Abstract
Objective.
To investigate the associations of thigh muscle and fat volumes with structural abnormalities on MRI related to knee osteoarthritis.
Materials and Methods.
MRI studies of the thighs and knees from 100 individuals were randomly selected from the Osteoarthritis Initiative Cohort. Whole Organ MR Scoring (WORMS) and effusion-synovitis scoring were performed in all knee MRI. Thigh muscles, intermuscular fat, and subcutaneous fat were manually segmented in 15 consecutive MR thigh images. Radiographic Kellgren-Lawrence grades (KLG) were also obtained in all knee radiographs. Independent t-tests were used to investigate the associations between thigh muscle and fat volumes, and sex. Mixed-effects analyses were obtained to investigate the associations between thigh muscle and fat volumes, KLG, WOMAC pain score, cartilage and bone marrow WORMS, as well as effusion-synovitis scores.
Results.
Women had higher subcutaneous fat volume than men (616.82 vs. 229.13 cm3, p<0.01) and men had higher muscle volumes than women (p<0.01). Quadriceps (coef=−2.15, p=0.01) and vastus medialis (coef=−1.84, p=0.03) volumes were negatively associated with the WORMS cartilage scores. Intermuscular fat volume (coef=0.48, p=0.01) was positively associated with WORMS bone marrow edema-like lesion (BMEL) scores. The quadriceps (coef=−0.99, p<0.01) and hamstring (coef=−0.59, p=0.01) volumes were negatively associated with WORMS BMEL scores. No evidence of an association was found between thigh muscle and fat volumes with KLG and effusion-synovitis grading (p>0.05).
Conclusion.
Increased quadriceps and hamstring volumes were negatively associated with cartilage lesion and BMEL scores while no evidence of an association was found between thigh muscle and fat volumes, and radiographic knee osteoarthritis or effusion-synovitis grading.
Keywords: knee osteoarthritis, muscle volume, fat volume, quadriceps, hamstring
Introduction
Knee osteoarthritis (KOA) is a very common disease worldwide that is influenced by multiple factors, including genetics, age, body mass index (BMI), synovitis, systemic inflammatory mediators, lower limb alignment, trauma, and metabolic conditions [1]. KOA has increasing prevalence, partly related to the worsening global obesity pandemic [2]. Metabolic syndrome, including obesity, can contribute to an increased risk of KOA due to increased joint load from excessive weight and low-grade systemic inflammation [3,4]. The increased level of obesity was reported to be related to an increased rate of patellar cartilage loss [5], as well as greater prevalence and severity of knee synovitis [6]. It has been hypothesized that adipokines, the proteins derived from adipocytes, are related to osteoarthritis (OA) and obesity by sustaining low-grade inflammatory processes [7]. More specifically, leptin - one of the adipokines- significantly correlates with cartilage degeneration and tissue senescence [8]. Another adipokine, resistin, is positively associated with the number and grade of cartilage defects and bone marrow edema-like lesions (BMELs) in knee MRIs of patients with KOA [9]. Moreover, increased fat mass was also shown to be a risk factor for cartilage defects and BMEL [10].
We also know that the intramuscular and subcutaneous adipose tissues are associated with radiographic knee osteoarthritis (RKOA) and knee cartilage loss on MRI [11–13]. Thigh adiposity was proven to be associated with knee-joint loads in older overweight and obese adults with KOA [11]. Teichtahl et al. reported that decreasing intramuscular fat in the vastus medialis muscle of the quadriceps muscle was associated with decreased medial tibial and patellar cartilage loss on MRI [13]. They also reported that vastus medialis fat infiltration can be altered by lifestyle modification.
Previous studies have already shown that the thigh muscle cross-sectional area (CSA) correlates with RKOA [12,14,15]. The prior longitudinal study by Wang et al. reported that an increase in vastus medialis muscle cross-sectional area (CSA) over a 2-year period was associated with reduced knee pain, reduced medial tibial cartilage loss, and reduced risk of knee replacement in the next 4 years (OR=0.61, p=0.03) [15]. Berry et al. also reported that increased skeletal muscle mass was associated with increased cartilage volume in healthy populations [10].
