journal article·2026-07Open access

Micromechanical characterisation of osteoarthritic subchondral bone by micropillar compression

Samuel McPhee, Marta Peña Fernández, Lekha Koria, Marlène Mengoni, Rainer J Beck, Jonathan D Shephard, Claire Brockett, Uwe Wolfram

Acta Biomaterialia· Volume 218

Abstract

Osteoarthritis (OA) is a multifaceted joint disease which poses significant socioeconomic burdens and remains a significant clinical challenge. Evidence suggests that structural and mechanical changes in subchondral bone influence the pathogenesis and development of OA, leading to diminished bone quality and cartilage degeneration. While changes in microstructure and tissue scale elastic properties are well reported, the tissue yield response of subchondral bone in OA and their correlation with compositional changes have not been investigated. Here, we performed quasistatic micropillar compression and nanoindentation within the subchondral bone plate and trabeculae of hydrated non-diseased (ND) and OA affected specimens retrieved from the distal tibia in vivo. The micropillars, extracted by laser ablation, exhibited a taper angle which mandated the use of an in silico micropillar compression routine to back-calculate elastic modulus and strength of the bone tissue that comprised each micropillar. Elastic modulus remained unchanged between ND and OA subchondral bone, whereas strength increased from 46.0 MPa to 57.3 MPa in OA subchondral trabecular bone but not in the bone plate. Micropillar matched Raman spectroscopy and quantitative backscattered electron imaging revealed mineralisation is the underlying determinant of elastic modulus and strength at the microscale. By combining micromechanical and tissue compositional analyses, we investigated how the mechanical properties are related and how these properties are affected in subchondral bone by OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis imposes significant socioeconomic burden, necessitating ever improving treatment strategies. Abnormal mechanical forces at the joint, such as injury, overloading, or aging are associated with osteoarthritis development. While healthy tissue is well understood, the impact of diseases on tissue mechanical properties needs to be brought on a similar level of understanding. We present in this study the first use of micropillar compression for assessing the tissue scale compressive strength of subchondral bone in osteoarthritis. Strength was increased in osteoarthritis compared to non-diseased tissue only in trabeculae subjacent to the bone plate. Compositional analysis confirmed mineralisation as a key determinant of tissue mechanical properties. This integration of micromechanical and compositional analyses sheds light on tissue properties and how these are affected by osteoarthritis in subchondral bone.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Bone and Joint Diseases · Osteoarthritis Treatment and Mechanisms · Bone health and osteoporosis research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (88)

