Bone density and shape adapt to loading. Bone remodeling simulation models. Bone remodeling. But... Frost: mechanostat theory. Bone remodeling theory

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1 Bone density and shape adapt to loading Bone remodeling simulation models Turkey Ulna experiments (Rubin et al) Sheep ulnar osteotomy (McNamara) Bert van Rietbergen Bone is deposited in regions of high loading Load-dependent response Only dynamic loading results in bone apposition Bone remodeling But... Generally accepted that ostecytes are mechanosensors and regulate the remodeling process because they: are sensitive to mechanical load are sensitive to fluid flow are the most abundant cell type in bone can regulate OCl and OBl activity How is this process regulated? How can this process leads to mechanically optimized structures? How can cells at the scale of 10 microns produce 'optimal' structures at a scale times larger? Frost: mechanostat theory Bone remodeling theory Cowin et al., Theory of Adaptive Elasticity (1974) Carter et al., Huiskes et al., Beaupre et al.,... Bone adapts its mass to mechanical ca demands ds Bone mass S ref Frost, 1960 'lazy zone' 1

2 Mechanical signal S? something that can be measured by osteocytes Stress/strain parameters peak/average strain strain-rate strain energy density U or U/ energy stress 2EU von Mises stress Mechanostat theory Can it explain bone shape adaptation? Physiological loading accumulated microdamage fluid flow cell wall shear stress... Analysis of stress/strain distribution: FE-method Simulation of bone remodeling process bone geometry? t=t+t FE-model Update Geometry Change in bone mass dm A S dt Sref Brown et al., 1990 Beaupre et al., 1990, Huiskes et al., 1991 Simulation of bone remodeling process: Turkey ulna Simulation of bone remodeling process: Bone straightening Martinez and Cerrolaza, 2005 Roberts and Hart,

3 Mechanostat theory Simulation of bone remodeling process Can it explain bone shape adaptation? Can it explain bone density distribution? t=t+t Stiffness distribution Update Stiffness E=c Change in bone mass d AS Sref dt Beaupre et al., 1990, Huiskes et al., 1991 Wolff's law can explain density distribution Bone remodeling simulation models as a pre-clinical tool to evaluate implants initial density final Weinans et al., 1995 Application: prediction of adverse bone resorption Bone loss around implants: result of "Stress shielding" 3

4 Simulation of bone remodeling process Bone remodeling simulation: cemented stems t=t+t Stiffness distribution Change in bone Stiffness E=c Change in bone mass d AS Sref dt Beaupre et al., 1990, Huiskes et al., 1991 Weinans et al, 1992 Bone remodeling simulation: uncemented stems Effect of stem fixation and material on normal stress Weinans et al, 1992 Weinans et al, D Simulation of bone remodeling process site specific remodeling required t=t+t Stiffness distribution Change in bone Stiffness E=c Site-specific vs. non-site specific Non-site specific S ref = constant Site specific: S ref = dependent on the location Usually large 'lazy zone' required Change in bone mass d AS Sref dt Bone mass reference signal: S ref S ref 'lazy zone' 4

5 Bone remodeling simulation: 3D Bone remodeling / interface stress analysis as a pre-clinical tool g/cm -3 0 MPa gcm pre-remodeling post-remodeling 1.8 pre-remodeling post-remodeling pre-remodeling post-remodeling Normal stresses Shear stresses Remodeling simulation validation Comparison with DEXA Mechanostat theory Can it explain bone shape adaptation? Can it also explain bone density distribution? Can it explain bone morphology? Kerner et al Predicted density not smooth "Plate model" Weinans et al., J.Biomech, 1992 Weinans et al., J.Biomech,

6 "Plate model" Problem Results will be mesh dependent Solution: decouple biology from FE-mesh Weinans et al., J.Biomech, 1992 Spatial decay osteocyte stimulus Simulation of bone morphogenesis 1 f d f ( d) e D 2 2 mm d 80x80 elements Mullender and Huiskes, JOR, 1995 Mullender and Huiskes, JOR, 1995 Simulation of bone morphogenesis Simulation morphogenesis 2 Mpa external stress, cycling at 1.0 Hz (1.5 mm) 3 Mullender and Huiskes, JOR, 1995 Ruimerman et al, J of Biomechanics,

7 Simulation of adaptation Tanck et al, Bone 28, 2001 Computer Simulation Ruimerman et al, J of Biomechanics, 2005 Ruimerman et al, J of Biomechanics, 2005 Mechanostat theory Can it explain bone shape adaptation? Can it also explain bone density distribution? Can it explain bone morphology? Can it explain remodeling at the tissue level osteoblasts and osteoclasts always go together Hypothesis: Strain as the coupling factor in remodeling Development trabecular BMU Quiescence Resorption cavity Mechanically regulated formation Quiescence stress LC Ocy Oc Ob e-ob n-ocy elevated strain recruitment stimulus Huiskes et al., Nature, x3 mm2 7

8 Development trabecular BMU Development trabecular BMU Eriksen, Endocr. Rev Can the theory also explain remodeling in cortical bone? Development cortical BMU Haversian system Osteon 2x2 mm 2 Development cortical BMU 30 degrees rotated load no load 2x2 mm 2 8

9 A unified theory for osteonal and hemiosteonal remodeling Clinical application Major problem: physiological loading conditions are not know? van Oers et al., Bone, 2008 Other hypotheses Mechanostat theory Can it explain bone shape adaptation? Can it also explain bone density distribution? Can it explain bone morphology? Can it explain remodeling at the tissue level This afternoon Use a matlab code to simulate bone remodeling 9