Bone Structure & Growth Quiz
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Questions and Answers

Which function of bones is primarily involved in storing calcium and phosphate?

  • Bone marrow storage
  • Movement
  • Ca2+ and PO43- storage (correct)
  • Support and protection

    • What type of collagen is primarily found in the bone matrix?

  • Type 2 collagen
  • Type 1 collagen (correct)
  • Type 4 collagen
  • Type 3 collagen

    • What is the primary role of proteoglycans in bone structure?

  • Providing tensile strength
  • Facilitating movement
  • Providing compressive strength (correct)
  • Storing minerals

    • Which hormones play key roles in calcium and phosphate regulation?

    <p>PTH and vitamin D</p> Signup and view all the answers

    What happens during defective bone remodelling?

    <p>Development of osteoporosis</p> Signup and view all the answers

    What is the primary role of Vitamin D in relation to calcium and phosphate regulation?

    <p>To promote the synthesis of calcium channels and phosphate absorption</p> Signup and view all the answers

    What is osteoporosis characterized by?

    <p>Low bone mass and microarchitectural deterioration of bone</p> Signup and view all the answers

    What condition occurs in children due to Vitamin D deficiency?

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

    Which of the following best describes osteomalacia in adults?

    <p>Bone weakness due to unmineralised osteoid</p> Signup and view all the answers

    What primarily triggers fractures in post-menopausal women over the age of 50?

    <p>Low bone mass due to osteoporosis</p> Signup and view all the answers

    What is the effect of vitamin D on kidney tubules?

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

    What happens to bone growth after the fusing of the epiphyseal plate?

    <p>Bone growth stops</p> Signup and view all the answers

    What is the primary consequence of Vitamin D deficiency on bone mineralization?

    <p>Alteration of calcium availability and decreased mineralization</p> Signup and view all the answers

    What effect does PTH have on phosphate reabsorption in the kidneys?

    <p>Inhibits phosphate reabsorption</p> Signup and view all the answers

    Which enzyme is stimulated by PTH for the synthesis of the active form of vitamin D?

    <p>1α-hydroxylase</p> Signup and view all the answers

    Where does the key step of 1α-hydroxylation for active vitamin D production occur?

    <p>In the kidney</p> Signup and view all the answers

    What is the chemical formula for bone mineral hydroxyapatite?

    <p>Ca10(PO4)6(OH)2</p> Signup and view all the answers

    What is the active form of vitamin D also called?

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

    In which part of the intestines does Ca2+ absorption primarily occur?

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

    What role does active vitamin D play in the gut?

    <p>Promotes Ca2+ absorption</p> Signup and view all the answers

    What is the initial process for vitamin D synthesis in the body?

    <p>UV-stimulated synthesis in the skin</p> Signup and view all the answers

    What is the primary role of Parathyroid Hormone (PTH) in the body?

    <p>Regulate free Ca2+ levels</p> Signup and view all the answers

    How does acidosis affect the levels of free Ca2+ in the body?

    <p>Increases free Ca2+ levels</p> Signup and view all the answers

    Which of the following organs is responsible for the absorption of dietary calcium?

    <p>Gastrointestinal Tract</p> Signup and view all the answers

    What is the effect of low plasma Ca2+ levels on the release of PTH?

    <p>It stimulates PTH release</p> Signup and view all the answers

    Which ion is primarily involved in the regulation of calcium levels in the body?

    <p>Ca2+</p> Signup and view all the answers

    What type of bone is characterized by high porosity and a spongy structure?

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

    What happens to urinary excretion of calcium when dietary intake is at 1000 mg?

    <p>It stays constant at 200 mg</p> Signup and view all the answers

    Which cells in the parathyroid glands are responsible for the release of PTH?

    <p>Chief cells</p> Signup and view all the answers

    Which mechanism primarily controls the elongation of long bones during childhood?

    <p>Growth hormone and IGF-1</p> Signup and view all the answers

    What is the primary function of osteoclasts in bone tissue?

    <p>Promote bone reabsorption</p> Signup and view all the answers

    What is the consequence of alkalosis on free Ca2+ levels?

    <p>Free Ca2+ levels decrease</p> Signup and view all the answers

    What role does vitamin D3 (1,25 dihydroxycholecalciferol) play in calcium regulation?