Knowing modifiable risk factors, such as decreased adiposity or increased muscle volumes in specific thigh compartments, to prevent structural KOA would help design effective preventive exercise strategies. Unfortunately, most of the studies published to date focused on the CSA of muscles or fat on single-slice CT or MR images rather than volumetric assessment [12,14,15], which may lead to inconsistent findings. In this cross-sectional study, we therefore investigated the associations of thigh muscle, intermuscular fat, and subcutaneous fat volumes with radiographic KOA, and MRI-based semi-quantitative parameters of OA severity.
Materials and Methods
The Osteoarthritis Initiative
The Osteoarthritis Initiative (OAI) is a large multi-center study with 4796 participants aged 45–79 years with, or at risk for, symptomatic femoral-tibial knee OA, including all ethnic minorities. Major exclusion criteria include inflammatory arthritis, bilateral end-stage KOA and contraindication to MRI. Study protocols and amendments were approved by the institutional review boards of all centers involved in this study, and informed consent was obtained from all participants.
Subject selection
A total of one hundred MRI studies of bilateral thighs (total of 200 thighs) were randomly selected from the OAI cohort to include approximately equal numbers based on sex, age (±10 years), and categorized BMI (normal, overweight, or obese using World Health Organization definitions), equally from each of the 4 OAI MRI scanners before and after upgrades. Our datasets included both thigh and knee MRIs as well as knee radiographs. Additionally, age, sex, height, weight, Kellgren-Lawrence grade (KLG) for bilateral knees, Western Ontario and McMaster Universities (WOMAC) pain score, and the physical activity scale for the elderly (PASE) scores were obtained from the OAI database.
Image acquisition
MR images were acquired at four centers (Columbus, Ohio; Baltimore, Maryland; Pittsburgh, Pennsylvania and Pawtucket, Rhode Island) using four identical 3 Tesla scanners (Siemens Magnetom Trio, Erlangen, Germany). Muscle and fat volume measurements were performed in an axial thigh T1 weighted spin echo sequence (T1w SE) [repetition time (TR) / echo time (TE); spatial resolution; field of view (FOV); slice thickness; gap] [500 ms / 10 ms; 0.977mm × 0.977 mm; 500 mm; 5 mm; 0 mm]. Acquired sequences of knee MRIs included: coronal 2D intermediate-weighted (IW) turbo spin-echo (TSE) [3700 ms / 29 ms; 0.365 mm × 0.456 mm; 140 mm; 3.0 mm; 0 mm), sagittal, fat-saturated (FS) 2D IW TSE [3200 ms / 30 ms; 0.357 mm × 0.511 mm; 160 mm; 3 mm; 0 mm), coronal 3D fast low angle shot with water excitation (FLASH WE) [7.57 ms / 20 ms; 0.313 mm × 0.313 mm; 160 mm; 1.5 mm; 0 mm] and sagittal 3D dual-echo steady state sequence with water excitation (DESS WE) [4.7 ms / 16.3 ms; 0.365 mm × 0.456 mm; 140 mm; 1.5 mm; 0 mm] with axial and coronal reformations.
Bilateral knee radiographs in posterior-anterior fixed flexion position and standing full-length anterior-posterior (AP) radiographs of femurs were obtained from all participants.
Image analysis
Muscle and fat measurements:
The femoral length was measured from the intercondylar notch to the superior femoral head using AP thigh radiographs. The axial T1W MRI images of bilateral thighs were standardized (starting 10 cm proximal to the distal epiphysis of the femur and extended 7.5 cm proximally; approximately middle 33% of the femoral length) and used for segmentation. Bilateral thigh muscle groups, including quadriceps (vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris), hamstrings, adductors, sartorius, and gracilis, along with deep fascia and subcutaneous fat border and neurovascular bundles, were semi-automatically segmented by two radiology residents (AMP with 4 years, and PJG with 4 years of experience in musculoskeletal imaging) in 15 consecutive slices using an online annotation platform (https://MD.ai). Subsequently, volume measurements were computed in cm3 (Figure 1). Intermuscular fat volume was computed as the difference between the volume defined by the deep fascia and the sum of the total muscle and femoral cortex volumes, as well as the neurovascular bundle. Subcutaneous fat volume was computed as the difference between the border of subcutaneous fat and deep fascia. Muscles were grouped according to anterior (quadriceps and sartorius), medial (adductors and gracilis), and posterior (hamstring including biceps short and long heads, semitendinosus, and semimembranosus) compartments.
