Effect of a local, one time, low-dose injection of zoledronic acid on titanium implant osseointegration in ovariectomized rats

Abstract

Introduction: Local application of bisphosphonates has been proven to be safer than systemic administration to promote implant fixation. The objective of this study was to introduce such a simple, convenient and efficient method to enhance titanium (Ti) implant osseointegration in ovariectomized (OVX) rats.

Material and methods: Twenty female Sprague-Dawley rats sequentially underwent bilateral ovariectomy and tibia implantation, and injection of 30 µg/implant zoledronic acid (ZOL) at the site of implantation was performed. At the end of the study, the tibiae, mandibles, femurs and vertebrae were harvested for dual energy X-ray absorptiometry, histology and micro-computed tomography examination.

Results: Ovariectomized rats showed poor bone density, bone mass and trabecular microstructure. OVX + ZOL rats were characterized by significantly improved peri-implant bone area (1.72-fold), bone contact (2.30-fold), bone mineral density (1.57-fold) and bone mineral content (1.67-fold), as well as moderately increased bone volume to total volume ratio (1.34-fold), percentage osteointegration (1.54-fold), connectivity density (1.45-fold), and trabecular number (1.43-fold), but decreased trabecular separation (57.69%) when compared with the control levels (p < 0.05). No histological signs of jaw osteonecrosis were observed in the rats treated with ZOL, and there was no significant difference between the OVX group and OVX + ZOL group in the bone mass of the mandible, femur and 5^th lumbar vertebra (p > 0.05). In addition, the overproduction of osteoporosis-induced advanced glycation end-products (AGEs) was completely prevented by local treatment with 30 µg/implant ZOL.

Conclusions: A local, one time, low-dose injection of ZOL at the site of implantation is able to promote the osseointegration of Ti implants following postmenopausal osteoporosis, and this action may be partly mediated by inhibition of the osteoporosis-induced AGE overproduction in the bone marrow.

Keywords: advanced glycation end products; bisphosphonate; implant; osteoporosis.

Figure 1

A – Scanning electron micrograph of titanium (Ti) implant. B – Radiograph of Ti implant in tibia. C – Radiographs of mandibles with and without the right mandibular first molar

Figure 2

A – Representative light micrograph of the implant-bone interface from ovariectomized (OVX) rats (original magnification 10×). B – Representative light micrograph of the implant-bone interface from OVX rats treated with zoledronic acid (ZOL) (original magnification 10×). C – Effects of local ZOL treatment on the bone area (BA) and bone contact (BC) values. Data are expressed as mean ± SE, and comparison was determined with t test. *p < 0.05 comparison with OVX group. D – Representative light micrograph of the 5^th lumbar vertebra (original magnification 10×). E – Representative light micrograph of the mandible (original magnification 10×). F – Representative light micrograph of the femur (original magnification 10×)

Figure 3

Representative 3D micro-CT images of the proximal tibia with titanium implants 3 months after implantation

Figure 4

Effects of local zoledronic acid (ZOL) treatment on the microstructure parameters around titanium implants inserted in the tibiae of ovariectomized (OVX) rats. Data are expressed as mean ± SE, and comparison was determined with the t test. *p < 0.05 comparison with OVX group BV/TV – bone volume/tissue volume, Conn.D – connectivity density, %OI – osseointegration, Tb.N – trabecular number, Tb.Th – trabecular thickness, Tb.Sp – trabecular separation.

Figure 5

Effects of local zoledronic acid (ZOL) treatment on the advanced glycation end products (AGEs) expressed in the bone marrow of the proximal tibia (original magnification 40×)