    <p>Enhances calcium absorption</p> Signup and view all the answers

    What comprises most of the human skeleton, approximately 80%?

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

    What is the unit of bone growth that consists of concentric circles around a blood vessel?

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

    What is the main effect of PTH on osteoclasts?

    <p>Stimulates bone reabsorption</p> Signup and view all the answers

    Which phase of bone remodelling involves the preparation of the resorbed bone surface for new deposition?

    <p>Reversal phase</p> Signup and view all the answers

    Which hormone is indirectly stimulated by parathyroid hormone (PTH) to promote bone reabsorption?

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

    Which component is NOT a direct function of osteocytes?

    <p>Promoting bone reabsorption</p> Signup and view all the answers

    What is the primary mineral that is deposited during the ossification of osteoid?

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

    What process describes the change of cartilage to mineralized bone during fetal development?

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

    Which cell type is responsible for laying down the bone matrix?

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

    After bone growth ceases, what is the ongoing process that maintains bone health?

    <p>Bone remodelling</p> Signup and view all the answers

    What is the purpose of calcium movement across membranes in the body?

    <p>Neuromuscular functions</p> Signup and view all the answers

    In what form is calcium predominantly found in the blood?

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

    What role do proteoglycans play in the structure of bone?

    <p>Providing compressive strength</p> Signup and view all the answers

    What is the primary cause of osteoporosis?

    <p>Defective bone remodelling</p> Signup and view all the answers

    Which statement accurately describes the structure of bones?

    <p>Bone is composed of an organic matrix largely made up of type 1 collagen.</p> Signup and view all the answers

    Which biological function of bones primarily aids in locomotion?

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

    What type of bone is characterized by its spongy structure and high porosity?

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

    What effect does PTH have on calcium and phosphate levels in the kidneys?

    <p>Inhibits calcium reabsorption and promotes phosphate excretion</p> Signup and view all the answers

    Which process is not involved in the activation of vitamin D?

    <p>Cytokine mediation for vitamin D activation</p> Signup and view all the answers

    Where does the crucial 1α-hydroxylation of vitamin D occur?

    <p>In the kidney</p> Signup and view all the answers

    What is the primary role of active vitamin D in the intestine?

    <p>Increases calcium absorption</p> Signup and view all the answers

    Which statement accurately describes the synthesis of the active form of vitamin D?

    <p>It requires two hydroxylation steps and is not rate-limited by the liver step.</p> Signup and view all the answers

    How does PTH influence the plasma concentration of calcium and phosphate?

    <p>Increases both through enhanced bone reabsorption</p> Signup and view all the answers

    What is the role of calcium-binding proteins in the intestine?

    <p>Transport calcium into circulatory system</p> Signup and view all the answers

    Which of the following statements about hydroxyapatite is true?

    <p>It contains calcium and phosphate in its structure.</p> Signup and view all the answers

    What effect does an increase in hydrogen ion concentration ([H+]) have on the levels of free calcium ions (Ca2+) in the body?

    <p>It increases the levels of free calcium ions.</p> Signup and view all the answers

    Which of the following describes the primary function of parathyroid hormone (PTH) in regulating plasma calcium levels?

    <p>Stimulating bone reabsorption.</p> Signup and view all the answers

    How does alkalosis affect free calcium ion levels in the body?

    <p>It results in a decrease in free calcium ions.</p> Signup and view all the answers

    What is the source of parathyroid hormone (PTH) in the body?

    <p>Chief cells of the parathyroid glands.</p> Signup and view all the answers

    What physiological condition is indicated by low plasma calcium levels in relation to PTH?

    <p>Hypocalcemia.</p> Signup and view all the answers

    What role does calcium play in relation to parathyroid hormone's activity?

    <p>It inhibits PTH release.</p> Signup and view all the answers

    What is the daily dietary intake of calcium required for maintaining health?

    <p>1000 mg.</p> Signup and view all the answers

    In bone metabolism, what is the primary action of osteoclasts as stimulated by PTH?

    <p>Stimulating bone reabsorption.</p> Signup and view all the answers

    What is a direct consequence of bone reabsorption stimulated by PTH?

    <p>Release of calcium and phosphate into the bloodstream.</p> Signup and view all the answers

    Which form of vitamin D is involved in enhancing calcium absorption in the body?

