Musculoskeletal Diseases

Symptoms and General Pathology

All Conditions

Osteonecrosis

Bone Diseases

Necrosis

Bone Density Conservation Agents

All Drugs and Chemicals

Denosumab

Diphosphonates

Patients in high-dose antiresorptives with bone metastases

Drug Holiday as standard operation procedure

We want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction. The experimental intervention in this trial is drug continuation starting before tooth extraction with primary closure.

We simply ask the participating cancer patients to continue their high dose antiresorptive treatment for 4 months (intervention-period: 1 month pre-operative, 3 months post-operative) instead of taking a drug holiday.

Continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)

The aim of this trial is to evaluate high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure (surgical extraction) including how a drug holiday affects the health related quality of life.

Research question: Does a drug holiday have any influence on health related quality of life or the incidence of developing osteonecrosis of the jaw after surgical tooth extraction? The investigators hypothesize that a drug holiday 1 month before to 3 months after surgical tooth extraction in cancer patients do not influence the development of osteonecrosis of the jaw and may even affect the health related quality of life negatively.

Osteonecrosis of the jaw is a known adverse reaction to antiresorptive medication, including bisphosphonate and denosumab. The globally accepted term is Medication-Related Osteonecrosis of the Jaws (MRONJ). Since 2003 there has been a worldwide focus at medication-related osteonecrosis, even though there still exist several of unanswered questions - one of them is the effect of a drug holiday in relation to tooth extraction. A drug holiday is a temporary discontinuation of a drug and has been suggested among risk reduction strategies in the literature. It is still unknown whether a drug holiday plays a significant role in relation to tooth extraction for the development of osteonecrosis. The investigators want to investigate the importance of an antiresorptive drug holiday (bisphosphonate, denosumab) in relation to tooth extraction.

The aim of this trial is therefore to clarify the meaning of high-dose antiresorptive drug holiday related to tooth extraction with primary mucosal closure in cancer patients and reveal how a drug holiday affects the health related quality of life. A continuation of the patients' antiresorptive treatment can possibly lead to increased risk of osteonecrosis of the jaw, but with the operation procedure with primary closure it is unlikely. It is beneficial for the cancer patients to continue the high dose antiresorptive therapy because a drug holiday is a stop in their anti-cancer treatment with risk of increased pain as well as unwanted skeletal events to occur, and potentially progress of metastases to follow.

This trial is designed as an investigator-initiated, parallel-group, randomized, clinical, single-blinded, trial investigating no antiresorptive drug holiday starting before tooth extraction with primary closure versus antiresorptive drug holiday starting before tooth extraction with primary closure in cancer patients

The allocation of the patients is not known to the clinical investigator, the surgeon or the outcome assessor but to the patient's oncologic doctor and nurse, who are in charge of drug delivery, and a supervisor (Klaus Gotfredsen) not involved in any registrations or surgeries.

The participating patients will not be blinded. The patients do know which group they are randomized to and therefore do know if they are treated with or without drug holiday during the trial period (1+3 months). The patients are carefully instructed not to reveal which group they belong during the trial to the assessor.

Klaus Gotfredsen will make sure that the patients randomized to the intervention group will continue their antiresorptive therapy and the patients randomized to the control group will be treated with drug holiday this in close collaboration with the oncological departments. The medicine will be giving to the patient by the department's nurse.

Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction

Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction - A Randomized Clinical Trial

The outcome assessor has 3 options for registration related to ONJ occurrence:

* Complete healing = mucosal covering = no sign of ONJ, defined as complete wound healing; Intact mucosa, that is total mucosal covering over the tooth extraction area.
* Incomplete healing = presence of fibrin covering partly or over all mucosal operation area; Defined as the presence of fibrin at the surface of the operation area, thus still being a wound.
* ONJ present, defined according to the AAOMS position paper 2014 (4), all three items have to be present:

  1. Current or previous treatment with antiresorptive agents.
  2. Exposed bone or bone that can be probed through an extraoral or intraoral fistula that has persisted for longer than 8 weeks.
  3. No history of radiation therapy to the jaws or obvious metastatic disease to the jaws.

The patients are given the EQ-5D-5L questionnaire. The 5-level EQ-5D version (EQ-%D-5L) was introduced by the EuroQol Group in 2009 and consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, serve problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The Danish dataset (SPSS syntax crosswalk values EQ-5D-5L Denmark) will be used to analyze patients´ responses.

Pain from the jaw is registered by a Visual Analogue Scale (VAS). The investigator will give the patient a paper with a VAS, see attached appendix 3, and ask following question: "On a scale from 0 to 10, where 0 is no pain and 10 is the worst thinkable pain, mark at the scale how much pain you feel from your jaw at tooth operation site".

The patient is giving a simple questionnaire, where they have to answer yes or no to following question: "Have you visited your own doctor or been hospitalized because of fractures or other skeletal complications during this trial period - yes or no. If yes, please write why." See attached appendix 4: Skeletal-related event questionnaire

The tumor-evaluation will be done by the oncologic doctor in due to their departments routine.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction	NCT04540601	Osteonecrosis D...	Continuation of...	-	University of Copenhagen
Antiresorptive Drug Continuation Compared With Drug Holiday in Cancer Patients Needing Tooth Extraction	NCT04540601	Osteonecrosis D...	Continuation of...	-	University of Copenhagen

Spots Global Cancer Trial Database for continuation of antiresorptives in relation to tooth extraction (surgical tooth removal)