Sebastian Cotofana

Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study

Background Modification of joint tissue damage is challenging in late-stage osteoarthritis (OA). Few options are available for treating end-stage knee OA other than joint replacement. Objectives To examine whether joint distraction can effectively modify knee joint tissue damage and has the potential to delay prosthesis surgery. Methods 20 patients (<60 years) with tibiofemoral OA were treated surgically using joint distraction. Distraction (∼5 mm) was applied for 2 months using an external fixation frame. Tissue structure modification at 1 year of follow-up was evaluated radiographically (joint space width (JSW)), by MRI (segmentation of cartilage morphology) and by biochemical markers of collagen type II turnover, with operators blinded to time points. Clinical improvement was evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) pain score. Results Radiography demonstrated an increase in mean and minimum JSW (2.7 to 3.6 mm and 1.0 to 1.9 mm; p<0.05 and <0.01). MRI revealed an increase in cartilage thickness (2.4 to 3.0 mm; p<0.001) and a decrease of denuded bone areas (22% to 5%; p<0.001). Collagen type II levels showed a trend towards increased synthesis (+103%; p<0.06) and decreased breakdown (−11%; p<0.08). The WOMAC index increased from 45 to 77 points, and VAS pain decreased from 73 to 31 mm (both p<0.001). Conclusions Joint distraction can induce tissue structure modification in knee OA and could result in clinical benefit. No current treatment is able to induce such changes. Larger, longer and randomised studies on joint distraction are warranted.

Quantitative MRI measures of cartilage predict knee replacement: a case–control study from the Osteoarthritis Initiative

Objective Knee osteoarthritis commonly requires joint replacement, substantially reduces quality of life and increases healthcare utilisation and costs. This study aimed to identify whether quantitative measures of articular cartilage structure predict knee replacement, and to establish their utility as outcomes in clinical trials of disease-modifying therapy. Methods A nested case–control study was performed in Osteoarthritis Initiative participants, a multicentre observational cohort of 4796 participants with or at risk of knee osteoarthritis. 127 knees were replaced between baseline and 4 years follow-up, and one control knee per case matched for baseline radiographic disease stage (Kellgren–Lawrence grade; KLG), gender and age. Quantitative cartilage measures were obtained from 3 T magnetic resonance images at the exam before knee replacement, and longitudinal change during the previous 12 months when available (n=110). Results Cartilage thickness loss in the central and total medial femorotibial compartment (primary and secondary predictor variables) was significantly greater in case than control knees (AUC=0.59/0.58). Differences in cartilage loss were greater at earlier than later radiographic disease stages (p<0.01 for interaction with KLG). Cartilage thickness loss in the central tibia was the most predictive longitudinal measure (AUC=0.64). Denuded bone areas in the medial femur were the most predictive and discriminatory cross-sectional measure between case and control knees (AUC=0.66). Conclusions This study demonstrates the predictive value of quantitative, MRI-based measures of cartilage for the clinically relevant endpoint of knee replacement, providing support for their utility in clinical trials to evaluate the effectiveness of structure-modifying intervention.

Greater Rates of Cartilage Loss in Painful Knees Than in Pain-Free Knees After Adjustment for Radiographic Disease Stage Data From the Osteoarthritis Initiative

OBJECTIVE To investigate whether rates of cartilage loss differ in knees with frequent baseline pain versus those without pain, after adjustment for radiographic osteoarthritis (OA) stage. METHODS One knee in each of 718 Osteoarthritis Initiative participants was examined: 310 with calculated Kellgren/Lawrence (K/L) grade 2, 299 with calculated K/L grade 3, and 109 with calculated K/L grade 4. Twelve-month change in (subregional) cartilage thickness was assessed by magnetic resonance imaging. Change in cartilage thickness in the central subregion of the weight-bearing medial femoral condyle and ordered value 1 (OV1) were selected as primary end points. Frequent knee symptoms were defined as pain, aching, or stiffness on most days of at least 1 month during the previous year. RESULTS The mean 12-month rate of change in cartilage thickness in the central subregion of the medial femoral condyle was -12 μm (standardized response mean [SRM] -0.15) in knees without pain (n = 146), -27 μm (SRM -0.25) in those with infrequent pain (n = 255), and -54 μm (SRM -0.32) in those with frequent pain (n = 317). Rates differed significantly between frequently painful knees and pain-free knees after adjustment for age, sex, body mass index, and calculated K/L grade (P = 0.011, R(2) = 2.6%, partial R(2) for frequent pain = 1.4%). Similar results were found in stratified samples of calculated K/L grade 2/calculated K/L grade 3 knees, and in analyses restricted to knees with consistent pain frequency between baseline and followup. OV1 results showed similar trends but were not significant. CONCLUSION Knees with frequent pain display greater rates of medial cartilage loss longitudinally than knees without pain, with or without adjustment or stratification for radiographic disease stage. Enrollment of participants with frequent knee pain in clinical trials can increase the observed rate of structural progression (i.e., cartilage loss) and sensitivity to change.

