It has been reported that intermittent administration of TPTD promotes bone healing after surgery for osteoporotic fractures [6]. If bone healing is promoted by the administration of TPTD during the preoperative waiting period, prolonged bed rest can be prevented. Conversely, it has also been reported that pretreatment with intermittent TPTD administration is not effective for bone union [29]. However, Tsuchie et al. evaluated the effects of TPTD treatment on bone union in the period before osteosynthesis surgery after a fracture occurred [8]. Wire fixation surgery resulted in significant enhancement of bone union after an osteotomy of the proximal tibia over that of sham surgery, with an obvious effect on cancellous bone union after osteosynthesis surgery (Fig. 10.1) [6]. OVX rats underwent an osteotomy of the proximal tibia as a fracture model, and TPTD or vehicle was administered as a preoperative treatment for 1 week. After treatment, the tibiae were fixed with wire for osteosynthesis, and TPTD or vehicle was administered. A number of parameters were investigated: bone histomorphometry, Alcian Blue/hematoxylin staining, and PCNA, Sox9, and Runx2 (Figs. 10.3 and 10.4). Preoperative treatment with TPTD significantly increased bone volume, bone union, and cartilage volume. Bone union was also promoted by pre- to postoperative treatment with TPTD for 2 weeks. This treatment also significantly increased the percentage of cells positive for Runx2, but not PCNA or Sox9. Preoperative administration of TPTD enhances bone union by promoting cartilage formation and cell differentiation to osteoblasts, but not by promoting cell proliferation. A number of factors are thought to be involved in the stimulation of bone formation by TPTD, such as the promotion of Runx2, IGF-1, and activating protein-I, and the suppression of sclerostin and Smad ubiquitin regulatory factor (Smurf) [21, 35–39]. The Wnt family has also been implicated in the actions of TPTD on the bone [40].

HA blocks have been widely used for the reconstruction of bone defects and as a bone substitute. Bone-implant bonding depends on both implant-related factors and patient variables. Kamo et al. evaluated whether intermittent TPTD administration enhances bone-HA block bonding in normal versus OVX rats. Cancellous bone osteotomy and HA-block implantation were performed in rats (Fig. 10.5) [7]. Newly formed cancellous bone around the HA block and bone-HA block bonding were evaluated. The administration of TPTD significantly increased cancellous bone volume by stimulating bone formation in OVX rats. Although bone-HA block bonding was significantly decreased in OVX rats compared with that of sham-operated rats, TPTD improved the bone-HA block bonding in OVX rats (Fig. 10.6). These results suggest that TPTD treatment may improve bone-HA bonding in osteoporosis by restoring cancellous bone volume and enhancing cancellous bone formation around the HA block. Figure 10.7 illustrates the HA block interface with fluorescent labels under UV light. Most of the fluorescent label at the newly formed trabecular bone on the HA blocks was observed in the sham-vehicle (Fig. 10.7a) and sham-TPTD (Fig. 10.7b) groups. TPTD treatment stimulated fluorescent labeling on the newly formed trabecular bone on the HA blocks even in the OVX groups (Fig. 10.7d). More osteoid was observed in the OVX-TPTD group (Fig. 10.7d), but not in the OVX-vehicle group (Fig. 10.7c), at the newly formed trabecular bone on the HA blocks compared to those in sham-vehicle (Fig. 10.7a) or sham-TPTD groups (Fig. 10.7b). However, there were no fluorescent labels at the interface between HA blocks and trabecular bones in any group.