Bone Marrow Lesions Size Research Articles

Fluctuation of Bone Marrow Lesions and Inflammatory MRI Markers over 2 Years and Concurrent Associations with Quantitative Cartilage Loss.

To assess whether change of semiquantitatively magnetic resonance imaging (MRI)-defined bone marrow lesions (BMLs) and inflammatory markers is associated with change in quantitatively-assessed cartilage loss in the femorotibial joint (FTJ) in knees with radiographic osteoarthritis (OA) over 24 months. Participants were included from the IMI-APPROACH and the Osteoarthritis Initiative FNIH studies. Semiquantitative MRI assessment was performed for BMLs, Hoffa- and effusion-synovitis. Quantitative cartilage thickness measurements were performed manually. Definitions of change included number of subregions with BMLs, change in sum and change in maximum increase in size. Change in Hoffa-synovitis and effusion-synovitis was categorized in addition. Between-group comparisons regarding cartilage loss in the FTJ, medial and lateral compartments were performed using analysis of variance (ANOVA). A total of 629 participants were included. Knees without any BMLs at baseline (BL) and follow-up (FU) had significantly less cartilage loss compared to the other subgroups. Change in both directions in the sum score of BMLs was associated with increased rates of cartilage loss. Maximum increase in size of BMLs was associated with increased rates of cartilage loss (FTJ increase by 2 grades -0.183 mm, 95% CI [-0.335, -0.031], by 3 grades -0.306 mm, [-0.511, -0.101]). Worsening of Hoffa-synovitis was associated with increased rates of cartilage loss. Knees without BMLs at BL and FU showed lowest rates of cartilage loss. Knees with an increase in BML size showed increased rates of concurrent cartilage loss. Approaches with the aim to inhibit BML development, avoidance of increase in size and avoidance of Hoffa-synovitis worsening may have beneficial effects on cartilage loss.

No Significant Differences between Bisphosphonates and Placebo for the Treatment of Bone Marrow Lesions of the Knee: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: The purpose of the present systematic review and meta-analysis is to summarize the current evidence on the role of bisphosphonates in the treatment of knee bone marrow lesions (BMLs), to understand whether they are truly effective in improving symptoms and restoring the subchondral bone status at imaging evaluation. Methods: A literature search was carried out on PubMed, Cochrane, and Google Scholar databases in accordance with the PRISMA guidelines. Potential risk of bias was evaluated using the Cochrane Risk of Bias 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies. Results: A total of 15 studies were included in the present systematic review and meta-analysis. Seven studies were RCTs, two were prospective cohort studies, three were retrospective, and three were case series. Our meta-analysis revealed that bisphosphonates did not significantly improve clinical scores or reduce BML size compared to placebo. Accordingly, the rate of adverse events was also non-significantly higher among bisphosphonate users versus placebo users. Conclusions: The main finding of the present meta-analysis and systematic review is that bisphosphonates show neither significant benefits nor significant adverse events when compared to placebo in the treatment of BMLs of the knee. Level of Evidence: Level IV systematic review of level II-III-IV studies. Level I meta-analysis of level I studies.

Dietary Inflammatory Index and Magnetic Resonance Imaging-Detected Knee Structural Change and Pain: A 10.7-Year Follow-up Study.

To determine whether the dietary inflammatory index (DII) scores were associated with knee structural changes and pain over a 10.7-year follow-up. This study used data from a prospective population-based cohort study (mean age 63 years, 51% female) in which 1,099, 875, 768, and 566 participants completed assessments at baseline, 2.6, 5.1, and 10.7 years, respectively. T1-weighted and T2-weighted magnetic resonance imaging was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and 10.7 years. The Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire was used to measure knee pain at each visit. Pain trajectories ("minimal pain," "mild pain," and "moderate pain") were previously identified. Baseline energy-adjusted DII (E-DII) scores were calculated. Linear, log-binomial regression, linear mixed-effects modeling, and multi-nominal logistic regression were used for analyses. The mean ± SD E-DII score at baseline was -0.48 ± 1.39. In multivariable analyses, higher E-DII scores were not associated with tibial CV loss or BML size increase except for medial tibial BML size increase. Higher E-DII scores were associated with a higher pain score (β=0.21; 95% confidence interval [CI] 0.004-0.43) and an increased risk of belonging to the "moderate pain" compared to the "minimal pain" trajectory group (relative risk ratio 1.19; 95% CI 1.02-1.39). A proinflammatory diet, as indicated by a higher DII score, may be associated with a greater pain score and higher risk of more severe pain trajectory over 10 years. However, inconsistent findings related to structural changes suggest a discordance between the potential impact of diet on structural damage and pain in knee OA.

