Responsiveness of Subcutaneous Fat, Intermuscular Fat, and Muscle Anatomical Cross-Sectional Area of the Thigh to Longitudinal Body Weight Loss and Gain: Data from the Osteoarthritis Initiative (OAI).

Thigh subcutaneous (SCF) and intermuscular (IMF) fat have been associated with joint health and function. Here, we explore the (sex-specific) responsiveness of SCF, IMF, and muscle during longitudinal weight loss and gain, as well as the change in questionnaire-based and physical performance-based knee function measures. This exploratory study included 103 Osteoarthritis Initiative (OAI) participants, who displayed a ≥10% weight loss or gain between baseline (BL) and 2-year (Y2) follow-up (and maintained half of that weight loss until year 4) and had axial 3T magnetic resonance images (MRI) for measuring SCF, IMF, and muscle cross sectional areas (CSAs). The standardized response mean (SRM = mean divided by the standard deviation of the change) was used as a measure of responsiveness. A total of 52 OAI participants (73% women) displayed ≥10% weight loss, and 51 (67% women) ≥10% weight gain. Both SCF and IMF CSAs showed a significant decrease (mean change) with weight loss (SCF: -22%, SRM = -1.2; IMF: -15%, SRM = -0.7) and a significant increase with weight gain (SCF: +27%, SRM = 1.1; IMF: +21%, SRM = 0.6). Muscle CSAs showed significant changes during weight loss (extensor: -8.3%, SRM = -1.1; flexor: -7.2%, SRM = -1.0), but not during weight gain. Knee function measures were not relevantly associated with bidirectional changes in body weight. SCF and IMF CSAs are highly responsive to bidirectional weight change, whereas muscle CSAs were only responsive to weight loss. These findings highlight that MRI represents a sensitive tool for monitoring changes in thigh adipose tissue composition that may be applied during specific diet and/or exercise interventions.

Responsiveness of Infrapatellar Fat Pad Volume Change to Body Weight Loss or Gain: Data from the Osteoarthritis Initiative.

Obesity is a potent risk factor for knee osteoarthritis (OA) that is driven by mechanical and potentially endocrine mechanisms, and it affects women more frequently than men. The infrapatellar fat pat (IPFP) represents a potential link between obesity, intra-articular inflammation and structural pathology. Here we investigate whether the IPFP is responsive to body weight loss/gain in women and how its responsiveness to weight change compares to that of subcutaneous fat (SCF) of the thigh. All female participants of the Osteoarthritis Initiative (OAI) with ≥10% weight loss/gain between baseline and a 2-year follow-up were included. Within-subject changes in IPFP volume and SCF cross-sectional areas (CSA) were determined from 3-T magnetic resonance imaging. Linear regression was used to assess the association between change in weight, IPFP volume, and SCF CSA. In the 38 participants with ≥10% weight loss over 2 years (age 59.3 ± 9.1 years, mean loss = 15.9%), there was a significant reduction in IPFP volume (-2.2%, p = 0.02) as well as in SCF CSA (-22%, p < 0.001). In the 34 participants with ≥10% gain (age 61.5 ± 8.7 years, mean gain = 15.9%), there was a significant increase in SCF CSA (+26%, p < 0.001) but not in IPFP volume (0.2%, p = 0.87). Weight change was significantly associated with SCF CSA change (r = 0.76, p < 0.001) but not with IPFP volume change (r = 0.11, p = 0.37). In this first longitudinal, observational study investigating the responsiveness of IPFP and SCF to weight change, IPFP morphology was found responsive to weight loss but not to weight gain. Overall, the responsiveness of the IPFP was substantially less than that of the SCF.

Variance in infra-patellar fat pad volume: Does the body mass index matter?-Data from osteoarthritis initiative participants without symptoms or signs of knee disease.

The infra-patellar fat pad (IPFP) has been proposed to represent an endocrine link between obesity and knee osteoarthritis (OA). The purpose of the current study has been to explore the extent to which IPFP volume is related to body mass index (BMI). A total of 152 participants (age 56±7 years) without knee OA were studied. These consisted of 19 men and 19 women of normal weight (BMI 18.5-25), 19/19 pre-obese (BMI 25-30), 19/19 obese class I (BMI 30-35) and 19/19 obese class II (BMI 35-40), who were matched 1:1 for age and height. The IPFP volume was manually segmented from sagittal fat-suppressed magnetic resonance images (MRI). An ANOVA of repeated measures was used to assess whether IPFP volume was related to BMI. The IPFP volume differed significantly between the BMI strata (ANOVA: p=0.001): It was 27.1±6.7cm3 (mean±SD) in normal weight, 29.3±6.9cm3 in pre-obese, 31.0±6.9cm3 in obese class I, and 30.4±6.6cm3 in obese class II participants; the difference in IPFP volume (and body weight) relative to normal weight subjects was 10% (18%) in pre-obese, 17% (39%) in obese class I, and 15% (59%) in obese class II participants. Stratification by sex showed similar results. In conclusion, IPFP volume is shown to be related to BMI, albeit the relative increase (compared with normal weight) does not appear to be proportional to that in body weight. Nonetheless, these findings support the hypothesis that the IPFP may represent a potential endocrine link between obesity and OA, with more intra-articular adipose tissue potentially releasing greater amounts of adipokines.