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

    What characterizes compact bone compared to trabecular bone?

    <p>Dense and stiff structure with low porosity</p> Signup and view all the answers

    Which of the following best describes the role of osteocytes?

    <p>Transfer minerals from the inner regions of bone to growth surfaces</p> Signup and view all the answers

    Which phase of bone remodelling is primarily focused on the release of growth factors?

    <p>Formation phase</p> Signup and view all the answers

    What is the primary function of osteoclasts in bone tissue?

    <p>Promoting bone resorption and removing mineralization</p> Signup and view all the answers

    What initiates the elongation of long bones during childhood and adolescence?

    <p>Cartilage proliferation at the growth plate</p> Signup and view all the answers

    Which protein framework is laid down by osteoblasts during bone formation?

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

    What happens to bone mass approximately every 10 years in adults?

    <p>It undergoes complete remodelling</p> Signup and view all the answers

    Which of these factors directly stimulates osteoclasts to promote bone resorption?

    <p>Parathyroid hormone acting indirectly through osteoblasts</p> Signup and view all the answers

    During which phase of bone remodelling are osteoclasts attracted to the bone surfaces?

    <p>Resorption phase</p> Signup and view all the answers

    What cellular mechanism underlies the sensing of mechanical load by bone?

    <p>Cytoplasmic projections of osteocytes</p> Signup and view all the answers

    What is the primary purpose of the epiphyseal growth plate during bone development?

    <p>Enables lengthening of long bones</p> Signup and view all the answers

    What distinguishes trabecular bone from compact bone?

    <p>Spongy, lightweight structure with high porosity</p> Signup and view all the answers

    How does bone remodelling adapt to mechanical loading?

    <p>Through a balance of osteoblast and osteoclast activity</p> Signup and view all the answers

    What condition is characterized by low bone mass and increased susceptibility to fractures, particularly in post-menopausal women?

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

    Which vitamin is essential for promoting calcium and phosphate absorption in the gut?

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

    What is the primary consequence of vitamin D deficiency in adults?

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

    Which mineral is actively pumped out at the basolateral side of epithelial cells after absorption?

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

    Which physiological change is associated with the increased risk of osteoporosis in aging populations?

    <p>Decreased bone remodeling</p> Signup and view all the answers

    What mechanism primarily allows continuous regulation of serum calcium levels?

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

    What defines the clinical condition of rickets in children resulting from vitamin D deficiency?

    <p>Unmineralised osteoid leading to bowing of long bones</p> Signup and view all the answers

    Which process in the kidneys is promoted by vitamin D regarding phosphate?

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

    What is the primary structural component of the bone matrix that provides tensile strength?

    <p>Type 1 collagen</p> Signup and view all the answers

    Which of the following roles best describes osteocytes within the bone tissue?

    <p>Regulating mineral content</p> Signup and view all the answers

    Which term refers to the resistance of a material or structure to deformation under compressive loads?

    <p>Compressive strength</p> Signup and view all the answers

    What condition arises from a deficiency in bone remodeling, leading to decreased bone density and increased fracture risk?

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

    Which substance acts as a store for calcium and phosphate in the body, playing a crucial role in maintaining mineral balance?

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

    What is the primary action of PTH on the kidneys in relation to calcium?

    <p>Promotes calcium reabsorption in the thick ascending limb</p> Signup and view all the answers

    Which enzyme is crucial for the conversion of 25-hydroxyvitamin D to its active form in the kidney?

    <p>1α-hydroxylase</p> Signup and view all the answers

    How does active vitamin D primarily facilitate calcium absorption in the intestine?

    <p>Through calcium-binding proteins and channels</p> Signup and view all the answers

    Which of the following statements about the production of active vitamin D is NOT true?

    <p>25-hydroxylation in the liver is a rate-limiting step.</p> Signup and view all the answers

    What minerals are increased in plasma as a result of bone resorption stimulated by PTH?

    <p>Both calcium and phosphate</p> Signup and view all the answers

    What is the primary regulatory site for the synthesis of the active form of vitamin D?

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

    Which step is NOT involved in the formation of active vitamin D?

    <p>Phosphate excretion in the gut</p> Signup and view all the answers

    Which action does vitamin D have in terms of bone health?

    <p>Stimulates mineralization of the bone</p> Signup and view all the answers

    What significant action does vitamin D promote in the kidneys?

