Seventeen different clinical studies were included covering implant-related factors (Table 1), while eleven studies were consulted following the patient- and surgery-related factors (Table 2). Studies covering the effects of multiple factors on bone density changes have been reviewed more than once over this section.

Table 1 Overview of reported data in clinical studies concerning implant-related factorsTable 2 Overview of reported data in clinical studies concerning patient- and surgery-related factorsEffects of Implant-Related Factors on Tibial Bone Density ChangesFixation Method

Tibial TKA components can be fixated to the bone using either a cemented fixation or a cementless press-fit fixation. Three clinical studies reported on the effect of fixation method in otherwise similar implants in periprosthetic tibial density changes [9,10,11] (Table 1). A study by Small et al. [9], based on DRD, found a significant reduction of bone loss around cemented implants relative to uncemented components at 5 years after TKA, but no significant differences at other time intervals up to 10 years. The same study also found that tibial density changes were significantly related to body mass index (BMI) in the cemented group, but not in the uncemented group, although no explanation for this observation was suggested [9]. Abu-Rajab et al. [10] reported no difference between cemented and uncemented fixation in the extent of relative bone mineral density (BMD) difference compared to the unoperated contralateral knee after a minimum postoperative time of 2 years. In a study by Li and Nilsson, no significant differences in relative density changes between the fixation methods were seen within any follow-up period up to 2 years [11]. Interestingly, implant migration, determined using radiostereometric analysis (RSA), was found to be related to preoperative BMD in the uncemented group up until 6 months after operation, but not in the cemented cohort [12]. In the same patient cohort, no relationship between migration and 2-year BMD changes has been established [13]. Another DEXA study comparing cemented and uncemented implants found reduced bone loss following uncemented implants, but both implant systems also differed distinctively in material stiffness and stem design [14].

Within uncemented implants, a distinction can be made in the type of coating at the bone contact surfaces, which may affect the course of periprosthetic bone remodeling [15, 16] (Table 1). One study reported a significant difference in lateral proximal density between hydroxyapatite-coated and uncoated implants, with higher BMD values found in the uncoated group at 2 years postoperatively [16]. In contrast, another study with similar implants did not find any density differences between different types of coating [15].

In summary, none of the abovementioned studies attributed measured differences in bone resorption solely to the implant fixation method. One study reported a relationship between BMI and bone density change in cemented implants, which was significantly different from uncemented implants only at the 5-year time point [9], providing minimal evidence for the role of fixation method in the course of periprosthetic bone remodeling.

Implant Stiffness

As periprosthetic bone loss is the result of a reduction in local bone stress, caused by the high stiffness of (metallic) implants compared to the replaced bone tissue, it is hypothesized that this stress shielding is reduced when using implants with a decreased stiffness. One way to achieve this is through the use of implant materials with a lower modulus of elasticity. Geometry may also affect the stress shielding potential of a specific implant, as the structural stiffness can be lowered by decreasing the thickness of the tibial baseplate.

Tibial baseplates are typically constructed out of one of the following materials: cobalt-chromium alloy (CoCrMo [CoCr]), titanium alloy (Ti6Al4V [Ti]), polyethylene (UHMWPE [all-poly]), or porous tantalum (trabecular metal [TM]). CoCr and Ti implants have an elasticity modulus of around 210 GPa and 105 GPa, respectively, which is significantly higher than the modulus of the human bone tissue it replaces. The TM modulus of 3 GPa is much more in line with the bone moduli of ~1–5 GPa measured in specimens of subchondral and trabecular bone tissues in the proximal tibia [17], therefore reducing potential stress shielding. The stiffness of polyethylene, typically only used as the material of the tibial insert, is significantly lower than bone, with an elastic modulus of 588 MPa. This could potentially introduce complications in all-poly implants, with the entire rigid tibial component made out of polyethylene, as a result of local periprosthetic bone overloading.

A paired cohort study compared relative BMD change between patient groups receiving a TM or a CoCr implant and observed a significant reduction in lateral bone loss within the TM group over 5 years (11.6% vs. 29.6% bone loss) [14]. No significant differences were found in the medial and distal regions of interest (ROIs). A prospective study comparing BMD in 41 subjects receiving a TM implant against their contralateral native knee reported no significant long-term proximal density changes in the operated knees due to TKA [18]. In contrast, other clinical studies reported a significant decrease in BMD relative to the unoperated contralateral knee for standard nonporous metallic stemmed implants [10, 19]. These results combined suggest that the use of TM implants reduces periprosthetic bone loss. Although an all-poly tibial component results in the highest load transfer to the proximal tibia, potentially leading to bone densification or local overloading, no longitudinal study has been found reporting on density changes after tibial TKA using such implants. However, excellent long-term outcomes of all-poly tibial components have been reported regarding implant survival, periprosthetic fracture, and aseptic loosening compared to metal-backed baseplates [20].

