Simulations of bone adaptation to total knee arthroplasty and bisphosphonates through remodeling stimulated by microdamage and disuse

A computation model of bone remodeling that is under the influence of microdamage, mechanical loading, and estrogen deficiency was developed to investigate (1) whether the interlocking screw system minimizes tibial bone loss following total knee arthroplasty (TKA), (2) the long-term effects of bisphosphonates on bone mass and microdamage in trabecular bone, and (3) the ability of bisphosphonates to prevent bone loss associated with stress shielding in TKA. Remodeling changes commenced with the model state variables---bone volume fraction, mechanical stimulus, microdamage, and the activation frequency (Ac.f) of basic multicellular units (BMUs)---at steady state as predicted by the intact tibia simulation or post-menopausal trabecular bone simulation. The tibia and TKA simulations were executed with a two-dimensional finite element model providing the mechanical stimulus as dictated by the loading conditions. In the post-menopausal simulation, the disuse threshold, the mechanical stimulus at which bone is neither removed or added, was linearly increased by 85% over a 3 year period to simulate estrogen withdrawal. After 15 years of post-menopausal bone remodeling, the anti-resorptive effects of bisphosphonates were simulated as follows: (1) BMW Ac.f was suppressed by a potency parameter (which incorporated the pharmacokinetic properties of bisphosphonates) and (2) BMU erosion was reduced. In regions below the tibial tray, the interlocking stern with full bony ingrowth and the cemented stem caused the least amount of bone loss. Furthermore, an interlocking stem with smooth, matted finish was not as effective as one with porous coating. To maximize increases in bone mass but minimize microdamage accumulation in estrogen-deficient trabecular bone, the model predicted that an ideal bisphosphonate would cause a large decrease in BMU erosion and have weak potency in suppressing BMU Ac.f. A plateau in the gain of bone mass following bisphosphonate treatment was found to occur because BMU formation decreases to match the reduction in BMU erosion as a result of disuse. Bisphosphonate was predicted to slow but not stop the process of bone loss following TKA. Unlike bisphosphonates for post-menopausal patients, ideal property of bisphosphonates for TKA was predicted to have a strong BMU Ac.f suppression potency because microdamage is not an issue.