bone minerals

• Calcium (Ca2+)


  One of the two main ions in bone mineral homeostasis
• Phosphate (PO4

  1. )

  One of the two main ions in bone mineral homeostasis
• Bone


  • The principal reservoir for calcium (98%) and phosphate (85%)
  • The remainder is in intracellular fluid and circulation
• Regulation of calcium and phosphate ions is important for the health and strength of bones, as well as electrical excitability of cells and intracellular signaling
• Outline and Objectives


  • To describe the principal ions, reservoir, and regulatory sites of bone mineral homeostasis
  • To describe the effects of parathyroid hormone (PTH)
  • To describe the effects of vitamin D3 metabolites, and interaction with PTH
  • To describe and understand disorders related to bone mineral homeostasis
  • To describe and discuss therapeutics related to disruption of bone mineral homeostasis in osteoporosis
• Bone remodeling


  A dynamic process of constant regeneration and resorption of bone, regulated by osteoblasts and osteoclasts
• Parathyroid hormone (PTH)


  A peptide hormone that promotes bone resorption, increases calcium absorption and phosphate excretion in the kidney, and stimulates vitamin D processing
• PTH actions


  Increases calcium and phosphate levels in the blood
• Vitamin D3 metabolites


  Secosteroid hormones that promote calcium and phosphate absorption in the gut, decrease their excretion in the kidney, and promote bone resorption
• Interaction between PTH and vitamin D3

  PTH stimulates the conversion of vitamin D3 to its active form (calcitriol), which then interacts with PTH to regulate calcium and phosphate homeostasis
• Disruptions in calcium homeostasis can lead to acute crises (hypocalcemia, hypercalcemia) as well as long-term disorders (secondary hyperparathyroidism, osteoporosis)
• Osteoporosis


  A long-term disorder characterized by abnormal bone loss and increased fracture risk, often due to an imbalance between bone formation and resorption
• Potential osteoporosis therapeutics


  • Teriparatide (recombinant PTH fragment)
  • Bisphosphonates (inhibit osteoclast-mediated bone resorption)
  • Denosumab (monoclonal antibody that inhibits RANKL, preventing osteoclast activation)