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Bone and Calcium

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Intro to Bone

•Specialized connective tissue

•hydroxyapatite (calcium phosphate & organic salts) deposited in collagenous matrix

•Highly vascularized

•Dense connective tissue that is hard and resilient, and capable of slowly changing as forces on the body change = viscoelastic

•Particularly strong because its mineral component imposes rigidity and resists compression & fibrous component provides some flexibility and resists tension and torsion

•Skeletal function- muscle attachment, RBC formation, support, calcium storage

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study question: 

  • why do bones need to be highly vascularized?

Bone Organization

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study question: 

  • what are the roles of the two different types of bone?

Cortical Bone

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  • arranged in osteons

  • osteons: rings of bone cells and layers of bone matrix (lamellae) around a central canal

  • other components: 

    • Canuliculi

    • Lacunae

    • Sharpey’s fibers

    • Trabeculae

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study question: 

  • describe this graph. 

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  • Cartilage has a lower modulus of elasticity than bone

    • more flexible and elastic

  • Viscoelasticity – a property of natural materials such as bone and cartilage

    • modulus of elasticity is not constant, it increases gradually with increased load

    • biomechanical behavior changes with the rate at which the material is loaded

Structure of Bone

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  • Fibroblasts - general connective tissue cell

    • Secrete an extracellular matrix

  • Transform into osteoblasts that produce a characteristic matrix of collagen fibers and protein polysaccharides (glycosaminoglycans/proteoglycans)

    • The first formed matrix, called osteoid, becomes calcified by binding of calcium phosphate crystals to the collagen fibers

    • These crystals are in the form of hydroxyapatite

  • Bones cells include:

    • osteoblasts – produce bone

    • osteoclasts – remove existing bone

    • osteocytes – maintain equilibrium

study question: 

  • what is the difference between osteoblasts, osteoclasts, and osteocytes?

Internal Design of Bone

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  • Wolff’s law -  remodeling of bone occurs in proportion to mechanical demands placed on it

  • Piezoelectricity - low-level electrical charges. 

    • Surface charges arise within any crystalline material under stress

    • Negative charges under compression

    • Positive charges under tension

    • Specific modeling response may follow charge patterns

Tissue Response to Metabolic Stress

  • Atrophy

    • unstressed tissue, declines and decreases in prominence

  • Hypertrophy

    • stressed tissue, builds up and increases in prominence

  • Hyperplasia

    • cell division under stress

  • Metaplasia

    • tissues types transform from one type to another

    • Cartilage that becomes ossified

study question: 

  • explain the differences between these. 

Tissue Response to Metabolic Stress

  • Hormonal control

  • Hypertrophy - loading stimulates osteoblasts & calcitonin prevents Ca+ release

  • Atrophy - disuse stimulates osteoclasts & parathyroid hormone causes Ca+ release

    • Ca+ blood levels trigger proper hormone to control negative feedback loop to maintain blood and bone Ca+ levels.

Bone Cells and Remodelling

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Normal Bone vs Bone with Osteoporosis

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study question: 

  • what causes osteoporosis?

Calcium Food Sources

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  • Most abundant divalent cation of the body

  • 99% in bones and teeth

  • In addition to milk and dairy, certain green vegetables are high in Ca

  • Meats, grains, and nuts are not good source

study question: 

  • what is the relationship between calcium and bone formation

Digestion, Absorption, Transportation

  • Acidity in the stomach helps solubilize dietary calcium

  • Active Transport (major mechanism)

    • Primarily in duodenum and proximal jejunum

    • Saturable

    • Vitamin D dependent

  1. TRPV6 (Ca Transporter 1)  transports Ca2+ across brush border membrane

  2. Calbindin D transports Ca2+  across brush border and across the cytoplasm of enterocytes

  3. Ca2+/Mg2+ ATPase pumps Ca2+ from inside enterocytes to blood

  4. Role of Calcitriol 

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  • Passive Process (paracellular)

    • Throughout the small intestine, mostly in jejunum and ileum

    • Enhancers: fructose, oligosaccharides, insulin

  • Large intestine also plays a role in calcium absorption

    • Bacteria in the colon can free calcium bound to some fermentable fiber such as pectin

    • Fermentation products lower colon pH

  • Calcium binds to albumin and pre-albumin while in transport in blood

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Regulation of Extracellular Calcium

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Regulation of Intracellular Calcium

  • Intracellular calcium concentration can be increased

    • By increased transport from outside of the cells triggered by depolarization, hormones, and neurotransmitters (first messengers) second messengers

    • By (such as cAMP) that triggers calcium release from endoplasmic reticulum and mitochondria

    • Increase of intracellular calcium concentration allows calcium to carry out its functions

      • Some consider calcium an example of “third messenger”

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Calcium Functions and Roles

  • Calcium and bones

    • 99% of total body calcium is found in bones and teeth.

    • Calcium plays a critical role in mineralization of bones

    • Bone serves as calcium reservoir in regulation of extracellular calcium concentration

  • Ca2+ blood clotting

    • Required for conversion of prothrombin to thrombin (also see Vitamin K)

      • Early step (damaged vessel)

      •   Fibrinogen (soluble)   --> Fibrin (insoluble)

  • EDTA ties up Ca2+  so no clotting -->  get plasma

  • Calcium and muscle contraction

    • Ca2+ acts as intermediate between nerves and muscles

    • Works with ATP for actin and myosin to connect

      • Afterward, Ca ions return to intracellular stores

  • Calcium and nerve transmission

    • Transfer of message to target cells via neurotransmitter release

  • Calcium and cellular metabolism

    • Via calcium binding protein = calmodulin

      • Leads to activation of enzymes (kinases)

study question: 

  • explain the different processes for internal and external regulation of calcium

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Calcium Deficiencey

  • RDA has been established (2010)

  • Risk factors

    • Vitamin D deficiency

    • Low dietary intake

    • Impaired absorption

      • Malabsorption

      • Atrophic gastritis (low acidity in the stomach)

  • Menopause

    • Low estrogen accelerates loss of calcium from the bones

  • Hypocalcemia may result in tetany

    • Intermittent muscle contractions that fail to relax

  • Chronic low dietary calcium intake has been associated with

    • Osteoporosis

    • Hypertension

    • Colon Cancer

    • Obesity

study question: 

  • who is most at risk for a calcium deficiency

Calcium Toxicity

  • UL has been established

  • Milk Alkali Syndrome

    • Due to consumption of large amount of milk or antacids

    • Hypercalcemia

    • Deposition of Ca in soft tissues (more prevalent in patients with renal failure)

    • Systemic Alkalosis

    • Constipation

study question: 

  • who is most at risk for calcium toxicity

Clinical Assessment

  • Colorectal cancer

    • Proposed mechanism: in the colon Ca binds to fatty acids and bile acids which act as promoters of cancer

    • More evidence is needed for a formal recommendation

  • Osteoporosis

  • Lead toxicity

    • Lead absorption is inversely related to dietary calcium intake

Assessment

  • Serum calcium is tightly regulated therefore is not a good marker for calcium status

  • Serum Ca2+ level reflects alterations of Ca metabolism

    • Needs to consider albumin level as well

  • Bone mass is best tool to assess calcium status

    • DEXA is used to measure bone mineral contents

    • Best method to measure bone mineral contents; accurate, repeatable

©2023 by Syracuse University Dr.Margaret Voss

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