Pharmacotherapeutics IV: CKD Bone Disorders

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Questions and Answers

Which of the following best describes the role of plasma calcium (Ca++) concentrations in bone mineral homeostasis?

  • Plasma Ca++ levels are primarily regulated by the parathyroid gland, which releases parathyroid hormone (PTH) to increase Ca++ absorption in the gut and reabsorption in the kidneys, ultimately impacting bone mineral homeostasis.
  • Plasma Ca++ concentrations are directly proportional to bone resorption, meaning higher plasma Ca++ leads to increased bone breakdown.
  • While Ca++ plays a role in bone mineralization, its primary function in bone mineral homeostasis is to act as a signaling molecule for osteoblasts and osteoclasts.
  • Plasma Ca++ levels serve as a feedback mechanism; when Ca++ levels are low, PTH is released, stimulating bone resorption and increasing Ca++ absorption, while high Ca++ levels suppress PTH release. (correct)

How does Chronic Kidney Disease (CKD) contribute to the development of bone mineral disorders?

  • CKD primarily disrupts the production and activation of vitamin D in the kidneys, leading to decreased intestinal calcium absorption and reduced bone mineralization.
  • CKD impairs the kidneys' ability to regulate phosphate levels, leading to hyperphosphatemia. This triggers increased parathyroid hormone (PTH) release, potentially contributing to bone resorption and bone mineral disorders. (correct)
  • CKD directly inhibits the function of osteoblasts, responsible for bone formation, contributing to weakened bones.

Which of the following statements accurately describes the mechanism of action of Vitamin D in bone mineral homeostasis?

  • Vitamin D primarily functions as a signaling molecule for osteoblasts, promoting bone formation.
  • Vitamin D binds to receptors in the parathyroid gland, inhibiting the release of parathyroid hormone (PTH) and thus reducing bone resorption.
  • Vitamin D directly stimulates bone resorption, releasing calcium into the bloodstream.
  • Vitamin D acts on the intestines to increase calcium absorption, thereby indirectly promoting bone mineralization. (correct)

In the context of CKD, which of the following medications directly targets the parathyroid gland to reduce hyperparathyroidism?

<p>Cinacalcet (C)</p> Signup and view all the answers

Which of the following pharmacological categories of medications are NOT commonly used in treating CKD mineral and Bone disorders?

<p>Antibiotics (B)</p> Signup and view all the answers

How does 1,25(OH)2D primarily contribute to the increase in serum calcium levels?

<p>By increasing calcium absorption from the gut, ultimately leading to a greater amount of calcium in the blood. (D)</p> Signup and view all the answers

Which hormone primarily regulates serum phosphate levels through its impact on renal excretion?

<p>Fibroblast growth factor 23 (FGF23) (D)</p> Signup and view all the answers

Which of the following best describes the effect of low doses of 1,25(OH)2D on bone formation?

<p>Low doses of 1,25(OH)2D indirectly stimulate bone formation by increasing calcium and phosphate absorption, promoting bone mineral deposition. (D)</p> Signup and view all the answers

In the context of bone mineral homeostasis, what is the primary role of parathyroid hormone (PTH)?

<p>To maintain calcium homeostasis by increasing serum calcium levels and promoting calcium deposition in bone. (C)</p> Signup and view all the answers

The text mentions an indirect effect of 1,25(OH)2D on urinary calcium excretion. What is the primary mechanism behind this indirect effect?

<p>Suppression of PTH secretion by 1,25(OH)2D, leading to reduced calcium resorption from bone. (A)</p> Signup and view all the answers

Which of the following statements accurately describes the relationship between 1,25(OH)2D and FGF23?

<p>1,25(OH)2D indirectly stimulates FGF23 production, contributing to increased urinary phosphate excretion. (A)</p> Signup and view all the answers

How does calcitonin (CT) influence serum calcium and phosphate levels in pharmacologic concentrations?

<p>Calcitonin inhibits bone resorption, reducing the release of calcium and phosphate into the bloodstream. (A)</p> Signup and view all the answers

Which of the following is NOT a primary function of 1,25(OH)2D in regulating serum calcium and phosphate levels?

