Dataset Information

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

ABSTRACT:

Background

Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA.

Methods

Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800?IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N?=?50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling.

Results

The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3?years (SD 6.5) and 74% were female. There was no significant difference at 2?years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9?mm³, 95% CI -1605.0 to 1792.7) and subchondral BML volume (-?313.5?mm³, 95% CI -4244.7 to 3617.7).

Conclusions

Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA.

Trial registration

VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/.

SUBMITTER: Perry TA

PROVIDER: S-EPMC6376763 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

Perry Thomas A TA Parkes Matthew J MJ Hodgson Richard R Felson David T DT O'Neill Terence W TW Arden Nigel K NK

BMC musculoskeletal disorders 20190214 1

<h4>Background</h4>Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA.<h4>Methods</h4>Data was acquired from participants who t ...[more]

PMID: 30764805

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Project description:BackgroundSubchondral bone marrow lesions (BMLs) detected on MRI in knee osteoarthritis (OA) are associated with knee pain. The prevalence and progression of subchondral BMLs are increased by mechanical knee load. However, associations of subchondral BML location with weight-bearing knee pain are currently unknown. In this study, we aim to demonstrate associations of subchondral BML location and size with weight-bearing knee pain in knee OA.MethodsWe analyzed 1412 and 582 varus knees from cross-sectional and longitudinal Osteoarthritis Initiative datasets, respectively. BML scores were semi-quantitatively analyzed with the MRI Osteoarthritis Knee Score for 4 subchondral regions (median and lateral femorotibial, medial and lateral patellofemoral) and subspinous region. Weight-bearing and non-weight-bearing pain scores were derived from WOMAC pain items. Correlation and negative binomial regression models were used for analysis of associations between the BML scores and pain at baseline and changes in the BML scores and changes in pain after 24-month follow-up.ResultsGreater BML scores at medial femorotibial and lateral patellofemoral compartments were associated with greater weight-bearing pain scores, and statistical significance was retained after adjusting for BML scores at the other 4 joint compartments and other OA features, as well as for non-weight-bearing pain, age, sex, and body mass index (BMI) (medial femorotibial; B?=?0.08, p?=?0.02. patellofemoral; B?=?0.13, p?=?0.01). Subanalysis revealed that greater medial femorotibial BML scores were associated with greater pain on walking and standing (B?=?0.11, p?=?0.01, and B?=?0.10, p?=?0.04, respectively). Lateral patellofemoral BML scores were associated with pain on climbing, respectively (B?=?0.14, p?=?0.02). Increases or decreases over 24?months in BML score in the medial femorotibial compartment were significantly associated with increases or decreases in weight-bearing pain severity after adjusting for non-weight-bearing pain, age, sex, baseline weight-bearing pain, BMI, and BML at the other 4 joint compartments (B?=?0.10, p?=?0.01).ConclusionsSubchondral BML size at the medial femorotibial joint compartment was specifically associated with the severity and the change in weight-bearing pain, independent of non-weight-bearing pain, in knee OA. Specific associations of weight-bearing pain with subchondral BMLs in weight-bearing compartments of the knee indicate that BMLs in subchondral bone contribute to biomechanically induced OA pain.

Project description:ImportanceKnee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression.ObjectiveTo determine whether vitamin D supplementation reduces symptom and structural progression of knee OA.Design, setting, and patientsA 2-year randomized, placebo-controlled, double-blind, clinical trial involving 146 participants with symptomatic knee OA (mean age, 62.4 years [SD, 8.5]; 57 women [61%], 115 white race [79%]). Patients were enrolled at Tufts Medical Center in Boston between March 2006 and June 2009.InterventionParticipants were randomized to receive either placebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36 ng/mL.Main outcome measuresPrimary outcomes were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary end points included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width.ResultsEighty-five percent of the participants completed the study. Serum 25-hydroxyvitamin D levels increased by a mean 16.1 ng/mL (95% CI, 13.7 to 18.6) in the treatment group and by a mean 2.1 mg/mL (95% CI, 0.5 to 3.7) (P < .001) in the placebo group. Baseline knee pain was slightly worse in the treatment group (mean, 6.9; 95% CI, 6.0 to 7.7) than in the placebo group (mean, 5.8; 95% CI, 5.0 to 6.6) (P = .08). Baseline knee function was significantly worse in the treatment group (mean, 22.7; 95% CI, 19.8 to 25.6) than in the placebo group (mean, 18.5; 95% CI, 15.8 to 21.2) (P = .04). Knee pain decreased in both groups by a mean -2.31 (95% CI, -3.24 to -1.38) in the treatment group and -1.46 (95% CI, -2.33 to -0.60) in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups (mean, -4.30; 95% CI, -5.48 to -3.12 vs mean, -4.25; 95% CI, -6.12 to -2.39) (P = .96). There were no differences in any of the secondary clinical end points.Conclusion and relevanceVitamin D supplementation for 2 years at a dose sufficient to elevate 25-hydroxyvitamin D plasma levels to higher than 36 ng/mL, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee OA.Trial registrationclinicaltrials.gov Identifier: NCT00306774.

