 34%, controls 31%, P 1⁄4 0.781) at the baseline. Furthermore, there was no significant difference between the two groups in terms of change in occupational knee bending over 10 years. Difficulty in bending to the floor was also assessed using the relevant question in the Western Ontario and McMaster Universities Index of OA (WOMAC)4 questionnaire. There was no significant difference (P 1⁄4 0.236) between the two groups for difficulty in bending to the floor (not the wholeWOMAC score). Adjusting for these factors did not change the effect size of the association we presented by any meaningful amount. In further analyses we were able to ascertain SEP of all the participants. Residential addresses were matched to Australian Bureau of Statistics (ABS) data5 to identify three markers of area level SEP: (i) relative social disadvantage, (ii) economic resources (iii) educational and occupational opportunity. Absolute score given to each area by ABS in all three categories, as well as scores categorized as deciles relative to the general Australian population, were computed for each participant. There was no significant difference between SEP of offspring and controls for all the three above mentioned categories and again adjustment for these factors did

Response to: ‘Does it make sense to investigate whether the offspring of people with a total knee replacement for severe primary knee osteoarthritis have a higher risk of worsening knee pain?’ by Lei et al

We would like to thank Lei et al 1 for their interest in and comments on our paper on the higher risk of worsening knee pain in the offspring with a family history of knee osteoarthritis (OA) as compared with control with no family history.2 First, we agree that the correlation between the radiographic OA and the presence of pain is weak and not significant in this cohort. Our group has published much of the research on this area and what does contribute to pain. Our contention is that radiographic OA is of limited significance and papers from this cohort show that. The MRI scans show many structural changes within the knee long before radiographic OA develops and these are …