The effect of baseplate thickness on bone resorption was studied by Martin et al. using similar CoCr implants with two different thicknesses (2.7 mm vs. 4 mm), reporting significantly greater medial resorption and seven times increased risk of bone loss medially in the thicker baseplate cohort [21]. Wong et al. reported no significant difference in clinical medial bone loss at 3-year follow-up between two groups with a different tray thickness and contradictorily even found significantly higher medial density following the thick tray after the first year [22]; however, as this study compared the baseplate thickness of two different implant designs, the difference in geometry could have also affected the overall structural stiffness and bone strain distributions.

Findings by Yoon et al. endorsed the theory that implants with greater overall stiffness lead to increased bone resorption, by reporting a greater degree of medial bone loss in various CoCr implants compared to lower modulus Ti implants with smaller baseplate thicknesses [23].

Implant Geometry

Besides thickness of the baseplate, there are additional design features that may influence periprosthetic bone density. The shape of the baseplate determines the coverage of the resected tibial bone, and therefore, the transfer of loads from the joint to the bone. There is also a variety of fixation features, which typically include a central stem and/or smaller pegs at the medial and lateral condyles (Fig. 1). Stem type and shape affect the way strains are transferred through the tibia and, to a lesser extent, influence the structural baseplate stiffness. Several studies have been conducted to study their effect on clinical BMD measurements [14, 19, 24, 25] (Table 1).

Fig. 1

Schematic impression of different fixation features used in tibial implant designs

The effect of the shape of the central stem was demonstrated in a study where a cylindrical stem showed increased and more concentrated medial bone loss compared to a cruciform-shaped stem, in which BMD decrease was more evenly spread over the proximal tibia, in an otherwise identical design [24]. A different study, comparing cruciform and cylindrical stems with different implant bearings, did not find any evidence for bone density differences up to 2 years [25]. Comparison between an implant with four short fixation pegs, and another cemented implant with a larger cylindrical central stem, found a significant proximal BMD reduction for the single-stem implant compared to the contralateral control, but not for the four-pegged design [19]. Minoda et al. found a similar difference between both distinct stem types [14]. However, multiple factors were varied simultaneously in this study, as the cylindrical single-stem component was also constructed out of a much stiffer material [14]. A single-implant study by Bohr and Lund found a high correlation between BMD of proximal and distal areas of the tibia over follow-up in an uncemented metallic implant with two fixation pegs and suggested that no stress shielding occurs around these smaller pegs [26]. However, a recent register study concluded that a single design of a cemented four-pegged baseplate had a higher risk of aseptic loosening than the corresponding implant using a single central stem [27]. Two single-center studies with a follow-up greater than 5 years did not find a difference in clinical outcome between both fixation options in two knee systems [28, 29].

Implant Bearing Type

Tibial components can be subdivided in either fixed bearing (FB) or rotating platform (RP) implants. RP components provide an additional rotational degree of freedom at the interface between the polyethylene insert and the tibial baseplate when compared to traditional FB implants. RP implants can therefore theoretically reduce shear stress at the contact area between the femoral component and insert and may affect stress shielding by facilitating a more equal distribution of compressive forces and reducing the axial torque acting on the tibial component.

In addition, a distinction can be made on the type of constraint of the articulating surface, with the most popular types being the cruciate retaining (CR) and posterior stabilized (PS) implant. While, in CR implants, the posterior cruciate ligament (PCL) is (at least partially) responsible for the anteroposterior (AP) stability, these forces are mainly transferred through the post − cam mechanism in PS implants, which, in turn, may affect the stresses in the periprosthetic bone.

Three different joint constraint studies found similar bone density reduction in FB and RP designs of a single implant system, indicating that bone resorption was not related to PCL retention [30,31,32] (Table 1). Additionally, Saari et al. also varied the shape of the bearing surface (flat vs. concave); the results indicated that the shape of the contact surface also did not affect periprosthetic BMD up to 5 years [31]. Similarly, a QCT-based investigation by Munro et al. did not show differences in BMD loss between RP and FB implants, although the implants in this particular study also had different stem shapes and were constructed from different nonporous metals (FB—cruciform, Ti vs. RP—cylindrical, CoCr) [25].

Effects of Patient- and Surgery-Related Factors on Tibial Bone Density ChangesAge

Bone density decreases with increasing age in a general non-TKA population, as observed in BMD measurements of three different bone sites across different age groups with a range of 29 to 87 years old [33]. The age of the patient, therefore, affects the initial BMD at the time of surgery, which could influence the subsequent progress of periprosthetic bone remodeling. However, since TKA is generally performed in older patients, the age range of a primary TKA cohort is limited. Several studies have therefore been unable to demonstrate an age-related effect on initial mean proximal tibial BMD, and on bone density changes after TKA [10, 13, 34,35,36] (Table 2). Conversely, Small et al. did find that higher age at time of surgery was associated with an increase in bone density loss after TKA (in lateral and distal regions) [9]. Similarly, Ishii et al. found a weak negative correlation between age and postoperative BMD formation [32].

