Key Points
- The buildup of senescent cells – cell death-resistant cells that release inflammatory molecules to surrounding tissue – drives postmenopausal osteoporosis.
- Administering senolytic agents – drugs that destroy senescent cells – dasatinib and quercetin ameliorates postmenopausal osteoporosis in rats.
- Applying a hydrogel matrix containing dasatinib and quercetin plus a pro-bone formation protein called bone morphogenetic protein 2 (BMP2) propels bone regeneration in a defective thigh bone rat model.
Estrogen deficiency-driven postmenopausal osteoporosis encompasses imbalanced bone metabolism, leading to bone fragility in aged women. Estrogen supplementation accounts for one of the few recommended treatment options, but its side effects include blood clots and increased risks for breast and uterine cancers. As such, researchers continue their search for safer and more effective ways to treat postmenopausal osteoporosis.
Published in Bioactive Materials, Liu and colleagues from East China University show that treatment with the two-senolytic combination of dasatinib and quercetin alleviates postmenopausal osteoporosis in rats. The researchers found that dasatinib and quercetin’s benefits stem from selectively eliminating senescent cells in bone. Applying a hydrogel matrix containing dasatinib and quercetin along with a bone regeneration-promoting protein BMP2 effectively stimulates new bone growth. These findings suggest that postmenopausal osteoporosis patients can utilize dasatinib and quercetin to alleviate their condition.
Senolytics Promote Bone Regeneration in Osteoporosis by Targeting Senescent Cells
Liu and colleagues initiated estrogen deficiency-driven postmenopausal osteoporosis in 12- to 14-month-old rats (equivalent to ~30 years old in humans) by removing their ovaries. They measured bone density in thigh bones (femurs) using a scan called a micro-computed tomography that imaged the bone’s microarchitecture. As expected, the ovary removal significantly reduced bone density, however, dasatinib and quercetin treatment restored the femur’s density. These findings suggest that dasatinib and quercetin treatment can ameliorate postmenopausal osteoporosis.
Since dasatinib and quercetin may have osteoporosis-countering effects other than senescent cell elimination, the China-based research team wanted to confirm that these compounds eliminate senescent cells. They quantified two proteins found in senescent cells – p16 and p53 – within bones. For both proteins, removing the ovaries more than doubled the proteins’ abundance, however, dasatinib and quercetin treatment curtailed their elevated levels. These results support that dasatinib and quercetin remove senescent cells as evidenced by lower levels of senescent cell-specific proteins. Although this experiment doesn’t negate the possibility that dasatinib and quercetin provide other beneficial effects, it supports that they likely alleviate osteoporosis by eliminating senescent cells.
Since dasatinib and quercetin were found to alleviate osteoporosis, Liu and colleagues wanted to know whether combining them with a protein used traditionally to promote bone regeneration, BMP2, could synergistically enhance bone growth. To generate a defective bone model, the researchers removed bone from rats’ femurs. Liu and colleagues then applied a hydrogel matrix with dasatinib and quercetin along with BMP2 to measure bone regeneration-promoting capacity. Interestingly, dasatinib and quercetin plus BMP2 improved bone regeneration better than either of the two treatments alone, suggesting they act synergistically to promote bone regeneration. If these findings apply to humans, they point to a new and potentially more effective treatment combination to regenerate bone.
“We for the first time proposed that senolytic drug [dasatinib and quercetin] ameliorated [postmenopausal osteoporosis] and related diseases, systematically preventing bone loss, and locally rejuvenating bone regeneration with a synergia of BMP2,” said Liu and colleagues.
Senolytics Could Alleviate Osteoporosis
Previous research has shown that targeting senescent cells with dasatinib and quercetin stimulates bone growth in an age-related form of osteoporosis – senile osteoporosis. This study provides the first evidence that dasatinib and quercetin can treat estrogen deficiency-associated osteoporosis by targeting senescent cell buildup. Dasatinib and quercetin also worked in synergy to promote bone regeneration in a defective thigh bone rat model. The results also suggest that applying a combination of senolytics with BMP2 can speed up bone regrowth following severe fractures.
If these findings apply to humans, women with postmenopausal osteoporosis could consider supplementing with dasatinib and quercetin for relief. As a chemotherapeutic, dasatinib is only available with a prescription. Quercetin, on the other hand, can be purchased over the counter for prices ranging from $15 to $40 for a month’s supply.
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