Bone Remodeling Quiz

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Questions and Answers

What is the role of osteoprotegerin (OPG) in bone remodelling?

  • Stimulates osteoclast progenitor differentiation
  • Acts as a decoy receptor for RANKL (correct)
  • Promotes osteoblast activity
  • Increases bone resorption in response to low calcium levels

Which hormone is primarily responsible for increasing calcium reabsorption in the kidneys?

  • Vitamin D
  • Parathyroid hormone (PTH) (correct)
  • Calcitonin
  • Estrogen

What effect does estrogen withdrawal during menopause typically have on bone density?

  • Promotes osteoporosis (correct)
  • Stabilizes the activity of osteoclasts
  • Stimulates bone formation
  • Increases mineralization of bone

How does calcitriol influence bone remodelling?

<p>Stimulates calcium and phosphate absorption in the intestine (A)</p> Signup and view all the answers

Which of the following statements about bone resorption is true?

<p>Bone resorption involves the interaction of RANKL and RANK. (C)</p> Signup and view all the answers

What affects the conversion of cholecalciferol to calcitriol?

<p>Presence of phosphate concentration (D)</p> Signup and view all the answers

What is the primary daily calcium turnover in the human body?

<p>700 mg (B)</p> Signup and view all the answers

Which of the following hormones is involved in both stimulating bone formation and resorption?

<p>Parathyroid hormone (PTH) (B)</p> Signup and view all the answers

What is the primary role of osteoblasts in bone remodelling?

<p>Form bone matrix components (A)</p> Signup and view all the answers

Which component is essential in linking calcium to collagen in the bone matrix?

<p>Osteonectin (A)</p> Signup and view all the answers

Which hormone is NOT involved in the process of bone remodelling?

<p>Insulin (A)</p> Signup and view all the answers

What initiates the process of bone remodelling in response to mechanical stress?

<p>Secretion of sclerostin by osteocytes (B)</p> Signup and view all the answers

Osteoclasts are primarily derived from which lineage?

<p>Macrophage-monocyte lineage (D)</p> Signup and view all the answers

Which of the following is a secondary function of bone, beyond providing structure?

<p>Playing a role in calcium homeostasis (B)</p> Signup and view all the answers

What is the main structure that forms when osteoid is mineralized?

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

Which cell type is responsible for the activation of osteoclasts during bone remodelling?

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

What is the mechanism of action of Denosumab?

<p>Inhibits RANKL, mimicking OPG and inhibiting osteoclast differentiation (B)</p> Signup and view all the answers

What is the primary role of calcitriol in bone metabolism?

<p>Increases the synthesis of osteocalcin (D)</p> Signup and view all the answers

Which of the following statements about osteoporosis is true?

<p>Its common causes include postmenopausal deficiency of oestrogen. (A)</p> Signup and view all the answers

Which of the following is NOT an indication for the use of vitamin D analogues?

<p>Treatment of osteoporosis in post-menopausal women (C)</p> Signup and view all the answers

Which of the following drugs is classified as an anabolic agent that increases bone formation?

<p>PTH, teriparatide (C)</p> Signup and view all the answers

What is a major adverse effect of excessive vitamin D intake?

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

What effect do bisphosphonates have on bone cells?

<p>Inhibit the activity of osteoclasts (A)</p> Signup and view all the answers

How often is Denosumab administered subcutaneously?

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

Which of the following is a primary action of Romosozumab?

<p>Inhibits osteoclast activity (B)</p> Signup and view all the answers

What is a common side effect associated with the use of bisphosphonates?

<p>Atypical femoral fractures (D)</p> Signup and view all the answers

Which mineral is essential for the formation of ATP and is influenced by bone metabolism?

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

What should be monitored during therapy with vitamin D?

<p>Plasma calcium levels (A)</p> Signup and view all the answers

Which calcium salt has the highest absorption rate?

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

What is a recommended dietary component to support bone health?

<p>Adequate protein and calcium intake (D)</p> Signup and view all the answers

Which statement about the adverse reactions of oral calcium salts is accurate?

<p>They can cause gastrointestinal disturbances (D)</p> Signup and view all the answers

How often should the use of bisphosphonates be reevaluated?

<p>Every 5 years (B)</p> Signup and view all the answers

What is a potential side effect of calcium carbonate administration in patients with renal failure?

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

Which mechanism of action is associated with cinacalcet in the treatment of hyperparathyroidism?

<p>Enhancing parathyroid Ca2+-sensing receptor sensitivity (B)</p> Signup and view all the answers

What is a common adverse drug reaction (ADR) associated with teriparatide?

<p>Headache (A)</p> Signup and view all the answers

What is the main therapeutic use of calcium salts?

