Perioperative discontinuation of intravenous bisphosphonate therapy reduces the incidence and severity of bisphosphonate-related osteonecrosis of the jaw: A randomized, controlled, prospective experimental study in rats.
OBJECTIVE
To evaluate the effects of intravenous bisphosphonate discontinuation on incidence and severity of bisphosphonate-related osteonecrosis of the jaw (BRONJ).


METHODS
Seventy rats were randomly divided into 7 groups. In control and S0 groups, weekly injection of saline and 0.06 mg/kg zoledronate (respectively) for 4 weeks, tooth extraction, continuation of injections for 2 months and euthanasia were performed. In group S1, zolendronate injection for 4 weeks, tooth extraction, zolendronate discontinuation for 2 months, and euthanasia were done. For groups S2, S3, S4, and S5, zolendronate injections for 4 weeks, drug holiday for 1-4 months (respectively) before and 2 months after tooth extraction, and euthanasia were performed. Presence of bone exposure, osteonecrosis, and new bone formation were clinically and histologically evaluated.


RESULTS
The rate of BRONJ in control, S0, S1, S2, S3, S4, and S5 groups was 0%, 85%, 80%, 65%, 60%, 50%, and 40%, respectively. In control group, epithelial healing, bone formation, and absence of osteonecrosis; and in S0 group, unhealed epithelium, osteonecrosis, and impaired bone formation were histologically observed. In study groups, prolongation of drug holiday caused diminished osteonecrosis, and improved bone and epithelial healing.


CONCLUSIONS
Zolendronate discontinuation significantly decreased the incidence and severity of BRONJ in rats.
Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran; Dental Research Center, Hamedan University of Medical Sciences, Hamedan, Iran. Electronic address: zandi88m@yahoo.com.
Mohammad
M
Zandi
Department of Pathology, Hamedan University of Medical Sciences, Hamedan, Iran.
Arash
A
Dehghan
Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran.
Khaled
K
Ghadermazi
Department of Oral and Maxillofacial Surgery, Hamedan University of Medical Sciences, Hamedan, Iran.
Hamid
H
Malekzadeh
Department of Biostatistics and Epidemiology, Hamedan University of Medical Sciences, Hamedan, Iran.
Mahdi
M
Akbarzadeh
D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007093:Imidazoles / Q000008:administration & dosage*; D007275:Injections, Intravenous; D010012:Osteogenesis / Q000502:physiology; D059035:Perioperative Period; D011446:Prospective Studies; D011897:Random Allocation; D017208:Rats, Wistar; D012307:Risk Factors; D014081:Tooth Extraction; D028761:Withholding Treatment; D014945:Wound Healing / Q000502:physiology; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
Animal study; Bisphosphonate; Drug holiday; Jaw; Osteonecrosis