Biomarkers for Osteonecrosis of Jaw: An In-vivo Animal Study

Jin-Woo Kim DDS,MSD, Ewha Womans University, Seoul, South Korea
Landayan Erika DDS, Ewha womans university, Seoul, South Korea
Tatad Jacquiline DDS, Ewha womans university, Seoul, South Korea
Sun-Jong Kim DDS, MSD, PhD, Oral and Maxillofacial Surgery, Ewha Womans University, Seoul, South Korea
Myung-Rae Kim DDS, PhD, Ewha Womans University, Seoul, South Korea
In-Ho Cha DDS,MSD,PhD, Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, South Korea
Statement of the Problem: Since the first report of osteonecrosis of the jaw associated with bisphosphonates administration in 2003, there have been many efforts to understand the nature of disease. This study was to investigate the potential biomarker of bisphosphonate related osteonecrosis of jaw. 

Materials and methods: A total of 48 ovariectomized 8-week SD rats were randomly divided into two groups. Case group was administrated zoledronic acid (0.2mg/kg/week) (n = 36). Control received normal saline (n = 12). After 6 weeks injection for each group, tooth extractions (lower M1-3) as a dental intervention inducing osteonecrosis of jaw were performed. Further injections followed after 8 weeks. Urine and blood samples were gathered for further analysis at the day of starting injection (T0), tooth extractions (T1), euthanasia (T2). Clinical and histological determination of BRONJ occurrence were assessed for case group. The animals were classified according to results.

Methods of data analysis: For biomarker evaluation, tartrate resistant acid phosphatase 5b (TRACP 5b), CTx, alpha and beta CTx, receptor activator of nuclear factor kB ligand (RANKL), osteoprotegerin (OPG), osteopontin and bone sialoprotein concentrations were determined using rat ELISA kits in accordance with the manufacturer’s instructions. For statistical analysis, Kruskal-Wallis test, Mann-Whitney test and Linear mixed model analysis were performed.

Results: When classifying case group animals to whether osteonecrosis occurred, TRACP 5b showed significant difference between groups. (p<0.05) At T1, values difference was not significant, however osteonecrosis groups at T2 were significantly lower than non-osteonecrosis group. Other markers showed no statistical significance.

Conclusions:TRACP 5b seems to be a possible candidate for biomarker of bisphosphonate - related osteonecrosis of jaw. Based on this report, additional clinical studies should follow for further validation.

References

  1. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115–7.
  2. Kim et al. Prospective biomarker evaluation in patients with osteonecrosis of the jaw who received bisphosphonates. Bone. 2013 Nov;57(1):201-5.
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