Bone marrow lesions in osteoarthritis: What lies beneath

Osteoarthritis (OA) is the most common joint disease in the United States, affecting more than 30 million people, and is characterized by cartilage degeneration in articulating joints. OA can be viewed as a group of overlapping disorders, which result in functional joint failure. However, the precise cellular and molecular events within which lead to these clinically observable changes are neither well understood nor easily measurable. It is now clear that multiple factors, in multiple joint tissues, contribute to degeneration. Changes in subchondral bone are recognized as a hallmark of OA, but are normally associated with late‐stage disease when degeneration is well established. However, early changes such as Bone Marrow Lesions (BMLs) in OA are a relatively recent discovery. BMLs are patterns from magnetic resonance images (MRI) that have been linked with pain and cartilage degeneration. Their potential utility in predicting progression, or as a target for therapy, is not yet fully understood. Here, we will review the current state‐of‐the‐art in this field under three broad headings: (i) BMLs in symptomatic OA: malalignment, joint pain, and disease progression; (ii) biological considerations for bone‐cartilage crosstalk in joint disease; and (iii) mechanical factors that may underlie BMLs and drive their communication with other joint tissues. Thus, this review will provide insights on this topic from a clinical, biological, and mechanical perspective. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1818–1825, 2018.

[1]  M. Koff,et al.  An in vivo model of a mechanically-induced bone marrow lesion. , 2017, Journal of biomechanics.

[2]  J. Raya,et al.  A novel rat model for subchondral microdamage in acute knee injury: a potential mechanism in post-traumatic osteoarthritis. , 2016, Osteoarthritis and cartilage.

[3]  C. Rimnac,et al.  Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure , 2016, Proceedings of the National Academy of Sciences.

[4]  F. Cicuttini,et al.  Bone marrow lesions detected by specific combination of MRI sequences are associated with severity of osteochondral degeneration , 2016, Arthritis Research & Therapy.

[5]  T. Aoyama,et al.  Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis. , 2016, Osteoarthritis and cartilage.

[6]  Bin Yu,et al.  Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats. , 2015, Bone.

[7]  E. V. Tkachenko,et al.  The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone. , 2014, Journal of biomechanics.

[8]  C. Rimnac,et al.  Quantitative relationships between microdamage and cancellous bone strength and stiffness. , 2014, Bone.

[9]  O. Kennedy,et al.  Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo. , 2014, Bone.

[10]  C. Rimnac,et al.  Microdamage Caused by Fatigue Loading in Human Cancellous Bone: Relationship to Reductions in Bone Biomechanical Performance , 2013, PloS one.

[11]  F. Berenbaum,et al.  Identification of soluble 14-3-3∊ as a novel subchondral bone mediator involved in cartilage degradation in osteoarthritis. , 2013, Arthritis and rheumatism.

[12]  L. Riley,et al.  Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis , 2013, Nature Medicine.

[13]  David B. Burr,et al.  Bone remodelling in osteoarthritis , 2012, Nature Reviews Rheumatology.

[14]  N. Fazzalari,et al.  Evidence for the dysregulated expression of TWIST1, TGFβ1 and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients. , 2012, Osteoarthritis and cartilage.

[15]  T. Alliston,et al.  Chondrocyte-intrinsic Smad3 represses Runx2-inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis. , 2012, Arthritis and rheumatism.

[16]  O. Kennedy,et al.  Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. , 2012, Bone.

[17]  L. Laslett,et al.  Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial , 2012, Annals of the rheumatic diseases.

[18]  D. Felson,et al.  Bone marrow lesions in knee osteoarthritis change in 6–12 weeks , 2011, Osteoarthritis and cartilage.

[19]  M. Bouxsein,et al.  Effects of preexisting microdamage, collagen cross‐links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[20]  Ali Guermazi,et al.  Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. , 2011, Arthritis and rheumatism.

[21]  T. Huizinga,et al.  Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review , 2010, Annals of the rheumatic diseases.

[22]  Joseph P DeAngelis,et al.  Traumatic Bone Bruises in the Athlete’s Knee , 2010, Sports health.

[23]  G. Niebur,et al.  Effects of trabecular type and orientation on microdamage susceptibility in trabecular bone. , 2010, Bone.

[24]  S. Doty,et al.  In situ measurement of transport between subchondral bone and articular cartilage , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  Haikuo Bian,et al.  Hypoxia and HIF-1alpha expression in the epiphyseal cartilage following ischemic injury to the immature femoral head. , 2009, Bone.

