The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors

Abstract

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.

Figure 1

Bone resorption: the osteoclast. Abbreviations: CSF, colony-stimulating factor; RANKL, receptor activator of nuclear factor kappa B ligand; TGF-β, transforming growth factor β. Reproduced with permission from Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–1664.

Figure 2

RANKL in osteoclast formation. Abbreviations: JNK, Jun N-terminal kinase; NF-kB, nuclear factor kappa B; PTH, parathyroid hormone; RANK, receptor activator of nuclear factor kappa B; RANKL, receptor activator of nuclear factor kappa B ligand. Reproduced with permission from Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655–1664.

Figure 3

Imaging modalities used to detect bone metastases. Abbreviation: SPECT, single-photon emission CT. Adapted from Hamaoka T, Madewell JE, Podoloff DA, et al. Bone imaging in metastatic breast cancer. J Clin Oncol 2004;22:2942–2953.

Figure 4

Estimated percent change and 95% confidence intervals from baseline to 12 months in lumbar spine and total hip bone mineral density (BMD). ^aP-values from paired t-rest for open-label, non-comparative groups. ^bP-values from ANCOVA in favor of anastrozole plus risedronate. Reproduced with permission from Van Poznak C, Hannon RA, Clack G, et al. The SABRE (Study of Anastrozole with the Bisphosphonate RisedronatE) study: 12-month analysis [abstract]. Presented at 30th Annual San Antonio Breast Cancer Symposium; December 13–16, 2007; San Antonio, Texas. Abstract 502.

Figure 5

Mean (± standard error) changed in baseline bone mineral density in men with prostate cancer treated with leuprolide or leuprolide plus pamidronate. P value is between-group comparison of the percentage change from baseline to 48 weeks. Reprinted with permission from Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001;345:948–955.