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MNSR - MCQ > MNSR 5 - Bone: Calcium, Biominerals, and Treatments for Osteoporosis > Flashcards

MNSR 5 - Bone: Calcium, Biominerals, and Treatments for Osteoporosis Flashcards

1
Q

What are some major parts in the chemistry of Calcium?

A

Alkaline earth metal
Number 20 in the periodic table.

Fifth most abundant element in the earth’s crust
3.4 % by mass

Found in many inorganic mineral forms
CaCO3 – Aragonite or Calcite
CaSO4 - Anhydrite (Gypsum aka Plaster of Paris)
Ca5(PO4)3(X) - Apatite (X = OH, F, Cl)

Found in ionic form as Ca2+ cation

Forms ionic complexes with many oxygen containing anions.

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2
Q

How is calcium present in soil?

A

Available for plants, adjust pH.

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3
Q

How is calcium present in water?

A

Freed from some minerals in acidic medium, present as Ca2+, Conc in sea water(10 mM) 100 – 1,000 times > fresh water (0.01-0.1 mM).

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4
Q

How is calcium present in plants?

A

Binds adjacent plant cells, structural component of cellular membranes and enzyme cofactor.

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5
Q

How is calcium present in invertebrates?

A

Present as CaCO3 (calcite and aragonite) in various sea creatures, invertebrates.

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6
Q

How is calcium present in vertebrates?

A

Present as calcite and aragonite in shell of eggs.
Present as hydroxyapatite in bones and teeth.

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7
Q

What are some of the functions of Calcium in the human body?

A

Structural: in bones and teeth

Signalling: Constriction and relaxation of blood vessels, nerve impulse transmission, muscle contraction, secretion of hormones (e.g. Insulin), mechanism of vision, taste and smell.

Co-factor: in proteins and enzymes Clotting/coagulation of blood in association with vitamin K dependent proteins.

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8
Q

Is Calcium soluble?

A

No

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9
Q

Calcium is absorbed as the ______________. Most dietary calcium is not ionic, and is therefore insoluble at neutral pH.

A

divalent cation (Ca++)

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10
Q

Absorption primarily occurs in _____________ since at a pH (7 – 8).

A

duodenum

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11
Q

Absorption can occur by __________________

A

active transport or passive diffusion.

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12
Q

Absorption of Calcium is enhanced by:

A

Vitamin D – promotes synthesis of calcium binding protein in intestinal cells.

Lactose – Sugar present in milk maintains calcium in soluble form.

Other sugars and protein – Keep calcium soluble.

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13
Q

Absorption of Calcium is inhibited by:

A

Vitamin D deficiency – Can lead to rickets.

Oxalic acid – Calcium forms insoluble complexes with oxalic acid and other organic acids (eg. phytic acid).

High fat diet – Unabsorbed fats can form soaps with calcium and prevent absorption.

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14
Q

Cortical bone (Compact bone) is a…

A

Dense, low porosity, found in the shaft and forms outer shell around cancellous bone.

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15
Q

Trabecular bone (Cancellous bone) is a…

A

Low density, high porosity, found in the end of long bones, vertebrae and flat bones.

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16
Q

What are a bone’s structural components?

A

Organic matrix
- Comprises mainly type 1 collagen (highly cross-linked triple helical protein structure).

Inorganic mineral hydroxyapatite
- Has a molecular formula:
Ca5(PO4)3(OH)
or
Ca10(PO4)6(OH)2 - (crystal unit cell formula)

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17
Q

In bone, collagen consists of tropocollagen subunits, in which each tropocollagen molecule contains…

A

three helices of protein chains wound around each other to form a helical rod 3000 Å long and 15 Å in diameter; The three protein chains are linked together by hydrogen bonds.

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18
Q

A collagen fibril consists of a…

A

staggered array of tropocollagen molecules.

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19
Q

400 Å gaps between the tropocollagen subunits serve as…

A

nucleation sites for the deposition of long, hard, fine crystals of the mineral component (hydroxyapatite)

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20
Q

Hydroxyapatite structure Ca5(PO4)3(OH) is made up of…

A

Phosphate tubes (PO4)

Internally lined with Ca2+ ions (Ca)

Hydroxyl at centre of tube (OH)

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21
Q

Three special types of cells only found in the bone:

A

Osteoclasts, osteoblasts, and osteocytes

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22
Q

Osteoclasts are…

A

Responsible for bone resorption.
Originate in bone marrow.

