Relationships Between Image-Based and Mechanical Bone Properties With Pain in Knee Osteoarthritis

Pain is the predominant symptom of OA, a debilitating disease marked by changes in cartilage and subchondral bone, but pain pathophysiology is poorly understood. Bone is densely innervated and may be linked to OA-related knee pain. Quantitative computed tomography (QCT) is an in vivo image-based technique with the potential to quantify bone mineral density (BMD) to explore the role of bone in OA-related pain. When coupled with subject-specific finite element (FE) modeling, it may be possible to clarify the mechanical role of bone in OA-related knee pain.

The objectives of this study were to assess if: 1) tibial subchondral BMD is associated with OA-related nocturnal knee pain using depth-specific QCT image processing, 2) tibial epiphyseal and metaphyseal BMD is associated with OA-related knee pain using a modified depth-specific CT image processing tool, 3) subchondral cyst characteristics are associated with OA-related knee pain, and 4) FE-derived mechanical outcomes at the proximal tibia are associated with OA-related pain.

Lateral focal subchondral BMD was 33% higher in participants with severe nocturnal pain than participants with no nocturnal pain at the 2.5-5mm depth (p=0.028) and 32% higher at 5-10mm from the subchondral surface (p=0.049). At the epiphyseal and metaphyseal depths, higher total pain was associated with lower medial epiphyseal BMD (R² =-0.40, p=0.002), and lower metaphyseal BMD (R² =-0.35, p=0.017). At the lateral region, subchondral cyst number (r=0.55, p<0.001) and cyst number per proximal tibial volume (r=0.52, p<0.001) were both associated with BMD, and lateral cyst number and volume were associated with joint space narrowing (r=0.52 to 0.68, p<0.001) and alignment (r=0.44 to 0.62, p<0.001). In our FE study, principal compressive stress was associated with nocturnal pain at most lateral regions (r=0.33 to 0.50, p<0.05). Principal compressive stress at the lateral region ranged from 47% to 67% higher (p<0.05) in participants with severe nocturnal pain than participants with no pain.

This series of studies suggests that pain in patients with knee OA may be associated with BMD throughout various depths at the proximal tibia as well as FE-based bone mechanical outcomes, such as principal compressive stress. These findings suggest previously unexplored associations between OA-related knee pain and BMD or mechanical outcomes, emphasizing that bone may have a mechanical role in OA-related pain pathogenesis.

