MPP: BLOCK 2: LOWERY: SKELETAL/BONE PHYS. & PHARM (PART 1 OF 4)
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Questions and Answers

Which laboratory test is commonly used to monitor osteoblasts?

  • Bone-Specific Alkaline Phosphatase (correct)
  • C-Reactive Protein
  • Vitamin D Levels
  • Creatine Kinase

    • What is one of the possible fates of osteoblasts after they perform their function?

  • They can become red blood cells.
  • They can become muscle cells.
  • They can undergo apoptosis. (correct)
  • They can enter the bloodstream as stem cells.

    • Which imaging technique is used for assessing osteoblast activity?

  • MRI
  • CT Scan
  • Bone scintigraphy using technetium-99m (correct)
  • Ultrasound

    • What histological technique is employed to count osteoblasts on bone surfaces?

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

    What happens to inactive osteoblasts when their activity is needed?

    <p>They can revert to active osteoblasts.</p> Signup and view all the answers

    What is the primary function of osteoblasts?

    <p>Secrete bone matrix</p> Signup and view all the answers

    Which lineage do osteocytes originate from?

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

    Which drug is targeted at osteoclasts?

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

    What is the lineage source of osteoclasts?

    <p>Monocyte/Macrophage</p> Signup and view all the answers

    Which cell type acts as a mechanosensor in bone tissue?

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

    Which of the following drugs is NOT associated with osteoblast activity?

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

    What is a key characteristic of osteocytes?

    <p>They are involved in mineral homeostasis.</p> Signup and view all the answers

    Which type of bone cell is primarily involved in bone matrix degradation?

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

    What is the primary process necessary for maintaining bone quality by repairing microdamage?

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

    Which of the following cells are primarily involved in bone formation?

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

    What is the role of RUNX2 in bone physiology?

    <p>It is a gene target that promotes osteoblast differentiation.</p> Signup and view all the answers

    Which factor is secreted by active mature osteoblasts that regulates osteoclast formation?

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

    What do osteoblasts secrete that is involved in the mineralization of bone?

    <p>Bone-specific alkaline phosphatase (BALP)</p> Signup and view all the answers

    What primarily directs the differentiation of mesenchymal stem cells (MSCs) into osteoprogenitors?

    <p>BMP signaling</p> Signup and view all the answers

    Which transcription factors are commonly associated with the activity of osteoblasts?

    <p>RUNX2 and osterix</p> Signup and view all the answers

    What is the function of osteocyte cells in bone tissue?

    <p>Maintenance of bone matrix and signaling</p> Signup and view all the answers

    Which molecule secreted by osteoblasts promotes the inhibition of osteoclast activity?

    <p>Osteoprotegerin (OPG)</p> Signup and view all the answers

    Which of the following statements is true regarding osteoprogenitors?

    <p>They can differentiate into various cell types including osteoblasts.</p> Signup and view all the answers

    What is the primary consequence of the overactivity of the Wnt pathway in sclerosteosis and Van Buchem Disease?

    <p>Increased osteoblast activity</p> Signup and view all the answers

    Which of the following best describes the role of Sclerostin in bone turnover?

    <p>It acts as an inhibitor of Wnt signaling</p> Signup and view all the answers

    What antibody is used to neutralize Sclerostin in patients with overactivity of the Wnt pathway?

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

    Which condition is most likely associated with over-secretion of Growth Hormone leading to high bone mass?

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

    What elevation is typically observed in patients with acromegaly after the growth hormone levels rise?

    <p>P1NP levels</p> Signup and view all the answers

    Which of the following statements about treatments for bone mass is true regarding GH-based therapies in osteoporosis?

    <p>They are not recommended for osteoporosis but are available for treating short stature.</p> Signup and view all the answers

    What is a significant observable effect of Van Buchem Disease?

    <p>Overactivity of Wnt signaling</p> Signup and view all the answers

    What is a potential outcome resulting from ineffective action of the Wnt inhibitor Sclerostin?