Fig. 1.
Axial MRI image of right (A) and left (B) thighs with annotations of thigh muscles at 33% of the femoral length from distal to the proximal thigh. Annotations include quadriceps (blue), hamstrings (purple), adductors (pink), sartorius (light yellow), gracilis (red), femoral cortex (yellow) with medulla (red), deep fascia (dark orange), and outer border of subcutaneous fat (orange). AD: Adductors, G: Gracilis, H: Hamstrings, NV: Neurovascular bundle, SCF: Subcutaneous fat, SH: Short head of biceps femoris, VM: Vastus medialis, VL: Vastus lateralis.
Inter-reader reliability was assessed using intraclass correlation coefficients (ICC) calculated from independent measurements of subcutaneous fat and muscle volumes from MRIs of 20 segmented limbs by each of the two readers (AMP, PJG).
Whole-Organ Magnetic Resonance Imaging Scores (WORMS):
Structural knee MRI abnormalities were graded using the UCSF-modified WORMS semi-quantitative grading system [16–20] by 4 readers (ZA, AMP, PJG, and UUB with 10, 4, 4, and 5 years of experience in musculoskeletal imaging, respectively). All equivocal images were adjudicated with a senior radiologist (TML) with more than 25 years of experience in musculoskeletal imaging. WORMS provided separate semi-quantitative scores of cartilage abnormalities, bone marrow edema-like lesions and subchondral cyst-like lesions in 6 compartments (patella, trochlea, medial and lateral femur and tibia). Both menisci were scored in the anterior and posterior horn as well as the meniscal body. Tendons (patella and popliteus tendons) and ligaments (anterior cruciate ligament (ACL), posterior cruciate ligament, medial collateral ligament and lateral collateral ligament) were also scored. Summation scores for each tissue abnormality (cartilage (0–36), menisci (0–24), tendons and ligaments (each 0–28), and BMELs and subchondral cyst-like lesions (each 0–18)) and for the entire knee (ranging from 0–124) were obtained.
Synovitis scoring:
Effusion-synovitis was graded using the Anterior Cruciate Ligament Osteoarthritis Score (ACLOAS) [6,21] and MRI Osteoarthritis Knee Score (MOAKS) [6,22], infrapatellar fat pad (IPFP) abnormalities were also scored to assess Hoffa synovitis as previously described [6,23,24].
Statistical analysis
Statistical analysis was performed using STATA version 17 software (StataCorp LP, College Station, TX, USA). A two-tailed p-value lower than 0.05 was considered statistically significant. Descriptive statistics were obtained from the demographical data, including age, sex, height, weight, WOMAC pain score, PASE score, KLG, as well as muscle and fat measurements using chi-squared tests for categorical and independent t tests for continuous data for comparison between men and women. Mixed-effects linear regression models (accounting for two thighs per person) were used to analyze the associations between the predictor (total muscle volume, quadriceps volume, quadriceps to total muscle ratio, vastus medialis volume, vastus medialis to quadriceps ratio, vastus lateralis volume, vastus lateralis to quadriceps ratio, hamstring volume, hamstring to total muscle ratio, intermuscular fat volume and subcutaneous fat volume) and outcomes of WORMS for cartilage lesions and BMELs (summation scores). Models were tested for non-linearity by including an interaction term of the primary predictors and testing for significance. All predictors that had statistical significance were linearly related to the outcome. All analyses were adjusted for age, sex, height, and weight. All regression models were performed using standardized values of muscle parameters as predictors. The coefficients and odds ratios therefore represent the change in outcome per standard deviation (SD) change in the predictor.