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

    What happens to the levels of free Ca2+ in the presence of increased concentrations of hydrogen ions (H+)?

    <p>Free Ca2+ levels increase</p> Signup and view all the answers

    Which age group is most at risk for osteoporosis-related fractures?

    <p>Women over 50 years</p> Signup and view all the answers

    What distinguishes osteomalacia from rickets?

    <p>Osteomalacia occurs in adults, whereas rickets occurs in children</p> Signup and view all the answers

    Which physiological condition promotes the binding of Ca2+ to proteins, resulting in decreased free Ca2+ levels?

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

    What triggers the release of Parathyroid Hormone (PTH) from the parathyroid glands?

    <p>Low plasma calcium levels</p> Signup and view all the answers

    How does vitamin D deficiency affect the structure of the bone?

    <p>It causes abnormal amounts of unmineralised osteoid</p> Signup and view all the answers

    How does PTH contribute to calcium regulation in the body?

    <p>By stimulating osteoclasts to increase bone reabsorption</p> Signup and view all the answers

    What process continues in bones throughout life after growth stops?

    <p>Bone turnover mediated by specific cells</p> Signup and view all the answers

    Which of the following is a direct consequence of aging on bone health?

    <p>Reduction in calcium absorption efficiency</p> Signup and view all the answers

    What is the primary effect of Parathyroid Hormone (PTH) on phosphate levels in the kidneys?

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

    What is the role of calbindin in calcium metabolism?

    <p>Facilitates calcium absorption across the gastrointestinal tract</p> Signup and view all the answers

    What role does 1,25 dihydroxycholecalciferol (vitamin D3) play in calcium regulation?

    <p>Enhances calcium absorption in the intestines</p> Signup and view all the answers

    What is the effect of low plasma calcium on the activity of osteoclasts?

    <p>Increases osteoclast activity to release calcium from bone</p> Signup and view all the answers

    What is a potential consequence of excessive activation of osteoclasts?

    <p>Bone fragility and higher fracture risk</p> Signup and view all the answers

    What substance is primarily involved in the detection of calcium levels by the parathyroid glands?

    <p>G-protein coupled receptors</p> Signup and view all the answers

    During acidosis, what is the effect on the binding of Ca2+ to proteins?

    <p>Decreases the binding of Ca2+ to proteins</p> Signup and view all the answers

    What is the daily dietary intake requirement for calcium?

    <p>1000 mg</p> Signup and view all the answers

    What occurs at the epiphyseal growth plate until approximately age 18?

    <p>Cartilage proliferation and elongation occur.</p> Signup and view all the answers

    What is the primary composition of trabecular bone?

    <p>High porosity structure.</p> Signup and view all the answers

    What role do osteocytes primarily play in bone physiology?

    <p>They sense mechanical load and communicate with osteoblasts.</p> Signup and view all the answers

    During which phase of bone remodeling do osteoclasts create resorption pits?

    <p>Resorption phase.</p> Signup and view all the answers

    What triggers osteoclast differentiation in bone remodeling?

    <p>Osteocyte signalling and PTH signaling.</p> Signup and view all the answers

    Which type of bone accounts for approximately 80% of human bone mass?

    <p>Compact bone.</p> Signup and view all the answers

    What initiates the process of endochondral ossification during fetal life?

    <p>Formation of ossification centers.</p> Signup and view all the answers

    What cellular process occurs after the growth plate fuses?

    <p>Vascularization and ossification of the mature bone.</p> Signup and view all the answers

    How does PTH influence the activity of osteoclasts?

    <p>It stimulates osteoblasts which indirectly activates osteoclasts.</p> Signup and view all the answers

    What limits osteocyte function in bone tissue?

    <p>Their low metabolic activity.</p> Signup and view all the answers

    What physiological role does calcium ion movement support?

    <p>Facilitation of neurotransmitter release at synapses.</p> Signup and view all the answers

    Which stage of bone remodeling has the longest duration?

    <p>Formation phase.</p> Signup and view all the answers

    What triggers the activation of circulating monocytes during bone remodeling?

    <p>Increased mechanical strain detected by osteocytes.</p> Signup and view all the answers

    Which structure is formed as a result of resorption of bone by osteoclasts?

