P.07 Agents that affect bones
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Questions and Answers

What is the principal role of bones in relation to calcium and phosphate?

  • Providing structural support for hematopoiesis and endocrine tissue
  • Serving as the main storage site for these minerals (correct)
  • Regulating the levels of calcium and phosphate in the extracellular fluid
  • Facilitating absorption of calcium and phosphate from the diet

    • What is the main function of osteocalcin in its uncarboxylated form?

  • Regulating calcium and phosphate absorption
  • Stimulating insulin secretion and testicular function (correct)
  • Supporting hematopoietic capacity
  • Maintaining bone mineral homeostasis

    • Which process contributes to the soluble forms of calcium and phosphate in the body?

  • Excretion of minerals by the kidneys
  • Absorption of calcium and phosphate by the intestines
  • Continuous exchange of calcium between bone and the extracellular compartment during bone remodeling (correct)
  • Metabolism of minerals by the liver

    • Where does most of the absorption of calcium from the diet occur?

    <p>Duodenum</p> Signup and view all the answers

    What is the fate of a large fraction of filtered calcium and phosphate in the kidneys?

    <p>Reabsorption by the kidney</p> Signup and view all the answers

    What percentage of calcium and phosphate serve as the principal structural support for the body?

    <p>98% of calcium and 85% of phosphate</p> Signup and view all the answers

    What are potential consequences of disturbances in bone mineral homeostasis?

    <p>Osteoporosis with fractures</p> Signup and view all the answers

    Which form of calcium is the metabolically active form and tightly regulated?

    <p>Ionized Ca</p> Signup and view all the answers

    What are potential cellular dysfunctions associated with abnormalities in bone mineral homeostasis?

    <p><strong>Tetany</strong>, coma, muscle weakness</p> Signup and view all the answers

    Which fraction of total serum calcium primarily binds with albumin?

    <p>Protein-bound fraction</p> Signup and view all the answers

    Which anions can calcium form a complex with in the body?

    <p>Phosphate, citrate, bicarbonate</p> Signup and view all the answers

    What is the main role of PTH in the regulation of serum calcium and phosphorus balance?

    <p>Increasing calcium retention in the kidneys and promoting absorption of calcium and phosphorus in the small intestine</p> Signup and view all the answers

    What is the function of FGF23 in the regulation of serum calcium and phosphorus balance?

    <p>Inhibiting production of PTH for decreased absorption of calcium and phosphate in the small intestine</p> Signup and view all the answers

    Which regulator promotes both increased absorption of calcium and phosphorus in the small intestine?

    <p>Vitamin D1,25</p> Signup and view all the answers

    What is the effect of PTH on phosphorus reabsorption in the kidneys?

    <p>Blocks phosphorus reabsorption leading to phosphorus excretion</p> Signup and view all the answers

    What is the net effect of FGF23 on serum phosphorus levels?

    <p>Decrease phosphorus levels</p> Signup and view all the answers

    What is the serum half-life of intact PTH?

    <p>Less than 8 minutes</p> Signup and view all the answers

    Which enzyme is responsible for producing 1,25 (OH)2D in the parathyroid gland?

    <p>CYP27B1</p> Signup and view all the answers

    What mediates the intracellular accumulation of inositol triphosphate in the parathyroid gland when activated by Ca?

    <p>Phospholipase C</p> Signup and view all the answers

    Where is the calcium-sensing receptor (CaR) also expressed?

    <p>Breast and bone</p> Signup and view all the answers

    Which type of protease is capable of cleaving intact PTH into fragments in the parathyroid gland?

    <p>Metalloprotease</p> Signup and view all the answers

    What effect does calcium have on PTH production in the parathyroid gland when the calcium-sensing receptor (CaR) is stimulated?

    <p>Reduces PTH production</p> Signup and view all the answers

    Which hormone makes the parathyroid gland more sensitive to suppression by calcium?

    <p>Vitamin D</p> Signup and view all the answers

    Which receptor is present in the parathyroid gland and promotes increased absorption of calcium and phosphorus in the small intestine?

    <p>(OH)2D3 receptor</p> Signup and view all the answers

    What effect does PTH have on osteoclasts?

    <p>Acts on osteoblasts to increase osteoclast activity</p> Signup and view all the answers

    What is the mechanism of action of denosumab in the treatment of osteoporosis?

    <p>Blocks the action of RANKL</p> Signup and view all the answers

    What is the function of sclerostin in bone physiology?

    <p>Inhibits WNT pathway</p> Signup and view all the answers

    How does romosozumab work in the treatment of osteoporosis?

    <p>Inhibits sclerostin production</p> Signup and view all the answers

    What is the specific cellular target of denosumab in bone physiology?