<p>Prevention and treatment of osteoporosis (A)</p> Signup and view all the answers

For how long should teriparatide treatment be limited according to safety concerns?

<p>24 months (A)</p> Signup and view all the answers

What is the primary purpose of administering supplemental calcium and vitamin D after a zoledronate infusion?

<p>To enhance the effectiveness of bisphosphonates (D)</p> Signup and view all the answers

Which condition can calcitonin be used to treat effectively?

<p>Severe back pain in acute osteoporotic vertebral fractures (D)</p> Signup and view all the answers

What adverse effect is most commonly attributed to calcitonin?

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

Which of the following statements regarding Raloxifene is correct?

<p>It is effective for secondary prevention in postmenopausal women who cannot tolerate bisphosphonates. (C)</p> Signup and view all the answers

What is one of the mechanisms of action of calcitonin?

<p>Induces osteoclast apoptosis (B)</p> Signup and view all the answers

For which disorder is long-term use of bisphosphonates most likely to require periodic re-evaluation?

<p>Teeth osteonecrosis (A)</p> Signup and view all the answers

Which complication is a known adverse reaction of Raloxifene?

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

How does calcitonin generally affect plasma calcium levels?

<p>Decreases plasma [Ca2+] (A)</p> Signup and view all the answers

Flashcards

Bone Remodelling

The process by which old bone is broken down and new bone is formed. Essential for maintaining bone strength and calcium homeostasis.

Osteoblasts

Cells responsible for bone formation, they synthesize and deposit the organic bone matrix, called osteoid.

Osteoclasts

Cells responsible for bone resorption, breaking down bone tissue by releasing enzymes and acids.

Osteoid

The organic component of bone that provides a framework for the deposition of calcium phosphate crystals.

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Osteonectin

A protein that binds to calcium and collagen, helping to link these two crucial components of the bone matrix.

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Hydroxyapatite

A mineral salt deposited in the osteoid, giving bone its rigidity and strength.

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Bone Homeostasis

The crucial role bone plays in maintaining a stable blood calcium level through ongoing bone remodeling.

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Osteocytes

Cells that are derived from osteoblasts and remain embedded within the bone matrix, they are responsible for sensing mechanical stress and initiating bone remodeling.

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What is Osteoprotegerin (OPG)?

A protein that inhibits the differentiation of osteoclasts.

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What is RANKL?

A surface ligand expressed by osteoblasts that promotes the differentiation and activation of osteoclast progenitors.

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What is RANK?

A receptor on the surface of osteoclast progenitors that binds RANKL, leading to their differentiation into mature osteoclasts.

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What is Bone Remodeling?

A process involving the simultaneous breakdown and rebuilding of bone tissue by osteoclasts and osteoblasts, respectively.

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What is Parathyroid Hormone (PTH)?

A hormone that plays a crucial role in regulating calcium levels in the blood, stimulating both bone formation and bone resorption.

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What is Calcitriol?

The active form of vitamin D, produced in the kidneys, which plays a vital role in calcium and phosphate absorption in the intestines and bone metabolism.

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What is Calcitonin?

A hormone produced by the thyroid gland that helps regulate calcium levels in the blood by inhibiting bone resorption.

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What is Osteoporosis?

A condition characterized by decreased bone density and increased fragility, often caused by estrogen deficiency during menopause.

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Osteoporosis

A condition where bone mass decreases and microarchitecture is distorted, leading to increased fracture risk.

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Osteopenia

A decrease in bone mineral content, but not necessarily a change in bone structure.

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Osteomalacia

A condition caused by Vitamin D deficiency, leading to soft bones and impaired bone mineralization.

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Rickets

A condition caused by Vitamin D deficiency in children, leading to soft bones and impaired bone growth.

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Paget's Disease

A bone disease characterized by abnormal bone remodeling, leading to enlarged and deformed bones.

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Antiresorptive Drugs

A type of drug that decreases bone loss by inhibiting osteoclast activity.

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Anabolic Agents

A type of drug that increases bone formation by stimulating osteoblast activity.

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Bisphosphonates

A class of drugs that inhibit bone resorption by targeting osteoclasts, reducing bone loss.

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Osteonecrosis

A condition where bone tissue dies due to lack of blood supply, often associated with long-term use of bisphosphonates.

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Calcitonin

A hormone produced by the thyroid gland that helps regulate calcium levels in the blood.

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Selective Estrogen Receptor Modulators (SERMs)

A class of drugs that selectively target estrogen receptors, acting as agonists in some tissues and antagonists in others.

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Raloxifene

A SERM used in the treatment of osteoporosis, particularly in postmenopausal women.

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Bone Resorption

The process by which bone cells called osteoclasts break down bone tissue.

