Bisphosphonates inhibit bone remodeling in the jaw bones of rats and delay healing following tooth extractions

• Published in: Oral oncology 2014-05, Vol.50 (5), p.485-490
• Main Authors: Jabbour, Zaher, El-Hakim, Michel, Henderson, Janet E, de Albuquerque, Rubens F
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bisphosphonates; Bone Remodeling - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Cancer treatment; Corticosteroid; Diphosphonates - pharmacology; Hematology, Oncology and Palliative Medicine; Jaw bone; Mandible - diagnostic imaging; Mandible - drug effects; Mandible - physiology; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Necrosis; Otolaryngology; Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Sequestra; Tooth Extraction; Tumors; Wound Healing; X-Ray Microtomography
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2014.02.013

Summary Objective This study aimed to evaluate the impact of concurrent administration of clinically relevant doses of zoledronic acid (ZA) and dexamethasone (DX) on bone healing after tooth extraction (EXO). Materials and Methods Forty-four Sprague–Dawley rats (6–8 month old) were randomized into five groups: ZA + DX = weekly injection of ZA with DX for 7 weeks; WD = ZA with DX for 3 weeks then DX alone for 4 weeks; C = control saline for 7 weeks; ZA = ZA alone for 7 weeks and DX = DX alone for 7 weeks. ZA was administered at 0.13 mg/kg/week and DX at 3.8 mg/kg/week and body weights recorded at the time of injection. All rats underwent extraction (EXO) of the mandibular and maxillary first molars at 3 weeks and were euthanized at 7 weeks. The extracted and non-extracted sides of both jaws were harvested for micro-CT analyses. Results All rats, particularly those injected with ZA, exhibited weight gain till EXO followed by decline then recovery. ZA + DX group demonstrated highest fractional bone to tissue volume (BV/TV) in the non-extracted side. ZA + DX rats exhibited also highest volume and surface of sequestra. Only sequestra volume was statistically higher in the WD group compared to C group. Conclusion Combined treatment with ZA and DX over a prolonged period inhibits bone remodeling and increased sequestra formation to a greater extent than either drug alone. Trauma caused by these sequestra cutting through the mucosa could play a key role in the development of BRONJ by potentially facilitating infection. ZA withdrawal may promote bone-remodeling reactivation following EXO.