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Questions and Answers
What is a primary clinical use of calcium carbonate in IV administration?
What is a primary clinical use of calcium carbonate in IV administration?
What action does cinacalcet primarily facilitate in the body?
What action does cinacalcet primarily facilitate in the body?
What is a notable adverse drug reaction (ADR) associated with teriparatide?
What is a notable adverse drug reaction (ADR) associated with teriparatide?
Which statement about teriparatide's mechanism of action is correct?
Which statement about teriparatide's mechanism of action is correct?
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What is a concern regarding the long-term use of teriparatide?
What is a concern regarding the long-term use of teriparatide?
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What is a primary consequence of vitamin D deficiency related to bone health?
What is a primary consequence of vitamin D deficiency related to bone health?
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Which condition is characterized by a reduction in the mineral content of bones?
Which condition is characterized by a reduction in the mineral content of bones?
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Which hormone is NOT directly involved in phosphate homeostasis?
Which hormone is NOT directly involved in phosphate homeostasis?
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What is the mechanism of action of bisphosphonates in the treatment of bone disorders?
What is the mechanism of action of bisphosphonates in the treatment of bone disorders?
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Which of the following is a type of anabolic agent used to increase bone formation?
Which of the following is a type of anabolic agent used to increase bone formation?
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What dietary recommendation is suggested for promoting bone health?
What dietary recommendation is suggested for promoting bone health?
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What is a common side effect associated with the long-term use of bisphosphonates?
What is a common side effect associated with the long-term use of bisphosphonates?
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What is the role of calcitriol in bone metabolism?
What is the role of calcitriol in bone metabolism?
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What is the primary function of osteoblasts in the bone remodelling process?
What is the primary function of osteoblasts in the bone remodelling process?
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Which hormone is NOT involved in the process of bone remodelling?
Which hormone is NOT involved in the process of bone remodelling?
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What key substance is a major component of the bone matrix known as osteoid?
What key substance is a major component of the bone matrix known as osteoid?
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What is an important monitoring requirement for long-term bisphosphonate use?
What is an important monitoring requirement for long-term bisphosphonate use?
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How do osteocytes contribute to the bone remodelling process?
How do osteocytes contribute to the bone remodelling process?
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Which of the following conditions is NOT treated with bisphosphonates?
Which of the following conditions is NOT treated with bisphosphonates?
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What is the primary mechanism of action of Denosumab?
What is the primary mechanism of action of Denosumab?
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What is the role of osteonectin in the bone matrix?
What is the role of osteonectin in the bone matrix?
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Which of the following cells is primarily responsible for the resorption of bone?
Which of the following cells is primarily responsible for the resorption of bone?
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What is a common side effect associated with calcitonin administration?
What is a common side effect associated with calcitonin administration?
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Which condition is Denosumab NOT indicated for?
Which condition is Denosumab NOT indicated for?
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Which mechanism does calcitonin NOT utilize to lower plasma calcium levels?
Which mechanism does calcitonin NOT utilize to lower plasma calcium levels?
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Which cytokine plays a significant role in regulating the activity of osteoblasts and osteoclasts?
Which cytokine plays a significant role in regulating the activity of osteoblasts and osteoclasts?
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What effect do vitamin D analogues have on calcium levels?
What effect do vitamin D analogues have on calcium levels?
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Which selective oestrogen receptor modulator is mentioned as an alternative for secondary prevention in postmenopausal women?
Which selective oestrogen receptor modulator is mentioned as an alternative for secondary prevention in postmenopausal women?
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What can excessive intake of vitamin D lead to?
What can excessive intake of vitamin D lead to?
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What role do macrophage/monocytes play in the bone remodelling process?
What role do macrophage/monocytes play in the bone remodelling process?
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What is a potential serious adverse effect associated with Raloxifene?
What is a potential serious adverse effect associated with Raloxifene?
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What is the mechanism of action for Romosozumab?
What is the mechanism of action for Romosozumab?
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What should be monitored during therapy with vitamin D?
What should be monitored during therapy with vitamin D?
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Which of the following is a clinical use for calcitonin?
Which of the following is a clinical use for calcitonin?
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Which of the following drugs is primarily used for hypocalcaemia due to hypoparathyroidism?
Which of the following drugs is primarily used for hypocalcaemia due to hypoparathyroidism?
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Which hormone works oppositely to Parathyroid Hormone (PTH) by increasing renal excretion of calcium?
