Abstract
ObjectiveTo evaluate the influence of the mtDNA haplogroups on knee osteoarthritis progression in Osteoarthritis Initiative (OAI) participants through longitudinal data from radiographs and magnetic resonance imaging (MRI).MethodsFour-year knee osteoarthritis progression was analyzed as increase in Kellgren and Lawrence (KL) grade, in addition to increase in OARSI atlas grade for joint space narrowing (JSN), osteophytes and subchondral sclerosis in the tibia medial compartment of 891 Caucasian individuals from the progression subcohort. The influence of the haplogroups on the rate of structural progression was also assessed as the four-year change in minimum joint space width (mJSW in millimetres) in both knees of (n = 216) patients with baseline unilateral medial-tibiofemoral JSN. Quantitative cartilage measures from longitudinal MRI data were those related to cartilage thickness and volume with a 24 month follow-up period (n = 381).ResultsDuring the four-year follow-up period, knee OA patients with the haplogroup T showed the lowest increase in KL grade (Hazard Risk [HR] = 0.499; 95% Confidence Interval [CI]: 0.261–0.819; p<0.05) as well as the lowest cumulative probability of progression for JSN (HR = 0.547; 95% CI: 0.280–0.900; p<0.05), osteophytes (HR = 0.573; 95% CI: 0.304–0.893; p<0.05) and subchondral sclerosis (HR = 0.549; 95% CI: 0.295–0.884; p<0.05). They also showed the lowest decline in mJSW (standardized response means (SRM) = −0.39; p = 0.037) in those knees without baseline medial JSN (no-JSN knees). Normalized cartilage volume loss was significantly lower in patients carrying the haplogroup T at medial tibia femoral (SRM = −0.33; p = 0.023) and central medial femoral (SRM = −0.27; p = 0.031) compartments. Cartilage thickness loss was significantly lower in carriers of haplogroup T at central medial tibia-femoral (SRM = −0.42; p = 0.011), medial tibia femoral (SRM = −0.32; p = 0.018), medial tibia anterior (SRM = +0.31; p = 0.013) and central medial femoral (SRM = −0.19; p = 0.013) compartments.ConclusionsMitochondrial genome seems to play a role in the progression of knee osteoarthritis. mtDNA variation could improve identification of patients predisposed to faster or severe progression of the disease.
Highlights
Osteoarthritis (OA), the most common joint disease related to ageing, is characterized by the degeneration of articular cartilage, affecting subchondral bone and soft tissue and leading to joint destruction and severe impairment of mobility [1]
The Osteoarthritis Initiative (OAI) is a public-private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators
We analyzed the increase of Kellgren and Lawrence (KL) grade in knee OA patients as well as the radiographic progression or development of joint space narrowing (JSN), osteophytes and subchondral sclerosis
Summary
Osteoarthritis (OA), the most common joint disease related to ageing, is characterized by the degeneration of articular cartilage, affecting subchondral bone and soft tissue and leading to joint destruction and severe impairment of mobility [1]. Clinical testing of new therapies is complicated by the highly variable way OA manifests in individual patients; it is established that some OA patients remain relatively stable over time, while others progress more rapidly to severe structural deterioration often leading to joint replacement. The usefulness of both genetic and protein biomarkers in OA is to predict, the risk of OA at an earlier stage of the disease [5], and which OA patients are more likely to progress to severe disease. Some studies have evaluated the role of genetic factors in the severity or progression of OA [6,7,8,9] and, to date, relatively little is known about risk factors for radiographic knee OA progression, despite their great clinical importance
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