Year	Entry
1992	Anderson MJ, Keyak JH, Skinner HB. Compressive mechanical properties of human cancellous bone after gamma irradiation. J Bone Joint Surg. June 1992;74A(5):747-752.
1975	Walker PS, Erkman MJ. The role of the menisci in force transmission across the knee. Clin Orthop Relat Res. June 1975;109:184-192.
1991	Snyder SM, Schneider E. Estimation of mechanical properties of cortical bone by computed tomography. J Orthop Res. May 1991;9(3):422-431.
1991	Schipplein OD, Andriacchi TP. Interaction between active and passive knee stabilizers during level walking. J Orthop Res. January 1991;9(1):113-119.
2001	Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR, Weinans H. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre‐arthritic cartilage damage. J Orthop Res. September 2001;19(5):914-918.
1983	Ahmed AM, Burke DL. In-vitro of measurement of static pressure distribution in synovial joints, I: tibial surface of the knee. J Biomech Eng. August 1983;105(3):216-225.
1993	Keaveny TM, Borchers RE, Gibson LJ, Hayes WC. Theoretical analysis of the experimental artifact in trabecular bone compressive modulus [published correction appears in J Biomech. 1993;26(9):1143]. J Biomech. April–May 1993;26(4-5):599-607.
1999	Setton LA, Elliott D., Mow VC. Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. January 1999;7(1):2-14.
1993	Dedrick DK, Goldstein SA, Brandt KD, O'Connor BL, Goulet RW, Albrecht M. A longitudinal study of subchondral plate and trabecular bone in cruciate-deficient dogs with osteoarthritis followed up for 54 months. Arthritis Rheum. October 1993;36(10):1460-1467.
1994	Zysset PK, Sonny M, Hayes WC. Morphology-mechanical property relations in trabecular bone of the osteoarthritic proximal tibia. J Arthoplast. 1994;9(2):203-216.
2003	Bobinac D, Spanjol J, Zoricic S, Maric I. Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone. March 2003;32(3):284-290.
1994	Goulet RW, Goldstein SA, Ciarelli MJ, Kuhn JL, Brown MB, Feldkamp LA. The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech. April 1994;27(4):375-389.
2007	van Ruijven LJ, Mulder L, van Eijden TMGJ. Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone. J Biomech. 2007;40(6):1211-1218.
2001	Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Annu Rev Biomed Eng. 2001;3:307-333.
1995	Glüer C-C, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK. Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int. July 1995;5(4):262-270.
2001	van der Linden JC, Birkenhäger-Frenkel DH, Verhaar JAN, Weinans H. Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution. J Biomech. December 2001;34(12):1573-1580.
2010	Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. April 2010;18(4):419-433.
2017	Kroker A, Zhu Y, Manske SL, Barber R, Mohtadi N, Boyd SK. Quantitative in vivo assessment of bone microarchitecture in the human knee using HR-pQCT. Bone. April 2017;97:43-48.
1995	Rho JY, Hobatho MC, Ashman RB. Relations of mechanical properties to density and CT numbers in human bone. Med Eng Phys. July 1995;17(5):347-355.
2016	Vijayakumar V, Quenneville CE. Quantifying the regional variations in the mechanical properties of cancellous bone of the tibia using indentation testing and quantitative computed tomographic imaging. Proc Inst Mech Eng Part H-J Eng Med. June 2016;230(6):588-593.
1998	Keyak JH, Rossi SA, Jones KA, Skinner HB. Prediction of femoral fracture load using automated finite element modeling. J Biomech. February 1998;31(2):125-133.
1997	Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. January 1997;12(1):6-15.
1977	Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.
1998	Hurwitz DE, Sumner DR, Andriacchi TP, Sugar DA. Dynamic knee loads during gait predict proximal tibial bone distribution. J Biomech. May 1998;31(5):423-430.
2000	Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights, I: the disease and its risk factors. Ann Intern Med. October 17, 2000;133(8):635-646.
1985	Frost DL. Effects of Ambient Pressure on the Instability of a Liquid Boiling Explosively At the Superheat Limit [PhD thesis]. California Institute of Technology; 1985.
1984	Radin EL, Martin RB, Burr DB, Caterson B, Boyd RD, Goodwin C. Effects of mechanical loading on the tissues of the rabbit knee. J Orthop Res. 1984;2(3):221-234.
1997	Burr DB, Schaffler MB. The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence. Microsc Res Tech. May 15, 1997;37(4):343-357.
1957	Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. December 1957;16(4):494-502.
2011	Zebaze RMD, Jones AC, Pandy MG, Knackstedt MA, Seeman E. Differences in the degree of bone tissue mineralization account for little of the differences in tissue elastic properties. Bone. June 1, 2011;48(6):1246-1251.
1991	Brandt KD, Myers SL, Burr D, Albrecht M. Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament. Arthritis Rheum. December 1991;34(12):1560-1570.
2015	Lerner ZF, DeMers MS, Delp SL, Browning RC. How tibiofemoral alignment and contact locations affect predictions of medial and lateral tibiofemoral contact forces. J Biomech. February 26, 2015;48(4):644-650.
2000	Boyd SK, Matyas JR, Wohl GR, Kantzas A, Zernicke RF. Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury. J Appl Physiol. December 2000;89(6):2359-2364.
2008	Helgason B, Perilli E, Schileo E, Taddei F, Brynjólfsson S, Viceconti M. Mathematical relationships between bone density and mechanical properties: a literature review. Clin Biomech (Bristol, Avon). 2008;23(2):135-146.
2011	Johnston JD, Kontulainen SA, Masri BA, Wilson DR. Predicting subchondral bone stiffness using a depth-specific CT topographic mapping technique in normal and osteoarthritic proximal tibiae. Clin Biomech (Bristol, Avon). December 2011;26(10):1012-1018.
1994	Keyak JH, Lee IY, Skinner HB. Correlations between orthogonal mechanical properties and density of trabecular bone: use of different densitometric measures. J Biomed Mater Res. November 1994;A28(11):1329-1336.
1991	Odgaard A, Linde F. The underestimation of Young's modulus in compressive testing of cancellous bone specimens. J Biomech. 1991;24(8):691-698.
2008	Austman RL, Milner JS, Holdsworth DW, Dunning CE. The effect of the density–modulus relationship selected to apply material properties in a finite element model of long bone. J Biomech. November 14, 2008;41(15):3171-3176.
2003	Morgan EF, Bayraktar HH, Keaveny TM. Trabecular bone modulus–density relationships depend on anatomic site. J Biomech. July 2003;36(7):897-904.
1972	Radin EL, Paul IL, Rose RM. Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet. March 4, 1972;299(7749):519-522.
1992	Hodgskinson R, Currey JD. Young's modulus, density and material properties in cancellous bone over a large density range. J Mater Sci Mater Med. September 1992;3(5):377-381.
2003	Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A(2):1081-1101.
2004	Burr DB. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis Cartilage. 2004;12(suppl):S20-S30.
1992	Linde F, Hvid I, Madsen F. The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens. J Biomech. 1992;25(4):359-368.
1997	Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A. Systematic and random errors in compression testing of trabecular bone [published correction appears in J Orthop Res. 1995;17(1):151]. J Orthop Res. 1997;15(1):101-110.

