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Cancer and Bone. Indirect affects of cancer on bone homeostasis and density. Types of Cancer. Acute Lymphoblastic Leukemia (ALL) Breast Cancer Prostate Cancer. Definitions. Cancer —an invasive tumor or growth that can be malignant Osteopenia —bone deficiency
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Cancer and Bone Indirect affects of cancer on bone homeostasis and density
Types of Cancer • Acute Lymphoblastic Leukemia (ALL) • Breast Cancer • Prostate Cancer
Definitions • Cancer—an invasive tumor or growth that can be malignant • Osteopenia—bone deficiency • Hypercalcemia—total serum calcium above 2.55 mmol/L or ionized calcium levels above 1.23 mmol/L • Bone Homeostasis—the continual actions of osteoclasts and osteoblasts resulting in a balanced resorption and formation of bone
Types of Effects on Bone • Indirect factors that act on the bone and kidney, successfully disrupting calcium homeostasis • By secondary spread of a tumor from an affected organ to bone • Directly, with a bone tumor
Regulation of Bone Density Through Calcium Homeostasis • Parathyroid Hormone (PTH) • Calcitriol (1,25-(OH)2D3) • Calcitonin
PTH • Increases number and activity of osteoclasts • Stimulates renal calcium absorption • Inhibits phosphate absorption • Stimulates production of renal 1,25-(OH)2D3
Calcitonin • Increases gastrointestinal absorption of Ca and P • Stimulates bone resorption • Increases capacity of PTH to stimulate renal tubules.
Calcitonin • Regulated by plasma-ionized calcium concentrations • Inhibits bone resorption
Tumor Secretions • Humoral secretions act on bone, kidneys, and intestine • Locally, they directly stimulate osteoclastic bone resorption • Work along side coexisting primary hyperparathyroidism
PTHrP • Purified from human lung cancer, breast cancer, and renal cell carcinoma • Shares 70% of first 13 N-terminal residues with PTH • Binds to PTH receptors • Shares similar biological activity with PTH
PTHrP (continued) • Stimulates adenylate cyclase in renal and bone systems • Increases reabsorption of Ca in renal tubule • Increases osteoclastic bone resorption • Decreases phosphate uptake in renal tubule • Stimulates 1a-hydroxylase