Results
The individuals analyzed in this study had a mean (±SD) age and BMI of 62.06 (11.12) years and 27.17 (3.95) kg/m2, respectively. Eighty of all knees (80/200; 40%) had RKOA with KL grade ≥ 2. Forty-two subjects (42%) were women. The mean (±SD) WOMAC pain score and PASE were 1.25 (1.92) and 164.50 (92.36), respectively. The mean (±SD) WORMS cartilage summation score and WORMS BMEL summation score were 8.39 (6.76) and 1.93 (1.99), respectively.
Overall, women had higher mean subcutaneous fat volumes than men (616.82±240.48 vs. 229.13±87.14 cm3, p<0.01). However, no significant differences in intermuscular fat volume between men and women were found (p=0.28). Men had higher total muscle, quadriceps, quadriceps ratio to total muscle, vastus medialis, vastus medialis ratio to quadriceps, vastus lateralis, vastus lateralis ratio to quadriceps and hamstring muscle volumes than women (p<0.01). The details of subject characteristics, RKOA status, fat volume, and muscle volumes in each sex are reported in Table 1.
Table 1.
Subject characteristics, RKOA status, fat volume, and muscle volumes in each sex
| Variable | Female N=42 |
Male N=58 |
P-value |
|---|---|---|---|
| Age (years), mean (±SD) | 63.81 (10.88) | 60.79 (11.16) | 0.18 |
| BMI (kg/m2), mean (±SD) | 27.04 (4.86) | 27.27 (3.16) | 0.77 |
| WOMAC pain score, mean (±SD) | 1.38 (2.04) | 1.16 (1.83) | 0.89 |
| PASE, mean (±SD) | 145 (83.09) | 178.79 (96.47) | 0.08 |
| Presence of RKOA, N (%) | 20 (47.62) | 20 (34.48) | 0.06 |
| Subcutaneous fat volume (cm3), mean (±SD) | 616.82 (240.48) | 229.13 (87.14) | <0.01 |
| Intermuscular fat volume (cm3), mean (±SD) | 160.19 (45.19) | 172.13 (60.87) | 0.28 |
| Total muscle volume (cm3), mean (±SD) | 567.54 (141.74) | 806.01 (158.90) | <0.01 |
| Quadriceps muscle volume (cm3), mean (±SD) | 286.82 (71.83) | 425.29 (75.99) | <0.01 |
| QM ratio to total muscle, mean (±SD) | 0.51 (0.04) | 0.53 (0.04) | <0.01 |
| Vastus medialis volume (cm3), mean (±SD) | 86.68 (25.08) | 151.29 (37.45) | <0.01 |
| VM ratio to QM, mean (±SD) | 0.31 (0.08) | 0.36 (0.08) | <0.01 |
| Vastus lateralis volume (cm3), mean (±SD) | 85.09 (30.98) | 111.85 (39.24) | <0.01 |
| VL ratio to QM, mean (±SD) | 0.29 (0.06) | 0.26 (0.06) | <0.01 |
| Hamstring volume (cm3), mean (±SD) | 170.82 (42.23) | 255 (58.74) | <0.01 |
| Hamstring ratio to total muscle, mean (±SD) | 0.31 (0.05) | 0.32 (0.04) | 0.22 |
The average values of fat and muscle parameters on the left and right thighs were used for the analysis.
Chi-squared and independent t tests were used for categorical and continuous data, respectively.
Quadriceps (coef=−2.15, 95% CI=−3.83,−0.46, p=0.01) and vastus medialis (coef=−1.84, 95% CI=−3.51,−0.17, p=0.03) volumes were negatively associated with WORMS cartilage summation scores. The remaining muscles and fat volumes showed no significant association (p>0.05) with cartilage scores. Table 2 provides detailed information on the association between fat and muscle volumes, and WORMS cartilage summation score.
