Effect of different doses and durations of teriparatide therapy on resolution of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats. Issue 3 (March 2018)

• Record Type: Journal Article
• Authors: Zandi, Mohammad; Dehghan, Arash; Zandipoor, Najmeh; Amini, Payam; Doulati, Shideh
• Is Part Of: Journal of cranio-maxillofacial surgery. Volume 46:Issue 3(2018)
• Page Start: 466
• Page End: 472
• Publication Date: 2018-03
• Subjects: Teriparatide -- Osteonecrosis -- Jaw -- Dose -- Animal study; Skull -- Surgery -- Periodicals; Maxilla -- Surgery -- Periodicals; Face -- Surgery -- Periodicals; Surgery, Plastic -- Periodicals; Maxilla -- surgery -- Periodicals; Face -- surgery -- Periodicals; Skull -- surgery -- Periodicals; Oral Surgical Procedures -- Periodicals; Reconstructive Surgical Procedures -- Periodicals; Surgery, Plastic -- Periodicals; Surgery, Oral -- Periodicals; Electronic journals; 617.514
• DOI: 10.1016/j.jcms.2017.12.027
• Languages: English
• ISSNs: 1010-5182

Abstract

Abstract: Objective: To evaluate the effects of different doses and durations of teriparatide therapy on MRONJ resolution in rats. Subjects and methods: A total of 120 rats that had been affected with MRONJ (after six weekly zoledronate injections and tooth extraction) were randomly divided into eight subgroups: 2, 10, and 20 μg/kg/day teriparatide were administered to L4, M4, and H4 for 4 weeks, and to L8, M8, and H8 for 8 weeks, respectively. C4 and C8 received saline for 4 and 8 weeks, respectively. One week after the final injection, rats were sacrificed and assessed clinically (bone exposure/fistula) and histologically (number of osteocytes in extraction socket and empty lacunae in alveolar bone). Results: MRONJ was clinically improved in 72.2%, 61.5%, and 40% of stage I, II, and III experimental rats, respectively. In the control rats, the results were 20.8% for stage I and no improvement for stages II and III. Aside from L4 and L8, the experimental subgroups had a significantly higher rate of clinical and histological improvement compared with their corresponding controls. There was a significantly higher number of osteocytes and lower number of empty lacunae in M4 and H4 compared with C4, in H4 compared with L4, in M8 and H8 compared with C8, and in H8 compared with L8. Conclusion: Teriparatide therapy improved clinical and histological features of MRONJ in a dose-dependent manner, but clinically relevant doses of teriparatide might not be sufficient for MRONJ resolution in rats. Extending the duration of teriparatide therapy from 4 to 8 weeks did not affect treatment outcomes. Highlights: Teriparatide therapy improves both clinical and histological features of MRONJ in a dose-dependent manner. The clinically relevant doses of teriparatide (2 μg/kg/day) may not be sufficient for treatment of MRONJ in rats, but the higher doses (10 and 20 μg/kg/day) are significantly effective. Extending the duration of teriparatide therapy from 4 to 8 weeks does not increase the success rate of MRONJ resolution.