The role of magnetic resonance imaging in efficacy of low-dose extracorporeal shock wave therapy for patients with knee osteoarthritis

Among many diseases of the joints, the most common is osteoarthritis and, in particular, knee osteoarthritis. Current medicine requires new and improved imaging techniques to assess patients with knee osteoarthritis, which enable early diagnosis, improved understanding of the pathophysiology of osteoarthritis, and the efficacy of the ongoing treatment. Scientific data on the use of magnetic resonance imaging (MRI) as an objective method to assess the impact of shock wave therapy (SWT) on the restoration of damaged cartilage and bone marrow in patients with knee osteoarthritis was analyzed. A search for publications in the PEDro and PubMed databases for the period from 2017 to 2022 was performed. The search was done using the following keywords: osteoarthritis/knee osteoarthritis, shock wave therapy, magnetic resonance imaging. Five foreign studies were included in the review as a result of the search (no Russian publications were available). Two studies analyzed the effects of SWT on altered cartilage in patients with knee osteoarthritis. Patients who received oral non-steroidal anti-inflammatory drugs were selected as a comparison group. The authors assessed SWT effects on cartilage using quantitative estimates of T2 relaxation time (T2 mapping) and the severity of bone marrow edema on MRI images. At 24 weeks after treatment, differences in relaxation time on T2-weighted MRI images of the patella, acetabulum, and medial and lateral articular surfaces of the femur and tibia showed no statistical significance compared to those before treatment (t= 1.859; P= 0.076). In conclusion, the authors suggested that the resulting effect of SWT in patients with knee osteoarthritis was due to the use of low energy and stated that research will continue using higher SWT parameters. Another study reported that patients with knee osteoarthritis showed a statistically significant reduction in the area of the subchondral bone marrow lesion 6 months after SWT. In addition, the authors found a correlation between the reduction in subchondral bone marrow lesion size and the improvement in pain scores resulting from the SWT treatment. In another study, MRI scans in patients with knee osteoarthritis documented a positive SWT effect by reducing bone marrow edema. After one year of follow-up, MRI images showed complete regression of bone marrow edema among patients who received SWT. The number of studies that investigated SWT effects on cartilage and bone marrow restoration in patients with knee osteoarthritis using MRI is limited, indicating the need for continued research in this area.

Worsening of Articular Tissue Damage as Defined by Semi-Quantitative MRI Is Associated With Concurrent Quantitative Cartilage Loss Over 24 Months.

To assess the association of worsening of magnetic resonance imaging (MRI) semi-quantitative (SQ) tissue features with concurrent change in quantitative (Q) cartilage thickness measurements over 24 months within the Foundation for the National Institutes of Health (FNIH) Biomarker Consortium study. In all, 599 participants were included. SQ assessment included cartilage damage, meniscal extrusion and damage, osteophytes, bone marrow lesions (BMLs), and effusion- and Hoffa-synovitis. Change in medial compartment Q cartilage thickness was stratified by concurrent ipsicompartmental SQ changes. Between-group comparisons were performed using analysis of covariance (ANCOVA) with adjustment for age, sex, and body mass index (BMI). Results were presented as adjusted mean difference. Knees with any increase in SQ cartilage scores in the medial compartment (n = 268) showed more Q cartilage loss compared to knees that remained stable (mean adjusted difference [MAD] = -0.16 mm, 95% confidence interval [CI]: [-0.19, -0.13] mm). Knees with any increase in meniscal extrusion in the medial compartment (n = 98) showed more Q cartilage loss than knees without (MAD = -0.18 mm, 95% CI: [-0.22, -0.14] mm. Comparable findings were seen for meniscal damage worsening. Regarding BMLs, an increase by one subregion resulted in a MAD of Q cartilage loss of -0.10 mm, 95% CI: [-0.14, -0.06] mm, while this effect almost tripled for change in two or more subregions. Increase in either effusion- and/or Hoffa-synovitis by one grade resulted in a MAD of -0.07 mm, 95% CI: [-0.10, -0.03] mm. Worsening of SQ cartilage damage, meniscal extrusion and damage, number of subregions affected by BML, maximum size of BMLs and worsening of effusion- and/or Hoffa synovitis is associated with increased Q cartilage loss.