<p>Directly increasing osteoblast activity, promoting bone formation. (C)</p> Signup and view all the answers

Which of the following statements accurately reflects the relationship between PTH and calcium levels?

<p>PTH stimulates the production of 1,25(OH)2D, which increases calcium absorption in the intestines, leading to increased blood calcium levels. (A)</p> Signup and view all the answers

How does FGF23 primarily influence calcium and phosphate levels in the body?

<p>It primarily influences phosphate levels by decreasing its absorption in the intestines and increasing its excretion in the kidneys, but has a minimal impact on calcium levels. (B)</p> Signup and view all the answers

What is the primary mechanism by which 1,25(OH)2D influences calcium levels in the body?

<p>Promoting calcium absorption in the intestines and its reabsorption in the kidneys, leading to increased blood calcium levels. (A)</p> Signup and view all the answers

How does FGF23 impact the production of 1,25(OH)2D?

<p>It directly inhibits the production of 1,25(OH)2D, resulting in decreased calcium and phosphate absorption and increased phosphate excretion. (B)</p> Signup and view all the answers

Which of the following correctly describes the combined effect of PTH and vitamin D on calcium levels?

<p>PTH indirectly stimulates calcium absorption through the production of 1,25(OH)2D, and this effect is enhanced by vitamin D, further increasing calcium levels in the blood. (A)</p> Signup and view all the answers

When high doses of vitamin D are administered, how does this affect calcium and phosphate levels in the body?

<p>It increases the production of 1,25(OH)2D, leading to a significant increase in calcium and phosphate absorption from the intestines and resorption from the bones, potentially resulting in hypercalcemia. (D)</p> Signup and view all the answers

Which of the following accurately describes the impact of FGF23 on bone mineral density?

<p>FGF23 directly inhibits the production of 1,25(OH)2D, leading to a decrease in calcium and phosphate resorption from the bones, resulting in lower bone mineral density. (C)</p> Signup and view all the answers

How do the interactions between PTH, vitamin D, and FGF23 maintain calcium and phosphate homeostasis?

<p>PTH and vitamin D collaborate to increase calcium levels, while FGF23 acts as a counter-regulatory mechanism to prevent excessive calcium and phosphate levels by increasing their excretion. (B)</p> Signup and view all the answers

Which of the following is NOT a consequence of CKD impacting bone mineral homeostasis?

<p>Increased calcitriol production in the kidney. (D)</p> Signup and view all the answers

Which of the following vitamin D products is NOT indicated for the treatment of secondary hyperparathyroidism in CKD patients?

<p>Ergocalciferol. (B)</p> Signup and view all the answers

How does calcitriol affect the body? Choose the BEST answer.

<p>Calcitriol increases calcium absorption in the intestines, suppresses parathyroid hormone synthesis, and indirectly inhibits bone resorption by promoting osteoblast activity. (D)</p> Signup and view all the answers

Which of these drugs is a NON-absorbable cationic ion-exchange resin that binds dietary phosphate, interrupting enterohepatic circulation and decreasing cholesterol absorption?

<p>Sevelamer carbonate. (B)</p> Signup and view all the answers

Which of the following is a CORRECT description of the action of phosphate binders?

<p>Phosphate binders bind to dietary phosphate in the gastrointestinal tract, preventing its absorption. (A)</p> Signup and view all the answers

Which of the following is considered an active form of vitamin D and directly promotes calcium absorption in the small intestine?

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

Which of these phosphate binders is LEAST likely to cause hypercalcemia?

<p>Sevelamer carbonate. (D)</p> Signup and view all the answers

What is the primary mechanism by which vitamin D exerts its effects on the body? Select the BEST answer.

<p>Vitamin D binds to vitamin D receptors (VDRs) in various organs, influencing gene expression and cellular activity. (C)</p> Signup and view all the answers

Which of the following is a CORRECT statement regarding the relationship between vitamin D deficiency and parathyroid hormone (PTH)?

<p>Vitamin D deficiency promotes PTH production, leading to increased calcium resorption from bone. (B)</p> Signup and view all the answers

Which of the following is an active vitamin D analog used in the treatment of secondary hyperparathyroidism in CKD patients?