Which hormone works oppositely to Parathyroid Hormone (PTH) by increasing renal excretion of calcium?
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What is a common adverse effect associated with oral calcium salts?
What is a common adverse effect associated with oral calcium salts?
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What is the role of RANKL in bone remodelling?
What is the role of RANKL in bone remodelling?
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How do estrogens influence bone resorption?
How do estrogens influence bone resorption?
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What effect does parathyroid hormone (PTH) have on calcium metabolism?
What effect does parathyroid hormone (PTH) have on calcium metabolism?
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Which statement is true regarding the roles of vitamin D?
Which statement is true regarding the roles of vitamin D?
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What primary action does osteoprotegerin (OPG) perform in bone remodelling?
What primary action does osteoprotegerin (OPG) perform in bone remodelling?
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What role does vitamin D's calcitriol play in renal function?
What role does vitamin D's calcitriol play in renal function?
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Which of the following statements about bone remodelling is accurate?
Which of the following statements about bone remodelling is accurate?
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Which hormone is primarily responsible for increasing calcium levels in the blood?
Which hormone is primarily responsible for increasing calcium levels in the blood?
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Study Notes
Calcium Homeostasis
- Lesson 27, 3rd Medicine, Academic year 2024/25
- Professor: Vittoria Carrabs PhD
Index
- Bone remodelling process
- Disorders of bone
- Non-pharmacological treatment
- Drugs used in bone disorders
Bone Remodelling
- Regulated by osteoblast (OB) and osteoclast (OC) activity
- Influenced by various cytokines
- Bone mineral turnover (calcium, phosphate) is key
- Actions of several hormones: parathyroid hormone (PTH), Vitamin D, oestrogens, growth hormone, steroids, calcitonin, and various cytokines
Bone Matrix
- Organic matrix is osteoid, primarily collagen
- Other components: proteoglycans, osteocalcin, phosphoproteins (e.g., osteonectin)
- Calcium phosphate crystals (hydroxyapatite) convert osteoid to hard bone matrix
- Plays crucial role in calcium homeostasis
Osteoblasts
- Cells that form bone tissue
- Derived from precursors in bone marrow and periosteum
- Form important components of bone matrix (osteoid), particularly collagen
- Involved in activating osteoclasts
Osteocytes
- Derived from osteoblasts embedded in bone matrix
- Influence response to mechanical stress
- Initiate bone remodelling
- Secrete sclerostin (reduces bone formation)
Osteoclasts
- Multinucleated cells that resorb bone
- Derived from macrophage-monocyte lineage
- Other important cells in bone: macrophages, monocytes, lymphocytes, vascular endothelium cells - they secrete cytokines and other mediators involved in bone remodelling
Activity of Osteoblasts and Osteoclasts
- The bone remodelling cycle:
- Bone resorption: precursor cells differentiate into osteoclasts (OCs) or osteoblasts (OBs); OCs digest bone
- Bone formation: OBs secrete osteoid (bone matrix); mineralization of osteoid occurs (hydroxyapatite deposition)
Bone Resorption
- Osteoblasts express RANKL
- RANKL interacts with RANK on osteoclast progenitors' surface
- This initiates osteoclast activation and differentiation
- Osteoprotegerin (OPG) acts as decoy receptor for RANKL, inhibiting osteoclast differentiation
Regulation of Bone Remodelling - Oestrogens
- Act on osteoblasts, increasing OPG, reducing bone resorption.
- Inhibit cytokines that recruit osteoclasts.
- Opposes PTH's bone-resorbing, calcium-mobilising action
- Menopause frequently leads to osteoporosis.
Regulation of Bone Remodelling - Parathyroid Hormone (PTH)
- Stimulates both bone formation and bone resorption
- Released when calcium levels are low
- Increases bone resorption to release calcium
- In kidneys, increases calcium reabsorption and phosphate excretion
Calcium and Phosphate Metabolism
- Daily calcium turnover: 700 mg
- Plasma calcium concentration must be precisely controlled by:
- PTH
- Calcitriol
- Calcitonin
Importance of Vitamin D
- Two forms: ergocalciferol (diet), cholecalciferol (sunlight)
- Liver converts cholecalciferol to calcifediol
- Kidney converts calcifediol to calcitriol
- Regulated by PTH and plasma phosphate concentration
Vitamin D - Main effects of calcitriol
- Stimulation of calcium and phosphate absorption in the intestine
- Mobilisation of calcium from bone and increased calcium reabsorption in renal tubules
- Promotion of osteoclast maturation and indirect stimulation of osteoclast activity
- Decreased collagen synthesis by osteoblasts
Disorders of the Bone
- Osteoporosis: Reduction of bone mass, distortion of microarchitecture; commonly due to postmenopausal estrogen deficiency or age-related deterioration
- Osteopenia: Reduction in mineral content
- Osteomalacia and Rickets: Vitamin D deficiency
- Paget's Disease: Distortion of bone processes of resorption and remodelling
Non-Pharmacological Treatment
- Physical activity
- Healthy habits
- Dietary recommendations:
- 100-200 mg calcium+proteins
- Vitamins A, D, P, K, Mg
- Alkaline diet
Drugs used in Bone Disorders
-
Antiresorptive drugs: Decrease bone loss.