Risk factors for the long-term incidence and progression of knee osteoarthritis in older adults: role of nonsurgical injury.

For one of the most chronic medical conditions, osteoarthritis, uncertainties remain on the impact of injury chronology, the role of repeat injury on the incidence/progression of this disease and the need for knee arthroplasty. To explore, in an older adult population, how nonsurgical knee injuries relate to osteoarthritis incidence/progression and the weight of independent risk factors for arthroplasty. A cohort study design evaluates the long-term impact of injuries on knee osteoarthritis outcomes. Knees with no prior injury (n = 6358) and with at least one injury (n = 819) ⩽20 years before study inclusion were from the Osteoarthritis Initiative cohort. Sociodemographic, clinical and structural [X-ray, magnetic resonance imaging (MRI)] data at study inclusion and changes within 96 months were analysed. Statistics included a mixed model for repeated measurements, generalized estimating equations and multivariable Cox regression with covariates. At inclusion, knees with prior injury demonstrated greater incidence and severity of osteoarthritis (p ⩽ 0.001). At 96 months, there was a greater increase in symptoms [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, p = 0.002], joint space width (JSW, p = 0.039) loss, medial cartilage volume loss (CVL, p ⩽ 0.001) and bone marrow lesion size (BML, p ⩽ 0.049). Knees with/without injury at inclusion but with new ones over time had a pronounced increase in symptoms (all WOMAC scores, p ⩽ 0.001), JSW loss, lateral (without) and medial CVL, lateral (without) and medial meniscal extrusion and medial BML (without; all p ⩽ 0.030). Levels of lateral and medial meniscal extrusion (without) and symptoms (with/without; all WOMAC scores, p ⩽ 0.001) were all accentuated with a repeated new injury. Risk factors associated with the highest knee arthroplasty occurrence are new meniscal extrusion and new injury (p ⩽ 0.001). This study highlights the importance of nonsurgical knee injury in older adults as an independent risk factor for knee osteoarthritis and arthroplasty. These data will be beneficial in clinical practice as they will help identify individuals at greater risk of significant disease progression and worst disease outcomes for a customized therapeutic approach.

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

NON-CHONDRAL MULTI-TISSUE PATHOLOGY AS ASSESSED BY MRI INCREASES RATES OF QUANTITATIVE MRI-DEFINED CARTILAGE THICKNESS LOSS OVER 24 MONTHS: THE APPROACH STUDY

Prospective Association Between Inflammatory Markers and Knee Cartilage Volume Loss and Pain Trajectory

IntroductionInflammation has been suggested to be involved in the pathogenesis of osteoarthritis and pain. We sought to explore the associations between inflammatory serum markers and magnetic resonance imaging-defined long-term structural change and pain trajectory.MethodsA total of 169 randomly selected participants (mean age 63 years; 47% female) from a prospective cohort study were included in this study. Circulating levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (CRP) were measured at baseline. A knee MRI scan was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and at 10.7 years. Knee pain at four visits was measured by the WOMAC pain questionnaire, and pain trajectories were identified using group-based trajectory modelling. Linear, log-binomial and multi-nominal logistic regression were used for the analyses.ResultsIL-6 was associated with lateral but not medial tibial CV loss (β = − 0.25% per annum, per standard deviation [SD] log pg/ml; P < 0.05) in the multivariate analysis. IL-6 was also associated with a ‘Moderate pain’ trajectory (relative risk ratio 1.93 per SD log pg/ml; 95% confidence interval 1.02–3.65) relative to the ‘Minimal pain’ trajectory group. There was no significant association of TNF-α and CRP with CV loss and pain trajectory groups with the exception of a beneficial relationship between CRP and medial tibial CV loss (β = 0.20% per annum, per SD log mg/l). No association between inflammatory markers and change in BML size was observed.ConclusionsIL-6 was independently associated with compartment-specific CV loss and worse pain trajectory, but the other markers studied were not, suggesting that components of inflammation are implicated in the pathogenesis of cartilage loss and developing a worse pain course.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00341-1.

