Bone marrow lesions in the knee are associated with increased local bone density
ABSTRACT Bone marrow lesions are associated with pain and compartment-specific progression of joint space narrowing in patients with knee osteoarthritis (OA). Bone marrow lesions occur in regions under increased loading, and excess loading produces increased bone mineral density (BMD). The ratio of BMD in the medial tibial plateau compared with that in the lateral tibial plateau (M:L BMD ratio) reflects loading in the knee. Therefore, we hypothesized that a higher M:L BMD ratio would be associated with medial bone marrow lesions, and that lower ratios would be associated with lateral bone marrow lesions.
Participants in the Framingham Osteoarthritis Study underwent magnetic resonance imaging (MRI), measurement of bone mineral density (BMD), and knee radiography between 2002 and 2004. MRI was used to define medial and lateral bone marrow lesions in the medial and lateral tibiofemoral compartments, respectively. We performed a logistic regression analysis with medial bone marrow lesions as the outcome, testing M:L BMD ratio groups as predictor variables. We adjusted for age, sex, body mass index, and systemic BMD, using generalized estimating equations to adjust for correlations between knees. An identical analysis evaluating lateral bone marrow lesions was performed.
Medial bone marrow lesions were strongly associated with a high M:L BMD ratio. The odds ratios (ORs) for prevalent medial bone marrow lesions, for the lowest to the highest quartile of M:L BMD ratios, were 1.0 (referent), 1.3, 5.0, and infinity (P for trend < 0.0001). Lateral bone marrow lesions were strongly associated with low M:L BMD ratios (the ORs for prevalent lateral bone marrow lesions, for the highest to the lowest quartile, were 1.0 [referent], 3.0, 26.8, and 54.0 [P for trend < 0.0001]).
Medial bone marrow lesions occur in knees with relatively higher local medial tibial bone density, and lateral bone marrow lesions occur in knees with relatively higher lateral tibial bone density, supporting the hypothesis that local BMD reflects loading within the knee. Our findings emphasize the importance of loading in the pathophysiology of OA.
SourceAvailable from: Marcin Binkowski[Show abstract] [Hide abstract]
ABSTRACT: The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of osteoarthritis but has failed in clinical trials. This may have occurred because AEA also activates transient receptor potential vanilloid type-1 (TRPV1), which contributes to pain development. Therefore, we investigated the effectiveness of the dual FAAH-TRPV1 blocker OMDM-198 in an MIA-model of osteoarthritic pain. We first investigated the MIA-induced model of osteoarthritis by 1) characterizing the pain phenotype and degenerative changes within the joint using X-ray microtomography and 2) evaluating nerve injury and inflammation marker (ATF-3 and IL-6) expression in the lumbar DRG of osteoarthritic rats and differences in gene and protein expression of the cannabinoid CB1 receptors FAAH and TRPV1. Furthermore, we compared OMDM-198 with compounds acting exclusively on FAAH or TRPV1. Osteoarthritis was accompanied by the fragmentation of bone microstructure and destroyed cartilage. An increase of the mRNA levels of ATF3 and IL-6 and an upregulation of AEA receptors and FAAH in the DRG was observed. OMDM-198 showed anti-hyperalgesic effects in the osteoarthritis model, which were comparable to those of a selective TRPV1 antagonist, SB-366,791, and a selective FAAH inhibitor, URB-597. The effect of OMDM-198 was attenuated by the CB1 receptor antagonist, AM-251, and by the non-pungent TRPV1 agonist, olvanil, suggesting its action as an "indirect" CB1 agonist and TRPV1 antagonist. These results suggest an innovative strategy for the treatment of osteoarthritis, which may yield more satisfactory results than those obtained so far with selective FAAH inhibitors in human osteoarthritis.Pain 02/2015; DOI:10.1097/j.pain.0000000000000132 · 5.84 Impact Factor
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ABSTRACT: We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes. The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change. The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m(2). We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively). BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.Arthritis Research & Therapy 10/2013; 15(5):R153. DOI:10.1186/ar4336 · 4.12 Impact Factor
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ABSTRACT: Introduction: There 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. Methods: A 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. Results: At 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 (beta = 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 (beta = 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. Conclusion: In 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.Arthritis Research & Therapy 07/2014; 16(4):R149. DOI:10.1186/ar4611 · 4.12 Impact Factor