The Effect of Parathyroid Hormone Analogues When Added to Mineralized Bone Xenografts
Implants can be a treatment option when there is sufficient quantity and quality of bone to provide support for long-term success. In the reconstruction of defects, autogenous bone remains the gold standard for its osteogenic and compatibility properties. However, the disadvantage of secondary surgery and the associated donor site morbidity prompts researchers to develop the ideal bone substitute for optimum bone reconstruction. Parathyroid hormone (PTH1-34) has provided a new option for improvement in bone regeneration. This study used a pig model to evaluate the effectiveness of parathyroid hormone when added to a xenograft, Bio-Oss, in reconstructing mandible defects. Six domestic pigs were used to create 3 posterior mandibular defects measuring 2 × 1-cm bilaterally with a total of 36 defects to simulate tooth extraction sites in humans. The defects were grafted in random order and divided into 3 groups as follows: control (no graft), Bio-Oss without PTH, and Bio-Oss with PTH. Defects were assessed with cone beam computerized tomography (CBCT), micro computerized tomography (microCT), nanoindentation, and histology. Results showed that adding PTH1-34 significantly enhanced the graft construct. CBCT showed a significant increase in the degree of bone mineralization. Nanoindentation showed increased hardness of regenerated bone and accelerated bone mineralization with PTH. MicroCT analysis revealed a trend toward higher bone regeneration and mineralization. The histological analysis showed a positive trend of the increase in cortical bone thickness and mineral apposition rate. In conclusion, the local addition of PTH1-34 to a xenograft has shown promising results to enhance bone regeneration in the reconstruction of mandibular defects.
Figure 1. Created osseous defects in the pig mandible. Figure 2. Surgical defects with graft material filled into capacity in 2 sites. In the shown photo: Bio-Oss (A), control (B), Bio-Oss + parathyroid hormone (C). Figure 3. Grafted sites covered with absorbable collagen membrane.
Figure 4. (a) Cone beam computerized tomography image of the pig mandible. The rectangle shows the segmented grafted area to be analyzed. (b) Gray-level histogram showing the bone mineral density distribution of all groups. (c) Histogram showing the low and high level percentiles of degree of bone mineralization (DBM). (d) Micro computerized tomography (microCT) image showing the selected region of interest. (e) Histogram showing DBM level obtained by microCT analysis. (f) Grafted site analysis by nanoindentation. (g) Microscope image with outline of nanoindentation data points (magnification, ×50). Figure 5. Fluorescent image of a decalcified horizontal section showing cortical plate thickness, mineral apposition rate, and mineral apposition zone.
Figure 6. (a) Cone beam computerized tomography–based gray-level histogram. (b) Micro computerized tomography–based degree of bone mineralization histogram. (c) Histogram showing nanoindentation modulus (E) of the 3 groups. Figure 7. (a) Parathyroid hormone (PTH) + Bio-Oss tend to have higher cortical bone thickness compared with the Bio-Oss–only samples (P > .05). The mean cortical bone thicknesses of the PTH + Bio-Oss and Bio-Oss groups were 1825 ± 146 μm and 1583 ± 143 μm, respectively. (b) Histogram comparing the mineral apposition rate between the PTH + xenograft and the xenograft-only sites. (c) Histogram comparing the mineral apposition zone between the PTH + xenograft and the xenograft-only site.
Fluorescent image showing the residual graft particles surrounded by newly formed bone.
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