Intravenous bisphosphonates do not improve knee pain or bone marrow lesions in people with knee osteoarthritis: a meta-analysis.

To summarize effects of intravenous bisphosphonates (IVBP) in patients with symptomatic knee OA and bone marrow lesions (BMLs), using a meta-analysis of randomized controlled trials (RCTs). Literature databases were searched for placebo-controlled RCTs of IVBPs for knee OA from inception, and included validated pain and function scales, BML size and incidence of adverse events. Efficacy was compared using standardized mean differences (SMD) and risk ratios (RR) with fixed-effect or random-effects models. Methodological quality was assessed using the Cochrane risk of bias tool, heterogeneity was assessed by I2 statistics. We included 428 patients in four RCTs of 2-24 months duration; most patients (84%) received zoledronic acid (ZA). Risk of bias was low-moderate. IVBP had large effect sizes on pain within 3 months [SMD = -2.33 (95% CI: -3.02, -1.65)] mainly driven by neridronate (resulting in substantial heterogeneity, I2 = 92%) with no effect for ZA alone. Differences in knee function were statistically significant at 3 months [SMD = -0.22 (-0.43, -0.01), I2 = 0.2%]. Effect sizes for pain did not reach statistical significance at any other time point. IVBPs improved a semi-quantitative measure of BML size within 6 months [SMD = -0.52 (-0.89, -0.14), I2 = 0%] but not at 12 months or two years. Adverse events [RR = 1.19 (1.00, 1.41) I2 = 52%], occurred more frequently with IVBP. ZA has no effect on knee pain, possibly a short-term effect on BML size and higher rates of adverse events. Neridronate may improve pain in the short term, but this is based on a single trial.

Postoperative Bone Marrow Lesions (BMLs) Are Associated with Pain Severity in Patients Undergoing Open Wedge High Tibial Osteotomy (OWHTO).

The purpose of the study was to investigate the relationship between postoperative bone marrow lesions (BMLs) and pain severity in patients undergoing open wedge high tibial osteotomy (OWHTO). We reviewed the patients undergoing OWHTO between April 2018 and April 2020. The demographic and clinical data of patients were collected. Clinically, VAS and Knee injury and Osteoarthritis Outcome Score (KOOS) were used to assess pain level and functional outcomes of patients. The MRI Osteoarthritis Knee Score (MOAKS) was used to assess the total BMLs size in medial tibiofemoral (MTF), lateral tibiofemoral (LTF), and patellofemoral (PF) joints. 98 patients were enrolled in the study, including 57 male and 41 female patients. The VAS scores improved significantly from 6.1 ± 0.8 to 1.5 ± 0.9 (p < 0.001), and all subscales of KOOS improved significantly after surgery (p < 0.001). There were no significant differences between the pre- and postoperative total BML size of PF and LTF joints (p > 0.05). We observed significant improvements in the total BML size of MTF joint (p < 0.001). The VAS scores and KOOS pain scores improved better in patients without postoperative MTF joint BMLs (p < 0.001). Postoperative MTF joint BMLs were correlated with postoperative VAS (p < 0.001) and KOOS pain (p < 0.001). Our study demonstrates that MTF joint BMLs improved significantly after OWTHO. We confirmed that the presence of postoperative MTF joint BMLs are strongly associated with pain severity. The greater the improvement in postoperative MTF joint BMLs, the less pain. Our findings provide valuable understandings of OWHTO in the treatment of knee osteoarthritis (KOA) and potential future directions for KOA treatment approaches.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms.

To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.

Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions

A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. anzctr.org.au Identifier: ACTRN12613000039785.

