ECTS Abstracts (2015) 1 P419

Bone Metabolism of Ovariectomised (OVX) Ewes Chronically Treated with High Doses of Zoledronic Acid (ZOL): Experimental Model of Osteonecrosis of the Jaw Associated to Bisphosphonates (ONJBPs)

Ricardo Davison1, Leandro Lyardet1, Mariana Preliasco1, Graciela Yaful1, Perla Torres1, Gretel Pelegrini2, Carlos Lugones2 & Susana Zeni2


1Rio Negro National University, Río Negro, Argentina; 2INIGEM, Buenos Aires, Argentina.


Background: ONJ has emerged as a complication of bisphosphonate (BPs) treatment which induces a strong reduction in bone remodelling. Ewes could be a useful experimental model because, among others, they allow making oral cavity interventions. The objective was to evaluate the effect of high doses of ZOL (equivalent to cancer treatment) on bone remodeling and maxillary bone mass in OVX ewes.

Methods: Adult Corriedale ewes’s were bilateral OVX or SHAM operated. Then, they received ZOL (n=6) or physiological solution (3 OVX and 3 SHAM). After one year (T=12) the first molar was extracted and a dental implant was done at T=24. A bone defect was done contra-laterally and calcium (Ca) and phosphorus (P) content was evaluated in the extracted material. After 4 additional months (T=28), ewes were sacrificed. Blood was drawn during all these interventions and serum Ca, P, crosslaps (CTX) and bone alkaline phosphatase (BAP) were evaluated. Hemimandible bone mineral content (BMC) was evaluated ex vivo.

Results: Results were expressed in the following order SHAM, OVX and ZOL: sCa (mg/dl): 9.1±0.8; 9.0±0.5; 8.9±0.4; sP (mg/dl): 4.63±0.21; 4.37±0.22; 3.96±0.36; BAP(mg/dl): 50.3±2.5; 58.3±0.6; 54.0±4.3; CTX; 644±8.7; 826±83*; 271±57*,**; Ca (g/g tissue): 0.707±0.263; 0.443±0.049*; 0.537±0.048*,**; P (g/g tissue): 0.290±0.084; 0.208±0.011; 0.211±0.048; BMC (g/cm2): 32.1±9.2; 24.0±6.1*; 42.3±3.0*,**. (* and **): p<0.05 vs. SHAM and OVX, respectively. OVX and SHAM survival was 100% and ZOL 77% (2 deaths). Two ewes showed ONJBPs for Actinomyces spp. No differences among the groups were observed in sCa and BAP levels; sP showed a tendency to be lower in ZOL, without differences between SHAM and OVX groups. At T=12, CTX increased in OVX and decreased in ZOL vs. SHAM group. ZOL treatment partially prevented the decrease in BMC observed in OVX group. At T=24, BMC was significantly lower in OVX and significantly higher in ZOL vs. SHAM (p<0.01).

Conclusion: Under our experimental conditions, two ewes treated with high doses of ZOL showed ONJBPs. These group also showed an increase in mandible BMC as a result of a great decrease in bone resorption. Dent. R. Davison doctoral thesis. Rio Negro National University. PICTO-2010-0181 and CONICET.

Disclosure: The authors declared no competing interests.