Agents of Bone Metabolism Flashcards
What are the actions of RANKL and how is osteoprotegrin involved?
RANKL is released by osteoblasts after PTH binding. It binds to RANK expressed by osteoclasts and their precursors. Osteoprotegrin is another protein released by osteoblasts which is a decoy ligand for RANKL.
Describe how PTH increase osteoblast proliferation?
PTH inhibits the production of sclerostin from osteocytes, which blocks osteoblast proliferation.
Note: The net effect of PTH is still bone resorption
What is teriparatide?
Recombinant human PTH
What are the MOA and uses of teriparratide? What is the limit of it’s use?
MOA - intermittent PTH induces bone growth
Uses - Women with osteoporotic fractures or risk of fractures, those who have failed other therapies, and men with hypogonadal osteoporosis
Limit - Therapy has not been studied past two years. Must stop at two years.
What are the ADRs and CIs of Teriparatide?
ADR - orthostatic hypotension, hypercalcemia, hyper uricemia, and angina
CI - don’t use in those at risk of osteosarcoma: paget’s, open epihpysis, irradiation of skeleton, increased alkaline phosphatase levels
What are Vitamin D2 and D3?
D2 = cholecalciferol D3 = plant-derived ergocalciferol
What are the actions of the active form of vitamin D, 1,25-dihydroxy vitamin D (calcitriol)?
Increases intestinal absorption of calcium and phosphate, increased reabsorption of calcium and phosphate from the kidneys, and expression of RANKL by osteoblasts.
What is the therapeutic use of Vitamin D Analogs?
- Can be used to cure nutritional rickets
- Metabolic Rickets - if patient is in renal failure calcitriol should be used
- Osteomalacia
- Hypoparathyroidism
- Prophylaxis of osteoporosis
What are the ADRs of Vitamin D analogs?
hypercalcemia, hyperphosphatemia, constipation, arrhythmias, and pancreatitis
What are the actions of FGF-23 and where is it produced?
FGF-23 is produced by osteocytes and osteoblasts. It inhibits the production of vitamin D and the reabsorption of phosphate.
What is the MOA, use, and ADR of calcitonin?
MOA - inhibits bone resorption and calcium and phosphate reabsorption
Use - paget’s and osteoporosis
ADR - urticaria and hand swelling
What is the therapeutic use of glucocorticoids with reference to hypercalcemia and what are the mechanisms which serve this purpose?
Glucocorticoids can be used to treat hypercalcemia of lymphomas and granulomatous diseases. They inhibit the absoprtion of calcium, increase calcium excretion, and inhibit bone formation. Prolonged use can result in oteoporosis.
What is raloxifene? Describe its use, ADR, and CI.
Raloxifene is a selective estrogen receptor modulator
Use - post-menopausal osteoporosis
ADRs - hot flashes, leg cramping, and increased risk of thromboembolism
CI - history of thromboembolism or CAD
What is a prototype bisphosphonate and its MOA?
Alendronate
These are analogs of pyrophosphates that have the P-O-P bond replaced by P-C-P. This causes chelation of Ca and decreased formation and dissolution of hydroxyapatite. Leading to increased mineral density.
Describe the administration and uses of alendronate.
Must be taken on an empty stomach, with a full glass of water and remaining standing.
Used for the Tx of osteoporosis, paget’s, and hypercalcemia of malignancy
What are the ADRs of bisphosphonates?
Gastric and esophageal mucosal irritation, osteonecrosis affecting the jaw and subtrochanteric femur.
Describe denosumab with respect to MOA, Use, and ADRs.
MOA - mAb which binds RANKL mimicking osteoprotegrin
Use - post-menopausal osteoporosis
ADR - increased risk of infection, possibility of osteonecrosis, posibility of transient hypocalcemia
What are the manifestations of hypercalcemia and the major causes?
Mx - CNS depression progressing towards coma
Etx - Hyperparathyroidism, hypercalcemia of malignancy, thiazide diuretics, vitaminosis D, sarcoidosis, milk-alkali, thyrotoxicosis, and adrenal insufficiency
How is hypercalcemia treated?
The mainstay treatment is fluids with furosemide diuretics. Phosphates are a rapid, but dangerous way to decrease calcium. Glucocorticoids can be used to treat the hypercalcemia of chronic disease.
Describe the Mx and Etx of hypocalcemia.
Mx - tetany and parasthesias
Etx - HypoPTH, vitamin D deficiency, malabsorption, or chronic renal failure
Describe the tx of hypocalcemia.
There are three tx methods of hypocalcemia: IV calcium gluconate (severe), oral calcium carbonate, and calcitriol (rapid action).
Describe the Etx and Tx of hyperphosphatemia.
Etx - Chronic renal failure, hypoPTH, vitamin D toxicity
Tx - limit phosphate intake and give phosphate binding agents