Year

Entry

1992

Anderson MJ, Keyak JH, Skinner HB. Compressive mechanical properties of human cancellous bone after gamma irradiation. J Bone Joint Surg. June 1992;74A(5):747-752.

1975

Walker PS, Erkman MJ. The role of the menisci in force transmission across the knee. Clin Orthop Relat Res. June 1975;109:184-192.

1991

Snyder SM, Schneider E. Estimation of mechanical properties of cortical bone by computed tomography. J Orthop Res. May 1991;9(3):422-431.

1991

Schipplein OD, Andriacchi TP. Interaction between active and passive knee stabilizers during level walking. J Orthop Res. January 1991;9(1):113-119.

2001

Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR, Weinans H. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre‐arthritic cartilage damage. J Orthop Res. September 2001;19(5):914-918.

1983

Ahmed AM, Burke DL. In-vitro of measurement of static pressure distribution in synovial joints, I: tibial surface of the knee. J Biomech Eng. August 1983;105(3):216-225.

1993

Keaveny TM, Borchers RE, Gibson LJ, Hayes WC. Theoretical analysis of the experimental artifact in trabecular bone compressive modulus [published correction appears in J Biomech. 1993;26(9):1143]. J Biomech. April–May 1993;26(4-5):599-607.

1999

Setton LA, Elliott D., Mow VC. Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. January 1999;7(1):2-14.

1993

Dedrick DK, Goldstein SA, Brandt KD, O'Connor BL, Goulet RW, Albrecht M. A longitudinal study of subchondral plate and trabecular bone in cruciate-deficient dogs with osteoarthritis followed up for 54 months. Arthritis Rheum. October 1993;36(10):1460-1467.

1994

Zysset PK, Sonny M, Hayes WC. Morphology-mechanical property relations in trabecular bone of the osteoarthritic proximal tibia. J Arthoplast. 1994;9(2):203-216.

2003

Bobinac D, Spanjol J, Zoricic S, Maric I. Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone. March 2003;32(3):284-290.

1994

Goulet RW, Goldstein SA, Ciarelli MJ, Kuhn JL, Brown MB, Feldkamp LA. The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech. April 1994;27(4):375-389.

2007

van Ruijven LJ, Mulder L, van Eijden TMGJ. Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone. J Biomech. 2007;40(6):1211-1218.

2001

Keaveny TM, Morgan EF, Niebur GL, Yeh OC. Biomechanics of trabecular bone. Annu Rev Biomed Eng. 2001;3:307-333.

1995

Glüer C-C, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK. Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int. July 1995;5(4):262-270.

2001

van der Linden JC, Birkenhäger-Frenkel DH, Verhaar JAN, Weinans H. Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution. J Biomech. December 2001;34(12):1573-1580.

2010

Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. April 2010;18(4):419-433.

2017

Kroker A, Zhu Y, Manske SL, Barber R, Mohtadi N, Boyd SK. Quantitative in vivo assessment of bone microarchitecture in the human knee using HR-pQCT. Bone. April 2017;97:43-48.

1995

Rho JY, Hobatho MC, Ashman RB. Relations of mechanical properties to density and CT numbers in human bone. Med Eng Phys. July 1995;17(5):347-355.

2016

Vijayakumar V, Quenneville CE. Quantifying the regional variations in the mechanical properties of cancellous bone of the tibia using indentation testing and quantitative computed tomographic imaging. Proc Inst Mech Eng Part H-J Eng Med. June 2016;230(6):588-593.

1998

Keyak JH, Rossi SA, Jones KA, Skinner HB. Prediction of femoral fracture load using automated finite element modeling. J Biomech. February 1998;31(2):125-133.

1997

Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. January 1997;12(1):6-15.

1977

Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.

1998

Hurwitz DE, Sumner DR, Andriacchi TP, Sugar DA. Dynamic knee loads during gait predict proximal tibial bone distribution. J Biomech. May 1998;31(5):423-430.