    <p>Resorption pits.</p> Signup and view all the answers

    Study Notes

    Bone Structure & Function

    • Bones provide support, protection, movement, calcium and phosphate stores, and red blood marrow production.
    • Bone is a living tissue composed of an organic matrix made of Type 1 collagen fibres (~90-95%) and proteoglycans (~5%).
    • Collagen provides tensile strength while proteoglycans provide compressive strength.
    • Compact bone (cortical bone) is dense and stiff with a low porosity (~5-25%).
    • Trabecular bone (cancellous/spongy bone) is spongy, light, and has a high porosity (up to 70%).

    Bone Growth

    • During fetal development, bones are modelled in cartilage and then ossified.
    • During childhood/adolescence, cartilage proliferates at the growth plate, elongating long bones.
    • Growth is controlled by Growth Hormone and Insulin-like Growth Factor 1 (IGF-1).
    • Once the epiphyseal growth plate fuses, cartilage proliferation and elongation stop.
    • The growth plate is located between the epiphysis and the metaphysis.

    Bone Remodelling

    • Bone is constantly being remodelled, with the entire adult skeleton undergoing turnover every 10 years.
    • Bone remodelling is a dynamic process involving osteoblasts, osteoclasts, and osteocytes.
    • Osteoclasts resorb mineralized bone, releasing calcium and phosphate into the blood.
    • Osteoblasts deposit new bone matrix.
    • Osteocytes sense mechanical loading and relay information to osteoblasts.
    • Bone remodelling is essential for bone adaptation to mechanical loading, fracture healing, and preventing bone fatigue.

    Calcium Homeostasis

    • Calcium movement across membranes is crucial for many physiological processes, including neurotransmitter release, muscle contraction, and hormone secretion.
    • Calcium exists in blood in three forms: free (ionized), bound to protein, and bound to small anions.
    • Ionized calcium is the most physiologically active form.
    • Parathyroid Hormone (PTH), secreted by parathyroid glands, is the primary regulator of free calcium levels.
    • PTH release is triggered by low plasma calcium concentrations.
    • PTH acts to increase calcium levels by stimulating bone resorption, calcium reabsorption in the kidneys, and activating vitamin D production.

    Vitamin D

    • Vitamin D is a steroid-like molecule, produced by the skin in response to sunlight and ingested in the diet.
    • The active form, 1,25 dihydroxycholecalciferol, is synthesized in the kidneys from inactive precursors.
    • Vitamin D promotes calcium absorption from the intestines and calcium and phosphate reabsorption in the kidneys.
    • Vitamin D deficiencies can lead to reduced bone mineralisation, resulting in rickets in children and osteomalacia in adults.

    Osteoporosis

    • Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue.
    • It leads to increased bone fragility and a higher risk of fractures.
    • Osteoporosis is more common in women, particularly after menopause, than in men.
    • Post-menopausal women are more likely to suffer a hip fracture than develop breast cancer.
    • The ageing population is facing an increase in the prevalence of osteoporosis.

    Bone Structure and Growth

    • Bones provide support, protection, movement, a calcium and phosphate store, and house bone marrow.
    • Bone is a mineralised organic matrix, with collagen providing tensile strength and proteoglycans providing compressive strength.
    • Compact bone (cortical bone) is dense and stiff with low porosity, making up most of human bone.
    • Trabecular bone (cancellous or spongy bone) is spongy and light with high porosity.
    • In long bones, cortical bone forms the shaft (diaphysis), while trabecular bone is found at the ends (epiphysis and metaphysis).
    • The epiphyseal growth plate is located between the epiphysis and metaphysis.
    • Long bone growth occurs at the growth plate until about 18 years of age, when it fuses with the metaphysis.
    • Bone growth during fetal life involves cartilage modelling and mineralisation (ossification).
    • During childhood and adolescence, cartilage proliferates at the growth plate, elongating long bones, controlled by growth hormone and insulin-like growth hormone (IGF-1).
    • Once the growth plate fuses, cartilage proliferation and elongation stop, and the bone undergoes vascularisation and ossification.
    • The basic unit of bone growth is the osteon, concentric circles of collagen deposited around a blood vessel.
    • Blood vessels run through Haversian canals within the osteon.
    • The collagen in the osteon is then mineralised with hydroxyapatite (Ca10(PO4)6(OH)2).