    <p>Osteoclasts</p> Signup and view all the answers

    Which cell type does PTH act on to induce the production of RANKL?

    <p>Osteoblasts</p> Signup and view all the answers

    What is the role of RANKL in bone physiology?

    <p>Increases bone resorption</p> Signup and view all the answers

    What is the main source of Vitamin D3 synthesis in humans?

    <p>Skin</p> Signup and view all the answers

    Which organ is responsible for the hydroxylation of 25(OH)D to 1,25(OH)2D?

    <p>Kidney</p> Signup and view all the answers

    What is the main form of Vitamin D synthesized in plants?

    <p>Ergocalciferol</p> Signup and view all the answers

    What is the primary storage site for excess vitamin D in the body?

    <p>Adipose tissue</p> Signup and view all the answers

    Which vitamin D metabolite has the longest half-life and is used to measure vitamin D stores in the body?

    <p>25OHD (calcidiol)</p> Signup and view all the answers

    What condition is associated with increased levels of Vitamin D binding protein (DBP)?

    <p>Estrogen therapy</p> Signup and view all the answers

    What is the bioactive form of vitamin D that stimulates intestinal calcium and phosphate transport as well as bone resorption?

    <p>Calcitriol</p> Signup and view all the answers

    What is the primary use of calcipotriene (calcipotriol)?

    <p>Treatment of psoriasis</p> Signup and view all the answers

    For what condition is doxercalciferol primarily used?

    <p>Secondary hyperparathyroidism in chronic kidney disease</p> Signup and view all the answers

    In which country is eldecalcitol approved for the treatment of osteoporosis?

    <p>Japan</p> Signup and view all the answers

    What is the primary function of fibroblast growth factor 23 (FGF23) in the kidney?

    <p>Inhibiting phosphate reabsorption via sodium phosphate co-transporters</p> Signup and view all the answers

    What stimulates the production of fibroblast growth factor 23 (FGF23)?

    <p>Low levels of circulating 1,25(OH)2D</p> Signup and view all the answers

    Which cells in bones are the primary site of fibroblast growth factor 23 (FGF23) production?

    <p>Osteoblasts and osteocytes</p> Signup and view all the answers

    What is the main effect of calcitonin in the bone?

    <p>Promotes osteoblastic bone formation</p> Signup and view all the answers

    What is the molecular weight of a human calcitonin monomer?

    <p>3600</p> Signup and view all the answers

    Which hormone stimulates the secretion of calcitonin?

    <p>Pentagastrin</p> Signup and view all the answers

    What role does calcitonin play in the treatment of Paget’s disease, hypercalcemia, and osteoporosis?

    <p>Useful drug for lowering serum calcium and inhibiting bone resorption</p> Signup and view all the answers

    What effect does calcitonin have on the reabsorption of calcium and phosphate in the kidneys?

    <p>Reduces reabsorption of calcium and phosphate</p> Signup and view all the answers

    What is the effect of calcitonin on gastrin secretion and gastric acid output?

    <p>Reduces gastrin secretion and gastric acid output</p> Signup and view all the answers

    What is the clearance route for calcitonin in the body?

    <p>Lungs</p> Signup and view all the answers

    How do glucocorticoids alter bone mineral homeostasis?

    <p>By antagonizing Vit D-stimulated intestinal calcium transport</p> Signup and view all the answers

    What is the common cause of osteoporosis in adults due to prolonged administration of glucocorticoids?

    <p>Blocking bone formation</p> Signup and view all the answers

    In what conditions are glucocorticoids useful in reversing hypercalcemia?

    <p>Granulomatous diseases and vitamin D intoxication</p> Signup and view all the answers

    What is the mechanism to explain the observation that estrogens prevent accelerated bone loss during the immediate postmenopausal period?

    <p>Estrogens reduce the bone-resorbing action of PTH</p> Signup and view all the answers

    What effect does estrogen administration have on 1,25(OH)2D level in the blood?

    <p>Estrogen administration transiently increases 1,25(OH)2D level in blood</p> Signup and view all the answers

    Where have estrogen receptors been found, and what is their effect on bone remodeling?

    <p>Estrogen receptors are found in bones and directly affect bone remodeling</p> Signup and view all the answers

    How does denosumab inhibit osteoclast formation and activity?

    <p>By interfering with RANKL function, inhibiting osteoclast formation and activity</p> Signup and view all the answers

    What is the primary concern associated with the use of denosumab in relation to immune system cells?

    <p>Increased risk of infection</p> Signup and view all the answers

    In what way is denosumab advantageous over bisphosphonates?

