Do Subchondral Bone Changes Exacerbate or Precede Articular Cartilage Destruction in Osteoarthritis of the Elderly?

Abstract

Research into the aetiology of osteoarthritis has for several decades been concentrated on the destruction of the articular cartilage, the initiating events being believed to be changes in the proteoglycans and subsequently in the supporting collagenous framework, whereafter the disease is irreversible. Recent evidence has supported an old contention that the underlying bone may be involved, namely, increased technetium scintigraphy correlated with increased severity of the osteoarthritis as demonstrated by joint narrowing, and a demonstration of increased metabolism of cancellous bone collagen compared to age-matched controls. These studies have not been able to answer the question of the primary initiating event: does increased bone metabolism initiate cartilage destruction or vice versa? However, recent detailed studies on animal models, particularly the macaque, have demonstrated that in this case thickening of the subchondral bone precedes fibrillation of the cartilage, which is possibly due to increased resistance of the bone to compression. Further, MRI studies on the guinea pig suggest that the initial site of activity is at the ligament bone insertion site, prior to endochondral bone sclerosis. We propose that the biomechanics of the joint are perturbed by the loss of tension from the ligament following trauma, leading to remodelling of the subchondral bone. Certainly in humans damage to the cruciate ligament often results in osteoarthritis. It may be that subclinical damage also ultimately results in osteoarthritis. Although the results from animal models will need to be treated with caution, the concept that bone ligament changes precede articular cartilage destruction should lead to a redirection of research, and perhaps therapy, for this important and cruelly disabling disease.

Abnormal cancellous bone collagen metabolism in osteoarthritis.

“…Certainly, the demonstration of high levels of metabolic activity in the subchondral zone opens up the question of the role of bone collagen in OA. Whether thickening of the subchondral bone precedes cartilage fibrillation is an interesting question and a subject of some debate (36).…”

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

“…The CASE assay includes a complete antibody-based detection system for colorimetric quantification of the relative amount of phosphorylated protein. Briefly, following treatment with ephrin B2 ligand at 100 ng/ml for different time periods (5,15,30, and 60 minutes), the cells were fixed to preserve any activation-specific protein modification. The procedure was performed according to the manufacturer's specifications (SuperArray Bioscience), and the amount of bound antibody was determined using a developing solution and an ELISA plate reader.…”

“…More than 30 years ago, Radin et al (10,11) suggested that changes in bone might be a cause of OA. Since that time, there has been substantial evidence that changes in the metabolism of bone, particularly in the area of the subchondral bone, are an integral part of the disease (12)(13)(14)(15)(16)(17)(18). Recent studies, however, point to the fact that the fate of articular cartilage is not determined exclusively by stiffening (sclerosis) of subchondral bone, but rather, by a remodeling of this tissue (19,20).…”

Ефективність І Безпечність Лікування Хворих На остеоартроз Колінних Суглобів Гідролізатом Колагену (FORTIGEL®)

“…До патологічного процесу при ОА долучаються всі складові суглоба: відбуваються фокусна та прогресу-юча втрата гіалінового хряща, зміни в субхондральній кістці (формування остеофітів, остеосклерозу), сино-віальній оболонці та суглобовій капсулі [1,9]. Ці зміни детермінують основні напрямки пошуку фармаколо-гічних засобів, які б уповільнювали їх і покращували якість життя.…”