Association of infra-patellar fat pad size with age and body weight in children and adolescents.

BACKGROUND: The infra-patellar fat pad (IPFP) represents a potential mediator between obesity, low grade inflammation, and knee osteoarthritis via endocrine pathways. Yet, not only in adults, but also in childhood obesity negatively impacts knee structures. OBJECTIVE: The current study therefore investigated the sex-specific growth of the IPFP with age and body weight in healthy children and adolescents. MATERIALS AND METHODS: Thirty young healthy subjects (60% girls; age 4-17 years, body weight 14-90 kg in girls and 29-105 kg in boys; BMI 12.2-32.4 kg/m2) without magnetic resonance imaging (MRI) knee pathology were studied. The IPFP volume was determined from sagittal T-1 weighted and proton-density spectral attenuated inversion recovery MRIs. The primary analysis focused on the sex-specific IPFP volume/body weight ratio as dependent, and age as independent variable, using linear regression models. A secondary analytic focus was the slope of the age-dependence of IPFP volume, without normalization to body weight. RESULTS: There was no statistically significant association of the IPFP volume/body weight ratio with age in girls (p = 0.57) or boys (p = 0.31), the R2 of ranging from -0.32 to 0.14. The ratio was greater in boys (0.54 ±â€¯0.10 cm3/kg) than in girls (0.45 ±â€¯0.07 cm3/kg) (p < 0.01). The IPFP volume increased by approx. 2 cm3 per annum in both girls and boys, without any indication of a non-linear relationship. CONCLUSION: Our findings reveal that the ratio of the IPFP volume and body weight remains constant between age 4 and 17 in both normal weight girls and boys, and that the IPFP volume increases linearly with age throughout this period.

Longitudinal change in thigh muscle strength prior to and concurrent with symptomatic and radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether symptomatic and/or radiographic knee osteoarthritis (KOA) progression is associated with prior and/or concurrent change in thigh muscle strength in men or women. DESIGN: Osteoarthritis Initiative (OAI) participants with isometric muscle strength measurements at baseline, 2- and 4-year follow-up (n = 1785: 1016 women) were grouped into 1) those with vs without symptomatic progression (i.e., increase ≥9 in WOMAC-pain [scale: 0-100]); and 2) those with vs without radiographic progression (i.e., decrease in minimum joint space width (JSW) ≥0.7 mm) between year-two and year-four follow-up. Sex-specific changes in thigh muscle strength concurrent (between year-two and year-four follow-up) and prior to (between baseline and year-two follow-up) symptomatic and radiographic progression were compared between groups (progression vs no progression) using analysis of covariance, with adjustment for age and body mass index. RESULTS: In women, but not in men, loss in knee extensor and flexor strength was greater concurrent with symptomatic progression (extensors: -3.7%, 95% confidence interval [CI] -6.4, -0.9; flexors: -7.2% 95% CI -10.7, -3.7) than in women without symptomatic progression (extensors: -0.3%, 95% CI -1.9, 1.3, P = 0.030; flexors: -2.6%, 95% CI -4.7, -0.6, P = 0.018). No association was found between extensor or flexor strength loss concurrent to radiographic progression, in either men or women, nor any statistically significant association between prior change in muscle strength with symptomatic or radiographic progression. CONCLUSION: These findings suggest that there is concurrent but not prior longitudinal association between loss in muscle strength and symptomatic KOA progression that is specific to women.

Between-group differences in infra-patellar fat pad size and signal in symptomatic and radiographic progression of knee osteoarthritis vs non-progressive controls and healthy knees - data from the FNIH Biomarkers Consortium Study and the Osteoarthritis Initiative.

OBJECTIVE: To examine cross-sectional and longitudinal between-group differences of infra-patellar fat pad (IPFP) size and magnetic resonance imaging (MRI) signal from fat-suppressed intermediate-weighted images with clinically relevant symptomatic and radiographic progression of knee osteoarthritis (OA), vs healthy references. METHODS: We studied 110 case knees (Kellgren-Lawrence Grade [KLG1-3]) with radiographic (≥0.7 mm loss in joint space width [JSW]) and symptomatic progression (≥+9/100 units on the Western Ontario and McMasters Universities Osteoarthritis Index [WOMAC] knee pain subscale) vs 118 control knees without progression from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium cohort. We further studied 88 knees from the Osteoarthritis Initiative (OAI) healthy reference cohort without (risk factors) of knee OA. The IPFP was manually segmented using baseline and year-2 sagittal fat-suppressed intermediate-weighted spin-echo 3 T MRIs. Baseline measures and longitudinal change in IPFP volume and 3D MRI signal (mean, standard deviation [SD]) were compared between groups. RESULTS: No statistically significant baseline differences in IPFP volume, 3D MRI signal mean or signal heterogeneity (SD) were observed between progressor and non-progressor OA knees. Yet, the IPFP 3D MRI signal SD, but not its volume, was statistically significantly greater in OA vs healthy knees. No statistically significant 2-year changes in IPFP volume were observed in either group, but the increase in 3D MRI signal heterogeneity (SD) was greater in progressor vs non-progressor knees, and was greater in OA vs healthy knees. CONCLUSION: Whereas IPFP-related morphometric measures did not statistically significantly differ between groups, a stronger increase in 3D IPFP MRI signal and signal heterogeneity may be associated with radiographic/symptomatic progression of OA, when compared to non-progressive OA or healthy knees.

