Bisphosphonate-Associated Osteonecrosis of the Jaw ; diagnosis ; etiology ; prevention & control ; therapy ; Diphosphonates ; chemistry ; pharmacokinetics ; pharmacology ; Humans ; Risk Factors

OBJECTIVE: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work. METHODS: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper. RESULTS: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery. CONCLUSION Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.
Humans ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Sclerosis/complications* ; Wound Healing ; Treatment Outcome ; Inflammation/complications* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/adverse effects*

OBJECTIVETo observe the effect of different concentrations of zoledronic acid on human gingival fibroblast (HGF) cells proliferation and apoptosis, and to investigate the mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) caused by zoledronic acid.

METHODSDifferent concentrations (0, 0.5, l.0, 5.0, 10.0 µmol/L) of zoledronic acid acted on the HGF. After 24 hours, flow cytometry was used to detect the rate of apoptosis and methyl thiazolyl terazolium (MTT) assay used to observe the proliferation of HGF. The effect of different concentrations of zoledronic acid on cell proliferation was examined by proliferation test on day 2, 4 and 7.

RESULTSFlow cytometry showed that when the concentration of zoledronic acid was 0, 0.5, 1.0, 5.0, 10.0 µmol/L, the apoptosis rate was (0.67 ± 0.50)%, (2.13 ± 0.21)%, (3.27 ± 0.23)%, (4.17 ± 0.35)%, (9.87 ± 1.79)% respectively. The difference in HGF cells between control group and zoledronic acid groups was significant (P < 0.05) at three concentrations of zoledronic acid (1.0, 5.0, 10.0 µmol/L). The cell proliferation test showed an concentration-time dependent effect. With increase of concentration and time, the cell proliferation was significantly inhibited. There was significant difference in absorbance value among the different concentration groups (P < 0.05).

CONCLUSIONSZoledronic acid can inhibit HGF proliferation and promote its apoptosis.

Apoptosis ; drug effects ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; etiology ; Bone Density Conservation Agents ; pharmacology ; Cell Proliferation ; drug effects ; Coloring Agents ; Diphosphonates ; pharmacology ; Dose-Response Relationship, Drug ; Fibroblasts ; drug effects ; physiology ; Flow Cytometry ; Gingiva ; cytology ; Humans ; Imidazoles ; pharmacology ; Tetrazolium Salts ; Thiazoles ; Time Factors