01.20.2016
Results may facilitate development of new treatment strategies
by Wayne Kuznar
Contributing Writer
Systemic inflammation was linked with bone marrow lesion scores and pain in patients with knee osteoarthritis (OA), researchers from Australia and China reported.
Serum high sensitivity-C-reactive protein (hs-CRP) was associated with the presence of knee bone marrow lesions and knee pain, as assessed by the Western Ontario McMaster Osteoarthritis Index (WOMAC), when examined cross-sectionally and longitudinally, reported Changhai Ding, MBBS, MD, of the University of Tasmania in Hobart, Australia, and colleagues.
Specifically, in a cross-sectional analysis, quartiles of baseline hs-CRP were positively associated with the presence of knee bone marrow lesions, before and after adjustment for age, sex, and body mass index (BMI), with an adjusted risk ratio of 1.07 (95% CI 1.00-1.15), they wrote in Arthritis Care & Research.
“These results add to the growing evidence that the clinical course of OA may be associated with systemic inflammation,” they stated. “Serum levels of hs-CRP may reflect the inflammatory process in bone marrow lesions among OA patients, which can be an underlying mechanism of OA knee pain. From a clinical perspective, our results may facilitate the development of new therapeutic strategies targeting low-grade inflammation for knee OA.”
The investigators examined associations between hs-CRP, knee bone marrow lesions, and knee pain in the first 192 patients who participated in the Vitamin D Effects on Osteoarthritis (VIDEO), which was a randomized controlled trial to study the effect of vitamin D in patients with symptomatic knee OA.
Patients were included if they had a pain score of at least 20 mm on a 100-mm visual analog scale and an American College of Rheumatology function class rating of I, II, or III. Mean age of patients in the substudy was 63. Serum levels of hs-CRP were measured at baseline and after 24 months. Bone marrow lesions (BML) were measured using a modified whole-organ MRI score.
The authors reported that bone marrow lesions were present in 80% of the study participants — 76.3% of those with baseline hs-CRP level below the median and 85.0% of those with baseline hs-CRP level at the median or above. The total WOMAC score was 103.4 in patients with baseline hs-CRP level below the median, compared with 141.2 in those with baseline hs-CRP level at the median or above (P=0.001).
In a longitudinal analysis, quartiles of baseline hs-CRP were significantly and positively associated with an increase in total knee bone marrow lesions, before and after adjustment for age, sex, BMI, vitamin D intervention, and baseline total knee bone marrow lesion scores (adjusted RR 1.37, 95% CI 1.10-1.70).
Significant associations were found between change in hs-CRP and changes in total knee bone marrow lesion scores, both before and after adjustment for potential confounders (adjusted RR 0.19, 95% CI 0.05-0.34).
In cross-sectional analyses, quartiles of baseline hs-CRP were significantly associated with total knee pain after adjustment for age, sex, and BMI (RR 13.83, 95% CI 2.46-24.21), and did not change after further adjustment for baseline total knee BML score (RR 13.66, 95% CI 2.26-25.07).
Change in hs-CRP was significantly associated with change in total WOMAC knee pain after adjustment for covariates (RR 4.71, 95% CI 0.48-8.94). This association decreased in magnitude and was no longer significant after further adjustment for change in total knee BMLs (adjusted RR 4.24, 95% CI -0.24-8.51).
This decrease in magnitude and loss of significance after adjustment for bone marrow lesions “suggests that the correlations between hs-CRP and total knee pain is at least partly explained by bone marrow lesions, which is consistent with our previous findings,” the investigators wrote.
In addition, quartiles of change in hs-CRP were significantly associated with an increase in total knee pain.
As a potential limitation, the authors state that the results could have been affected by the intervention (vitamin D supplementation) of the original randomized controlled VIDEO trial, although all associations from longitudinal analyses remained significant after adjusting for the intervention. Also, because inclusion and exclusion criteria were applied in the larger trial, the findings may not be generalizable to all patients with knee OA.
“Last, the period of 2 years follow-up may not be sufficient to detect associations between hs-CRP and change in pain; previous studies suggest that 5 years may be required to detect the associations,” they wrote.