Alterations of the subchondral bone in osteochondral repair – translational data and clinical evidence

Abstract

Alterations of the subchondral bone are pathological features associated with spontaneous osteochondral repair and with articular cartilage repair procedures. The aim of this review is to discuss their incidence, extent and relevance, focusing on recent knowledge gained from both translational models and clinical studies of articular cartilage repair. Efforts to unravel the complexity of subchondral bone alterations have identified (1) the upward migration of the subchondral bone plate, (2) the formation of intralesional osteophytes, (3) the appearance of subchondral bone cysts, and (4) the impairment of the osseous microarchitecture as potential problems. Their incidence and extent varies among the different small and large animal models of cartilage repair, operative principles, and over time. When placed in the context of recent clinical investigations, these deteriorations of the subchondral bone likely are an additional, previously underestimated factor that influences the long-term outcome of cartilage repair strategies. Understanding the role of the subchondral bone in both experimental and clinical articular cartilage repair thus holds great promise of being translated into further improved cell-or biomaterial-based techniques to preserve and restore the entire osteochondral unit. Keywords IntroductionA complete restoration of the osteochondral unit is the goal of all articular repair techniques (Brittberg et al., 1994; Johnson, 1986;Pridie, 1959;Steadman et al., 2001). Traditionally, a focus was placed on the cartilaginous repair tissue, but it is now clear that complex structural changes of the subchondral bone are associated with spontaneous osteochondral repair and with the use of cartilage repair procedures . They include (1) the upward migration of the subchondral bone plate, (2) the formation of intralesional osteophytes, (3) the appearance of subchondral bone cysts, and (4) the impairment of the osseous microarchitecture ( Fig. 1).There is accumulating experimental evidence for these subchondral bone alterations in small (Aroen et al., 2006;Chen et al., 2009;Chen et al., 2011a;Heir et al., 2012;Marchand et al., 2011;Marchand et al., 2012;Nam et al., 2004;Qiu et al., 2003) and large preclinical animal models (Dorotka et al., 2005;Frisbie et al., 1999; Hanie et al., 1992;Hoemann et al., 2005;Howard et al., 1994;Ishimaru et al., 1992;Lane et al., 2004;Orth et al., 2012b;Vachon et al., 1986) of cartilage defects. Supporting these findings, such pathological alterations were also reported in up to one third of patients treated with microfracture (Kreuz et al., 2006;Mithoefer et al., 2005; Saris et al., 2009). Moreover, autologous chondrocyte implantation (ACI) for articular cartilage defects previously treated with marrow stimulation techniques has a three-fold higher failure rate than for untreated defects Minas et al., 2009;Vasiliadis et al., 2010). In addition, upward migration of the subchondral bone plate or the development of intralesional osteophytes might also occur spontaneously in...

Evaluation and analysis of graft hypertrophy by means of arthroscopy, biochemical MRI and osteochondral biopsies in a patient following autologous chondrocyte implantation for treatment of a full-thickness-cartilage defect of the knee

“…The subchondral bone was abnormal by micro-CT analysis of the osteochondral biopsies, and restricted evidence for an advancement of the subchondral bone plate was seen in some regions. Such alteration of the subchondral bone is a rather common pathological feature that may be associated with articular cartilage repair procedures [20]. Taken together, the repair tissue appears histologically as relatively good, which is in accordance with previous reports on biopsies of the repair tissue 1-2 years after ACI [13,25].…”

Cartilage Repair and Subchondral Bone Remodeling in Response to Focal Lesions in a Mini-Pig Model: Implications for Tissue Engineering

“…33 It is still unclear how closely these subchondral changes mimic the human condition, and this is an active area of research. 44 In addition, the time point for evaluation may be critical, as studies have noted early remodeling ( < 3 months), but a new bony structure by 12 months. 30,34 Thus, multiple factors (age, species, location of injury, time point for evaluation, etc.)…”

Unravelling the Role of Mechanical Stimuli in Regulating Cell Fate During Osteochondral Defect Repair

“…between the differentiating cells and the forming blood vessels which may affect tissue formation [55][56][57][58] . Such a relationship has been explored as a potential mechanism which may be used to direct the course of endochondral ossification during the repair of osteochondral defects in a number of tissue engineering studies [59][60][61] .…”