# A Review of the Impacts of Implant Stiffness on Fracture Healing
## 4 Clinical Applications of Low Young's Modulus Metallic Materials to Accelerate Fracture Healing
The TiNbSn alloy group exhibited a more robust formation of intramedullary callus with a well-developed bone structure than the Ti6 Al4V alloy and CP-Ti groups. At the osteotomy site, the TiNbSn alloy group demonstrated a more advanced formation of mature bone, accompanied by improved orientation of the bone structure (Figure 3). Figure 2: Radiographs after osteotomy in rabbit tibia. (**A**) Commercially pure titanium (CP-Ti), 4 weeks after osteotomy; (**B**) TiNbSn alloy, 4 weeks after osteotomy; (**C**) CP-Ti, 6 weeks after osteotomy; (**D**) TiNbSn alloy, 6 weeks after osteotomy. Arrowheads indicate fracture callus. The scale bar indicates 10 mm. Reproduced from ref. [58] with permission [58]. These improvements may promote bone repair. TiNbSn alloy has emerged as a promising biomaterial for fracture treatment plates. Excessive plate stiffness can potentially hinder callus formation and impede the process of bone healing [59]. The accelerated callus formation observed in the bone defect at the site of plate installation in the group receiving TiNbSn alloy plates is attributed to the effective load-sharing capabilities afforded by the low Young's modulus of the TiNbSn alloy. Similarly, fracture treatment plates made from Ti29 Nb13 Ta4.6 Zr alloy, which also possesses a low Young's modulus, demonstrated a propensity to enhance osteosynthesis, even though a quantitative assessment was not conducted [49; 60]. Studies on fracture treatment devices using low Young's modulus titanium alloys are shown in Table 1.  
Clinical applications of TiNbSn alloys with low Young's moduli have been explored. A TiNbSn alloy stem for a hip prosthesis was developed, and the findings from the clinical trial indicated that TiNbSn alloy stems contributed to a reduction in stress shielding, which included improvements in thigh pain and a decrease in hip prosthesis loosening [61; 62]. In addition to other TiNbSn alloys, TiNbZrTaSi alloys, TiNbZrSn alloys, TiNoZrSnNb alloys, and TiNbTaO alloys have been reported for their low Young's moduli, biocompatibility, and osteoinductive effects [63; 64; 65; 66; 67]. However, there are few preclinical studies reporting their bone healing-promoting effects as fracture treatment plates or intramedullary nails. Although the usefulness of low Young's TiCr alloys has been reported for implant rods for \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **Materials** & **Implant Types** & **References** \\ \hline
1 & TiNbSn alloy & Intramedullary nail & [55; 56; 57] \\  & & Plate & [11] \\  & & Locking plate & [58] \\
2 & TiNbTaZr alloy & Intramedullary nail & [49] \\  & & Plate & [60] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Experimental models for the development of fracture treatment devices using low Young’s modulus titanium alloys. Figure 3: These images are from a non-demineralized specimen stained with [PERSON] bone stain. (**A**) CP-Ti, (**B**) TiNbSn alloy at 4\(\times\) magnification (scale bar indicates 2 mm), (**C**) CP-Ti, (**D**) TiNbSn alloy at 20\(\times\) magnification (scale bar indicates 100 mm). The TiNbSn alloy group exhibited a more robust formation of intramedullary callus with a definite bone structure compared with that of the CP-Ti group. Beneath the plate at the osteotomy site, the TiNbSn alloy group demonstrated a more advanced formation of mature bone, accompanied by an improved orientation of the bone structure. Reproduced from ref. [58] with permission [58]. spinal fusion, their clinical application has not been realized [68; 69; 70]. Furthermore, there is no low Young's modulus titanium alloy other than our TiNSbSn alloy that has achieved clinical application in joint prostheses [61; 62]. Considering the established safety, durability, and material availability of the TiNSbSn alloy, future research should concentrate on the clinical utilization of this alloy in fracture treatment devices with the objective of reducing the duration of the fracture treatment.