Cartilage thickening in early radiographic knee osteoarthritis: A within‐person, between‐knee comparison

To determine whether the presence of definite osteophytes (in the absence of joint space narrowing [JSN]) on radiographs is associated with (subregional) increases in cartilage thickness in a within‐person, between‐knee cross‐sectional comparison of participants in the Osteoarthritis Initiative. Based on previous results, the external weight‐bearing medial femoral condyle (ecMF) and external weight‐bearing lateral femoral condyle (ecLF) subregions were selected as primary end points.

Hand Joint Space Narrowing and Osteophytes Are Associated with Magnetic Resonance Imaging-defined Knee Cartilage Thickness and Radiographic Knee Osteoarthritis: Data from the Osteoarthritis Initiative

Objective. To evaluate whether features of radiographic hand osteoarthritis (OA) are associated with quantitative magnetic resonance imaging (MRI)-defined knee cartilage thickness, radiographic knee OA, and 1-year structural progression. Methods. A total of 765 participants in Osteoarthritis Initiative (OAI; 455 women, mean age 62.5 yrs, SD 9.4) obtained hand radiographs (at baseline), knee radiographs (baseline and Year 1), and knee MRI (baseline and Year 1). Hand radiographs were scored for presence of osteophytes and joint space narrowing (JSN). Knee radiographs were scored according to the Kellgren-Lawrence (KL) scale. Cartilage thickness in the medial and lateral femorotibial compartments was measured quantitatively from coronal FLASHwe images. We examined the cross-sectional and longitudinal associations between features of hand OA (total osteophyte and JSN scores) and knee cartilage thickness, 1-year knee cartilage thinning (above smallest detectable change), presence of knee OA (KL grade ≥ 3), and progression of knee OA (KL change ≥ 1) by linear and logistic regression. Both hand OA features were included in a multivariate model (if p ≤ 0.25) adjusted for age, sex, and body mass index (BMI). Results. Hand JSN was associated with reduced knee cartilage thickness (ß = −0.02, 95% CI −0.03, −0.01) in the medial femorotibial compartment, while hand osteophytes were associated with the presence of radiographic knee OA (OR 1.10, 95% CI 1.03–1.18; multivariate models) with both hand OA features as independent variables adjusted for age, sex, and BMI). Radiographic features of hand OA were not associated with 1-year cartilage thinning or radiographic knee OA progression. Conclusion. Our results support a systemic OA susceptibility and possibly different mechanisms for osteophyte formation and cartilage thinning.

Trajectory of cartilage loss within 4 years of knee replacement - a nested case-control study from the Osteoarthritis Initiative

OBJECTIVE Knee replacement (KR) represents a clinically important endpoint of knee osteoarthritis (KOA). Here we examine the 4-year trajectory of femoro-tibial cartilage thickness loss prior to KR vs non-replaced controls. METHODS A nested case-control study was performed in Osteoarthritis Initiative (OAI) participants: Cases with KR between 12 and 60 month (M) follow-up were each matched with one control (without KR through 60M) by age, sex, and baseline radiographic stage. Femoro-tibial cartilage thickness was measured quantitatively using magnetic resonance imaging (MRI) at the annual visit prior to KR occurrence (T0), and at 1-4 years prior to T0 (T-1 to T-4). Cartilage loss between cases and controls was compared using paired t-tests and conditional logistic regression. RESULTS One hundred and eighty-nine knees of 164 OAI participants [55% women; age 64 ± 8.7; body mass index (BMI) 29 ± 4.5] had KR and longitudinal cartilage data. Comparison of annualized slopes of change across all time points revealed greater loss in the central medial tibia (primary outcome) in KRs than in controls [94 ± 137 vs 55 ± 104 μm; P = 0.0017 (paired t); odds ratio (OR) 1.36 (95% confidence interval (CI): 1.08-1.70)]. The discrimination was stronger for T-2 → T0 [OR 1.61 (1.33-1.95), n = 127] than for T-1 → T0, and was not statistically significant for intervals prior to T-2 [i.e., T-4 → T-2, OR 0.97 (0.67-1.41), n = 60]. Results were similar for total medial femoro-tibial cartilage loss (secondary outcome), and when adjusting for pain and BMI. CONCLUSIONS In knees with subsequent replacement, cartilage loss accelerates in the 2 years, and particularly in the year prior to surgery, compared with controls. Whether slowing this cartilage loss can delay KR remains to be determined.