Show source-provided references
1. Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales10.1136/ard.2003.007526 ↗
2. The epidemiology and impact of pain in osteoarthritis10.1016/j.joca.2013.03.018 ↗
3. The individual and socioeconomic impact of osteoarthritis10.1038/nrrheum.2014.44 ↗
4. Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 202110.1016/S2665-9913(23)00163-7 ↗
5. Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions10.1038/s12276-021-00710-y ↗
6. Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines10.1038/s41584-020-00523-9 ↗
7. Phenotypes of osteoarthritis: current state and future implications
8. Ankle osteoarthritis: comprehensive review and treatment algorithm proposal10.1530/EOR-21-0117 ↗
9. Intra-articular osteotomy for ankle arthritis10.1016/j.mporth.2022.11.005 ↗
10. Ankle arthrodesis: a systematic approach and review of the literature10.5312/wjo.v7.i11.700 ↗
11. Ten-year revision rates of contemporary total ankle arthroplasties equal 22%. A meta-analysis10.1016/j.fas.2021.05.014 ↗
12. Long-term outcomes after total ankle arthroplasty: a systematic review10.1177/24730114241294073 ↗
13. Biomechanics and pathomechanisms of osteoarthritis10.4414/smw.2012.13583 ↗
14. Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis10.1016/j.mbm.2024.100043 ↗
15. Changes in subchondral bone morphology with osteoarthritis in the ankle10.1371/journal.pone.0290914 ↗
16. Tibial subchondral trabecular bone micromechanical and microarchitectural properties are affected by alignment and osteoarthritis stage10.1038/s41598-020-60464-x ↗
17. The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint10.1038/s41598-018-24258-6 ↗
18. Characterization of nano-structural and nano-mechanical properties of osteoarthritic subchondral bone10.1186/s12891-016-1226-1 ↗
19. Nanoscale deformation mechanisms and yield properties of hydrated bone extracellular matrix10.1016/j.actbio.2017.07.030 ↗
20. The elasto-plastic nano- and microscale compressive behaviour of rehydrated mineralised collagen fibres10.1016/j.actbio.2023.03.041 ↗
21. Compressive strength of Iliac bone ECM is not reduced in osteogenesis imperfecta and increases with mineralization10.1002/jbmr.4286 ↗
22. Composition and micromechanical properties of the femoral neck compact bone in relation to patient age, sex and hip fracture occurrence10.1016/j.bone.2023.116920 ↗
23. Microscale compressive behavior of hydrated lamellar bone at high strain rates10.1016/j.actbio.2021.07.005 ↗
24. Combining polarized Raman spectroscopy and micropillar compression to study microscale structure-property relationships in mineralized tissues10.1016/j.actbio.2020.10.034 ↗
25. In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone10.1038/nmat3959 ↗
26. Compressive behaviour of uniaxially aligned individual mineralised collagen fibres at the micro- and nanoscale10.1016/j.actbio.2019.02.053 ↗
27. Multiscale mechanical consequences of ocean acidification for cold-water corals10.1038/s41598-022-11266-w ↗
28. Assessing minipig compact jawbone quality at the microscale10.1016/j.jmbbm.2022.105405 ↗
29. Heat impact during laser ablation extraction of mineralised collagen fibres10.1038/s41598-021-89181-9 ↗
30. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis10.1007/s11999-016-4732-4 ↗
31. Mechanical properties of cortical bone and their relationships with age, gender, composition and microindentation properties in the elderly10.1016/j.bone.2015.11.018 ↗
32. Transverse isotropic elastic properties of vertebral trabecular bone matrix measured using microindentation under dry conditions (Effects of age, gender and vertebral level)10.1142/S0219519410003241 ↗
33. Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies10.1016/S8756-3282(98)00112-4 ↗
34. Image processing with imageJ
35. D. Erb, pybaselines: A Python library of algorithms for the baseline correction of experimental data, (2022). 10.5281/ZENODO.7255880.
36. A perfect smoother10.1021/ac034173t ↗
37. Raman assessment of bone quality10.1007/s11999-010-1692-y ↗
38. Contributions of Raman spectroscopy to the understanding of bone strength
39. Compositional assessment of bone by Raman spectroscopy10.1039/D1AN01560E ↗
40. Novel Raman spectroscopic biomarkers indicate that postyield damage denatures bone’s collagen10.1002/jbmr.2768 ↗
41. Assessing matrix quality by Raman spectroscopy helps predict fracture toughness of human cortical bone10.1038/s41598-019-43542-7 ↗
42. Validation of fourier transform infrared microspectroscopy for the evaluation of enzymatic cross-linking of bone collagen10.1007/s00223-023-01105-z ↗
43. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments10.1557/JMR.1992.1564 ↗
44. Critical review of analysis and interpretation of nanoindentation test data10.1016/j.surfcoat.2005.03.018 ↗
45. An experimentally informed statistical elasto-plastic mineralised collagen fibre model at the micrometre and nanometre lengthscale10.1038/s41598-021-93505-0 ↗
46. Compressive strength of Iliac bone ECM is not reduced in osteogenesis imperfecta and increases with mineralization10.1002/jbmr.4286 ↗
47. The design of accurate micro-compression experiments10.1016/j.scriptamat.2005.06.043 ↗
48. Experimental validation of a nonlinear μ FE model based on cohesive-frictional plasticity for trabecular bone10.1002/cnm.2739 ↗