Validation of an active shape model-based semi-automated segmentation algorithm for the analysis of thigh muscle and adipose tissue cross-sectional areas.

OBJECTIVE: To validate a semi-automated method for thigh muscle and adipose tissue cross-sectional area (CSA) segmentation from MRI. MATERIALS AND METHODS: An active shape model (ASM) was trained using 113 MRI CSAs from the Osteoarthritis Initiative (OAI) and combined with an active contour model and thresholding-based post-processing steps. This method was applied to 20 other MRIs from the OAI and to baseline and follow-up MRIs from a 12-week lower-limb strengthening or endurance training intervention (n = 35 females). The agreement of semi-automated vs. previous manual segmentation was assessed using the Dice similarity coefficient and Bland-Altman analyses. Longitudinal changes observed in the training intervention were compared between semi-automated and manual segmentations. RESULTS: High agreement was observed between manual and semi-automated segmentations for subcutaneous fat, quadriceps and hamstring CSAs. With strength training, both the semi-automated and manual segmentation method detected a significant reduction in adipose tissue CSA and a significant gain in quadriceps, hamstring and adductor CSAs. With endurance training, a significant reduction in adipose tissue CSAs was observed with both methods. CONCLUSION: The semi-automated approach showed high agreement with manual segmentation of thigh muscle and adipose tissue CSAs and showed longitudinal training effects similar to that observed using manual segmentation.

Thigh Muscle Specific-Strength and the Risk of Incident Knee Osteoarthritis: The Influence of Sex and Greater Body Mass Index.

OBJECTIVE: To determine whether lower thigh muscle specific-strength increases the risk of incident radiographic knee osteoarthritis (RKOA), and whether there exists a sex-specific relationship between thigh muscle specific-strength and body mass index (BMI). METHODS: A total of 161 Osteoarthritis Initiative participants (62% female) with incident RKOA (Kellgren/Lawrence grade 0/1 at baseline, developing an osteophyte and joint space narrowing grade ≥1 by year 4) were matched to 186 controls (58% female) without incident RKOA. Thigh muscle anatomical cross-sectional areas (ACSAs) were determined at baseline using axial magnetic resonance imaging scans. Isometric extensor and flexor muscle strength was measured at baseline, and specific strength (strength ÷ ACSA) was calculated. Logistic regression assessed the risk of incident RKOA associated with muscle specific-strength (with and without adjustment for BMI). RESULTS: Lower knee extensor- and flexor-specific strength significantly increased the risk of incident RKOA in women but not in men (odds ratio 1.47 [95% confidence interval (95% CI) 1.10-1.96] and 1.41 [95% CI 1.06-1.89], respectively). The significant relationship in women was lost after adjustment for BMI. Lower specific strength was associated with higher BMI in women (r = -0.29, P < 0.001), but not in men, whereas absolute strength was associated with BMI in men (r = 0.28, P = 0.001), but not in women. CONCLUSION: Lower thigh muscle specific-strength predicts incident RKOA in women, with this relationship being confounded by BMI. The sex-specific relationship between muscle specific-strength and BMI provides a possible explanation why women with muscle-strength deficits typically have a poorer prognosis than men with similar strength deficits.