Effects of Exercise Intervention on Knee Morphology in Middle-Aged Women: A Longitudinal Analysis Using Magnetic Resonance Imaging

Introduction:Epidemiological studies show a positive relationship between physical activity and cartilage volume, suggesting that exercise may protect against osteoarthritis. Cross-sectional experimental studies, however, have failed to show significant differences in knee cartilage morphology between athletes and nonathletic controls. The aim of the study was to test the hypothesis that knee cartilage morphology, specifically regional cartilage thickness and global subchondral bone area, is modified in sedentary, untrained adult women who increased their physical fitness during a 3-month supervised exercise intervention. Materials and Methods: Thirty-eight untrained women, aged 45–55 years, were randomly assigned to: endurance training (n = 18), strength training (n = 15) and autogenic training (control group, n = 5). Patellar and femorotibial knee cartilage morphology was determined before and after the 3-month supervised training intervention, using magnetic resonance imaging and state-of-the-art image analysis. Results: Whereas the endurance training group showed a significant increase in cardiorespiratory fitness and the strength training group a significant increase in the maximal voluntary isometric contraction force of the leg, this study did not show significant differences in knee cartilage thickness and volume, subchondral bone area or regional cartilage thickness between baseline and follow-up acquisitions within any intervention group. Discussion:This randomized longitudinal study provides no evidence that a 3-month exercise intervention in untrained middle-aged women can significantly alter knee joint morphology. Longitudinal evidence supporting that a training program, successful in increasing physical fitness, can also induce functional adaptation of articular tissues and may protect against knee osteoarthritis, remains to be presented.

The Facial Adipose Tissue: A Revision.

Recent advantages in the anatomical understanding of the face have turned the focus toward the subcutaneous and deep facial fat compartments. During facial aging, these fat-filled compartments undergo substantial changes along with other structures in the face. Soft tissue filler and fat grafting are valid methods to fight the signs of facial aging, but little is known about their precise effect on the facial fat. This narrative review summarizes the current knowledge about the facial fat compartments in terms of anatomical location, histologic appearance, immune-histochemical characteristics, cellular interactions, and therapeutic options. Three different types of facial adipose tissue can be identified, which are located either superficially (dermal white adipose tissue) or deep (subcutaneous white adipose tissue): fibrous (perioral locations), structural (major parts of the midface), and deposit (buccal fat pad and deep temporal fat pad). These various fat types differ in the size of the adipocytes and the collagenous composition of their extracellular matrix and thus in their mechanical properties. Minimal invasive (e.g., soft tissue fillers or fat grafting) and surgical interventions aiming to restore the youthful face have to account for the different fat properties in various facial areas. However, little is known about the macro- and microscopic characteristics of the facial fat tissue in different compartments and future studies are needed to reveal new insights to better understand the process of aging and how to fight its signs best.

The Anatomy of the Aging Face: A Review

Rejuvenative procedures of the face are increasing in numbers, and a plethora of different therapeutic options are available today. Every procedure should aim for the patients safety first and then for natural and long-lasting results. The face is one of the most complex regions in the human body and research continuously reveals new insights into the complex interplay of the different participating structures. Bone, ligaments, muscles, fat, and skin are the key players in the layered arrangement of the face.Aging occurs in all involved facial structures but the onset and the speed of age-related changes differ between each specific structure, between each individual, and between different ethnic groups. Therefore, knowledge of age-related anatomy is crucial for a physicians work when trying to restore a youthful face.This review focuses on the current understanding of the anatomy of the human face and tries to elucidate the morphological changes during aging of bone, ligaments, muscles, and fat, and their role in rejuvenative procedures.

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.