Association of knee pain with a reduction in thigh muscle strength - a cross-sectional analysis including 4553 osteoarthritis initiative participants.

OBJECTIVE: To cross-sectionally determine the quantitative relationship of age-adjusted, sex-specific isometric knee extensor and flexor strength to patient-reported knee pain. METHODS: Difference of thigh muscle strength by age, and that of age-adjusted strength per unit increase on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain scale, was estimated from linear regression analysis of 4553 Osteoarthritis Initiative (OAI) participants (58% women). Strata encompassing the minimal clinically important difference (MCID) in knee pain were compared to evaluate a potentially non-linear relationship between WOMAC pain levels and muscle strength. RESULTS: In OAI participants without pain, the age-related difference in isometric knee extensor strength was -9.0%/-8.2% (women/men) per decade, and that of flexor strength was -11%/-6.9%. Differences in age-adjusted strength values for each unit of WOMAC pain (1/20) amounted to -1.9%/-1.6% for extensor and -2.5%/-1.7% for flexor strength. Differences in torque/weight for each unit of WOMAC pain ranged from -3.3 to -2.1%. There was no indication of a non-linear relationship between pain and strength across the range of observed WOMAC values, and similar results were observed in women and men. CONCLUSION: Each increase by 1/20 units in WOMAC pain was associated with a ∼2% lower age-adjusted isometric extensor and flexor strength in either sex. As a reduction in muscle strength is known to prospectively increase symptoms in knee osteoarthritis (KOA) and as pain appears to reduce thigh muscle strength, adequate therapy of pain and muscle strength is required in KOA patients to avoid a vicious circle of self-sustaining clinical deterioration.

Intra- and inter-observer reliability of quantitative analysis of the infra-patellar fat pad and comparison between fat- and non-fat-suppressed imaging--Data from the osteoarthritis initiative.

The infra-patellar fat pad (IPFP), as intra-articular adipose tissue represents a potential source of pro-inflammatory cytokines and its size has been suggested to be associated with osteoarthritis (OA) of the knee. This study examines inter- and intra-observer reliability of fat-suppressed (fs) and non-fat-suppressed (nfs) MR imaging for determination of IPFP morphological measurements as novel biomarkers. The IPFP of nine right knees of healthy Osteoarthritis Initiative participants was segmented by five readers, using fs and nfs baseline sagittal MRIs. The intra-observer reliability was determined from baseline and 1-year follow-up images. All segmentations were quality controlled (QC) by an expert reader. Reliability was expressed as root mean square coefficient of variation (RMS CV%). After QC, the inter-observer reliability for fs (nfs) imaging was 2.0% (1.1%) for IPFP volume, 2.1%/2.5% (1.6%/1.8%) for anterior/posterior surface areas, 1.8% (1.8%) for depth, and 2.1% (2.4%) for maximum sagittal area. The intra-observer reliability was 3.1% (5.0%) for volume, 2.3%/2.8% (2.5%/2.9%) for anterior/posterior surfaces, 1.9% (3.5%) for depth, and 3.3% (4.5%) for maximum sagittal area. IPFP volume from nfs images was systematically greater (+7.3%) than from fs images, but highly correlated (r=0.98). The results suggest that quantitative measurements of IPFP morphology can be performed with satisfactory reliability when expert QC is implemented. The IPFP is more clearly depicted in nfs images, and there is a small systematic off-set versus analysis from fs images. However, the high linear relationship between fs and nfs imaging suggests that fs images can be used to analyze IPFP morphology, when nfs images are not available.

Longitudinal (4 year) change of thigh muscle and adipose tissue distribution in chronically painful vs painless knees--data from the Osteoarthritis Initiative.