Quantitative relationship of thigh adipose tissue with pain, radiographic status, and progression of knee osteoarthritis: longitudinal findings from the osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the relationship of thigh subcutaneous fat (SCF) and intermuscular fat (IMF) content with knee osteoarthritis (KOA) cross-sectionally and longitudinally, using quantitative magnetic resonance imaging. Specifically, we examined relationships with frequent knee pain, various radiographic strata, and structural progression status of KOA. MATERIALS AND METHODS: Subjects who showed between-knee discordance of frequent versus no pain (n = 48), osteophyte versus no radiographic KOA (n = 55), and radiographic joint space narrowing versus no joint space narrowing (n = 44) were selected from the Osteoarthritis Initiative. Knees with structural progression of KOA (n = 23) were compared with knees without progression. Axial thigh magnetic resonance images were used to determine IMF and SCF. Differences between knees and between baseline and 2-year follow-up were examined using paired t tests. RESULTS: Women displayed similar amounts of IMF, but twice the SCF of men. Limbs of women with frequently painful knees had statistically significant greater IMF areas (+4.2%; P = 0.05) than contralateral pain-free limbs did. No significant cross-sectional differences were observed between other strata. Men with structural progression appeared to have a greater longitudinal increase in SCF (+13.2%; P < 0.05) than did men without progression (-1.9%), and women with progression appeared to have a greater increase in IMF (+11.6%) than did those without progression (+1.5%). CONCLUSION: In women, painful knees display greater IMF content than do contralateral pain-free knees. Other between-knee comparisons did not reveal a regional association between radiographic KOA and thigh adipose tissue status. Structural progression of KOA may be associated with greater longitudinal increases in SCF in men and greater increases of IMF in women, compared with nonprogressive controls.

Longitudinal sensitivity to change of MRI-based muscle cross-sectional area versus isometric strength analysis in osteoarthritic knees with and without structural progression: pilot data from the Osteoarthritis Initiative.

OBJECT: Biomechanical measurement of muscle strength represents established technology in evaluating limb function. Yet, analysis of longitudinal change suffers from relatively large between-measurement variability. Here, we determine the sensitivity to change of magnetic resonance imaging (MRI)-based measurement of thigh muscle anatomical cross sectional areas (ACSAs) versus isometric strength in limbs with and without structural progressive knee osteoarthritis (KOA), with focus on the quadriceps. MATERIALS AND METHODS: Of 625 "Osteoarthritis Initiative" participants with radiographic KOA, 20 had MRI cartilage and radiographic joint space width loss in the right knee isometric muscle strength measurement and axial T1-weighted spin-echo acquisitions of the thigh. Muscle ACSAs were determined from manual segmentation at 33% femoral length (distal to proximal). RESULTS: In progressor knees, the reduction in quadriceps ACSA between baseline and 2-year follow-up was -2.8 ± 7.9 % (standardized response mean [SRM] = -0.35), and it was -1.8 ± 6.8% (SRM = -0.26) in matched, non-progressive KOA controls. The decline in extensor strength was more variable than that in ACSAs, both in progressors (-3.9 ± 20%; SRM = -0.20) and in non-progressive controls (-4.5 ± 28%; SRM = -0.16). CONCLUSION: MRI-based analysis of quadriceps muscles ACSAs appears to be more sensitive to longitudinal change than isometric extensor strength and is suggestive of greater loss in limbs with structurally progressive KOA than in non-progressive controls.

Thigh muscle cross-sectional areas and strength in advanced versus early painful osteoarthritis: an exploratory between-knee, within-person comparison in osteoarthritis initiative participants.

OBJECTIVE: To compare cross-sectional and longitudinal side differences in thigh muscle anatomic cross-sectional areas (ACSAs), strength, and specific strength (strength/ACSA) between knees with early versus advanced painful radiographic osteoarthritis in the same person. METHODS: Forty-four of 2,678 Osteoarthritis Initiative participants (31 women and 13 men) met the inclusion criteria of bilateral frequent knee pain, medial joint space narrowing (JSN) in 1 knee, and no medial (or lateral) JSN in the contralateral knee. Thigh muscle ACSAs of the quadriceps, hamstrings, adductors, and individual quadriceps heads at consistent locations were determined using magnetic resonance imaging. Isometric muscle strength was determined in extension/flexion (Good Strength Chair). Baseline quadriceps ACSAs and strength were considered primary end points, and longitudinal changes of these factors were considered secondary end points (by paired t-tests). RESULTS: No significant side differences in quadriceps (or other thigh muscle) ACSAs, strength, or specific strength were observed between medial JSN knees versus knees without JSN, or between specific medial JSN knee strata and contralateral knees without JSN, either in men or women. Two-year longitudinal changes in thigh muscle ACSAs and strength were small (≤5.2%) and did not differ significantly between medial JSN knees and knees without JSN. CONCLUSION: In the context of previous findings that side differences in pain are associated with side differences in quadriceps ACSAs, the current results suggest that quadriceps (and other thigh muscle) properties are not independently associated with radiographic disease status (JSN) once knees have reached frequent pain status. Further, our longitudinal findings indicate that a more advanced radiographic stage of knee osteoarthritis is not necessarily associated with a longitudinal decline in muscle function.