Beyond Cartilage Regeneration: Targeting the Subchondral Bone with Extracorporeal Shock Wave Therapy and Regenerative Medicine in Knee Osteoarthritis.

Knee osteoarthritis (OA) has long been viewed as a cartilage-centered disease, but a whole-joint model now positions the subchondral bone and the osteochondral unit as biologically active, mechanically decisive participants. Bone marrow lesions (BMLs), abnormal subchondral remodeling, and progressive deterioration of the subchondral bone plate (SBP) precede cartilage failure, suggesting a potential pre-collapse therapeutic window before irreversible articular surface collapse. We review evidence for combining extracorporeal shock wave therapy (ESWT), which provides mechanotransductive conditioning of the subchondral compartment, with regenerative therapies-platelet-rich plasma (PRP), autologous protein solution (APS), mesenchymal stromal cells (MSCs), and bone marrow aspirate concentrate (BMAC)-delivered intra-articularly and intra-osseously. Two clinical messages emerge: (i) BMLs are initially reversible but may progress to SBP discontinuity, subchondral cysts, and articular surface collapse if untreated, so subchondral-directed therapy should ideally be delivered before SBP discontinuity and cyst formation become imaging-overt, and (ii) advanced radiographic disease, including Kellgren-Lawrence grade 4, does not by itself mandate arthroplasty, because intra-osseous orthobiologics with ESWT may-as a hypothesis requiring prospective validation-preserve the joint and defer surgery in selected patients. This hypothesis-generating framework positions the osteochondral unit as a tractable target for hard-tissue engineering and requires prospective validation.