Patterns of femorotibial cartilage loss in knees with neutral, varus, and valgus alignment.

Paracelsus Medical University, Salzburg, Austria.
Arthritis & Rheumatology (Impact Factor: 7.87). 12/2008; 59(11):1563-70. DOI: 10.1002/art.24208
Source: PubMed

ABSTRACT Malalignment is known to alter medial-to-lateral femorotibial load distribution and to affect osteoarthritis (OA) progression in the mechanically stressed compartment. We investigated the pattern of cartilage loss in neutral, varus, and valgus knees.
Alignment was measured from full-limb radiographs in 174 participants with symptomatic knee OA. Coronal magnetic resonance images were acquired at baseline and a mean +/- SD of 26.6 +/- 5.4 months later. The weight-bearing femorotibial cartilages were segmented from paired images. Cartilage volume, surface area, and thickness were determined in total cartilage plates and defined subregions using proprietary software.
The medial-to-lateral ratio of femorotibial cartilage loss was 1.4:1 in neutral knees (n = 74), 3.7:1 in varus knees (n = 57), and 1:6.0 in valgus knees (n = 43). The relative contribution of cartilage thickness change tended to be greater in knees with mild cartilage loss, whereas the increase of denuded area was greater in knees with accelerated cartilage loss. In both varus and neutral knees, the greatest changes were observed in the same subregions of the medial femorotibial compartment (central and external medial tibia, and central medial femur). In valgus and neutral knees, the subregions with the greatest changes in the lateral femorotibial compartment were also similar (internal and central lateral tibia, external lateral femur).
The medial-to-lateral rate of femorotibial cartilage loss strongly depended on alignment. Subregions of greater-than-average cartilage loss within the stressed compartment were, however, similar in neutral, varus, and valgus knees. This indicates that the medial-to-lateral loading pattern is different, but that the (sub)regional loading pattern may not differ substantially between neutral and malaligned knees.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Anti-catabolic disease modifying drugs (DMOADs) aim to reduce cartilage loss in knee osteoarthritis (KOA). Testing such drugs in clinical trials requires sufficient rates of loss in the study participants to occur, preferably at a mild disease stage where cartilage can be preserved. Here we analyze a “progression” model in mild radiographic KOA (RKOA), based on contra-lateral radiographic status. Methods We studied 837 participants (62.4±9yrs; 30±4.9kg/m²; 61.8% women) from the Osteoarthritis Initiative (OAI) with mild to moderate RKOA (Kellgren Lawrence grade [KLG] 2 to 3) and with/without OARSI atlas radiographic joint space narrowing (JSN). These had quantitative measurements of subregional femorotibial cartilage thickness from magnetic resonance imaging (MRI) at baseline and 1-year follow-up. They were stratified by contra-lateral knee status: no (KLG 0/1), definite (KLG2) and moderate RKOA (KLG 3/4). Results KLG2 knees with JSN and moderate contra-lateral RKOA had (p=0.008) greater maximum subregional cartilage loss -220μm [95% confidence interval -255, -184μm] than those without contra-lateral RKOA -164μm [-187, -140μm]. Their rate of subregional cartilage loss was similar and not significantly different (p=0.61) to that in KLG 3 knees without contra-lateral RKOA (-232μm; [-266;-198μm]). The effect of contra-lateral RKOA status was less in KLG2 knees without JSN, and in KLG3 knees. Conclusion KLG2 knees with JSN and moderate contra-lateral RKOA, display relatively high rates of subregional femorotibial cartilage loss, despite being at a relatively mild stage of RKOA. They may therefore provide a unique opportunity for recruitment in clinical trials that explore the efficacy of anti-catabolic DMOADs on structural progression.
    Osteoarthritis and Cartilage 09/2014; · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imaging in clinical trials is used to evaluate subject eligibility, and/or efficacy of intervention, supporting decision making in drug development by ascertaining treatment effects on joint structure. This review focusses on imaging of bone and cartilage in clinical trials of (knee) osteoarthritis. We narratively review the full-text literature on imaging of bone and cartilage, adding primary experience in the implementation of imaging methods in clinical trials. Aims and constraints of applying imaging in clinical trials are outlined. The specific uses of semi-quantitative and quantitative imaging biomarkers of bone and cartilage in osteoarthritis trials are summarized, focusing on radiography and magnetic resonance imaging (MRI). Studies having compared both imaging methodologies directly and those having established a relationship between imaging biomarkers and clinical outcomes are highlighted. To make this review of practical use, recommendations are provided as to which imaging protocols are ideal for capturing specific aspects of bone and cartilage tissue, and pitfalls in their usage are highlighted. Further, the longitudinal sensitivity to change, of different imaging methods is reported for various patient strata. From these power calculations can be accomplished, provided the strength of the treatment effect is known. In conclusion, current imaging methodologies provide powerful tools for scoring and measuring morphological and compositional aspects of most articular tissues, capturing longitudinal change with reasonable to excellent sensitivity. When employed properly, imaging has tremendous potential for ascertaining treatment effects on various joint structures, potentially over shorter time scales than required for demonstrating effects on clinical outcomes.
    Osteoarthritis and Cartilage 10/2014; 22(10):1516-1532. · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cartilage morphometry based on magnetic resonance images (MRIs) is an emerging outcome measure for clinical trials among patients with knee osteoarthritis (KOA). However, current methods for cartilage morphometry take many hours per knee and require extensive training on the use of the associated software. In this study we tested the feasibility, reliability, and construct validity of a novel osteoarthritis cartilage damage quantification method (Cartilage Damage Index [CDI]) that utilizes informative locations on knee MRIs.
    BMC Musculoskeletal Disorders 08/2014; 15(1):264. · 1.90 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014