Association of Serum Low‐Density Lipoprotein, High‐Density Lipoprotein, and Total Cholesterol With Development of Knee Osteoarthritis

Abstract

Objective Studies suggest an association between elevated total serum cholesterol, particularly low‐density lipoprotein (LDL), and osteoarthritis (OA). The present study was undertaken to evaluate the association between total cholesterol, LDL, and high‐density lipoprotein (HDL) and risk of knee OA. Methods We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee radiographs and magnetic resonance images (MRIs) were obtained, and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined 2 sets of patients: those developing radiographic OA, and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of cartilage loss and synovitis on MRI and of knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index scale. We carried out logistic regression adjusting for age, sex, body mass index, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures, and we performed sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL, or low HDL increased risk. Results We studied 337 patients with incident symptomatic OA and 283 patients with incident radiographic OA. The mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL, nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis, or worsening knee pain. Conclusion Our data do not support an association between total cholesterol, LDL, or HDL with OA outcomes.

Circular RNA circARPC1B functions as a stabilisation enhancer of Vimentin to prevent high cholesterol‐induced articular cartilage degeneration

“…was even more direct in finding that pravastatin significantly reduced IL‐1β induced MMP‐1 and MPP‐13 expression as well as intracellular cholesterol expression in human chondrocytes of OA patients. However, numerous studies have reported that there is no direct link between OA and cholesterol metabolism 12,56 . Our research identified an obvious and significant increase in serum and synovial fluid TC levels of patients with OA among 74 patients and synovial fluid TC levels correlated better with OA severity compared to serum TC levels.…”

“…However, numerous studies have reported that there is no direct link between OA and cholesterol metabolism. 12,56 Our research identified an obvious and significant increase in serum and synovial fluid TC levels of patients with OA among 74 patients and synovial fluid TC levels correlated better with OA severity compared to serum TC levels. Our in vitro experiments revealed increased cholesterol uptake in OA cartilage, and the increased cholesterol further exacerbated the progression of OA.…”

Causal Associations of Circulating Lipids with Osteoarthritis: A Bidirectional Mendelian Randomization Study

“…One previous study reported no significant difference in serum APOA1 levels between OA patients and healthy controls [ 37 ]. Schwager et al also found no significant association between HDL and OA based on the Multicenter Osteoarthritis Study (MOST) cohort [ 12 ]. Genetic causality between HDL and TG with OA was also absent in a UKBB based MR study [ 15 ].…”

“…An association between serum cholesterol levels and OA was subsequently reported with hand OA in women [ 9 ] and with knee OA [ 10 ]. Nevertheless, many studies have presented contradictory results [ 11 , 12 ], including the lack of a significant correlation between serum cholesterol and radiographic knee OA in an early study from Gothenburg [ 11 ], and no association between plasma low density cholesterol (LDL) or low HDL and the radiographic or symptomatic OA risks in the Multicenter Osteoarthritis Study (MOST) cohort [ 12 ]. By contrast, two recent large meta-analyses studies have shown a strong relationship between dyslipidemia and OA [ 13 , 14 ].…”

Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets

“…The relationship between dyslipidemia and OA is a controversial issue [ 44 , 45 ]. However, various studies revealed a significant relationship between lipotoxicity resulting from dyslipidemia and OA [ 41 , 43 , 46 ].…”