Effect of chronic kidney disease on the healing of titanium implants

Abstract

Chronic kidney disease (CKD) has become a worldwide public health problem. However, its effect on osseointegration of dental implants is largely unknown. The aim of this study is to investigate whether CKD impairs the quality of the osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in mice, and serum levels of BUN, FGF23, PTH and ALP were significantly increased. For in vitro tests, bone marrow mesenchymal stem cells (BMMSCs) were obtained and cultured on titanium discs. There was no significant difference in term of expression of osteogenic marker genes including Osx, Col-1, Ocn, and Opn, as quantified by qPCR. Moreover, Alizarin Red S staining showed comparable mineralized nodules formation. Histomorphometrical analysis of experimental implants inserted in the femurs of CKD mice revealed a trend of decreased BIC ratio at 2-week healing. The strength of bone-implant integration, as measured by a push-in method, was significantly lower for the CKD group at 2 weeks, although a comparable level was reached at 4 weeks. These results demonstrated that CKD only negatively affects the osseointegration of titanium implants at the early stage.

Keywords: Bone mineralization; Chronic kidney diseases; Dental implants; Fibroblast growth factor 23 (FGF23); Osseointegration; Parathyroid hormone (PTH).

Fig. 1

Illustration of the work flow and serum biochemical measurements. (A) Illustration of the work flow. (B) Serum BUN. (C) Serum FGF23. (D) Serum PTH. (E) Serum vitamin D. (F) Serum phosphate. (G) Serum calcium. *: p < 0.05.

Fig. 2

Analysis of osteoblastic differentiation markers. (A) serum ALP activity. (B) ALP staining of cells seeded on titanium discs. (C) ALP staining of cells cultured on titanium discs. (D) Alizarin S staining of cells cultured on titanium discs. Gene expression of Osx (E), Col-1a (F), Opn (G) and Ocn (H). *: p < 0.05.

Fig. 3

Implant surgery. (A&B) Experimental titanium implants. (C) Implant sites prepared in the distal end of femur. (D) Implant inserted into the distal end of femur. (E) X-ray examination of the femurs with implants.

Fig. 4

Histology and biomechanical test. (A&B) Representative images of the histological sections at 2-week healing. (C) Bone-implant contact ratio at 2-week healing. (D&E) Representative images of the histological sections at 4-week healing. (F) Bone-implant contact ratio at 4-week healing. (G) Resistance of push-in tests. *: p < 0.05.