Table 2.
Association between the fat and muscle volumes, and WORMS cartilage lesion summation score
| Outcome: Sum cartilage score | Beta coefficient (95% CI) | P-value |
|---|---|---|
| Subcutaneous fat volume | −0.28 (−2.07, 1.51) | 0.76 |
| Intermuscular fat volume | 1.04 (−0.17, 2.24) | 0.09 |
| Total muscle volume | −0.92 (−2.47, 0.63) | 0.25 |
| Quadriceps volume | −2.15 (−3.83, −0.46) | 0.01 |
| QM ratio to total muscle | −23.62 (−47.41, 0.17) | 0.05 |
| Vastus medialis volume | −1.84 (−3.51, −0.17) | 0.03 |
| VM ratio to QM | 3.26 (−8.76, 15.29) | 0.59 |
| Vastus lateralis volume | −1.15 (−2.31, 0.02) | 0.05 |
| VL ratio to QM | 1.35 (−14.17, 16.87) | 0.87 |
| Hamstring volume | −0.74 (−2.22, 0.74) | 0.33 |
| Hamstring ratio to total muscle | 4.82 (−15.53, 25.18) | 0.64 |
Mixed-effects linear regression models (accounting for two thighs per person) were used to analyze the associations between the predictor and outcome. All analyses were adjusted for age, sex, height, and weight. The coefficients were standardized, therefore representing the outcome change per standard deviation change in the predictor.
Intermuscular fat volume (coef=0.48, 95% CI=0.12,0.85, p=0.01) was positively associated with WORMS BMEL summation scores while total muscle (coef=−0.66, 95% CI=−1.12,−0.19, p<0.01), quadriceps (coef=−0.99, 95% CI=−1.49,−0.48, p<0.01), vastus medialis (coef=−0.71, 95% CI=−1.22,−0.21, p<0.01), vastus lateralis (coef=−0.54, 95% CI=−0.89,−0.19, p<0.01), and hamstring (coef=−0.59, 95% CI=−1.04,−0.14, p=0.01) volumes were negatively associated with WORMS BMEL summation scores. The remaining muscles and fat volumes showed no evidenceof an association with WORMS BMEL scores (p>0.05). Detailed information on the association between fat and muscle volumes, and WORMS BMEL summation score is provided in Table 3.
Table 3.
Association between the fat and muscle volumes, and WORMS BMEL summation score
| Outcome: Sum BMEL score | Beta coefficient (95% CI) | P-value |
|---|---|---|
| Subcutaneous fat volume | −0.08 (−0.63, 0.47) | 0.77 |
| Intermuscular fat volume | 0.48 (0.12, 0.85) | 0.01 |
| Total muscle volume | −0.66 (−1.12, −0.19) | <0.01 |
| Quadriceps volume | −0.99 (−1.49, −0.48) | <0.01 |
| QM ratio to total muscle | −6.76 (−14.18, 0.67) | 0.08 |
| Vastus medialis volume | −0.71 (−1.22, −0.21) | <0.01 |
| VM ratio to QM | 0.77 (−2.92, 4.46) | 0.68 |
| Vastus lateralis volume | −0.54 (−0.89, −0.19) | <0.01 |
| VL ratio to QM | −1.82 (−6.64, 3.01) | 0.46 |
| Hamstring volume | −0.59 (−1.04, −0.14) | 0.01 |
| Hamstring ratio to total muscle | 0.77 (−5.53, 7.07) | 0.81 |
Mixed-effects linear regression models (accounting for two thighs per person) were used to analyze the associations between the predictor and outcome. All analyses were adjusted for age, sex, height, and weight. The coefficients were standardized, therefore representing the outcome change per standard deviation change in the predictor.
