The ability of an interlocking screw fixation technique to minimize bone loss related to stress shielding in the tibia was investigated and compared to cement and pressfit fixation. Full bony ingrowth has been associated with greater stress shielding than partial ingrowth;​ therefore, the effect of intimate bonding of the stem to bone in interlocking fixation on bone loss was also studied. A damage- and disuse-based remodeling theory was coupled with a two dimensional finite element model of the tibia to predict changes in bone remodeling following long stemmed total knee arthroplasty (TKA) for 4 different fixation techniques (cement, press-fit, interlock with bony ingrowth, and interlock without bony ingrowth). Remodeling changes commenced with the model state variables - bone area fraction, mechanical stimulus, damage, and remodeling activity - at steady state values predicted by the intact tibia simulation. After TKA and irrespective of fixation technique, the model predicted elevated remodeling due to disuse, in which more bone was removed than replenished. In regions below the tibial tray and along the cortices, the interlocking stem with full bony ingrowth and the cemented stem caused the least amount of bone loss. An interlocking stem with a smooth, matted finish did not reduce bone loss.

To investigate how bisphosphonates affect changes in microdamage and bone mass, a computational model of bone adaptation was employed. A greater suppression of bone remodeling activation increased microdamage, but the increase was limited when remodeling was incompletely suppressed. Furthermore, of the bisphosphonate effects, a reduction in resorption relative to formation had a greater contribution to a long-term gain in bone mass than a suppression of remodeling activation.

A strain-adaptive model of bone remodeling was developed for a continuum-level volume of post-menopausal trabecular bone by invoking Frost’s mechanostat hypothesis. Bisphosphonate effects were simulated as follows:​ low, intermediate, high, or complete suppression of bone remodeling activation either without a change in resorption area or with a decrease in erosion depth while formation was unaffected (i.e. formation initially exceeded resorption).

The level of damage increased with an increase in suppression potency and decreased with a decrease in resorption area. For a long-term gain in bone mass, suppression of remodeling activation had to be coupled with a decrease in resorption area. Decreasing resorption area caused the model to decrease formation area over time until the two were equal at which time the increase in bone mass plateaus. The results of this simulation suggest creating bisphosphonates that provide minimal suppression of remodeling and a large decrease in resorption area because this would minimize damage accumulation and increase bone mass, respectively. Yet, clinical evidence suggest higher suppression of remodeling is required to achieve the lower erosion depth associated with greater increase in the bone balance.

Lastly, the ability of bisphosphonates to minimize tibial bone loss following TKA with a press-fit long stem was investigated. Using the bone adaptation model that was developed for the long stemmed TKA, the activation frequency of remodeling by basic multicellular units (BMUs) was suppressed and the resorption area of the BMUs was reduced either on the day that the TKA became active, 3 months prior to its inclusion, or after 3.5 years of TKA. Bone loss as percent decrease in intact bone area fraction was predicted over time for each scenario and compared to bone loss following TKA without bisphosphonate effects. Compared to the untreated simulation, bisphosphonates slowed the rate of bone loss following TKA. Activating the drug 3 months prior to TKA reversed bone loss associated with the reduction in loading activity, but it did not provide any substantial benefit in the long-term. Bisphosphonate effects did not reverse the bone loss that occurred after 3.5 years of TKA, though it saved 3% of bone normally lost at 6.5 years. Increasing the suppression of BMU activation frequency had a greater influence on preserving bone over the long-term than did improving the bone balance. The model suggests that bisphosphonate treatment cannot completely stop bone loss associated with stress shielding because preservation of bone prolongs the disuse state imparted by the stiffer implants.