- Bisphosphonates
- Calcitonin
- Selective estrogen receptor modulators (SERMs)
- Denosumab
- Vitamin D, Calcium
- Calcimimetic compounds
-
Anabolic agents: Increase bone formation.
- PTH, teriparatide
Bisphosphonates
- Inhibit bone resorption—mainly on osteoclasts
- Oral administration, empty stomach, with water; seated/standing at least 30 minutes before breakfast
- ADRs: gastrointestinal disturbances, atypical femoral fractures, osteonecrosis (IV)
- Long-term use requires periodic reevaluation
Calcitonin
- Thyroid hormone, opposite action to PTH
- Increases renal excretion of calcium
- Reduced osteocyte activity
- Mechanism of action:
- Falls in plasma calcium leads to parathyroid hormone secretion, leading to calcitriol conversion, and increased calcium absorption in the intestine - Overall decrease in plasma calcium
- ADRs: Nausea, vomiting, facial flushing
Estrogens and Related Compounds
- Important for bone integrity in females.
- Deficiency at menopause leads to osteoporosis.
- Large doses of glucocorticoids can lead to osteoporosis.
- Vitamin D is used to treat bone diseases.
- HRT, raloxifene
Selective Estrogen Receptor Modulators (SERMs): Raloxifene
- Acts as agonist in bones and liver and antagonist in breast and uterus
- Alternative to bisphosphonates for postmenopausal osteoporosis prevention (in women not tolerating bisphosphonates)
- ADRs: Hot flushes, leg cramps, flu-like symptoms, peripheral oedema, less common thrombophlebitis, and thromboembolism
Denosumab
- Recombinant human monoclonal antibody that inhibits RANKL (mimics OPG), inhibits osteoclast differentiation
- Administered sc every 6 months
- Used for osteoporosis in high-risk fracture patients
Romosozumab
- Monoclonal antibody that inhibits sclerostin, enabling bone formation and osteoblast matrix production
Vitamin D Analogues Preparations: Ergocalciferol, Calcifediol, Calcitriol
- Activate nuclear steroid receptors that increase calcium absorption in the intestine, mobilise calcium from bone by activating osteoclasts, and decrease renal excretion
- Used for deficiency states, hypocalcaemia
Calcium Salts
- Increased absorption by increased vitamin D, acid pH, oestrogens
- Decreased absorption with fiber, phosphorus, and intolerance
- Orally, calcium salts can lead to GI disturbances
- IV administration used for emergency treatment of hyperkalaemia.
- Calcium carbonate is poorly absorbed in the gut and could lead to arterial calcification in patients with renal failure
Calcicimimetic Compounds: Cinacalcet
- Enhances the sensitivity of parathyroid Ca2+-sensing receptor to blood calcium concentration.
- Decrease in parathyroid hormone secretion and reduction in serum calcium concentration
Parathyroid Hormone: Teriparatide
- Recombinant parathyroid hormone for osteoporosis treatment
- Administered at low doses intermittently
- Reverses osteoporosis by stimulating new bone formation (anabolic function)
- Increases osteoblast numbers and stimulates osteoblast activity
- Reduces osteoblast apoptosis
- ADRs: Nausea, dizziness, headache, arthralgias, mild hypercalcemia, transient orthostatic hypotension, leg cramps - limited to 24 months (not repetetive)
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Description
Explore the intricacies of calcium homeostasis in the context of bone remodeling in this detailed quiz from 3rd Medicine. Understand the roles of osteoblasts, osteoclasts, and various hormones regulating bone health. Dive into disorders of bone and treatments available, both pharmacological and non-pharmacological.