49. A generalized anisotropic quadric yield criterion and its application to bone tissue at multiple length scales10.1007/s10237-013-0472-5 ↗
50. Continuum damage interactions between tension and compression in osteonal bone10.1016/j.jmbbm.2015.05.007 ↗
51. Fabric-based Tsai-Wu yield criteria for vertebral trabecular bone in stress and strain space10.1016/j.jmbbm.2012.07.005 ↗
52. Microtensile properties and failure mechanisms of cortical bone at the lamellar level10.1016/j.actbio.2020.04.030 ↗
53. Digital volume correlation based nonlinear micro finite element models predict early microdamage in newly formed bone10.1016/j.jmbbm.2022.105303 ↗
54. Statsmodels: econometric and statistical modeling with Python10.25080/Majora-92bf1922-011 ↗
55. Lenth · 2022 · 2
56. Rehydration of vertebral trabecular bone: influences on its anisotropy, its stiffness and the indentation work with a view to age, gender and vertebral level10.1016/j.bone.2009.09.035 ↗
57. Association between subchondral bone structure and osteoarthritis histopathological grade10.1002/jor.23312 ↗
58. Nanoindentation discriminates the elastic properties of individual human bone lamellae under dry and physiological conditions10.1016/S8756-3282(01)00624-X ↗
59. Nanoindentation of wet and dry compact bone: influence of environment and indenter tip geometry on the indentation modulus10.1080/14786430903201853 ↗
60. Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur10.1016/S0021-9290(99)00111-6 ↗
61. Microtensile failure mechanisms in lamellar bone: influence of fibrillar orientation, specimen size and hydration10.1016/j.actbio.2021.06.032 ↗
62. Comparison of the elastic and yield properties of human femoral trabecular and cortical bone tissue10.1016/S0021-9290(03)00257-4 ↗
63. The nanocomposite nature of bone drives its strength and damage resistance10.1038/nmat4719 ↗
64. Effects of osteoporosis on bone morphometry and material properties of individual human trabeculae in the femoral head10.1002/jbm4.10503 ↗
65. P. Zysset, A constitutive law for trabecular bone, 1252 (1994) 231.
66. Post-yield and failure properties of cortical bone10.1038/bonekey.2016.60 ↗
67. Mechanisms of uniformity of yield strains for trabecular bone10.1016/j.jbiomech.2004.02.045 ↗
68. Bone mineralization density distribution in health and disease10.1016/j.bone.2007.10.021 ↗
69. Large-scale quantification of human osteocyte lacunar morphological biomarkers as assessed by ultra-high-resolution desktop micro-computed tomography10.1016/j.bone.2021.116094 ↗
70. SciPy 1.0: fundamental algorithms for scientific computing in Python10.1038/s41592-019-0686-2 ↗
71. Elastic anisotropy of bone lamellae as a function of fibril orientation pattern10.1007/s10237-010-0218-6 ↗
72. Investigation of the three-dimensional orientation of mineralized collagen fibrils in human lamellar bone using synchrotron X-ray phase nano-tomography10.1016/j.actbio.2013.05.015 ↗
73. Extrafibrillar matrix yield stress and failure envelopes for mineralised collagen fibril arrays10.1016/j.jmbbm.2019.103563 ↗
74. Plastic deformation and residual stresses in amorphous silica pillars under uniaxial loading10.1016/j.actamat.2012.07.016 ↗
75. Conventional finite element models estimate the strength of metastatic human vertebrae despite alterations of the bone’s tissue and structure10.1016/j.bone.2020.115598 ↗
76. Raman microspectroscopic analysis of the tissue-specific composition of the human osteochondral junction in osteoarthritis: a pilot study10.1016/j.actbio.2020.02.020 ↗
77. The associations between mineral crystallinity and the mechanical properties of human cortical bone10.1016/j.bone.2007.12.001 ↗
78. Raman spectroscopic detection of changes in bioapatite in mouse femora as a function of age and In vitro fluoride treatment10.1007/s002230001206 ↗
79. Raman spectroscopic determination of bone matrix quantity and quality augments prediction of human cortical bone mechanical properties10.1016/j.jbiomech.2021.110342 ↗
80. On the repeated measures designs and sample sizes for randomized controlled trials10.1093/biostatistics/kxv047 ↗
81. Random-effects models for longitudinal data10.2307/2529876 ↗
82. Alternative models for small samples in psychological research: applying linear mixed effects models and generalized estimating equations to repeated measures data10.1177/0013164415580432 ↗
83. Micropillar fabrication on bovine cortical bone by direct write femtosecond laser ablation
84. Extracellular bone matrix exhibits hardening elastoplasticity and more than double cortical strength: evidence from homogeneous compression of non-tapered single micron-sized pillars welded to a rigid substrate10.1016/j.jmbbm.2015.03.001 ↗
85. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis10.1359/jbmr.1997.12.4.641 ↗
86. Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis10.1016/j.bone.2012.01.024 ↗
87. Subchondral bone plate thickness is associated with micromechanical and microstructural changes in the bovine patella osteochondral junction with different levels of cartilage degeneration
88. Characterization of nano-structural and nano-mechanical properties of osteoarthritic subchondral bone10.1186/s12891-016-1226-1 ↗