Quadriceps ratio to total muscle volume (coef=−7.75, 95% CI=−14.98,−0.51, p=0.04), vastus medialis volume (coef=−0.01, 95% CI=−0.02,−0.01, p<0.01), and vastus medialis ratio to quadriceps volume (coef=−4.31, 95% CI=−7.81,0.81, p=0.02) were negatively associated with WOMAC pain scores. Table 4 lists the associations between fat and muscle volumes, and WOMAC pain score. There was no evidence of an association between thigh subcutaneous fat volumes, intermuscular fat volumes, muscle volumes and RKOA or effusion-synovitis grading using ACLOAS, MOAKS, and IPFP abnormality (p>0.05).
Table 4.
Association between the fat and muscle volumes, and WOMAC pain score
| Outcome: WOMAC pain | Beta coefficient (95% CI) | P-value |
|---|---|---|
| Subcutaneous fat volume | 0.01 (−0.01, 0.01) | 0.09 |
| Intermuscular fat volume | 0.01 (−0.01, 0.01) | 0.33 |
| Total muscle volume | 0.01 (−0.01, 0.01) | 0.46 |
| Quadriceps volume | −0.01 (−0.01, 0.01) | 0.73 |
| Quadriceps ratio to total muscle | −7.75 (−14.98, −0.51) | 0.04 |
| Vastus medialis volume | −0.01 (−0.02, −0.01) | <0.01 |
| VM ratio to QM | −4.31 (−7.81, 0.81) | 0.02 |
| Vastus lateralis volume | 0.01 (−0.01, 0.01) | 0.67 |
| VL ratio to QM | 2.29 (−2.39, 6.99) | 0.34 |
| Hamstring volume | 0.01 (−0.01, 0.01) | 0.44 |
| Hamstring ratio to total muscle | −1.37 (−7.54, 4.79) | 0.66 |
Mixed-effects linear regression models (accounting for two thighs per person) were used to analyze the associations between the predictor and outcome. All analyses were adjusted for age, sex, height, and weight. The coefficients were standardized, therefore representing the outcome change per standard deviation change in the predictor.
Regarding the inter-reader reliability, subcutaneous fat volume and volumes of individual muscles and groups had good inter-reader reliability with ICCs in the range 0.92 [95% CI 0.70–0.98] (gracilis muscle) to 0.9992 [95% CI 0.9972–0.9998] (subcutaneous fat).
Discussion
To the best of our knowledge, our study is one of the first studies which showed that higher quadriceps and vastus medialis volumes were associated with less knee cartilage abnormalities using standard WORMS semi-quantitative assessment (Figure 2). Our study also showed that higher quadriceps, vastus medialis, vastus lateralis, and hamstrings volumes were associated with lower knee BMEL scores, while higher intermuscular fat volume was associated with higher BMEL scores. Our results document the important associations between cartilage and bone marrow abnormalities with muscle and fat volumes, which may provide therapeutic pathways in the management of knee OA.
Fig. 2.
MRI image of a 70-year-old woman with a BMI of 28.3 kg/m2 with relatively high subcutaneous fat volume (842 cm3), low quadriceps volume (267.23 cm3), low vastus medialis volume (68.77 cm3) and high WORMS cartilage summation score (15; an average score of our study=8.39). (A) Axial T1w SE image at the left mid-thigh showed relatively large subcutaneous fat (SCF) and small vastus medialis muscle (VM). (B) Sagittal IW TSE image of the left knee revealed large full-thickness cartilage lesions (WORMS-cartilage=5) at the patella (arrows) and the femoral trochlea (arrowheads). Note associated subjacent BMEL at the femoral trochlea (WORMS-BMEL=2) and Hoffa’s synovitis.
Previous longitudinal MRI study with symptomatic KOA subjects by Wang et al. showed a negative association between increasing vastus medialis CSA and medial tibial cartilage volume loss (coef=−16.8, 95% CI=−28.9,−4.6, p=0.01) over a two-year period [15]; however, investigators reported no evidence of an association between baseline vastus medialis CSA and baseline tibial cartilage volume.
Our study showed that lower quadriceps, vastus medialis, vastus lateralis, and hamstring volumes were associated with higher number and severity of BMELs; to the best of our knowledge, no other study has found the association between BMEL and muscle volume. These muscles might act as the bumper to the bone; when the muscle volumes decreased, the bone marrow became more susceptible to the injury, leading to BMEL on the MRI.
