Osteoporosis induced by cellular senescence: A mathematical model

Area of Science:

• Gerontology
• Biomedical Engineering
• Cell Biology

Background:

• Osteoporosis is characterized by bone mass loss, increasing fracture risk, particularly after age 50.
• Cellular senescence, a state of permanent cell cycle arrest, increases with age and is implicated in aging-related diseases.
• The link between increased senescent cells and age-related bone density loss in osteoporosis warrants investigation.

Purpose of the Study:

• To mathematically model the contribution of cellular senescence to bone density loss in osteoporosis.
• To simulate bone loss in men and women aged 50-100.
• To assess the efficacy of senolytic drugs in mitigating osteoporosis-related bone loss.

Main Methods:

• Development and application of a mathematical model to simulate bone density changes.
• Inclusion of the rate of net senescent cell formation (η) as a key parameter.
• Simulation of treatment scenarios involving senolytic drugs (fisetin, quercetin) and estrogen hormonal therapy.

Main Results:

• Model simulations at η = 1 align with empirical data on bone loss.
• Senescent cells significantly contribute to bone density loss, with the rate of formation (η) being a critical factor.
• Early treatment with fisetin, combined with estrogen therapy, can reduce bone density loss below the osteoporosis threshold (e.g., 23.4% by age 75 for women).

Conclusions:

• Cellular senescence is a significant driver of age-related bone loss and osteoporosis.
• Senolytic therapies, such as fisetin, show promise in preventing or reducing osteoporosis.
• Mathematical modeling provides a valuable tool for understanding disease progression and evaluating therapeutic interventions.