Abstract
Bone is the preferential site of metastasis for breast and prostate tumor. Cancer cells establish a tight relationship with the host tissue, secreting factors that stimulate or inhibit bone cells, receiving signals generated from the bone remodeling activity, and displaying some features of bone cells. This interplay between tumor and bone cells alters the physiological bone remodeling, leading to the generation of a vicious cycle that promotes bone metastasis growth. To prevent the skeletal-related events (SRE) associated with bone metastasis, approaches to inhibit osteoclast bone resorption are reported. The bisphosphonates and Denosumab are currently used in the treatment of patients affected by bone lesions. They act to prevent or counteract the SRE, including pathologic fractures, spinal cord compression, and pain associated with bone metastasis. However, their primary effects on tumor cells still remain controversial. In this review, a description of the mechanisms leading to the onset of bone metastasis and clinical approaches to treat them are described.
Highlights
Bone is the third most frequent site of metastasis after lung and liver and typically indicates a short-term prognosis in cancer patients [1,2]
Tumor cells deploy complex mechanisms to survive: on one hand, they modify the foreign microenvironment via the establishment of a “premetastatic niche” [30], which consists in predisposing changes of the distant microenvironment into a more hospitable site for their future settling of; on the other hand, disseminated tumor cells use cell-autonomous programs in order to adapt to the new home [11]
IL-6 has many effects on bone tissue: (1) It induces the expression of RANK-L from stromal cells and osteoblasts [45]; (2) It stimulates tumor cells to express parathyroid hormone-related peptide (PTHrP), IL-8, IL-11, RANK-L, and Cyclooxygenase 2 (Cox-2), inducing bone resorption [44,46]; (3) It inhibits osteogenesis regulated by Wnt [47]; (4) It stimulates the activity of estradiol 17 β-hydroxysteroid dehydrogenase, countering the protective role of the estrogens on bone and enhancing bone resorption and hypercalcemia in breast cancer patients; (5) It reduces the expression of genes like type II collagen and aggrecan, reducing bone formation
Summary
Bone is the third most frequent site of metastasis after lung and liver and typically indicates a short-term prognosis in cancer patients [1,2]. Patients’ survival after a diagnosis of bone metastasis depends on the primary tumor: 48 months for thyroid tumors, 19–25 for breast cancer, 12–53 for prostate cancer, 12 for renal cell carcinoma, 6–9 for bladder cancer, 6–7 for lung cancer, and 6 for melanoma [4]. Hypercalcemia is the most common metabolic complication of bone metastatic disease and frequently occurs in lung squamous cell carcinoma, breast cancer, multiple myeloma, and lymphoma [8]. Hypercalcemia is due to focal and generalized osteolysis induced by the tumor cells, increased tubular calcium reabsorption by the kidney, and impaired renal function [9]. When one of these signs and symptoms occurs, a basic screen needs to be performed. The analysis of all these parameters needs to be combined with imaging data, including bone scintigraphy, radiographs, magnetic resonance imaging (MRI), and positron emission tomography (PET) [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
