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Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative.

ABSTRACT: BACKGROUND:Metabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8?years in subjects with and without HIV infection determined based on the use of ART. METHODS:We studied 10 participants from the Osteoarthritis Initiative who received ART at baseline and 20 controls without ART, frequency matched for age, sex, race, baseline body mass index (BMI) and Kellgren & Lawrence grade. Knee abnormalities were assessed using the whole-organ magnetic resonance imaging score (WORMS) and cartilage T2 including laminar and texture analyses were analyzed using a multislice-multiecho spin-echo sequence. Signal abnormalities of the infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) were assessed separately using a semi-quantitative scoring system. Linear regression models were used in the cross-sectional analysis to compare the differences between ART/HIV subjects and controls in T2 (regular and laminar T2 values, texture parameters) and morphologic parameters (subscores of WORMS, scores for signal alterations of IPFP and SPFP). Mixed effects models were used in the longitudinal analysis to compare the rate of change in T2 and morphological parameters between groups over 8?years. RESULTS:At baseline, individuals on ART had significantly greater size of IPFP signal abnormalities (P?=?0.008), higher signal intensities of SPFP (P?=?0.015), higher effusion scores (P?=?0.009), and lower subchondral cysts sum scores (P?=?0.003) compared to the controls. No significant differences were found between the groups in T2-based cartilage parameters and WORMS scores for cartilage, meniscus, bone marrow edema patterns and ligaments (P?>?0.05). Longitudinally, the HIV cohort had significantly higher global knee T2 entropy values (P?=?0.047), more severe effusion (P?=?0.001) but less severe subchondral cysts (P?=?0.002) on average over 8?years. CONCLUSIONS:Knees of individuals with HIV on ART had a more heterogeneous cartilage matrix, more severe synovitis and abnormalities of the IPFP and SPFP, which may increase the risk of incident knee osteoarthritis.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6500016 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative.

Liu Yao Y Foreman Sarah C SC Joseph Gabby B GB Neumann Jan J Tien Phyllis C PC Li Xiaoming X Lane Nancy E NE Nevitt Michael C MC McCulloch Charles E CE Link Thomas M TM

BMC musculoskeletal disorders 20190504 1

<h4>Background</h4>Metabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8 years in subjects with and without HIV infection determined based on the use of ART.<h4>Methods</h4>We studied 10 participants from the Osteoarthritis Initiative who ...[more]

PMID: 31054571

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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:Background Longitudinal data on the association of quantitative thigh muscle MRI markers with knee osteoarthritis (KOA) outcomes are scarce. These associations are of clinical importance, with potential use for thigh muscle-directed disease-modifying interventions. Purpose To measure KOA-associated longitudinal changes in MRI-derived muscle cross-sectional area (CSA) and adipose tissue and their association with downstream symptom worsening and knee replacement (KR). Materials and Methods In a secondary analysis of the Osteoarthritis Initiative multicenter prospective cohort (February 2004 through October 2015), knees of participants with available good-quality thigh MRI scans at baseline and at least one follow-up visit were included and classified as with and without KOA according to baseline radiographic Kellgren-Lawrence grade of 2 or higher and matched for confounders with use of propensity score matching. An automated deep learning model for thigh MRI two-dimensional segmentation was developed and tested. Markers of muscle CSA and intramuscular adipose tissue (intra-MAT) were measured at baseline and 2nd- and 4th-year follow-up (period 1) and compared between knees with and without KOA by using linear mixed-effect regression models. Furthermore, in knees with KOA, the association of period 1 changes in muscle markers with risk of KR (Cox proportional hazards) and symptom worsening (mixed-effect models) during the 4th to 9th year (period 2) was evaluated. Results This study included 4634 matched thighs (2317 with and 2317 without KOA) of 2344 participants (mean age, 62 years ± 9 [SD]; 1292 women). Compared with those without, knees with KOA had a decrease in quadriceps CSA (mean difference, -8.21 mm2/year; P = .004) and an increase in quadriceps intra-MAT (1.98 mm2/year; P = .007). Decreased CSA and increased intra-MAT of quadriceps during period 1 was predictive of downstream (period 2) KOA symptom worsening (Western Ontario and McMaster Universities Osteoarthritis Index total score: odds ratio, 0.24 [negative association] [P < .001] and 1.38 [P = .012], respectively). Quadriceps CSA changes were negatively associated with higher future KR risk (hazard ratio, 0.70; P < .001). Conclusion Knee osteoarthritis was associated with longitudinal MRI-derived decreased quadriceps cross-sectional area and increased intramuscular adipose tissue. These potentially modifiable risk factors were predictive of downstream symptom worsening and knee replacement. Clinical trial registration no. NCT00080171 © RSNA, 2022 Online supplemental material is available for this article.

Project description:BackgroundWe examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence.MethodsUsing the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes.ResultsWe included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: - 16.06 mm2/year, - 26.70 to - 5.41) but not thigh muscles' composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15-2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19-3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use.ConclusionsOur exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

Project description:BackgroundThough anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated.PurposeTo determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years.Study designCohort study; Level of evidence, 2.MethodsParticipants' knees in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren-Lawrence grading (Kellgren-Lawrence grading) of 0 or 1 at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0-3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA.Results337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points.ConclusionsACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case-control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

Dataset Information

Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative.

Publications

Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative.

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