Senolytics to Improve Osteoporosis Therapy (SENIOR)
Osteopenia, Osteoporosis
About this trial
This is an interventional treatment trial for Osteopenia, Osteoporosis focused on measuring Age related bone loss, Cellular senescence
Eligibility Criteria
Inclusion Criteria: Men and women (menopause > 5 years and FSH and LH in the postmenopausal range) aged 60-90 years with increased fracture risk according to WHO 10 years absolute Fracture Risk Assessment Tool (FRAX) osteopenia (ICD10 DM858A) based on a T-score ≤ -2 to -2.5 at the total hip/femoral neck, or lumbar spine (FRAX score ranging from 10-70) osteopenia (ICD10 DM858A) based on a T-score < -1 to -2.5 and a fragility fracture at any time (excluding hip and vertebral fractures within the last 2 years) (FRAX ranging from 11-68) osteoporosis (ICD10 DM819) based on a T-score between >-3 and ≤ -2.5, which includes candidates suitable for conventional osteoporosis therapies, but who prefer to participate in the trial, despite being candidates for conventional osteoporosis therapy, or candidates which cannot be treated with conventional therapies due to contraindications. Ability to provide informed consent Exclusion Criteria: DXA of hip or spine not possible e.g., due to a prosthesis Inability to provide fasting blood samples Primary hyperparathyroidism Vitamin D deficiency (<50 nM) (re-test after substitution acceptable) Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, chronic kidney disease defined as eGFR <30 or liver dysfunction, rheumatism, celiac disease/malabsorption, hypogonadism, severe COPD, hypopituitarism, Cushing's disease, uncontrolled diabetes (HbA1c > 58 mmol/mol). Antiresorptive or bone anabolic drugs for the last 2 years (5 years if treated with zoledronic acid) Concomitant treatments known to influence bone metabolism e.g., glucocorticoids (systemic treatments), anabolic steroids, etc. Subjects taking the following other drugs if they cannot be held for at least 2 days before and during administration of D+Q: digoxin, lithium, all statins, repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate, corticosteroids, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide, enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacrolimus, sirolimus, carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline, warfarin, heparin, clopidogrel, celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron Subjects taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). If antifungals are necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic. Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two days before and during the study drug dosing periods. Anti-arrhythmic medications known to cause QTc prolongation Tyrosine kinase inhibitor therapy Subjects with an abnormal Complete Blood Count (clinically insignificant changes would be acceptable based on the judgement of the investigators) Subjects on antiplatelet agents (Clopidogrel; Dipyridamole + ASA; ASA, Ticagrelor; Prasugrel; Ticlopidine or other) who are unable or unwilling to reduce or hold therapy prior to and during the study drug dosing periods and collection of bone biopsies. Subjects may continue their previous regimen between study drug dosing periods. Known allergy to dasatinib, quercetin, or nicotinamide riboside Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin, erythromycin), antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir) Presence of any condition the Investigator believes would place the subject at risk or would preclude the subject from successfully completing all aspects of the trial e.g., heart failure, malignancy etc. QTc >470 msec Inability to take oral medication The study will exclude subjects with inability to speak and understand Danish and with inability to cooperate
Sites / Locations
- Odense University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
No Intervention
Dasatinib plus Quercetin (DQ)
Nicotinamide Riboside (NR)
Control
Study participants will receive a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d quercetin (oral) for three consecutive days followed by 25 days without treatment, with treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times)
The participants will receive treatment with 1g Nicotinamide Riboside (oral) daily for 20 weeks
The participants in the Control group, will not receive any treatment for 20 weeks.