Animal Models of Bone Marrow Lesions in Osteoarthritis

Abstract

Bone marrow lesions are abnormalities in magnetic resonance images that have been associated with joint pain and osteoarthritis in clinical studies. Increases in the volume of bone marrow lesions have been associated with progression of joint degeneration, leading to the suggestion that bone marrow lesions may be an early indicator of-or even a contributor to-cartilage loss preceding irreversible damage to the joint. Despite evidence that bone marrow lesions play a role in osteoarthritis pathology, very little is known about the natural history of bone marrow lesions and their contribution to joint degeneration. As a result, there are limited data regarding the cell activity within a bone marrow lesion and any associated bone-cartilage cross-talk. Animal models provide the best approach for understanding bone marrow lesions at their early, reversible stages. Here, we review the few animal studies of bone marrow lesions. An ideal animal model of a bone marrow lesion occurs in joints large enough to accurately measure bone marrow lesion volume. Additionally, the ideal animal model would facilitate the study of bone-cartilage cross-talk by generating the bone marrow lesion immediately adjacent to subchondral bone and would do so without causing direct damage to neighboring soft tissues to isolate the effects of the bone marrow lesion on cartilage loss. Early reports demonstrate the feasibility of such an animal model. Given the irreversible nature of osteoarthritic changes in the joint, factors such as bone marrow lesions that are present early in disease pathogenesis remain an enticing target for new therapeutic approaches. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Keywords: BONE; BONE MARROW LESION; JOINT; MICRODAMAGE; OSTEOARTHRITIS.

Fig. 1

Hypothesized association of bone marrow lesions with osteoarthritis after trauma. Derived from Alliston and colleagues.^{( 2 )}

Fig. 2

Comparison of findings from previous studies measuring bone marrow lesions via MRI in animal models of traumatic surgical induction of osteoarthritis. Reprinted by permission from John Wiley and Sons: Veterinary Radiology & Ultrasound.^{( 31 )} Reprinted by permission from Georg Thieme Verlag KG: Journal of Knee Surgery.^{( 40 )} Reprinted by permission from Elsevier: Osteoarthritis and Cartilage.^{( 30 )} Reprinted by permission from Springer Nature: Nature Medicine.^{( 32 )}

Fig. 3

A rabbit model of a bone marrow lesion in epiphyseal bone. (A) Placement of the implant and alignment of loading platen. (B) MR images at 2 weeks after surgery/loading: Raw image (top) with overlay from micro–computed tomography with the bone marrow lesion colored (bottom). (C) Micro–computed tomography image with overlay of the bone marrow lesion (pink). From Matheny and colleagues,^{( 24 )} used with permission.

Fig. 4

(A) The position of the mechanical load used to induce the bone marrow lesion on the distal medial femur is shown. (B) The relationship between maximum load magnitude and the presence of microscopic tissue damage or overt failure of the cortical shell. Number of joints at each load magnitude is shown in the bottom row. (Inset) Microscopic tissue damage (green) in underlying cancellous bone (blue) caused by the selected loading waveform is shown. Yellow arrowhead = microdamage; white arrowhead = microfracture. (C) STIR MR images with bone marrow lesions are shown. (D) The volume of bone marrow lesions over time is shown for mechanical loading insufficient to generate microscopic tissue damage and mechanical loading sufficient to generate microscopic tissue damage. Each line represents a single limb studied longitudinally (n = 2 for each type).