Key Points:
- Aged mice and mice with chemotherapy-induced osteoporosis have decreased bone-forming cells.
- Treatment with senolytics – compounds that selectively eliminate aged (senescent) cells – increases bone marrow stem cells, which promote bone cell growth.
- Bone-targeted senolytic delivery more effectively promotes bone growth than conventional administration.
Senile osteoporosis is an age-related condition in which the delicate balance between bone resorption (breakdown of bone for use by the body) and bone formation is skewed towards bone resorption leading to an increased risk of bone breakage. A recent study has shown how bone-targeted senolytics can help increase bone formation in this age-related osteoporosis.
The study, out of China and published in Acta Biomaterialia, focused on mouse models of age-related osteoporosis. Stem cells from the bone marrow of these mice had increased levels of senescent cells. To specifically target these bone marrow stem cells (BMSCs), the scientists developed liposomes – fat packets that can help deliver molecules – with bone-targeting peptides (small proteins). Quercetin, encased in these liposomes, eliminated senescent bone cells and helped increase bone formation in the aged mice.
“The bone-targeted delivery of senolytics efficiently eliminates senescent cells to recover bone mass and microarchitecture, showing an effective treatment for senile osteoporosis,” the scientists wrote.
Treating Age-related Osteoporosis with Bone-targeted Quercetin
In two senile osteoporosis mouse models – a chemotherapy-induced accelerated senescence model and a naturally aging 24-month-old (approximately 70 years) model – the scientists saw decreased bone formation due to decreased osteoblasts – the bone cells that help secrete proteins to aid in bone formation. Additionally, both models had increased senescence markers as compared to young mice, with many bone marrow stem cells (BMSCs) – stem cells necessary for osteoblast formation – exhibiting senescence.
To target bone marrow, a bone-targeted delivery system is needed because senolytics don’t easily penetrate bone tissue. Xing and colleagues found that quercetin-loaded bone-targeting liposomes were more effective in eliminating senescent cells in mice as compared to conventional quercetin solution.
Additionally, quercetin-loaded liposomes in mice positively affected osteoblasts and other bone-forming cells, restoring the delicate balance between bone resorption and bone formation. Imaging showed that the liposomal quercetin enhanced bone volume and protected the bone microarchitecture in the aged mice, suggesting that the bone-targeted elimination of senescent cells may actually promote the treatment of age-related osteoporosis.
Quercetin in Aging and the Use of Targeted Therapies
Many studies have shown that quercetin has multiple anti-aging benefits due to its anti-inflammatory and antioxidant properties. It’s been shown to be beneficial in multiple age-related diseases, including cardiovascular diseases, osteoporosis, and bone fractures which occur in the elderly. However, the usual oral administration methods are plagued by the need for more frequent and higher doses to achieve the desired therapeutic effect, which increases side effects, such as headaches and gastrointestinal issues.
The work that Xing and colleagues have done on bone-targeted quercetin shows promise in specifically targeting senolytic treatments with minimal effects on other organs and may pave the way toward targeting senolytics to other organs for other conditions. However, this, too, has limitations due to its intravenous (IV) administration methods. Whether this method is going to be used in the future is still up in the air.
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