<p>Paricalcitol. (D)</p> Signup and view all the answers

Which of these phosphate binders is most likely to lead to iron deficiency?

<p>Aluminum hydroxide. (D)</p> Signup and view all the answers

What is the primary reason why calcitriol should NOT be administered to CKD patients unless hyperphosphatemia is controlled?

<p>Calcitriol increases calcium absorption, which can worsen hypercalcemia in CKD patients. (A)</p> Signup and view all the answers

What is a potential adverse effect of using aluminum hydroxide as a phosphate binder?

<p>Neurotoxicity. (D)</p> Signup and view all the answers

What is the rationale behind administering phosphate binders with meals?

<p>To ensure they bind dietary phosphate before it is absorbed. (D)</p> Signup and view all the answers

What is the primary target organ for the actions of vitamin D?

<p>Kidney. (D)</p> Signup and view all the answers

Flashcards

Bone Mineral Homeostasis

The regulation of minerals like calcium and phosphate in bones and blood.

Hormones in Bone Health

PTH, vitamin D, and FGF23 regulate mineral balance in gut, bone, and kidneys.

CKD and Bone Disorders

Chronic Kidney Disease causes vitamin D deficiency and imbalance of calcium and phosphate.

Hyperparathyroidism

An overproduction of parathyroid hormone affecting calcium levels and bone health.

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Vitamin D Production

Vitamin D is synthesized through skin exposure to sunlight and needs healthy kidneys and liver.

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PTH (Parathyroid Hormone)

A hormone that increases calcium and phosphate absorption, decreasing calcium excretion.

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Vitamin D

A vitamin that increases calcium and phosphate absorption and decreases excretion of these minerals.

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FGF23 (Fibroblast Growth Factor 23)

A hormone that decreases phosphate absorption and promotes phosphate excretion in the kidneys.

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1,25(OH)2D

The active form of Vitamin D that enhances calcium absorption and resorption in the bones.

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Calcium Excretion

The process of eliminating excess calcium through urine, heavily influenced by PTH.

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Phosphate Resorption

The process by which phosphate is absorbed back into the bloodstream from the bones.

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Calcium and Phosphate Absorption

The intake of calcium and phosphate from the intestines, enhanced by 1,25(OH)2D.

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Bone Mineralization

The process of depositing minerals like calcium and phosphate into bones, affected by hormone levels.

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Hypophosphatemia

A condition characterized by low phosphate levels in the serum.

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Role of 1,25(OH)2D

Increases calcium and phosphate absorption from the gut and reduces renal excretion.

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Serum calcium increase

The net effect of vitamin D and PTH leading to higher calcium levels in the blood.

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PTH function

Parathyroid hormone increases serum calcium by releasing calcium from bones and increasing renal absorption.

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FGF23 action

Fibroblast growth factor 23 promotes renal excretion of phosphate to lower serum phosphate levels.

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Calcitonin's role

A hormone that decreases serum calcium and phosphate levels by inhibiting bone resorption.

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Bone formation stimulation

Triggered by 1,25(OH)2D and PTH, promoting the building of new bone.

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Urinary Calcium Excretion

1,25(OH)2D indirectly increases urinary calcium excretion due to enhanced intestinal absorption.

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CKD and Bone Disease

Chronic Kidney Disease can lead to bone disease due to disrupted mineral balance.

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1,25(OH)2D Production Loss

CKD leads to reduced production of the active form of Vitamin D, crucial for calcium absorption.

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Secondary Hyperparathyroidism

A condition resulting from low calcium levels due to CKD, leading to increased PTH secretion.

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Vitamin D Mechanism of Action (MOA)

Vitamin D binds to VDR in various organs to control gene transcription, affecting calcium absorption.

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Calcitriol

The active form of Vitamin D that enhances dietary calcium absorption in the intestine.

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Calcifediol

25(OH)D form of Vitamin D; boosts calcium absorption and is used in CKD stages 3 or 4.

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Active Vitamin D Products

Includes calcitriol, calcifediol, and analogs; crucial for treating CKD-related bone disorders.