[26]  O. Verborgt,et al.  Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  Matthew J. Silva,et al.  Single high‐energy impact load causes posttraumatic OA in young rabbits via a decrease in cellular metabolism , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  Won C. Bae,et al.  Increased hydraulic conductance of human articular cartilage and subchondral bone plate with progression of osteoarthritis. , 2008, Arthritis and rheumatism.

[29]  C. P. Winlove,et al.  Solute transport in the deep and calcified zones of articular cartilage. , 2008, Osteoarthritis and cartilage.

[30]  S. Gabriel,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. , 2008, Arthritis and rheumatism.

[31]  A. Tsykin,et al.  Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-β/bone morphogenic protein signalling , 2007, Arthritis research & therapy.

[32]  J. Mcclure,et al.  The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces , 2006, BMC musculoskeletal disorders.

[33]  D. Burr,et al.  The importance of subchondral bone in the progression of osteoarthritis. , 2004, The Journal of rheumatology. Supplement.

[34]  Wei Li,et al.  Bone Marrow Edema and Its Relation to Progression of Knee Osteoarthritis , 2003, Annals of Internal Medicine.

[35]  A. Boyde,et al.  Nanomechanical properties and mineral concentration in articular calcified cartilage and subchondral bone , 2003, Journal of anatomy.

[36]  P. Mantyh,et al.  Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur , 2002, Neuroscience.

[37]  H. Imhof,et al.  Subchondral Bone and Cartilage Disease: A Rediscovered Functional Unit , 2000, Investigative radiology.

[38]  D Vashishth,et al.  In vivo diffuse damage in human vertebral trabecular bone. , 2000, Bone.

[39]  O. Verborgt,et al.  Loss of Osteocyte Integrity in Association with Microdamage and Bone Remodeling After Fatigue In Vivo , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[40]  B. Manthey,et al.  Three-dimensional confocal images of microdamage in cancellous bone. , 1998, Bone.

[41]  D P Fyhrie,et al.  Intracortical remodeling in adult rat long bones after fatigue loading. , 1998, Bone.

[42]  T. Klestil,et al.  Bone bruise of the knee: histology and cryosections in 5 cases. , 1998, Acta orthopaedica Scandinavica.

[43]  D. Burr,et al.  The importance of subchondral bone in osteoarthrosis. , 1998, Current opinion in rheumatology.

[44]  F Eckstein,et al.  Thickness of the subchondral mineralised tissue zone (SMZ) in normal male and female and pathological human patellae , 1998, Journal of anatomy.

[45]  D. Burr,et al.  Bone Microdamage and Skeletal Fragility in Osteoporotic and Stress Fractures , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[46]  D B Burr,et al.  Alterations to the en bloc basic fuchsin staining protocol for the demonstration of microdamage produced in vivo. , 1995, Bone.

[47]  R. Putz,et al.  Quantitative morphology of the subchondral plate of the tibial plateau. , 1994, Journal of anatomy.

[48]  J Dequeker,et al.  Generalized osteoarthritis associated with increased insulin-like growth factor types I and II and transforming growth factor beta in cortical bone from the iliac crest. Possible mechanism of increased bone density and protection against osteoporosis. , 1993, Arthritis and rheumatism.

[49]  L. Sokoloff Microcracks in the calcified layer of articular cartilage. , 1993, Archives of pathology & laboratory medicine.

[50]  D. Burr,et al.  Microcracks in articular calcified cartilage of human femoral heads. , 1992, Archives of pathology & laboratory medicine.

[51]  T. Brown,et al.  Mechanical determinants of osteoarthrosis. , 1991, Seminars in arthritis and rheumatism.

[52]  J. Clark,et al.  The structure of the human subchondral plate. , 1990, The Journal of bone and joint surgery. British volume.

[53]  M. Lotz,et al.  Transforming growth factor-beta and cellular immune responses in synovial fluids. , 1990, Journal of immunology.

[54]  J. Crues,et al.  Bone abnormalities of the knee: prevalence and significance at MR imaging. , 1989, Radiology.

[55]  J. Riddle,et al.  The tibial subchondral plate. A scanning electron microscopic study. , 1987, The Journal of bone and joint surgery. American volume.

[56]  W. T. Green,et al.  Microradiographic study of the calcified layer of articular cartilage. , 1970, Archives of pathology.

[57]  温春毅,et al.  Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis , 2013 .

[58]  B. Manaster Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology , 2009 .

[59]  Atlanta,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. , 2008, Arthritis and rheumatism.

[60]  L. Kazis,et al.  The Association of Bone Marrow Lesions with Pain in Knee Osteoarthritis , 2001, Annals of Internal Medicine.