Project description:BackgroundSynovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.MethodsPersons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association.Results120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain.ConclusionsSynovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA.Trial registration numberISRCTN07329370.

Project description:ObjectivesTo determine the association between statin therapy and knee MRI-detected subchondral bone marrow lesion (BML) longitudinal worsening in patients with Heberden's nodes (HNs) as the hallmark of generalized osteoarthritis (OA) phenotype.MethodsAll participants gave informed consent, and IRB approved HIPAA-compliant protocol. We assessed the worsening in BML volume and number of affected subregions in the Osteoarthritis Initiative (OAI) participants with HNs at baseline clinical examination (HN+), using the semi-quantitative MRI Osteoarthritis Knee Scores at baseline and 24 months. Participants were classified according to baseline BML involvement as "no/minimal" (≤ 2/14 knee subregions affected and maximum BML score ≤ 1) or "moderate/severe." Statin users and non-users were selected using 1:1 propensity-score (PS) matching for OA and cardiovascular disease (CVD)-related potential confounding variables. We assessed the association between statin use and increasing BML score and affected subregions using adjusted mixed-effect regression models.ResultsThe PS-matched HN+ participants (63% female, aged 63.5 ± 8.5-year-old) with no/minimal and moderate/severe BML cohorts consisted of 332 (166:166, statin users: non-users) and 380 (190:190) knees, respectively. In the HN+ participants with no/minimal BML, statin use was associated with lower odds of both BML score worsening (odds ratio, 95% confidence interval: 0.62, 0.39-0.98) and increased number of affected subregions (0.54, 0.33-0.88). There was no such association in HN- participants or those HN+ participants with baseline moderate/severe BML.ConclusionIn patients with CVD indications for statin therapy and generalized OA phenotype (HN+), statin use may be protective against the OA-related subchondral bone damage only in the subgroup of participants with no/minimal baseline BML.Key points• Statin use may reduce the risk of subchondral bone damage in specific osteoarthritis patients with a generalized phenotype, minimal subchondral bone damage, and cardiovascular statin indications.

Project description:Introduction:Bone marrow lesions (BMLs) are frequently identified by MRI in the subchondral bone in knee osteoarthritis (KOA). BMLs are known to be closely associated with joint pain, loss of the cartilage and structural changes in the subchondral trabecular bone (SCTB). Despite this, understanding of the nature of BMLs at the trabecular tissue level is incomplete. Thus, we used Raman microspectroscopy to examine the biochemical properties of SCTB from KOA patients with presence or absence of BMLs (OA-BML, OA No-BML; respectively), in comparison with age-matched cadaveric non-symptomatic controls (Non-OA CTL). Methods:Tibial plateau (TP) specimens were collected from 19 KOA arthroplasty patients (6-Male, 13-Female; aged 56-74 years). BMLs were identified ex-vivo by MRI, using PDFS- and T1-weighted sequences. The KOA specimens were then categorized into an OA-BML group (n = 12; containing a BML within the medial condyle only) and an OA No-BML group (n = 7; with no BMLs identified in the TP). The control (CTL) group consisted of Non-OA cadaveric TP samples with no BMLs and no macroscopic or microscopic evidence of OA-related changes (n = 8; 5-Male, 3-Female; aged 44-80 years). Confocal Raman microspectroscopy, with high spatial resolution, was used to quantify the biochemical properties of SCTB tissue of both the medial and the lateral condyle in each group. Results:The ratios of peak intensity and integrated area of bone matrix mineral (Phosphate (v1), Phosphate (v2) and Phosphate (v4)), to surrogates of the organic phase of bone matrix (Amide I, Proline and Amide III), were calculated. Within the medial compartment, the mineral:organic matrix ratios were significantly lower for OA-BML, compared to Non-OA CTL. These ratios were also significantly lower for the OA-BML medial compartment, compared to the OA-BML lateral compartment. There were no group or compartmental differences for Carbonate:Phosphate (v1, v2 and v4), Amide III (?-helix):Amide III (random-coil), Hydroxyproline:Proline, or Crystallinity. Conclusion:As measured by Raman microspectroscopy, SCTB tissue in BML zones in KOA is significantly less mineralized than the corresponding zones in individuals without OA. These data are consistent with those obtained using other methods (e.g. Fourier transform infrared spectroscopy; FTIR) and with the increased rate of bone remodeling observed in BML zones. Reduced mineralization may change the biomechanical properties of the trabecular bone in BMLs and the mechanical interaction between subchondral bone and its overlying cartilage, with potential implications for the development and progression of OA.

Project description:IntroductionBone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN).MethodsA BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume).ResultsThis sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume.ConclusionLarge baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.

Project description:BackgroundSubchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.MethodsThe preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.ResultsAt both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.ConclusionCyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

Dataset Information

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

Background

Methods

Results

Conclusions

Trial registration

Publications

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

Similar Datasets

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