Research Progress on Subchondral Bone Lesions in Knee Osteoarthritis
Download PDF

Keywords

Knee osteoarthritis
Subchondral bone
Bone-cartilage unit

DOI

10.26689/bas.v4i2.14128

Submitted : 2026-04-14
Accepted : 2026-04-29
Published : 2026-05-14

Abstract

This article reviews the research on subchondral bone lesions in knee osteoarthritis. Subchondral bone is closely related to articular cartilage in terms of embryonic development and anatomical structure, and the two form bone-cartilage units. These units interact and crosstalk with each other in biomechanics and molecular biology. Subchondral bone lesions include various pathological forms. There are certain research prospects for the prevention and treatment of knee osteoarthritis targeting the subchondral bone.

References

Sharma L, 2021, Osteoarthritis of the Knee. N Engl J Med, 384(1): 51–59.

Helmick CG, Felson DT, Lawrence RC, et al., 2008, Estimates of the Prevalence of Arthritis and Other Rheumatic Conditions in the United States. Part I. Arthritis Rheum, 58(1): 15–25.

Gelber AC, 2024, Knee Osteoarthritis. Ann Intern Med, 177(9): Itc129–itc144.

Kasaeian A, Roemer FW, Ghotbi E, et al., 2023, Subchondral Bone in Knee Osteoarthritis: Bystander or Treatment Target? Skeletal Radiol, 52(11): 2069–2083.

Sasano Y, Mizoguchi I, Kagayama M, et al., 1992, Distribution of Type I Collagen, Type II Collagen and PNA Binding Glycoconjugates During Chondrogenesis of Three Distinct Embryonic Cartilages. Anat Embryol (Berl), 186(3): 205–213.

Hoemann CD, Lafantaisie-Favreau CH, Lascau-Coman V, et al., 2012, The Cartilage-Bone Interface. J Knee Surg, 25(2): 85–97.

Walsh DA, McWilliams DF, Turley MJ, et al., 2010, Angiogenesis and Nerve Growth Factor at the Osteochondral Junction in Rheumatoid Arthritis and Osteoarthritis. Rheumatology (Oxford), 49(10): 1852–1861.

Pan J, Wang B, Li W, et al., 2012, Elevated Cross-Talk Between Subchondral Bone and Cartilage in Osteoarthritic Joints. Bone, 51(2): 212–217.

Goldring MB, Goldring SR, 2010, Articular Cartilage and Subchondral Bone in the Pathogenesis of Osteoarthritis. Ann N Y Acad Sci, 1192: 230–237.

Zhu S, Zhu J, Zhen G, et al., 2019, Subchondral Bone Osteoclasts Induce Sensory Innervation and Osteoarthritis Pain. J Clin Invest, 129(3): 1076–1093.

Jiang W, Jin Y, Zhang S, et al., 2022, PGE2 Activates EP4 in Subchondral Bone Osteoclasts to Regulate Osteoarthritis. Bone Res, 10(1): 27.

Zhu J, Zhu Y, Xiao W, et al., 2020, Instability and Excessive Mechanical Loading Mediate Subchondral Bone Changes to Induce Osteoarthritis. Ann Transl Med, 8(6): 350.

She G, Zhou Z, Zha Z, et al., 2017, Protective Effect of Zoledronic Acid on Articular Cartilage and Subchondral Bone of Rabbits with Experimental Knee Osteoarthritis. Exp Ther Med, 14(5): 4901–4909.

Ealahi T, Azad MAK, Islam MN, et al., 2025, Zoledronic Acid in the Treatment of Primary Knee Osteoarthritis: A Randomized Clinical Trial. Cureus, 17(5): e85087.

Mohan G, Perilli E, Parkinson IH, et al., 2013, Pre-Emptive, Early, and Delayed Alendronate Treatment in a Rat Model of Knee Osteoarthritis: Effect on Subchondral Trabecular Bone Microarchitecture and Cartilage Degradation of the Tibia, Bone/Cartilage Turnover, and Joint Discomfort. Osteoarthritis Cartilage, 21(10): 1595–1604.

Ren P, Niu H, Cen H, et al., 2021, Biochemical and Morphological Abnormalities of Subchondral Bone and Their Association with Cartilage Degeneration in Spontaneous Osteoarthritis. Calcif Tissue Int, 109(2): 179–189.

Meng Z, Xin L, Fan B, 2023, SDF-1α Promotes Subchondral Bone Sclerosis and Aggravates Osteoarthritis by Regulating the Proliferation and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells. BMC Musculoskelet Disord, 24(1): 275.

Zhao W, Wang T, Luo Q, et al., 2016, Cartilage Degeneration and Excessive Subchondral Bone Formation in Spontaneous Osteoarthritis Involves Altered TGF-β Signaling. J Orthop Res, 34(5): 763–770.

Kanemitsu M, Nakasa T, Shirakawa Y, et al., 2020, Role of Vasoactive Intestinal Peptide in the Progression of Osteoarthritis Through Bone Sclerosis and Angiogenesis in Subchondral Bone. J Orthop Sci, 25(5): 897–906.

Feng XF, Zhang RK, Qi WZ, et al., 2019, Metformin Intervenes in Cartilage and Subchondral Bone Changes in the Early Stage of Osteoarthritis in a Mouse Model of Osteoarthritis. Chinese Journal of Tissue Engineering Research, 23(19): 3031–3036.

Li X, Sun Y, Zhou Z, et al., 2019, Mitigation of Articular Cartilage Degeneration and Subchondral Bone Sclerosis in Osteoarthritis Progression Using Low-Intensity Ultrasound Stimulation. Ultrasound Med Biol, 45(1): 148–159.

Xu L, Hayashi D, Roemer FW, et al., 2012, Magnetic Resonance Imaging of Subchondral Bone Marrow Lesions in Association with Osteoarthritis. Semin Arthritis Rheum, 42(2): 105–118.

Moradi K, Mohammadi S, Roemer FW, et al., 2024, Progression of Bone Marrow Lesions and the Development of Knee Osteoarthritis: Osteoarthritis Initiative Data. Radiology, 312(3): e240470.

Scher C, Craig J, Nelson F, 2008, Bone Marrow Edema in the Knee in Osteoarthrosis and Association with Total Knee Arthroplasty within a Three-Year Follow-Up. Skeletal Radiology, 37(7): 609–617.

Varenna M, Zucchi F, Failoni S, et al., 2015, Intravenous Neridronate in the Treatment of Acute Painful Knee Osteoarthritis: A Randomized Controlled Study. Rheumatology (Oxford), 54(10): 1826–1832.