Conservative Versus Surgical Treatment for Medication Related Osteonecrosis of the Jaws (MRONJ) Stages I and II, a Quasi-experimental Clinical Trial With Discovery of Salivary Biomarkers
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Complete clinical resolution
研究概览
简要总结
Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients receiving antiresorptive therapies, such as Bisphosphonates and Denosumab. It is defined by the presence of exposed bone or a fistula that probes bone in the jaws for a period greater than 8 weeks in patient with a history of current or past antiresorptive or antiangiogenic treatment, and in the absence of prior radiotherapy or maxillary bone metastases. Depending on the severity of the disease 4 stages are described.
On the other hand, although the presence of alterations in the levels of certain biomarkers in saliva has been documented in patients with MRONJ compared to healthy patients, its applicability in clinical practice is still unknown.
Until recently, the status quo favored the adoption of a conservative strategy (non-surgical) for the initial management of patients with stage I and II. However, in recent years, this paradigm has been challenged by multiple authors who report better and more predictable outcomes with surgical treatment.
Based on the hypothesis that patients with MRONJ stage I and II subjected to initial surgical treatment have better results than those undergoing conservative (non-surgical) treatment, te research group has designed a unicentric, quasi-experimental clinical trial where the clinical and radiological outcome at the third month of 2 groups of patients with stages I and II MRONJ undergoing non-surgical treatment (Group 1 / control) versus initial surgical treatment (Group 2 / intervention) will be compared.
Also, the investigators hypothesize that the patients with complete resolution of the disease will also normalize salivary biomarkers levels unlike those with stable or progressive disease, meaning there is a correlation between clinical and biochemical response. Accordingly, the levels of specific salivary biomarkers at baseline and at the third month will be determined and compared with the clinical outcome.
After enrollment patients will be instructed and offered both treatment strategies, and assigned to the corresponding group according to their choice. Patients in group 1 (non-surgical) will receive traditional conservative treatment while patients undergoing surgical treatment will receive the same guidelines of conservative treatment plus surgery according to a specific surgical protocol.
详细描述
- Type of study: unicentric quasi-experimental clinical trial
- Hypothesis:
2.1. Patients with MRONJ stage I and II subjected to initial surgical treatment have better results than those undergoing conservative (non-surgical) treatment.
2.2. There is a correlation between clinical and biochemical outcome and the detection in saliva of certain biomarkers such as Amino Terminal Crosslinked Telopeptides of Type 1 Collagen (NTX), Matrix metallopeptidase 9 (MMP-9), Interleukin 1a (IL-1a), Interleukin 1b (IL-1b), Interleukin 6 (IL-6), Interleukin 17 (IL-17) and Interleukin 36α (IL-36α) may be useful to monitor treatment response. 3. Main Objectives:
3.1. To compare the clinical and radiological outcome after 3 months of conservative treatment versus initial surgical treatment in patients with MRONJ stage I and II.
3.2. To determine the levels of salivary biomarkers at the beginning and after 3 months of treatment while correlating them with the clinical outcome. 4. Secondary Aims
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of stage I or stage II medication related osteonecrosis of the jaws (MRONJ) according to the 2014 AAOMS position paper.
排除标准
- •Coexistence of any medical or social condition that prevents proper adherence to treatment or follow-ups (dependent patients without adequate socio-familiar support, drug addiction, severe psychiatric illness, terminal disease with life expectancy less than 3 months).
- •Coexistence of Brown's Tumor, Paget's Disease or other bone diseases with the exception of Osteoporosis or bone metastases.
结局指标
主要结局
Complete clinical resolution
时间窗: Third month
This is the first of the three possible clinical outcome. The patient has achieved complete mucosal healing meaning there is no signs of bone exposure or fistula, the patient is asymptomatic and thus, can be considered cured.
Clinically stable disease
时间窗: Third month
Second possible clinical outcome. The patient has not been cured but has neither gotten worse meaning that the area of bone exposure (in square centimeters) is equal or not greater than 50 percent of the initial measurement, and has not developed disease up-staging.
Clinical progression or up-staging
时间窗: Third month
Third possible clinical outcome. The patient has gotten worse meaning that the area of bone exposure (in square centimeters) is greater than 50 percent of the initial measurement, or the patient has progressed to a higher stage.
Level of salivary NTX
时间窗: Third Month
Expressed in nanomoles of bone collagen equivalents
Level of salivary MMP-9
时间窗: Third Month
Expressed in nanograms/milliliters
Levels of IL-1a, IL-1b, IL-6, IL-17 and IL-36α.
时间窗: Third Month
Expressed in picograms/milliliters
次要结局
- Radiologically stable disease(Third Month)
- Radiological absence of radiolucent areas or complete ossification.(Third month)
- Radiological progression(Third month)
研究者
Juan Martin Zarate Gonzalez
Principal Investigator
Fundació d'investigació Sanitària de les Illes Balears