    <p>It is readily reversible and does not deposit in bone</p> Signup and view all the answers

    What is the recommended frequency for administering denosumab?

    <p>Every 6 months</p> Signup and view all the answers

    Which condition is denosumab used to limit the development of?

    <p>Bone metastases resulting from cancer</p> Signup and view all the answers

    What potential risk is comparable between denosumab and potent bisphosphonates?

    <p>Potential risk of osteonecrosis of the jaw</p> Signup and view all the answers

    What effect can denosumab have on calcium levels in patients with marked bone loss or compromised calcium regulatory mechanisms?

    <p>Transient hypocalcemia</p> Signup and view all the answers

    What cell type expresses RANKL and may pose a potential risk when using denosumab?

    <p>T lymphocytes</p> Signup and view all the answers

    What is the primary effect of cinacalcet on the parathyroid gland?

    <p>Inhibiting PTH secretion</p> Signup and view all the answers

    For which condition is cinacalcet approved for treatment?

    <p>Secondary hyperparathyroidism in chronic kidney disease</p> Signup and view all the answers

    In what conditions may CaSR antagonists be useful?

    <p>Hypoparathyroidism</p> Signup and view all the answers

    How do thiazide diuretics reduce the incidence of urinary stone formation in subjects with idiopathic hypercalciuria?

    <p>By decreasing sodium reabsorption in the distal tubule</p> Signup and view all the answers

    What is the primary mechanism by which thiazide diuretics increase the effectiveness of PTH in stimulating reabsorption of calcium by the renal tubules?

    <p>By blocking sodium reabsorption at the luminal surface</p> Signup and view all the answers

    What adverse effects can higher doses of fluoride cause?

    <p>Nausea and vomiting</p> Signup and view all the answers

    What is the role of thiazide diuretics in reducing hypercalciuria and urinary stone formation in subjects with idiopathic hypercalciuria?

    <p>Reducing renal calcium excretion</p> Signup and view all the answers

    How does fluoride affect the resistance of teeth to dental caries?

    <p>By stabilizing the hydroxyapatite crystal</p> Signup and view all the answers

    What do clinical studies suggest about fluoride's effect on fractures?

    <p>An increase in fracture rate</p> Signup and view all the answers

    How can the adverse effects of fluoride be prevented?

    <p>Giving fluoride with meals</p> Signup and view all the answers

    How does strontium ranelate affect bone resorption?

    <p>Inhibiting osteoclast differentiation</p> Signup and view all the answers

    What is the primary effect of strontium ranelate on osteoclasts?

    <p>Promoting their apoptosis</p> Signup and view all the answers

    Which treatment for hypercalcemia has the potential to cause sudden hypocalcemia, ectopic calcification, acute renal failure, and hypotension if not done properly?

    <p>Phosphate</p> Signup and view all the answers

    What has been demonstrated in large clinical trials regarding the efficacy of strontium ranelate?

    <p>Increasing bone mineral density and decreasing fractures in the spine and hip</p> Signup and view all the answers

    Which medication is used for the management of hypercalcemia of malignancy and proved superior to calcitonin in reducing serum calcium in cancer patients?

    <p>Gallium nitrate</p> Signup and view all the answers

    Which medication is observed to have an effect on serum calcium within 4-6 hours and lasts for 6-10 hours?

    <p>Calcitonin</p> Signup and view all the answers

    Which medication has no clear role in the immediate treatment of hypercalcemia, but may be effective in chronic hypercalcemia of sarcoidosis, vitamin D intoxication, and certain cancers?

    <p>Glucocorticoids</p> Signup and view all the answers

    Which medication is used only after other methods of treatment have failed to control symptomatic hypercalcemia and must be given slowly to avoid side effects such as sudden hypocalcemia and acute renal failure?

    <p>Phosphate</p> Signup and view all the answers

    Which medication is used for the immediate treatment of hypercalcemia and can be administered at high doses without causing toxicity?

    <p>Calcitonin</p> Signup and view all the answers

    Which medication may respond within several days to chronic hypercalcemia of sarcoidosis, vitamin D intoxication, and certain cancers?

    <p>Glucocorticoids</p> Signup and view all the answers

    Which medication is used for the management of hypercalcemia of malignancy and has potential nephrotoxicity that requires patients to be well hydrated and have good renal output before starting the infusion?

    <p>Gallium nitrate</p> Signup and view all the answers

    Which medication is the fastest and surest way to reduce serum calcium but is used only after other methods of treatment have failed to control symptomatic hypercalcemia?

    <p>Phosphate</p> Signup and view all the answers

    Which medication should be switched to oral administration as soon as symptoms of hypercalcemia have cleared to avoid side effects such as sudden hypocalcemia and renal failure?