A multicentre randomised double-blind placebo-controlled trial of zoledronic acid for knee osteoarthritis - the zap2 trial

Purpose: A proof of principle study suggests that zoledronic acid may reduce knee pain and size of bone marrow lesions (BMLs) in people with knee osteoarthritis, but data from large trials is lacking. The aim of this study was to compare the efficacy of zoledronic acid vs placebo on knee cartilage volume, knee pain and BML size in patients with symptomatic knee osteoarthritis and BMLs.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms - results from the ZAP2 trial

Purpose: Subchondral bone marrow lesions (BMLs) are an early sign of knee osteoarthritis (OA) that predicts both cartilage loss and symptomatic progression of OA. Previous studies have suggested targeting BMLs in short-term structure modification trials. A key hypothesis is that shrinkage of BMLs is associated with reduced cartilage loss and improved knee symptoms, but this has been debated. This study used data from a multicentre randomised controlled trial (ZAP2), in which all participants had symptomatic knee OA and BMLs, and the aim was to describe the association between change in BMLs and change in tibiofemoral cartilage volume and knee symptoms.

Subchondroplasty of the Ankle and Hindfoot for Treatment of Osteochondral Lesions and Stress Fractures: Initial Imaging Experience.

Objective:To describe the imaging findings of patients treated with subchondroplasty (SCP) of the ankle and hindfoot. Materials and Methods: Eighteen patients (10 men, 8 women; age mean 43.1 years [range 20.1-67.7 years]) underwent ankle and hindfoot SCP at a single center over a 14-month period. Imaging data were reviewed retrospectively by 2 radiologists by consensus interpretation, including preoperative radiography (18), computed tomography (CT) (11), and magnetic resonance imaging (MRI) (13) and postoperative radiography (10), CT (4), and MRI (6). Follow-up imaging was acquired 1 month to 1.6 years following SCP. Results: Indications for SCP included symptomatic bone marrow lesions (BMLs) secondary to an osteochondral lesion (OCL) (16/18) or stress fracture (2/18). While focal radiodensity related to the SCP procedure was retrospectively identifiable on postoperative radiography in all except 1 case (10/11), postprocedural findings were not described by the interpreting radiologist in 6/11 cases. On CT, the average injected synthetic calcium phosphate (CaP) volume was 1.15 cm3 (SD = 0.33 cm3); mean CT attenuation of the injectate was 1220 HU (range 1058-1465 HU). In all patients who had pre- and postoperative MRI (5/18), BML size decreased on follow-up MRI. Extra-osseous extrusion of CaP was not seen on postoperative radiography, CT, or MRI. Conclusion: Physicians should be aware of the expanding preoperative indications and postoperative imaging findings of SCP, which is being performed with increasing frequency in the ankle and hindfoot.Levels of Evidence: Diagnostic, Level III: Retrospective cohort study.

Association between metabolic syndrome and knee structural change on MRI.

To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change. Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program-Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing. Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = -0.30%; central obesity, β = -0.26%; and low HDL, β = -0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment. MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change.

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial.

Background:The aim of this study was to compare the efficacy and safety of zoledronic acid (ZA) plus intravenous methylprednisolone (VOLT01) to ZA, and placebo for knee osteoarthritis.Methods:A single-center, double-blind, randomized controlled trial (RCT) was carried out. Adults (aged ⩾50 years) with knee osteoarthritis, significant knee pain [⩾40 mm on a 100 mm visual analog scale (VAS)], and magnetic resonance imaging-detected bone marrow lesion (BML) were randomized to receive a one-off administration of VOLT01, ZA, or placebo. The primary hypothesis was that VOLT01 was superior to ZA in having a lower incidence of acute phase responses (APRs) over 3 days. Secondary hypotheses were that VOLT01 was noninferior to ZA, and both treatments were superior to placebo in decreasing BML size over 6 months and in improving knee pain [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and VAS] and function (WOMAC) over 3 and 6 months.Results:A total of 117 patients (62.2 ± 8.1 years, 63 women) were enrolled. The incidence of APRs was similar in the VOLT01 (90%) and ZA (87%) groups (p = 0.74). VOLT01 was superior to ZA in improving knee pain and function after 6 months and noninferior to ZA in reducing BML size. However, BML size change was small in all groups and there were no between-group differences. Compared with placebo, VOLT01 but not ZA improved knee function and showed a trend toward improving knee pain after 6 months.Conclusions:Administering intravenous methylprednisolone with ZA did not reduce APRs or change knee BML size over 6 months, but in contrast to ZA or placebo, it may have a beneficial effect on symptoms in knee osteoarthritis.Trial registration:Australian New Zealand Clinical Trials Registry: ACTRN12613000039785.