    Bone Cells and Remodelling

    • Bone contains three main cell types: osteoblasts, osteoclasts, and osteocytes.
    • Osteoblasts promote bone formation, laying down osteoid and initiating mineralisation.
    • Osteoclasts promote bone reabsorption, removing mineralisation and releasing calcium and phosphate.
    • Osteocytes transfer mineral from bone's inner regions to the growth surfaces.
    • Osteoblasts are derived from mesenchymal stem cells and lay down osteoid (type 1 collagen matrix) to facilitate ossification.
    • Osteocytes are derived from osteoblasts, have cytoplasmic projections that sense mechanical load, and relay information to osteoblasts.
    • Osteoclasts are derived from the macrophage lineage, resorb mineralized bone, and create resorption pits.
    • Osteoclasts solubilise mineral at low pH, phagocytose the organic matrix, and are indirectly stimulated by PTH to promote bone reabsorption.
    • Bone remodelling is a continuous process in adults, with the entire skeleton being remodelled every 10 years.
    • Bone remodelling involves a balance between osteoblast and osteoclast activity, which enables adaptation to mechanical loading, fracture healing, and prevents "bone fatigue".
    • Osteocyte detected mechanical strain is relayed to osteoblasts, triggering NFκB signalling in circulating monocytes.
    • NFκB signalling activates monocytes into osteoclasts, which move to the region needing reabsorption.
    • Growth factors stimulate osteoblast formation, leading to new osteoid deposition and mineralisation.
    • Bone remodelling consists of four phases: resorption, reversal, formation, and quiescence (resting).

    Calcium and Phosphate Regulation

    • Calcium movement across membranes is crucial for various physiological mechanisms.
    • Calcium exists in three forms in body fluids: ionised (free), bound to proteins, and bound to small anions.
    • The ionised form (Ca2+) is responsible for most physiological functions.
    • Acid-base status influences bound calcium levels; acidosis increases free calcium, while alkalosis decreases free calcium.
    • Parathyroid hormone (PTH) is the major controller of free calcium in the body.
    • PTH is released from the parathyroid glands when plasma calcium levels are low.
    • PTH stimulates bone reabsorption, leading to an increase in plasma calcium and phosphate levels.
    • PTH promotes calcium reabsorption in the kidneys and inhibits phosphate reabsorption, promoting phosphate excretion.
    • PTH stimulates 1α-hydroxylase, the key enzyme in the synthesis of active vitamin D.
    • Active vitamin D (1,25 dihydroxycholecalciferol or calcitriol) is produced through 25-hydroxylation in the liver and 1α-hydroxylation in the kidneys.
    • Vitamin D promotes calcium and phosphate absorption in the gut, calcium and phosphate reabsorption in the kidneys, and mineralisation in bone.

    Bone Disorders

    • Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to bone fragility and fracture risk.
    • Vitamin D deficiency in children leads to rickets, characterized by abnormal unmineralised osteoid and bone bowing.
    • Vitamin D deficiency in adults leads to osteomalacia, characterized by bone weakness due to unmineralised osteoid but without bone bowing.

    Bone Functions & Structure

    • Bones provide support, protection, movement, a calcium and phosphate store, and a bone marrow store.
    • Bone is a mineralised organic matrix.
    • The matrix is mainly type 1 collagen fibres (90-95%) with some proteoglycans (5%).
    • Collagen provides tensile strength while proteoglycans provide compressive strength.

    Bone Types

    • Two main types of bone: compact bone (cortical bone) and trabecular bone (cancellous or spongy bone).
    • Compact bone is dense, stiff with low porosity (5-25%).
    • Trabecular bone is spongy, light with high porosity (up to 70%).
    • The combination of these two types provides mechanical strength despite being lightweight.

    Bone Growth

    • Bones are modelled in cartilage during fetal life and then mineralised through ossification.
    • Cartilage proliferates at the growth plate elongating bones during childhood/adolescence.
    • Bone growth is controlled by growth hormone and insulin-like growth hormone (IGF-1).
    • Growth plate fuses around age 18, stopping cartilage proliferation and elongation.
    • Vascularisation and ossification of the bone occur after the growth plate fuses.