Our study also revealed that quadriceps ratio to total muscle volume (p=0.04), vastus medialis volume (p<0.01), and vastus medialis ratio to quadriceps volume (p=0.02) were negatively associated with WOMAC pain scores. A previous study by Hafez et al. demonstrated that strengthening exercises focusing on the hamstring and quadriceps muscles for a 12 week-period resulted in better WOMAC subscales of pain and also stiffness and physical function in patients with KOA [25]. These data suggest that muscle volumes may serve as mediators for knee degeneration, but longitudinal studies as well as the mediation analysis are required to study this relationship better.
Previous studies reported the importance of the vastus medialis muscle, as the stabilizer for the patellofemoral joint, by pulling the patella medially [26,27]. For that reason, low vastus medialis muscle volume might lead to a lateral shift of the patella, and eventually more susceptibility for the medial KOA. This might be the reason why the vastus medialis shows significant association with WORMS cartilage lesion score, BMEL score and WOMAC pain score in our study.
Dannhauer et al. reported that the progression of RKOA was associated with a longitudinal increase in thigh subcutaneous fat in men and a longitudinal increase in thigh intramuscular fat in women [12] which is consistent with our findings. On the other hand, Ikeda et al. reported that the incidence of RKOA increased with a higher hamstrings/quadriceps cross-sectional area ratio in women in their sixties (OR=2.5, p=0.04) [14] which is not supported by our cross-sectional data. This may be explained by different study populations and study designs. Our cross-sectional study showed no evidence of an association between the intermuscular fat volume and RKOA, similar to the 2-year longitudinal study by Beaties et al., which demonstrated no evidence of an association between intermuscular fat volume and OA status [28]. Our study also showed no evidence of an association between either thigh fat volume or muscle volume and synovial inflammation in knees using the semiquantitative MRI scores, which is an area that has not been well explored.
Potential limitations of our study were mainly related to our study design. Firstly, the cross-sectional design may not provide information on the impact of increased or decreased muscle or fat volumes on OA progression over time. However, a longitudinal study using volumetric assessment with longer follow-up periods is currently work in progress. Secondly, we used the fixed distance related to the distal epiphysis of the distal femur to determine the location for the volumetric study. This method can potentially lead to the relatively larger size of rectus femoris, vastus intermedius and vastus lateralis muscles, and smaller size of vastus medialis muscle in patients with shorter femur length [26]. Finally, we used the same location for the measurement for all muscles, but Yamauchi et al. showed that the most appropriate location for studying the vastus medialis muscle is at the mid-thigh region and at the muscle belly for the semimembranosus muscle [26]. Using measurements as suggested in this previous study may lead to a more significant values.
In conclusion, this study demonstrated significant associations between quadriceps and vastus medialis volumes with WORMS cartilage lesion scores, as well as quadriceps, vastus medialis, vastus lateralis, and hamstrings volumes with WORMS BMEL scores suggesting that certain higher muscle volumes may be protective of joint degeneration. On the other hand, increased fat was positively associated with signs of joint degeneration, highlighting the importance of local body composition. Based on our results exercise and physical activity and other interventions that increase thigh muscle volumes may aid in protecting the knee joint against knee structural abnormalities.
Acknowledgments:
The analyses in this study were funded through the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01-AR078917). We would like to thank the faculty and staff of the Coordinating Center of the OAI at the NIH and UCSF for their invaluable assistance with patient selection, statistical analysis, and technical support. The OAI is a public-private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services and conducted by the OAI Study Investigators. Private funding partners include Pfizer, Inc.; Novartis Pharmaceuticals Corporation; Merck Research Laboratories; and GlaxoSmithKline. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health.
Data availability:
The data that support the findings of this study are not openly available due to reasons of patient privacy (HIPAA) and are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are not openly available due to reasons of patient privacy (HIPAA) and are available from the corresponding author upon reasonable request.