Aminobisphosphonate-treated ewes as a model of osteonecrosis of the jaw and of dental implant failure.

Abstract

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) and dental implant failure are two negative side effects of chronic aminoBP treatment. Eleven ovariectomized (OVX) ewes and four ewes subjected to sham surgery (SHAM) were treated as follows: OVX (n=5): OVX plus saline solution; zoledronic acid-treated group (ZOL) (n=6): OVX plus ZOL; SHAM (n=4): SHAM plus saline solution. Extraction of the first upper molar was performed at 1 year, dental implant placement at 2 years, and sacrifice at 28 months. Implants remained in place in SHAM and OVX ewes but were lost in all ZOL ewes. ZOL sheep (2/6) showed inflammation and necrotic bone at mandibular region. No differences in serum calcium (Ca), inorganic phosphate (Pi) or 25-hydroxyvitamin D were observed, whereas bone alkaline phosphatase levels decreased in the three studied groups (P<0.05). The significantly lowest levels of carboxy-terminal telopeptide of type I collagen were observed in ZOL (P<0.05), and showed no differences between SHAM and OVX. OVX showed the lowest and ZOL the highest Ca and Pi contents in femur and maxilla (P<0.05). Bone volume (BV/TV%) and iliac crest were similar at baseline and at month 4. At the end of the study, BV/TV%, proximal femur and hemi-mandible bone mineral content and bone mineral density, and trabeculae number were similar in SHAM and ZOL, and lower in OVX (P<0.05). All ZOL-treated ewes on a schedule similar to that used in cancer patients showed extensive suppression of bone remodeling and implant failure. Some of the ZOL ewes developed BRONJ.