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.

Changes in Bone Turnover Marker Levels and Clinical Outcomes in Patients with Advanced Cancer and Bone Metastases Treated with Bone Antiresorptive Agents

“…Bone is a frequent and often the only site of metastasis in patients with advanced solid tumors such as breast cancer, prostate cancer, or lung cancer (1)(2)(3)(4)(5)(6)(7), and bone metastases are often associated with significant morbidity and poor prognosis (3,6,8). Metastatic bone disease disrupts the homeostasis of osteoclastmediated bone resorption and osteoblast-mediated bone formation, leading to dysregulation of normal bone remodeling processes (2,3).…”

“…Patients with advanced cancer and bone metastases typically have elevated levels of the bone turnover markers (BTM) urinary N-telopeptide (uNTx), an indicator of osteoclast activity, and serum bone-specific alkaline phosphatase (sBSAP), an indicator of osteoblast activity (6,7,(30)(31)(32). Both denosumab and zoledronic acid have been shown to significantly reduce uNTx and sBSAP levels (33,34), and these two BTMs have been investigated as potential prognostic factors for monitoring patients with cancer who are receiving bone antiresorptive agents.…”

Effect of adjuvant chemotherapy on carboxytelopeptide of cross-linked type I collagen of egyptian women with non-metastatic breast cancer

“…BC accounts for 37.6% of all reported tumors in Egyptian females, with an age-adjusted incidence rate of 49.6 per 100,000 females [2]. BC, prostate cancer, and multiple myeloma have particularly shown strong doi: 10.7243/2057-1631-1-1 association with skeletal metastases and related bone loss, resulting in fracture, hypercalcemia, pain, and declines in mobility and performance status [3,4].…”

“…Thus, women with BC are at increased risk for the development of osteoporosis and skeletal fractures, giving rise to significant morbidity and some mortality [3], as a consequence of aromatase inhibition or chemotherapyinduced ovarian failure [4,5]. Exemestane and anastrozole, two chemotherapeutic aromatase inhibitors, have been shown to directly inhibit osteoclast differentiation and bone resoption markers leading to osteoporosis in postmenopausal women with non-metastatic breast cancer (NMBC) [6].…”

Molecular target therapy for bone metastasis: starting a new era with denosumab, a RANKL inhibitor

“…One important emerging therapy includes, as part of its mechanism, the blocking of the receptor activator of nuclear factor kappa B (NF-kB) ligand (RANKL) to its natural receptor (RANK). This inhibits osteoclastogenesis and, thus, reduces bone resorption and interferes with mechanisms that stimulate osteoblastic bone formation, while inhibiting osteoclastic resorption [6].…”