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Hypercalcemia

A condition marked by abnormally high levels of calcium in the blood, often linked to certain cancers.

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Calcium Carbonate

Calcium salt used to treat hyperphosphatemia, a condition where there is too much phosphate in the blood.

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Cinacalcet

A drug that enhances the sensitivity of the parathyroid Ca2+-sensing receptor, leading to a decrease in PTH secretion and lower blood calcium levels.

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Teriparatide

A synthetic form of parathyroid hormone used to treat osteoporosis, a condition that weakens bones.

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Calcium Salts (IV)

This medication is used to treat hyperkalaemia, a condition where there is too much potassium in the blood.

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What is Denosumab's mechanism of action?

A monoclonal antibody that targets and inhibits RANKL, a protein important in bone resorption. This action mimics the effect of OPG, another protein that blocks RANKL. Denosumab is used to manage osteoporosis in high-risk patients, preventing bone fractures.

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How often is Denosumab administered?

Denosumab is administered subcutaneously (SC) every 6 months, providing prolonged protection against bone loss.

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What are some clinical indications for Denosumab?

Denosumab is prescribed for postmenopausal women with osteoporosis who are at a high risk of fractures. It also helps manage bone loss associated with hormonal suppression in men with prostate cancer.

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Explain Romosozumab's mechanism of action.

A monoclonal antibody that binds to and inhibits sclerostin, a protein that normally suppresses bone formation. By inhibiting sclerostin, romosozumab promotes bone formation and enhances bone matrix production by osteoblasts. It also has some effects on osteoclasts, potentially reducing their resorptive activity.

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What is the mechanism of action of Vitamin D analogues?

These compounds are synthetic forms of vitamin D that are used to treat vitamin D deficiency and related conditions. They work by activating specific receptors in cells, impacting calcium levels in the body. This impacts calcium absorption in the gut, mobilization from bone, and elimination by the kidneys.

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What are some clinical uses for Vitamin D analogues?

Vitamin D analogues like ergocalciferol are used for various conditions like rickets, osteomalacia, and vitamin D deficiency caused by malabsorption or liver disease. They are also prescribed for hypocalcemia due to hypoparathyroidism. In chronic renal failure, calcitriol or alfacalcidol can help manage osteodystrophy, a complication caused by reduced calcitriol production.

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What are the potential adverse effects of Vitamin D analogues?

Excess intake of vitamin D can lead to hypercalcemia, which can cause severe complications such as kidney stones and renal failure, particularly when combined with high phosphate levels.

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How do calcium salts affect bone health?

Calcium salts like gluconate, lactate, and carbonate are used to supplement calcium levels. They work through various mechanisms, including increasing absorption with vitamin D and acidic pH, and decreasing absorption with fiber-rich diets and phosphorus intake.

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Study Notes

Lesson 27: Calcium Homeostasis

  • Focuses on calcium homeostasis within the body, specifically relating to bone health.

Index

  • Bone remodelling process
  • Disorders of bone
  • Non-pharmacological treatment
  • Drugs used in bone disorders

Bone Remodelling Process

  • Regulated by osteoblasts (OB) and osteoclasts (OC).
  • Affected by various cytokines.
  • Turnover of bone minerals, particularly calcium and phosphate.
  • Several hormones (parathyroid hormone (PTH), vitamin D family, oestrogens, growth hormone, steroids, calcitonin) and various cytokines are also involved.
  • Bone matrix is the osteoid, mainly collagen.
  • Other components (proteoglycans, osteocalcin) participate.
  • Osteonectin binds calcium and collagen.
  • Deposition of calcium phosphate crystals (hydroxyapatite) converts osteoid into hard bone matrix.

Osteoblasts

  • Cells forming bone, derived from precursors in bone marrow and periosteum.
  • Form important components of bone matrix, particularly collagen (osteoid).
  • Participate in activating osteoclasts.
  • Osteocytes—derived from osteoblasts embedded in bone matrix; they influence mechanical stress response, initiate bone remodelling and secrete sclerostin

Osteoclasts

  • Multinucleated cells that resorb bone.
  • Derived from macrophage-monocyte lineage.
  • Other important cells in bone include macrophages/monocytes, lymphocytes and vascular endothelium cells, which secrete cytokines and mediators in bone remodelling.

Activity of Osteoblasts and Osteoclasts

  • Bone formation, and resorption stages are outlined, with depictions of the differentiation processes to osteoblasts/osteoclasts
  • The processes are described in detail, including the cells, chemical actions and outcomes.

Bone Remodelling and Osteoclasts/Osteoblasts Activity

  • RANKL interacts with RANK to activate osteoclasts.
  • OPG (osteoprotegerin) acts as a decoy receptor for RANKL, inhibiting osteoclast differentiation and activation.

