Skeletal Impact of Cancer Therapies

Abstract

Both cancer and therapies used in the treatment of cancer can have significant deleterious effects on the skeleton, increasing the risks for both bone loss and fracture development. While advancements in cancer therapies have resulted in enhanced cancer survivorship for patients with many types of malignancies, it is increasingly recognized that efforts to reduce bone loss and limit fractures must be considered for nearly all patients undergoing cancer therapy in order to diminish the anticipated future skeletal consequences. To date, most studies examining the impact of cancer therapies on skeletal outcomes have focused on endocrine associated cancers of the breast and prostate, with more recent advances in our understanding of bone loss and fracture risk in other malignancies. Pharmacologic efforts to limit the adverse effects of cancer therapies on bone have nearly universally employed anti‐resorptive approaches, although studies have frequently relied on surrogate outcomes such as changes in bone mineral density or bone turnover markers, rather than on fractures or other skeletal‐related events, as primary study endpoints. Compounding current deficiencies for the provision of optimal care is the recognition that despite clearly written and straightforward society‐based guidelines, vulnerable eligible patients are very often neither identified nor provided with appropriate treatments to limit the skeletal impact of their cancer therapies.

Even before the initiation of cancer treatment therapies, patients with cancer
are at increased risk for accelerated bone loss, as evidenced by lower bone mineral
density in cancer patients relative to subjects without cancer, regardless of cancer
type 1
. Adding to this underlying skeletal insult is the further damage that results
from many cancer therapies. Thus bone loss in patients with cancer reflects both the
effects of the cancer itself, as well as the skeletal response to therapies currently
used to treat cancer including a wide range of chemotherapeutics, as well as agents
such as glucocorticoids, aromatase inhibitors, and androgen deprivation therapies. In
addition, bone is also a very common site of cancer metastasis, with tumor cells
exerting both direct and indirect effects on bone cells to cause systemic as well as
localized bone loss. When viewed through the prism of the increased survivorship
now commonly seen in patients with many types of malignancies, efforts to limit
bone loss and fractures that can significantly diminish quality of life, have become
increasingly important for the care of cancer patients.
This manuscript will focus on currently used cancer therapies, the impact of
these therapies on the skeleton, and available data for limiting bone loss and
fractures in cancer patients treated with these therapies. Given that the majority of
work to date has focused on patients with breast and prostate cancers, this review
will emphasize those cancers, but will also include discussion of more general
treatments such as glucocorticoids, as well as data on cancer therapies for
hematologic malignancies.

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13866