    <p>Phosphate</p> Signup and view all the answers

    Which medication is not recommended for the immediate treatment of hypercalcemia but may be used in chronic hypercalcemia of sarcoidosis, vitamin D intoxication, and certain cancers?

    <p>Glucocorticoids</p> Signup and view all the answers

    What is the first step in reducing serum calcium levels in the treatment of hypercalcemia?

    <p>Providing hydration with saline and diuresis with furosemide</p> Signup and view all the answers

    What is the role of furosemide in the treatment of severe hypercalcemia?

    <p>Inhibits calcium reabsorption in the ascending limb of the loop of Henle</p> Signup and view all the answers

    What is a potential side effect of repeated doses of pamidronate and zoledronate?

    <p>Renal deterioration and osteonecrosis of the jaw</p> Signup and view all the answers

    What effects generally persist for weeks after the infusion of pamidronate or zoledronate?

    <p>Flu-like syndrome</p> Signup and view all the answers

    What is the main concern associated with the use of furosemide in severe hypercalcemia?

    <p>Prerenal azotemia due to dehydration</p> Signup and view all the answers

    What is the primary adverse effect associated with repeated doses of pamidronate and zoledronate?

    <p>Renal failure</p> Signup and view all the answers

    What is the function of saline diuresis in the treatment of hypercalcemia?

    <p>Reversing dehydration and restoring urine flow</p> Signup and view all the answers

    What is the main role of pamidronate and zoledronate in treating hypercalcemia of malignancy?

    <p>Decreasing serum calcium levels</p> Signup and view all the answers

    What is a potential side effect following the initial infusion of pamidronate or zoledronate?

    <p>Flu-like syndrome</p> Signup and view all the answers

    What can prevent excretion of more calcium in the urine during severe hypercalcemia due to dehydration?

    <p>Prerenal azotemia</p> Signup and view all the answers

    What enhances urine flow and inhibits calcium reabsorption in the ascending limb of the loop of Henle during treatment for severe hypercalcemia?

    <p>Furosemide infusion</p> Signup and view all the answers

    What is the preferred intravenous form of calcium for treating hypocalcemia?

    <p>Calcium gluconate</p> Signup and view all the answers

    What is the recommended oral preparation for treating less severe hypocalcemia?

    <p>Calcium carbonate</p> Signup and view all the answers

    Which form of vitamin D has rapid action and is capable of raising serum calcium within 24-48 hours?

    <p>Vitamin D3</p> Signup and view all the answers

    Which medication is a synthetic PTH used for hypoparathyroidism?

    <p>Teriparatide</p> Signup and view all the answers

    What is the preferred intravenous treatment for severe symptomatic hypocalcemia?

    <p>Calcium gluconate</p> Signup and view all the answers

    Which oral preparation is often the choice for less severe hypocalcemia due to its high calcium percentage, availability, and low cost?

    <p>Calcium carbonate</p> Signup and view all the answers

    Which form of vitamin D has rapid action and is capable of raising serum calcium within 24-48 hours?

    <p>1,25(OH)2D3</p> Signup and view all the answers

    Which medication is used for hypoparathyroidism?

    <p>Teriparatide</p> Signup and view all the answers

    Which vitamin D form raises serum phosphate levels and requires careful monitoring to prevent ectopic calcification?

    <p>1,25(OH)2D3</p> Signup and view all the answers

    Which oral preparation provides approximately 1000–1500 mg of elemental calcium per day for treating less severe hypocalcemia?

    <p>Calcium carbonate</p> Signup and view all the answers

    What is the primary storage site for excess vitamin D in the body?

    <p>Liver</p> Signup and view all the answers

    What is a potential emergency treatment for hyperphosphatemia?

    <p>Dialysis</p> Signup and view all the answers

    What is a risk associated with the use of large doses of calcium to control hyperphosphatemia?

    <p>Ectopic calcification</p> Signup and view all the answers

    What is used in the control of hyperphosphatemia in patients with chronic kidney disease?

    <p>Phosphate-binding gels such as Sevelamer</p> Signup and view all the answers

    Which of the following is a long-term effect of hypophosphatemia?

    <p>Proximal muscle weakness</p> Signup and view all the answers

    Which condition is associated with increased bioactive FGF23?

    <p>Osteomalacia</p> Signup and view all the answers

    What condition should hypophosphatemia be avoided when using forms of therapy that can lead to it?

    <p>Osteoporosis</p> Signup and view all the answers

    What is a consequence of overzealous use of phosphate binders?

    <p>Hypophosphatemia</p> Signup and view all the answers

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