Circulatory pathology in osteoarthritic subchondral bone

With the recognition that crosstalk between articular cartilage and subchondral bone may contribute to osteoarthritis (OA), interest in the subchondral osteoblast secretome has grown significantly. Osteoblasts respond to alterations in their microenvironment by expressing a range of signaling and structural cytokines affecting bone remodeling and cartilage breakdown characteristic of OA. This narrative review explores observations made with circulatory imaging of subchondral bone in OA and presents a reconciliation of them in the context of a subchondral hypoxic microenvironment and osteoblast synthetic responses. The pathogenesis of OA is multifactorial and venous stasis, the resulting intraosseous microenvironment, and the consequent osteoblast responses appear to play significant roles.

This is a narrative review. A literature search was conducted in PubMed (Medline), Google Scholar, and the Cochrane Library. Search criteria included OA associated with vascularity or perfusion status, osteoblast secretome and cytokines, and hypoxia.

Bone is a highly vascular tissue, and its circulatory integrity is a major determinant of the osteoblast microenvironment and secretome. Static imaging studies have shown an altered venous pattern in human OA compared to normal hips with slower elimination of contrast agent consistent with venous stasis. Intraosseous hypertension and hypoxia have also been observed in OA compared to normal subchondral bone. Subchondral osteoblasts respond to an abnormal microenvironment by an altered secretome consistent with bone remodeling and cartilage breakdown typical of OA. Dynamic imaging with contrast-enhanced MRI and ¹⁵O-Oxygen and ¹⁸F-Fluoride PET have allowed kinetic analyses of bone circulation including temporal and spatial patterns of blood flow in conjunction with cartilage breakdown and subchondral bone remodeling, lending insight into the early pathogenesis of OA.

Subchondral hypertension and hypoxia as consequences of circulatory pathology have emerged as stimuli to pathologic osteoblast cytokine expression.