Short summary

This clinical trial aims to study the effects and safety of senolytics and antioxidant therapy on bone. 120 men and women aged 60-90 years with low bone mass (T-score < -1) will be randomised to 1 of 3 treatment groups that will receive either oral dasatinib + oral quercetin, oral nicotinamide riboside, or no treatment for 20 weeks. Effects will be assessed by changes in bone turnover, microarchitecture, bone mineral density and physical function.

Rationale

Evidence suggests that it is feasible to alleviate chronic age-related disorders by targeting the biology of aging. Recent studies implicate cellular senescence at the nexus of skeletal aging, suggesting that selectively eliminating senescent cells may emerge as a conceptually novel approach to manage the enormous problem of age-related bone loss. In addition, previous studies have demonstrated that antioxidants inhibit cellular senescence. The aim of this randomised clinical trial is to study osteoporosis as a disease of accelerated skeletal aging caused by accumulation of senescent cells within the skeleton and investigate the effects and safety of senolytics and antioxidant therapy on bone. The main trial endpoint is the percent change in circulating marker of bone resorption (CTX) measured at baseline and at week 20. Secondary endpoints are the changes in bone resorption marker tartrate resistant acid phosphatase (TRAcP) and bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase) measured at baseline and at 20 weeks.

Description of the cohort

This trial will include 120 Men and women (menopause > 5 years and FSH and LH in the postmenopausal range) aged 60-90 years with increased fracture risk. - osteopenia (ICD10 DM858A) based on a T-score ≤ -2 to -2.5 at the total hip/femoral neck, or lumbar spine - 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) - 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

Data and biological material

We use biomarkers for bone formation and bone resorption measured in fasting blood samples. We would also assess bone microsrchitecture and bone mass density using HR-pQCT resp. DXA-scans, and changes in physical function.

Collaborating researchers and departments

OPEN, Open Patient data Explorative Network, OUH Odense

• Janni Brødbæk

GCP-enheden ved Odense Universitetshospital

• Charlotte Calov
• Josephine Malmström Kroman

Blodprøver og Biokemi

• Pernille Just Vinholt
• Maria Skyum Jørgensen