    Bone Cells

    • Three main cell types in bone: osteoblasts, osteoclasts, and osteocytes.
    • Osteoblasts promote bone formation, laying down osteoid and initiating mineralisation.
    • Osteoclasts promote bone reabsorption, removing mineralisation and liberating calcium and phosphate.
    • Osteocytes transfer mineral from inner regions of bone to the growth surfaces.

    Osteoblasts

    • Modified fibroblasts derived from mesenchymal stem cells.
    • Lay down osteoid (type 1 collagen matrix) and facilitate ossification.
    • Some osteoblasts become embedded in the lining of the new bone and become osteocytes.

    Osteocytes

    • Derived from osteoblasts.
    • Transfer mineral from inner regions of bone to the growth surfaces.
    • Sense mechanical load on the bone.
    • Cytoplasmic projections into the bone pass information to osteoblasts.

    Osteoclasts

    • Derived from the macrophage lineage of cells.
    • Attracted to and resorb mineralized bone, creating resorption pits.
    • Solubilise mineral at low pH and phagocytose the organic matrix.
    • Indirectly stimulated by PTH, which promotes bone reabsorption.

    Bone Remodelling

    • Constant process of bone turnover throughout life (adults remodel every 10 years).
    • Balances bone mineralisation through osteoblast and osteoclast activation.
    • Enables adaptation to mechanical loading, fracture healing, and prevents "bone fatigue" by renewing bone matrix.

    Bone Remodelling Phases

    • Resorption phase (2 weeks): bone lining cells pull away, osteoclasts are attracted, pockets of bone resorbed, resorption pits, osteoclast apoptosis.
    • Reversal phase (2 weeks): resorbed bone surface prepared for bone deposition, cement line formation.
    • Formation phase (13 weeks): resorption of bone releases growth factors, osteoblasts attracted, osteoid deposited, mineralises, osteoblasts become osteocytes or bone-lining cells.

    Calcium Regulation

    • Calcium movement across membranes triggers physiological mechanisms like neurotransmitter release, smooth muscle contraction, heart muscle contraction, and hormone and enzyme secretions.
    • Ca2+ found in three forms: ionised (free), bound to protein, and bound to small anions.
    • Most physiological functions are mediated by ionised Ca2+.
    • Acid-base status can affect levels of bound Ca2+.

    Parathyroid Hormone (PTH)

    • Major controller of free Ca2+ in the body.
    • Released from chief cells in the parathyroid glands at low plasma Ca2+.
    • Detected by a membrane-bound G-protein receptor coupled to cAMP.
    • Decreases cAMP and inhibits PTH release.

    PTH & Negative Feedback

    • PTH release is regulated by negative feedback: High plasma Ca2+ decreases PTH secretion, while low plasma Ca2+ increases secretion. This mechanism ensures calcium homeostasis.

    PTH Actions

    • PTH stimulates bone reabsorption by activating osteoclasts, increasing plasma Ca2+ and phosphate.
    • Promotes Ca2+ reabsorption in the kidneys (thick ascending limb of the loop of Henle).
    • Inhibits phosphate reabsorption in the proximal and distal tubules (promotes phosphate excretion).
    • Stimulates 1α-hydroxylase enzyme in the kidneys, crucial for the synthesis of active vitamin D.

    Active Vitamin D Production

    • Active form is 1,25 dihydroxycholecalciferol (DHCC).
    • Synthesised through two hydroxylation steps: 25-hydroxylation in the liver and 1α-hydroxylation in the kidney.
    • 1α-hydroxylation is the rate-limiting step and is regulated by PTH.
    • Vitamin D acts by binding to intracellular receptors.

    Vitamin D Actions

    • Promotes calcium absorption in the duodenum by increasing synthesis of calcium channels and binding proteins.
    • Promotes phosphate absorption in the gut.
    • In the kidneys, vitamin D promotes Ca2+ and phosphate reabsorption.
    • Overall effect is to increase the flux of calcium and phosphate into bone.

    Osteoporosis

    • Systemic skeletal disease characterized by low bone mass and microarchitectural deterioration.
    • Leads to bone fragility and susceptibility to fractures.
    • Affects 33% of females after age 50 and 20% of males.

    Vitamin D Deficiency

    • Rickets (in children): abnormal amounts of unmineralised osteoid, bowing of long leg bones.
    • Osteomalacia (in adults): bone weakness due to unmineralised osteoid, but no bowing of the legs.

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