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

    How does acromegaly primarily develop in relation to Growth Hormone?

    <p>It is typically caused by a pituitary adenoma.</p> Signup and view all the answers

    What is a major function of the skeleton related to mineral regulation?

    <p>Reservoir for minerals</p> Signup and view all the answers

    Which type of skeletal disorder includes conditions like osteoporosis?

    <p>Metabolic disorders</p> Signup and view all the answers

    How does advanced age affect fracture risk?

    <p>Increases fracture risk</p> Signup and view all the answers

    What can significantly weaken bone material properties?

    <p>Defects in packaging or mineralization</p> Signup and view all the answers

    Which demographic has a notably higher prevalence of osteoporosis and related mortality after fractures?

    <p>Black women with post-menopausal osteoporosis</p> Signup and view all the answers

    What is the relationship between bone mass and fracture risk?

    <p>Higher bone mass leads to lower fracture risk</p> Signup and view all the answers

    What structure in the bone contributes to its material strength?

    <p>Collagen fibrils</p> Signup and view all the answers

    What is NOT a function of the skeleton?

    <p>Regulating digestive enzymes</p> Signup and view all the answers

    What is osteogenesis imperfecta commonly referred to as?

    <p>Brittle bone disease</p> Signup and view all the answers

    What is the projected increase in worldwide hip fracture incidence by 2050 for men compared to 1990?

    <p>310%</p> Signup and view all the answers

    Study Notes

    Major Bone Functions

    • Provides structural support and enables locomotion.
    • Plays a significant role in hematopoiesis (blood cell production) in adults.
    • Serves as a storage site for lipids.
    • Acts as a reservoir for minerals and regulates kidney function.
    • Participates in energy metabolism and satiety.

    Skeletal Disorders

    • Classified into two main categories: non-metabolic and metabolic.
    • Non-metabolic disorders arise from trauma or injury, such as osteoarthritis.
    • Metabolic disorders are associated with issues like low bone mass.

    Osteoporosis

    • In the US, the prevalence of osteoporosis in adults aged 50 and over is 11.0%, affecting approximately 12 million adults.
    • Prevalence is significantly higher in women (16.5%) than men (5.1%).
    • The overall prevalence of low bone mass is 44.5%, impacting about 45 million adults.
    • Increased fracture risk is inversely proportional to bone mass. Lower bone mass leads to higher fracture risk.
    • Advanced age is a contributing factor to increased fracture risk.

    Osteoporosis Impact

    • Hospitalizations for osteoporotic fractures in the US surpass those for heart attack, stroke, and breast cancer.
    • Up to 25% of hip fracture patients die within a year of their injury.
    • In the US, only 1 in 5 patients aged 50 and above who experience a hip fracture receive osteoporosis pharmacotherapy.
    • Worldwide, hip fracture incidence is projected to increase by 310% in men and 240% in women by 2050 compared to 1990.
    • Black women with postmenopausal osteoporosis experience significantly higher rates of mortality, debility, and destitution after fracture than white women.

    Bone Definition

    • Bone can be defined at three different levels:
      • As a matrix, composed of inorganic minerals and organic components.
      • As a tissue, characterized by its unique cellular structures and organization.
      • As an organ, a complete structure with specific functions.

    Bone Tissue Organization

    • The basic structural unit of compact bone is the osteon.
    • Osteons consist of concentric layers of bone matrix called lamellae, surrounding a central canal containing blood vessels and nerves.
    • Osteocytes reside in lacunae, small spaces between lamellae, connected by canaliculi for nutrient and waste exchange.

    Bone Material Properties

    • The strength of bone material is attributed to:
      • Collagen fibrils organized into fibers, acting like rebar in concrete.
      • Hydroxyapatite crystals (calcium phosphate) embedded within the collagen matrix.
    • Defects in collagen packaging and mineralization can weaken bone material.

    Osteogenesis Imperfecta

    • Various mutations affecting type 1 collagen expression, structure, or mineralization are linked to osteogenesis imperfecta, also known as brittle bone disease.