OBJECTIVE: To evaluate 4-year longitudinal change in thigh muscle and adipose tissue content in chronically painful vs painless knees. METHODS: Knees from Osteoarthritis Initiative (OAI) participants with non-acceptable symptom status (numerical rating scale (NRS) ≥4) and frequent pain (≥6 months at baseline, year 2 and year 4 follow-up) were studied. These were matched with painless controls (bilateral NRS pain intensity ≤1 and ≤infrequent pain at all 3 timepoints). 4-year longitudinal changes in thigh muscle anatomical cross-sectional areas (CSAs), isometric muscle strength, and in subcutaneous (SCF) and intermuscular fat (IMF) CSAs were obtained from magnetic resonance images (MRI) and were compared between groups (paired t-tests). RESULTS: 43 participants fulfilled the inclusion criteria of chronic pain, had complete thigh muscle MRI acquisitions and strength measurements, and a matched control. Quadriceps CSAs, but not extensor strength, showed a significant longitudinal decrease in chronically painful knees (-3.9%; 95% confidence interval [95 CI] -6.3%, -1.5%) and in painless controls (-2.4%; 95% CI -4.1%, -0.7%); the difference in change was not statistically significant (P = 0.33). There was a significant 4-year gain in SCF in painful knees (8.1%; 95% CI 3.1%, 13%) but not in controls (0.0%; 95% CI -4.4%, +4.4%) with the difference in change being significant (P = 0.03). The gain in IMF (∼5.2%) was similar between painful and painless knees. CONCLUSION: This is the first paper to show a significant impact of (chronic) knee pain on longitudinal change in local subcutaneous adipose tissue. The effect of pain on subcutaneous fat appeared stronger than that on intermuscular adipose tissue and on muscle status.

Sex-differences of the healthy infra-patellar (Hoffa) fat pad in relation to intermuscular and subcutaneous fat content--data from the Osteoarthritis Initiative.

The infra-patellar fat pad (IPFP) is composed of intra-articular adipose tissue; it represents a potential source of pro-inflammatory cytokines and has been associated with osteoarthritis of the knee. Yet, to what extent the size of the IPFP differs between healthy men and women, and how sex differences compare to those in inter-muscular and subcutaneous fat tissue content is unknown. We studied healthy reference subjects from the Osteoarthritis Initiative, without knee pain, without radiographic signs or without risk factors of femorotibial osteoarthritis. Sagittal magnetic resonance images (MRIs) of 99 right knees were used to segment the IPFP; in a subset, axial images of the thigh were available to segment inter-muscular and subcutaneous fat. Healthy men (n=40) displayed a 41% greater (p<0.001) IPFP volume and a 9% greater (p<0.01) ratio of IPFP volume/body weight than women (n=59). Men (n=13) displayed 15% greater intermuscular fat content (not significant), and a 50% lesser (p<0.01) subcutaneous fat content than women (n=12); when related to total thigh cross-sectional areas, these sex differences were +2% (not significant) and -53% (p<0.001). This is the first study to explore quantitative measures of the IPFP in healthy men and women, and to relate these to sex differences of inter-muscular and subcutaneous fat tissue content. Men displayed a significantly greater ratio of IPFP volume/body weight than women, similar amounts of inter-muscular fat, and strikingly less subcutaneous fat. These data provide a basis for further systematic studies of the variability of the IPFP with the body mass index and its role in knee osteoarthritis.

Thigh muscle cross-sectional areas and strength in knees with early vs knees without radiographic knee osteoarthritis: a between-knee, within-person comparison.

OBJECTIVE: To compare cross-sectional and longitudinal side-differences in thigh muscle anatomical cross-sectional areas (ACSAs), muscle strength, and specific strength (strength/ACSA), between knees with early radiographic change vs knees without radiographic knee osteoarthritis (RKOA), in the same person. DESIGN: 55 (of 4796) Osteoarthritis Initiative (OAI) participants fulfilled the inclusion criteria of early RKOA in one limb (definite tibiofemoral osteophytes; no radiographic joint space narrowing [JSN]) vs no RKOA (no osteophyte; no JSN) in the contralateral limb. ACSAs of the thigh muscles and quadriceps heads were determined using axial MRIs at 33%/30% femoral length (distal to proximal). Isometric extensor and flexor muscle strength were measured (Good Strength Chair). Baseline quadriceps ACSA and extensor (specific) strength represented the primary analytic focus, and 2-year changes of quadriceps ACSAs the secondary focus. RESULTS: No statistically significant side-differences in quadriceps (or other thigh muscle) ACSAs, muscle strength, or specific strength were observed between early RKOA vs contralateral limbs without RKOA (P ≥ 0.44), neither in men nor in women. The 2-year reduction in quadriceps ACSA in limbs with early RKOA was -0.9 ± 6% (mean ± standard deviation) vs -0.5 ± 6% in limbs without RKOA (statistical difference P = 0.85). CONCLUSION: Our results do not provide evidence that early unilateral radiographic changes, i.e., presence of osteophytes, are associated with cross-sectional or longitudinal differences in quadriceps muscle status compared with contralateral knees without RKOA. At the stage of early unilateral RKOA there thus appears to be no clinical need for countervailing a potential dys-balance in quadriceps ACSAs and strength between both knees.