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Paricalcitol

An analog of 1,25(OH)2D used to treat secondary hyperparathyroidism in CKD patients.

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Phosphate Binders

Drugs that reduce phosphate absorption, critical in managing CKD bone disorders.

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Aluminum Hydroxide

An early phosphate binder that lowers phosphate but has risks of toxicity.

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Iron-Based Phosphate Binders

Such as sucroferric oxyhydroxide; lower phosphorus and improve iron levels in CKD patients.

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Calcium Carbonate

A common phosphate binder that inhibits phosphate absorption but can cause hypercalcemia.

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Sevelamer Carbonate

A non-absorbable phosphate binder that also reduces cholesterol absorption.

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Lanthanum Carbonate

A phosphate binder that forms insoluble complexes with phosphate, lowering serum levels.

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Study Notes

Pharmacology of Agents Treating CKD Mineral and Bone Disorders

  • This presentation covers medications for treating mineral and bone disorders associated with Chronic Kidney Disease (CKD).
  • The course is Pharmacotherapeutics IV, Renal Disorders and Electrolytes/Fluids, PHAR 4245, taught by Dr. Helen E. Smith in January 2025.

Bone Mineral Homeostasis

  • Hormones, specifically those presented in class, maintain bone mineral homeostasis through their action in bone, kidneys, and the gut.
  • Plasma calcium concentrations are crucial for bone mineral homeostasis.

CKD Contribution to Bone Mineral Disorders

  • CKD contributes to bone disorders due to impact on Vitamin D production.
  • CKD affects calcium plasma concentrations, causing phosphate retention, and affecting parathyroid hormone (PTH) levels, leading to hyperparathyroidism.
  • Hyperparathyroidism negatively affects bone health.
  • The presentation details various pharmacological categories of medications used to treat CKD mineral and bone disorders.
  • It discusses how Vitamin D is produced in the body and how renal and hepatic health impact this production.
  • The lecture explains the mechanisms of action for each medication presented in class and the treatment of CKD mineral and bone disorders.
  • The slide set illustrates side effects and their mechanisms for the medications presented in class.

Primary Endogenous Regulators

  • Parathyroid Hormone (PTH), Vitamin D, and FGF23 are primary endogenous regulators.
  • PTH increases calcium and phosphate absorption, while decreased 1,25(OH)2D production causes decreased calcium and phosphate absorption.
  • Vitamin D increases calcium and phosphate absorption. FGF23 decreases calcium and phosphate absorption.
  • Multiple organs affect PTH, Vitamin D, and FGF23 production and functioning. Results in the net effect on serum levels.

Hormone Effects

  • Hormones play a role in maintaining bone mineral homeostasis.
  • Calcium and phosphorus are crucial for proper bone health, with PTH and vitamin D actively regulating these levels.
  • The kidney, gut and bone are targeted by hormones to control calcium and phosphorus levels.

Hormone Interactions

  • The intricate interplay of hormones in regulating bone mineral homeostasis is detailed via visual aid showing how hormones are released and work together.

Ca²+ Influence on PTH

  • Calcium levels directly influence the release of parathyroid hormone.
  • The presentation covers the interplay between the thyroid, parathyroid glands, bone, kidney, and gut in the regulation of calcium levels.

CKD Contribution to Bone Mineral Disorders: Summary

  • CKD can cause primary bone disease due to a loss of 1,25(OH)2D production. This leads to phosphate retention causing lowered ionized calcium.
  • Secondary hyperparathyroidism results from the body's attempt to regulate calcium levels when 1,25(OH)2D is decreased.

Pharmacology of Treatments

  • Multiple strategies exist for the treatment of bone mineral disorders in CKD, involving diverse medications categorized to address the affected processes.
  • Specific approaches focus on active vitamin D analogs (eg., calcitriol, calcifediol, paricalcitol, and doxercalciferol).
  • Phosphate binders (eg., aluminum hydroxide, iron-based binders, calcium carbonate/acetate, sevelamer carbonate, lanthanum carbonate) target serum phosphate levels.
  • Calcimimetics (eg., cinacalcet, etelcalcetide) work to modulate calcium sensing receptors in the parathyroid glands to help regulate calcium levels.

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