    Bone Remodeling

    • Continuous repair of microdamage in bones occurs through a process called bone remodeling.
    • This dynamic process involves the coordinated action of osteoblasts and osteoclasts.
    • Markers of bone remodeling include:
      • Collagen I fragments (CTx): indicate bone resorption.
      • Collagen I propeptide (P1NP): reflects bone formation.

    Bone Cell Types

    • Four main types of bone cells contribute to skeletal physiology:
      • Osteoprogenitors: undifferentiated cells that can differentiate into osteoblasts.
      • Osteoblasts: responsible for bone matrix synthesis and mineralization.
      • Osteocytes: mature bone cells embedded in bone matrix, acting as mechanosensors and regulators of bone turnover.
      • Osteoclasts: multinucleated cells responsible for bone resorption.

    Osteoblasts and Osteocytes

    • Osteoblasts and osteocytes originate from mesenchymal stem cells (MSCs).
    • The transcription factor RUNX2 is critical for osteoblast differentiation and is regulated by the Bone Morphogenetic Protein (BMP) pathway.
    • Multiple molecular switches control the decision for MSCs to become osteoprogenitors rather than chondroprogenitors.
    • Mature osteoblasts secrete various molecules:
      • Type 1 collagen (COL1A1) as uncalcified osteoid.
      • Bone-specific alkaline phosphatase (BALP) for matrix mineralization.
      • RANKL and OPG for regulating osteoclast formation.

    Monitoring Osteoblast Activity

    • Osteoblast activity can be assessed through laboratory tests:
      • Serum, plasma, and urine levels of alkaline phosphatase, bone-specific alkaline phosphatase, P1NP, and other markers.
    • Bone biopsy with histomorphometry allows for:
      • Counting osteoblasts on bone surface.
      • Visualizing bone matrix mineralization using fluorescent dyes.
    • Bone scintigraphy using technetium-99m provides insights into bone metabolism.

    Osteoblast Fate

    • Osteoblasts have three possible fates:
      • Apoptosis: the majority undergo programmed cell death.
      • Inactivity: becoming bone lining cells, a reversible process.
      • Differentiation: enclosing themselves in matrix and transforming into osteocytes.

    Factors Regulating Osteoblast Activity

    • Factors regulating osteoblast activity include:
      • Wnt pathway: a signaling pathway promoting bone formation.
      • Growth Hormone pathway: stimulates bone growth.
      • Parathyroid Hormone (PTH) pathway: influences bone turnover.

    Sclerosteosis and Van Buchem Disease

    • Sclerosteosis and Van Buchem Disease demonstrate the role of Wnt signaling in promoting osteoblast activity.
    • Both conditions are caused by overactivity of the Wnt pathway due to absent or ineffective action of the Wnt inhibitor, Sclerostin.
    • Romosozumab, a neutralizing antibody against Sclerostin, is used to inhibit its function and potentially treat osteoporosis.

    Acromegaly

    • Overproduction of Growth Hormone, often from a pituitary adenoma, results in high bone mass, particularly noticeable in the face, hands, and feet.
    • This is referred to as Acromegaly.
    • Elevated levels of P1NP are typically observed in patients with acromegaly, declining after removal of the pituitary adenoma.

    Summary of Bone Cell Types and Functions

    • Osteoblast ("Bob the Blast"):
      • Primary function: Secrete bone matrix.
      • Targeted by drugs: Teriparatide, Abaloparatide, Romosozumab.
    • Osteocyte ("Sally the Cyte"):
      • Major function: Mechanosensor, mineral homeostasis.
    • Osteoclast ("Carl the Clast"):
      • Primary function: Degrade bone matrix.
      • Targeted by drugs: Bisphosphonates, Denosumab, Romosozumab.

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    Description

    This quiz covers major functions of bones and the classification of skeletal disorders, including osteoporosis. Discover critical statistics about osteoporosis prevalence and its impact on different demographics. Test your knowledge on skeletal health and diseases!

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