Regulation of Bone Remodelling: Oestrogens

  • Increase OPG to reduce bone resorption.
  • Inhibit osteoclast-recruiting cytokines and counter the bone-resorbing, calcium-mobilising effect of PTH
  • Withdrawal leads to osteoporosis.

Regulation of Bone Remodelling: Parathyroid Hormone (PTH)

  • Stimulates both bone formation and resorption.
  • Released when blood calcium levels are low.
  • Increases bone resorption to release calcium.
  • Increases calcium reabsorption and phosphate excretion in the kidneys.

Calcium and Phosphate Metabolism

  • Daily turnover of calcium is 700mg.
  • Concentration of ionized Ca2+ in extracellular fluid and plasma must be tightly controlled.
  • The plasma concentration of Ca2+ is controlled by PTH, calcitriol, and calcitonin.

Vitamin D

  • Importance in calcium and phosphate metabolism
  • Two types in humans: ergocalciferol (diet) and cholecalciferol (skin).
  • Liver converts cholecalciferol to calcifediol, then to calcitriol in the kidney.
  • Process regulated by PTH and influenced by plasma phosphate.

Bone Disorders (Osteoporosis, Osteopenia, Osteomalacia, Rickets and Paget's Disease)

  • Osteoporosis is a reduction in bone mass with microarchitecture distortion.
  • Commonest causes include postmenopausal estrogen deficiency and age-related deterioration.
  • Osteopenia is a reduction in mineral content.
  • Osteomalacia and rickets are caused by vitamin D deficiency.
  • Paget's disease involves distorted bone resorption and remodelling processes.

Non-Pharmacological Treatment

  • Physical activity
  • Healthy habits
  • Dietary recommendations: 100-200mg calcium + proteins, Vitamin A, D, P, K and Mg, Alkaline diet

Drugs used in Bone Disorders

  • Antiresorptive drugs: Bisphosphonates, Calcitonin, SERMs (Selective estrogen receptor modulators), Denosumab, Vitamin D, Calcium, Calcimimetic compounds.
  • Anabolic agents: PTH, teriparatide.

Specific Drugs (Bisphosphonates)

  • Inhibit bone resorption mainly by acting on osteoclasts.
  • Should be taken orally on an empty stomach for better absorption.
  • Adverse Effects (ADRs) include gastrointestinal problems, atypical femoral fractures, and osteonecrosis (especially with IV administration).
  • Long-term use should be re-evaluated regularly.

Specific Drugs (Calcitonin)

  • Thyroid hormone, opposite action of PTH, increases renal excretion of Ca2+.
  • Given by SC or IM or intranasally (less effective).
  • Mechanism of action involves inhibiting osteoclast activity and increasing renal calcium excretion.

Specific Drugs (Denosumab)

  • Recombinant human monoclonal antibody that inhibits RANKL and mimics OPG.
  • Inhibits osteoclast differentiation.
  • Administered every 6 months.

Specific Drugs (Romosozumab)

  • Monoclonal antibody that inhibits sclerostin to enhance bone formation, and inhibits osteoclasts.

Specific Drugs (Vitamin D Analogues)

  • Vitamin D analogues (ergocalciferol, calcifediol, calcitriol)
  • Mechanism involves activating nuclear steroid receptors and increasing Ca2+ absorption, mobilisation from bone, decreasing renal excretion.
  • Clinical use involves deficiency states (rickets, osteomalacia, vitamin D deficiency), hypocalcemia, and osteodystrophy of chronic renal failure.
  • ADRs include excessive intake causing hypercalcemia and elevated phosphate.

Specific Drugs (Calcium Salts)

  • Calcium salts (e.g. calcium gluconate, lactate, carbonate)
  • Indirect antagonists of PTH
  • Oral administration for dietary deficiency, hypocalcemia, hypoparathyroidism, acute tetany; and calcium carbonate use to treat hyperphosphatemia and prevent/treat osteoporosis
  • ADRs include gastrointestinal disturbance and potential arterial calcification.

Specific Drugs (Calcimimetic Compounds)

  • Cinacalcet - Enhances parathyroid Ca2+ sensing receptors to decrease PTH secretion, reducing serum Ca levels.

Specific Drugs (Parathyroid Hormone)

  • Teriparatide (recombinant PTH)
  • Used in low doses intermittently to reverse osteoporosis by stimulating new bone formation, increasing osteoblast numbers and preventing osteoblast apoptosis.
  • Adverse effects include nausea, dizziness, headache, arthralgias, and mild hypercalcemia.. Maximum treatment duration is 24 months.

Specific Additional information

  • All of these drugs are meant to regulate bone remodeling

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