Does Relaxin Treat BRONJ or Prevent The Development of BRONJ?: an Experimental Study in Rats
Statement of the problem: Bisphosphonate related osteonecrosis of the jaw (BRONJ) has become one of the most obstinate and complicated pathology in oral and maxillofacial surgery. Currently, BRONJ management remains controversial, and there is no definitive standard of care for this disease. In fact, several articles in the recent literature discuss treatments that range from topical to surgical treatment, without definitive conclusion about treatment.
The pathogenesis of BRONJ appeared related to the potent osteoblast-inhibiting properties of bisphosphonates which act by blocking osteoclast recruitment, decreasing osteoclast activity and promoting osteoclast apoptosis. Moreover, long-term bisphosphonates use leads to the development of abnormal osteoclasts, as well as a direct inhibitory effect on osteogenesis in bone-healing process.
Relaxin is a peptide hormone with a two chain structure, similar to that of insulin. This hormone primarly produced in the ovaries and placenta during pregnancy. In recent studies, effects of relaxin in bone metabolism; differantiation, activation and stimulation of osteoclasts existance of relaxin receptors on osteoclast have been reported. Relaxin can act as a bisphosphanate antagonist.
The aim of the study was to evaluate the effect of relaxin hormon on prevention and management of BRONJ
Materials and Methods:Thirty-six Sprague-Dawley rats were divided into four groups randomly (each group has 10 and control group has 6 animals). In the first group, relaxin (0.17 µg/hr) with mini osmotic pump and simultaneously zoledronate (0.1 mg/kg) with intraperitoneal injection 3 times per week for 12 weeks were applied. In the second group, relaxin was applied for 12 weeks following zoledronate (0.1 mg/kg) injection 3 times per week for 12 weeks. In third group, zoledronate (0.1 mg/kg) injection was applied for 12 weeks. In the 4th group, as a control group, 0.1 mg/kg sterile saline injection was applied 3 times per week and sterile saline applied by mini osmotic pump for 12 weeks. Any surgical procedure were not performed on the animals. Rats were sacrificed 2 days after the end of drug therapy, and the jaws were extracted for histopathological evaluation. This study was supported by TUBITAK (Project no: 111S118) and approved by the Baskent University Animal Care and Ethics Committee.
Methods of Data Analysis: The specimens were processed for paraffin embedding, and sections were cut and stained with hematoxylin eosin and histopathologic evaluations were performed for the existance of necrosis, inflammation and quantity of the osteoblasts. Pearson chi-square and Fischer exact test were used for statistical analysis.
Results: There were statistically significant differences between the groups when necrosis, inflammation and quantity of the osteoblasts were considered. (P<0.05) Necrosis was not detected in the first and fourth group while it was detected in the 50% of the second group and 90% of the third group. Inflammation was not detected in the first group and fouth group while it was detected in the 20% of the second group and 60% of the third group. The densities of osteoblasts of group 1,2,3,4 were %20, %10, %50, %0 respectively.
Conclusions: Administration of systemically applied relaxin had positive effects on the prevention and the treatment of BRONJ in animals. However, further studies are required to verify the effectiveness of this form of treatment before its use in humans.
References:
- Ferlin A, Pepe A, Facciolli A, Gianesello L, Foresta C. Relaxin stimulates osteoclast differentiation and activation. Bone 2010; 46: 504-513
- Senel FC, Kadioglu Duman M, Muci E, Cankaya M, Pampu AA, Ersoz S, Gunhan O. Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Mar;109(3):385-91