2000

Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, Kington RS, Lane NE, Nevitt MC, Zhang Y, Sowers M, McAlindon T, Spector TD, Poole AR, Yanovski SZ, Ateshian G, Sharma L, Buckwalter JA, Brandt KD, Fries JF. Osteoarthritis: new insights, I: the disease and its risk factors. Ann Intern Med. October 17, 2000;133(8):635-646.

1985

Frost DL. Effects of Ambient Pressure on the Instability of a Liquid Boiling Explosively At the Superheat Limit [PhD thesis]. California Institute of Technology; 1985.

1984

Radin EL, Martin RB, Burr DB, Caterson B, Boyd RD, Goodwin C. Effects of mechanical loading on the tissues of the rabbit knee. J Orthop Res. 1984;2(3):221-234.

1997

Burr DB, Schaffler MB. The involvement of subchondral mineralized tissues in osteoarthrosis: quantitative microscopic evidence. Microsc Res Tech. May 15, 1997;37(4):343-357.

1957

Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. December 1957;16(4):494-502.

2011

Zebaze RMD, Jones AC, Pandy MG, Knackstedt MA, Seeman E. Differences in the degree of bone tissue mineralization account for little of the differences in tissue elastic properties. Bone. June 1, 2011;48(6):1246-1251.

1991

Brandt KD, Myers SL, Burr D, Albrecht M. Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament. Arthritis Rheum. December 1991;34(12):1560-1570.

2015

Lerner ZF, DeMers MS, Delp SL, Browning RC. How tibiofemoral alignment and contact locations affect predictions of medial and lateral tibiofemoral contact forces. J Biomech. February 26, 2015;48(4):644-650.

2000

Boyd SK, Matyas JR, Wohl GR, Kantzas A, Zernicke RF. Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury. J Appl Physiol. December 2000;89(6):2359-2364.

2008

Helgason B, Perilli E, Schileo E, Taddei F, Brynjólfsson S, Viceconti M. Mathematical relationships between bone density and mechanical properties: a literature review. Clin Biomech (Bristol, Avon). 2008;23(2):135-146.

2011

Johnston JD, Kontulainen SA, Masri BA, Wilson DR. Predicting subchondral bone stiffness using a depth-specific CT topographic mapping technique in normal and osteoarthritic proximal tibiae. Clin Biomech (Bristol, Avon). December 2011;26(10):1012-1018.

1994

Keyak JH, Lee IY, Skinner HB. Correlations between orthogonal mechanical properties and density of trabecular bone: use of different densitometric measures. J Biomed Mater Res. November 1994;A28(11):1329-1336.

1991

Odgaard A, Linde F. The underestimation of Young's modulus in compressive testing of cancellous bone specimens. J Biomech. 1991;24(8):691-698.

2008

Austman RL, Milner JS, Holdsworth DW, Dunning CE. The effect of the density–modulus relationship selected to apply material properties in a finite element model of long bone. J Biomech. November 14, 2008;41(15):3171-3176.

2003

Morgan EF, Bayraktar HH, Keaveny TM. Trabecular bone modulus–density relationships depend on anatomic site. J Biomech. July 2003;36(7):897-904.

1972

Radin EL, Paul IL, Rose RM. Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet. March 4, 1972;299(7749):519-522.

1992

Hodgskinson R, Currey JD. Young's modulus, density and material properties in cancellous bone over a large density range. J Mater Sci Mater Med. September 1992;3(5):377-381.

2003

Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A(2):1081-1101.

2004

Burr DB. Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. Osteoarthritis Cartilage. 2004;12(suppl):S20-S30.

1992

Linde F, Hvid I, Madsen F. The effect of specimen geometry on the mechanical behaviour of trabecular bone specimens. J Biomech. 1992;25(4):359-368.

1997

Keaveny TM, Pinilla TP, Crawford RP, Kopperdahl DL, Lou A. Systematic and random errors in compression testing of trabecular bone [published correction appears in J Orthop Res. 1995;17(1):151]. J Orthop Res. 1997;15(1):101-110.

Year	Entry
2020	Zaluski D. Validation of Subject Specific Computed Tomography-Based Finite Element Models of the Human Proximal Tibia Using Full-Field Experimental Displacement Measurements from Digital Volume Correlation [Master's thesis]. University of Saskatchewan; December 2020.

Year

Entry

2020

Zaluski D. Validation of Subject Specific Computed Tomography-Based Finite Element Models of the Human Proximal Tibia Using Full-Field Experimental Displacement Measurements from Digital Volume Correlation [Master's thesis]. University of Saskatchewan; December 2020.