Cancer and Bone

1. Cancer and Bone Indirect affects of cancer on bone homeostasis and density

2. Types of Cancer • Acute Lymphoblastic Leukemia (ALL) • Breast Cancer • Prostate Cancer

3. 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

4. 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

5. Regulation of Bone Density Through Calcium Homeostasis • Parathyroid Hormone (PTH) • Calcitriol (1,25-(OH)2D3) • Calcitonin

7. PTH • Increases number and activity of osteoclasts • Stimulates renal calcium absorption • Inhibits phosphate absorption • Stimulates production of renal 1,25-(OH)2D3

8. Calcitonin • Increases gastrointestinal absorption of Ca and P • Stimulates bone resorption • Increases capacity of PTH to stimulate renal tubules.

9. Calcitonin • Regulated by plasma-ionized calcium concentrations • Inhibits bone resorption

10. Bone Density Regulators

11. Tumor Secretions • Humoral secretions act on bone, kidneys, and intestine • Locally, they directly stimulate osteoclastic bone resorption • Work along side coexisting primary hyperparathyroidism

12. PTHrP Presentation

13. 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

14. 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