The adverse effects of chemotherapy on bone mass are not prevented by senolytics
Abstract Cancer survivors experience many short- and long-term side effects caused by chemotherapy, including low bone mineral density and deterioration of bone microarchitecture. Administration of chemotherapy drugs to disease free mice causes rapid bone loss. However, whether the bone effects pers...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-01717-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849731774377099264 |
|---|---|
| author | Md Mohsin Ali Pilar Simmons Aaron Warren Landon B. Gatrell Ana Resende-Coelho Taylor McElroy Antiño R. Allen Maria Almeida |
| author_facet | Md Mohsin Ali Pilar Simmons Aaron Warren Landon B. Gatrell Ana Resende-Coelho Taylor McElroy Antiño R. Allen Maria Almeida |
| author_sort | Md Mohsin Ali |
| collection | DOAJ |
| description | Abstract Cancer survivors experience many short- and long-term side effects caused by chemotherapy, including low bone mineral density and deterioration of bone microarchitecture. Administration of chemotherapy drugs to disease free mice causes rapid bone loss. However, whether the bone effects persist throughout life and the mechanisms responsible remain unclear. One plausible cause of chemotherapy-induced bone loss is cellular senescence. Here, female mice were administered doxorubicin, cyclophosphamide and docetaxel, a chemotherapy regimen commonly used in breast cancer patients, in combination with two types of drugs that kill senescent cells (senolytics), namely dasatinib + quercetin or piperlongumine. Mice receiving chemotherapy experienced a rapid decrease in trabecular bone mass, which was detectable two weeks after initiation of treatment and was associated with increased expression of senescence markers. None of the senolytics prevented the effects of chemotherapy on bone mass. In separate experiments, we examined the skeletal effects of chemotherapy six and twelve months after the cessation of treatment. The deleterious effects of chemotherapy on bone mass remained up to 12 months after cessation of treatment, while no markers of senescence could be detected in bone. Together, these results suggest that the deleterious effects of this chemotherapy regimen on bone health are not due to the accumulation of senescent cells. |
| format | Article |
| id | doaj-art-2d1b0f91a0124f0c8af513cccbb83a1b |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2d1b0f91a0124f0c8af513cccbb83a1b2025-08-20T03:08:25ZengNature PortfolioScientific Reports2045-23222025-05-0115111510.1038/s41598-025-01717-5The adverse effects of chemotherapy on bone mass are not prevented by senolyticsMd Mohsin Ali0Pilar Simmons1Aaron Warren2Landon B. Gatrell3Ana Resende-Coelho4Taylor McElroy5Antiño R. Allen6Maria Almeida7Division of Endocrinology and Metabolism, University of Arkansas for Medical SciencesDivision of Radiation Health, University of Arkansas for Medical SciencesDivision of Endocrinology and Metabolism, University of Arkansas for Medical SciencesDivision of Endocrinology and Metabolism, University of Arkansas for Medical SciencesDivision of Endocrinology and Metabolism, University of Arkansas for Medical SciencesDivision of Radiation Health, University of Arkansas for Medical SciencesDivision of Radiation Health, University of Arkansas for Medical SciencesDivision of Endocrinology and Metabolism, University of Arkansas for Medical SciencesAbstract Cancer survivors experience many short- and long-term side effects caused by chemotherapy, including low bone mineral density and deterioration of bone microarchitecture. Administration of chemotherapy drugs to disease free mice causes rapid bone loss. However, whether the bone effects persist throughout life and the mechanisms responsible remain unclear. One plausible cause of chemotherapy-induced bone loss is cellular senescence. Here, female mice were administered doxorubicin, cyclophosphamide and docetaxel, a chemotherapy regimen commonly used in breast cancer patients, in combination with two types of drugs that kill senescent cells (senolytics), namely dasatinib + quercetin or piperlongumine. Mice receiving chemotherapy experienced a rapid decrease in trabecular bone mass, which was detectable two weeks after initiation of treatment and was associated with increased expression of senescence markers. None of the senolytics prevented the effects of chemotherapy on bone mass. In separate experiments, we examined the skeletal effects of chemotherapy six and twelve months after the cessation of treatment. The deleterious effects of chemotherapy on bone mass remained up to 12 months after cessation of treatment, while no markers of senescence could be detected in bone. Together, these results suggest that the deleterious effects of this chemotherapy regimen on bone health are not due to the accumulation of senescent cells.https://doi.org/10.1038/s41598-025-01717-5 |
| spellingShingle | Md Mohsin Ali Pilar Simmons Aaron Warren Landon B. Gatrell Ana Resende-Coelho Taylor McElroy Antiño R. Allen Maria Almeida The adverse effects of chemotherapy on bone mass are not prevented by senolytics Scientific Reports |
| title | The adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| title_full | The adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| title_fullStr | The adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| title_full_unstemmed | The adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| title_short | The adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| title_sort | adverse effects of chemotherapy on bone mass are not prevented by senolytics |
| url | https://doi.org/10.1038/s41598-025-01717-5 |
| work_keys_str_mv | AT mdmohsinali theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT pilarsimmons theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT aaronwarren theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT landonbgatrell theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT anaresendecoelho theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT taylormcelroy theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT antinorallen theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT mariaalmeida theadverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT mdmohsinali adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT pilarsimmons adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT aaronwarren adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT landonbgatrell adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT anaresendecoelho adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT taylormcelroy adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT antinorallen adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics AT mariaalmeida adverseeffectsofchemotherapyonbonemassarenotpreventedbysenolytics |