Patellar tendon enthesis abnormalities and their association with knee pain and structural abnormalities in older adults

To describe associations between presence of patellar tendon enthesis (PTE) abnormalities and symptoms, structural abnormalities, and total knee replacement (TKR) in older adult cohort. PTE abnormalities (presence of abnormal bone signal and/or bone erosion), were measured on T2-weighted magnetic resonance (MR) images at baseline in 961 community-dwelling older adults. Knee pain and function limitation were assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bone marrow lesions (BMLs), cartilage volume and defects score, and infrapatellar fat pad (IPFP) area were measured using validated methods. Incidence of TKR was determined by data linkage. Participants with abnormal PTE bone signal and/or erosion was 20%. Cross-sectionally, presence of PTE abnormalities was associated with greater pain intensity while going up and down stairs (β=0.22 (95% confidence interval (CI); 0.03, 0.41)), greater risk of femoral BMLs (RR=1.46 (1.12, 1.90)) and worse tibial cartilage defects score (RR=1.70 (1.16, 2.47), and smaller IPFP area (β=-0.27 (-0.47,-0.06) cm2), after adjustment of confounders. Longitudinally, presence of baseline PTE abnormalities was associated with a deleterious increase in tibial BML size (RR=1.52 (1.12, 2.05)) over 10.7 years but not symptoms, other structural changes, or TKR. PTE abnormalities are common in older adults. Presence of cross-sectional but not longitudinal associations suggests they are commonly co-exist with other knee structural abnormalities but may not play a major role in symptom development or structural change, excepting tibial BMLs.

Bone marrow lesions of the knee: longitudinal correlation between lesion size changes and pain before and after conservative treatment by extracorporeal shockwave therapy.

Bone marrow lesions (BMLs) of the knee have become a common finding on magnetic resonance imaging (MRI), leading to a growing interest in BML, not only for its potential role in the progression of several musculoskeletal conditions, but also for its clinical impact and treatment implications. At present, there is limited and conflicting evidence regarding whether or not pain may be correlated to BML size or not. To verify the longitudinal correlation between BML size and knee pain. Longitudinal. Italian Orthopedic Institute. The study sample was composed of 72 patients, 27 males and 45 females, with a mean age of 55.9±10.22 years and a mean BMI of 26.1±3.7 kg/m2. All patients presented with BMLs and acute knee pain. All 72 patients underwent a knee MRI before and 6 months after a course of high energy ESWT, in order to perform a quantitative measurement of the BML areas. KOOS (Knee Injury and Osteoarthritis Outcome Score) Pain subscale scores were obtained at the same time point. A regression analysis was performed to verify the correlation between knee BML size and KOOS pain subscale score before treatment and the correlation between the reduction of BML size and the improvement of KOOS pain score 6 months after treatment. A statistically significant correlation between the KOOS Pain subscale and the BML size (beta=-0.362 [CI95%: -0.019/-0.05], P=0.002) was demonstrated. The clinical score and BML area significantly improved after treatment (P<0.001). The clinical improvement was correlated to the BML size reduction (beta=0.254 [CI95%: 0.001/0.017], P=0.031). This study confirmed a significant correlation between the BML size and the intensity of knee pain. Furthermore, the before and after study using ESWT to treat symptomatic BMLs, revealed a correlation between size reduction of BML and KOOS pain subscale score improvement, demonstrating the utility of BML reduction as a therapeutic goal. Finally, ESWT was validated as a safe and potentially effective treatment of subchondral bone marrow lesions. Our results confirm that severity of pain is correlated with BML size, and furthermore, demonstrate that increases and decreases in the amount of pain reflect growth or reduction in BML size, respectively. This information may be useful for rehabilitation and decrease the reliance on MRIs for checking the progress of bone lesions. Absence or marked reduction of pain should allow for the resumption of weight-bearing and more strenuous exercises for an adequate musculoskeletal recovery.

A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24\xa0months in knee osteoarthritis patients \u2013 ZAP2

BackgroundBisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients.MethodsTwo hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm3) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses.DiscussionThis study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12613000039785, registered on 14 January 2013.