Dataset Information

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

ABSTRACT:

Objectives

We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms.

Methods

The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration.

Results

After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM.

Conclusions

Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA.

Key points

• Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

SUBMITTER: Mohajer B

PROVIDER: S-EPMC10448875 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

Mohajer Bahram B Moradi Kamyar K Guermazi Ali A Dolatshahi Mahsa M Zikria Bashir B Najafzadeh Nima N Kalyani Rita R RR Roemer Frank W FW Berenbaum Francis F Demehri Shadpour S

European radiology 20220811 1

<h4>Objectives</h4>We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms.<h4>Methods</h4>The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders usi ...[more]

PMID: 35951046

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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:BackgroundMuscle function deterioration in female patients with severe knee osteoarthritis (KOA) is linked to alterations in muscle morphology, composition, and mechanical properties. This study evaluates thigh muscle features in female patients with severe KOA and explores correlations with knee joint function.MethodsUltrasound and shear wave elastography measured physiological cross-sectional area (PCSA), echo intensity (EI), and shear modulus (G) in the rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris long head (BFL), and semitendinosus (ST) of 24 KOA patients and 24 controls. EI indicates intramuscular fat, while G reflects stiffness. Muscle characteristics were compared between groups, and correlations with knee function scores (WOMAC, KSS, HSS) were analyzed.ResultsIn patients, the symptomatic side displayed reduced PCSA for RF, VL, VM, BFL, and ST (15.85[Formula: see text], 28.18[Formula: see text], 21.53[Formula: see text], 11.67[Formula: see text], 6.59[Formula: see text] respectively) vs. controls (19[Formula: see text], 36.32[Formula: see text], 23.37[Formula: see text], 14.15[Formula: see text], 7.12[Formula: see text] respectively). EI was elevated (128.95, 121.12, 105.72, 90.52, 93.15) vs. controls (100.39, 93.97, 88.14, 77.69, 78.73), and G values (9.48 kPa, 7.88 kPa, 6.9 kPa, 7.2 kPa, 9.03 kPa) was higher than controls (8.85 kPa, 5.28 kPa, 5.98 kPa, 6.58 kPa, 6.73 kPa). BFL`s G, ST`s G, and VM`s EI, negatively correlated with knee function, whereas BFL`s PCSA positively correlated. The variable importance of BFL's PCSA and G ranked at the top in all scores.ConclusionsCompared to controls, PCSAs in muscles on both sides of KOA patients were lowered by up to 22%, indicative of muscle loss and diminished strength. The G value is 20.65% higher, suggesting poor flexibility and elevated passive tension. EI in muscles on both sides of KOA patients was greater, reaching up to 23.88%, possibly reducing contractile components and muscle force. G, PCSA, and EI are closely correlated with function scores, and PCSA and G of BFL are the most significant predictors of knee function. These results may help explain muscle dysfunction in KOA patients.Clinical trial numberNot applicable.

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:ObjectiveTo determine whether thigh muscle strength predicts the risk of undergoing knee replacement surgery, independent of radiographic severity of osteoarthritis and pain.MethodsParticipants in the Osteoarthritis Initiative study who had received a knee replacement between the 12-month and 60-month follow-up visits (cases) were each matched with 1 control subject (who did not receive a knee replacement over 60 months) for age, sex, height, body mass index, baseline radiographic stage, and location of joint space narrowing. Isometric knee extensor and flexor strength was recorded biennially. The strength examination prior to knee replacement (≤2 years) was termed time 0, that 2 years prior to time 0 was termed time -2, and that 4 years prior to time 0 was termed time -4. Muscle strength in patients and controls was compared using paired t-tests and conditional logistic regression analysis adjusted for pain.ResultsOne hundred thirty-six participants (60% women, mean ± SD age 65 ± 9 years, body mass index 29 ± 4 kg/m(2) ) received a knee replacement during follow-up, had strength data for at least time 0, and had a matched control. Knee extensor strength at time 0 (primary outcome measure) was significantly lower in female patients compared with controls (P < 0.001, pain-adjusted odds ratio [ORadj ] 1.72, 95% confidence interval 1.16-2.56), but no significant difference was observed in men. Results were similar for knee flexor strength at time 0 and for longitudinal change in extensor and flexor strength between time -2 and time 0. Thigh muscle strength at time -2 or time -4, or change between time -4 and time -2, did not predict the risk of undergoing knee replacement surgery in men or women.ConclusionThigh muscle strength predicted the risk of undergoing knee replacement surgery in women, but not in men. The results of this study may identify a window during which the risk of undergoing knee replacement surgery in women can be modified.

Dataset Information

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

Objectives

Methods

Results

Conclusions

Key points

Publications

Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study.

Similar Datasets

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