Sex

General age-related bone loss is more pronounced in females, due to postmenopausal-related effects [33]. Consequently, higher baseline BMD levels have been found in male than in female TKA patients, but this did not result in differences in relative BMD changes when compared to the contralateral knee [10]. These findings were in line with several other studies that were unable to demonstrate significant differences in postoperative BMD changes by sex [13, 32, 35, 36] (Table 2). Conversely, a study by Small et al. found significantly less bone loss in male patients than in female patients in all lateral and distal regions [9], possibly caused by correction of preoperative varus deformity in unreported native knee alignment, which is more common in men than in women [37], leading to a shift in load distribution towards lateral. No studies were found considering menopausal status regarding bone loss after TKA.

Knee Alignment

In line with Wolff’s Law, the mediolateral (ML) bone density distribution in intact tibiae has been found to vary based on native knee alignment [11, 38, 39]. TKA patients with varus preoperative alignment, therefore, have a higher baseline BMD in the medial compartment, while valgus knees typically show greater initial lateral densification [11, 12, 35, 40]. In terms of overall mean density over the proximal tibia, Hvid et al. and Levitz et al. found no significant difference between preoperative varus and valgus knees [34, 36], while Li and Nilsson found greater general BMD in knees with native varus alignment [11]. Interestingly, this study also found a greater relative bone resorption in native varus knees 2 years after TKA, while subsequent postoperative alignment was not found to be a predictor for relative 24-month BMD change [11].

The same study also investigated the effect of intrasubjective alignment change by making a distinction between compartments based on increase or decrease in load following the alignment difference (e.g., an increase in load was assumed in the lateral compartment when correcting a varus knee to neutral). They found an increase in bone formation underneath the load-increased condyle over the load-decreased side, but only in patients with a low mean baseline BMD over the proximal tibia [11]. A different study, based on dual photon absorptiometry (DPA), demonstrated a similar effect of alignment change, with extensive resorption observed in the compartment with reduced postoperative loading, and a slight but significant increase in density in the compartment with increased load [41]. Several other studies demonstrated a BMD decrease in the load-decreased condyle but did not find a significant density change in the load-increased side based on the change between pre- and postoperative varus angles [34, 35, 42]. Hvid et al. found this effect solely in the lateral region, with no significant decrease of medial density in the preoperative varus group separately after 2 years [34], while other studies only found significant differences in medial decrease related to preoperative varus knees at 1-year follow-up [35, 42]. Jaroma et al. also reported a significant medial decrease of density in valgus preoperative knees, while no significant density changes were found in the lateral ROI, regardless of preoperative alignment [40]. The extent of medial resorption was found to differ significantly between postoperative alignments within the varus preoperative group, with considerably more relative resorption in alignments towards valgus [40]. Densification in the distal region, underneath a central implant stem, was found to be related to postoperative varus alignment in uncemented implants according to Small et al. [9]. This correlation was not found in cemented implants, and no preoperative alignment was reported.

Although osteoarthritis (OA), the most common indication of TKA, was reported to be related to increased constitutional varus angles [43] and higher medial proximal preoperative BMD [44], no significant differences in density changes were found based on OA severity or TKA indication, respectively [35, 36].

In general, the findings over the studies indicate bone density to relatively shift towards the ML side which is increasingly loaded following postoperative knee alignment, relative to the preoperative situation. This change in ML density distribution is typically observed as an increase of bone loss in the load-decreased side but, in some studies, was (also) measured as densification in the predominantly loaded side (Table 2); however, a distribution shift was not observed over all alignment combinations in the studies, which could be influenced by implant-related factors.

Preoperative Bone Density

Few studies investigated the effect of preoperative BMD level on the course of periprosthetic bone density changes, with varying outcomes. Abu-Rajab et al. did not find a relationship between relative density changes and preoperative BMD [10]. Conversely, Li and Nilsson found that a higher preoperative BMD led to greater relative bone loss [11]. Hvid et al. concluded remodeling to be characterized by bone resorption in the denser condyle according to preoperative alignment, while BMD in the lower density condyle was constant over 2 years [34].

Body Weight

Higher body weight (BW) evidently leads to greater mechanical bone loading and, accordingly, has been linked to higher BMD measurements in non-TKA cohorts [45, 46]. Meanwhile, obesity has been associated with lower bone metabolism through different biochemical pathways [47], which could account for the lower rates of bone formation observed in obese postmenopausal women [48]. The same biochemical effects could play an important role in a two-fold increased risk of revision surgery due to tibial aseptic loosening encountered in TKA patients with a BMI greater than 35 kg/m2, regardless of knee alignment or age [49].

Several radiographic TKA studies failed to find a correlation between initial BMD values and BW or BMI [13, 34]. Interestingly, BW does seem to affect mid- to long-term bone density after TKA. Hvid et al. found a positive correlation between body weight index and BMD after 2 years [