Multi-scale Delineation of Articular Cartilage Deterioration in Aging and Osteoarthritis

Neil Chang, MS1, Esther Cory, MA1, Albert C. Chen, PhD1, Martin K. Lotz, PhD2, Robert Sah, MD, ScD1. 1University of California, San Diego, La Jolla, CA, USA, 2The Scripps Research Institute, La Jolla, CA, USA.

Disclosures: N. Chang: None. E. Cory: None. A.C. Chen: None. M.K. Lotz: None. R. Sah: None.

Introduction: Articular cartilage functions as a load-bearing surface of synovial joints, facilitating the

movement of one bone relative to another.1 In osteoarthritis (OA), sites of cartilage erosion are localized

typically in one or more particular compartments, with common patterns being medial, lateral, or

patellofemoral compartmental OA.2 Within each such sub-pattern of OA, a gradation and localization of

erosion is apparent, such as when examining knees from many individuals at a variety of ages. Specific

regions, subjected to particular types of loading that include weight-bearing activities, may be

predisposed to early cartilage degradation and erosion. Such changes in the articular cartilage, which

may precede full thickness erosion, such as loss of glycosaminoglycan3 and gradual thinning of the

cartilage,4 may be present in normally aging as well as degenerate and OA tissue, such as that showing

fibrillation of the surface. The hypothesis of this study is that certain regions of femoral condyle

cartilage, predisposed to full-thickness erosion, exhibit graded alterations such as partial thinning and

FCD loss. The aim of this study was to determine the specific spatial patterns of cartilage loss and fixed

charge density (FCD) depletion, with increasing macroscopic deterioration of the articular cartilage.

Methods: Osteochondral Block Preparation. The left knees of n=40 adult cadavers were analyzed.

Longitudinal blocks were isolated from the central region of n=24 lateral femoral condyles (LFC, age

range 45-72 yrs, avg±SD 62±14, 12 M, 12 F), and n=24 medial femoral condyles (MFC, age range 43-79

yrs, avg±SD 67±14, 12 M, 12 F). Tissue blocks were fixed with 4% paraformaldehyde, and assigned a

morphological grade based on the worst deterioration in the block: 1) Normal, 2) Mild fibrillation, 3)

Partial-thickness erosion, 4) Full-thickness erosion. The condyles were divided into 4 groups of n=6 each

based on the highest grade at the condyle: with two normal Grade 1 groups divided by age (middle-age

normal, age avg±SD, 44±11 and old normal (age-matched to the last two groups), 70±13), Grade 2 group

(75±18), and the Grades 3/4 group (two grades combined to one group, 68±11). μCT Imaging. Samples

were equilibrated in PBS with 20% Hexabrix, and then imaged by μCT at (36 μm)3 resolution, along with

calibration phantoms. The area of analysis in each condyle was the anterior-posterior length from the

proximal to distal sulci, in a 2-D section across the center of the slab. Profiles of cartilage thickness and

FCD were determined using custom software. FCD profiles were expressed by layer-based distance from

the articular surface, with the first layer of analysis from surface to 0.25 mm deep, the next from surface

to 0.50 mm, and so forth. Statistics. Averaged thickness and FCD profiles were expressed as mean±SEM

for each group. Effects of the highest grade in the condyle on cartilage thickness and FCD at 10%

intervals from anterior to posterior were assessed by repeated measures ANOVA with Tukey post hoc

tests between the different groups at each location.

Results: Cartilage Thickness Profile. Cartilage thickness profiles exhibited distinct variations for the MFC

and LFC, from anterior to posterior, for different grades of tissue deterioration (Fig. 1). In the MFC of the

normal groups, cartilage thickness increased to a peak at the 30-40% position. In this same position,

cartilage thickness was lower with normal aging. With deterioration to Grade 3/4, this lowering of

cartilage thickness was accentuated and broadened, especially to the 20-40% positions. In the LFC,

cartilage thickness also increased to a peak at the 30-50% position. With increasing deterioration,

cartilage thickness increased in the 40-100% position.

Fixed Charge Density Profile. The profiles of cartilage FCD, as indicated inversely by Hexabrix uptake,

from anterior to posterior, varied little with grade and layer (Figs. 2-3). In the MFC, FCD was not

markedly different between groups except near the posterior end, where FCD trended to be lower with

increasing grade. In the LFC, the starkest FCD difference between grades was towards the center of the

condyle.

Discussion: The thickness and FCD differences across grades, showed specific patterns that may give

insight into mechanically-induced deterioration. While the MFC exhibited gradual thinning with aging

and deterioration, as expected, the LFC exhibited paradoxical increase in thickness with aging and

deterioration. Subsequent analysis of selected individual samples suggested that the Grade 4 LFC

samples were afflicted by small focal defects and apparent swelling of the surrounding regions. The

variation in FCD, was consistent with other changes with aging and OA, with the MFC tending to

decrease with from mild to severe OA. In the LFC, the site-specific graded decrease in the center of the

condyle may distinguish regions of FCD loss, based on the compartment of the condyle, with the MFC

more susceptible to FCD and thickness loss in the non-contact regions (posterior), and the LFC more

susceptible to FCD loss in the contact regions (anterior to center).

Significance: This study is the first to map, quantitatively, the thickness and FCD of the femoral condyle,

identifies potential locations of predisposal to thickness and FCD loss in the LFC and MFC, and also helps

localize regions of specific interest for higher resolution or 3-D analysis.

ORS 2015 Annual Meeting

Poster No: 0365