23
Q

Osteoblasts are…

A

Are the cells that form new bone.
Originate in bone marrow .
They produce new bone called “osteoid” which is made of collagen and other proteins, then control calcium and mineral deposition.

24
Q

Osteocytes are…

A

Most abundant cells in bone; found inside the bone.
Originate from osteoblasts that are encapsulated in bone matrix.
Sense bone deformation and then signal the need for adaptive remodelling of bone size, shape.

25
Q

What happens during osteogenesis of the bone?

A

Bone formed on soft tissue.
Embryonic development, early stages of growth and during healing.
Osteoblast cells act independent of osteoclast cells.
Potential to create large amounts of bone.

26
Q

What happens during modeling of the bone?

A

Bone formed on existing bone tissue.
Occurs during growth and healing.
Osteoblasts and osteoclasts can act independently at different sites.
Potential to create or resorb large amounts of bone.

27
Q

What happens during remodeling of the bone?

A

Bone both resorbed and formed at the same site.
Occurs from growth through death.
The only normal physiologic mechanism for changing bone in adult skeleton.
Maintenance of bone but leads to net loss of bone with increasing age.

28
Q

During osteogenesis, the osteoblast creates a production of…

A

extracellular organic matrix.

29
Q

What does the extracellular organic matrix consist of?

A

Consists of type 1 collagen and osteocalcin. Collagen provide structural support of matrix and osteocalcin promote calcium binding
Collagen and osteocalcin deposited in parallel and concentric layers (mature bone) or in interwoven parallel array (fetal bone, pathological conditions, e.g. fracture callus, hyperparathyroidism).

30
Q

What happens during mineralisation?

A

Mineralisation occurs soon after deposition of extracellular matrix, where calcium and phosphate are derived from blood plasma.
Mineral crystals form along the collagen fibrils and osteocalcin chains.
Osteocalcin contain carboxyl groups for binding calcium.

31
Q

Osteocytes release local factors that ________________________ into the remodeling compartment.

A

attract cells from blood and marrow

32
Q

Osteoclasts resorb __________________, then successive teams of osteoblasts deposit new bone.

A

matrix and microcrack

33
Q

During remodeling, we see a ________________ and __________________ of bone at the same site.

A

Formation and resorption

34
Q

Osteoblast and osteoclast activity are _____________ on each other.

A

dependent

35
Q

During activation, the preosteoclasts are __________________________ under the influence of cytokine and growth factors to ________________.

A

stimulated and differentiated, mature into active osteoclasts.

36
Q

During resorption, osteoclasts _____________________.

A

digest mineral matrix, old bone.

37
Q

Reversal is the…

A

end of resorption

38
Q

During formation, osteoblasts are responsible for _________________

A

bone matrix synthesis (collagen) and controlled mineralisation.

39
Q

How does the Parathyroid Hormone (PTH) regulate bone mass?

A

PTH can increase the recruitment of osteoblasts and osteoclasts.
Both osteoblasts and osteoclasts have PTH receptors.
High PTH secretion (Hyperparathyroidism) leads to acceleration of the bone turnover.

40
Q

How does Vitamin D regulate bone mass?

A

Vitamin D increases recruitment of osteoclasts and also plays a part in the mineralization of bone matrix.

41
Q

Low Vitamin D results in

A

osteomalacia

42
Q

Many other important factors regulating bone mass are:

A

Estrogens, calcitonin, glucocorticoids, progesterone, androgens.

43
Q

What is osteoporosis?

A

Bone disease in which the amount of bone is reduced significantly

Structural integrity of trabecular bone is impaired.

Cortical bone becomes more porous and thinner.

Bone becomes weaker and more likely to fracture.

WHO
Bone density < 648 mg cm-2

44
Q

How can osteoporosis be prevented?

A

By taking Calcium, Vitamin D, and Exercising

45
Q

What are some of the treatments for osteoporosis?

A

Estrogen, Calcitonin, SERMs, Bisphosphonates, Parathyroid Hormone Related Proteins

46
Q

How does Calcitonin work?

A

Calcitonin suppresses resorption of bone by inhibiting the activity of osteoclasts, a cell type that “digests” bone matrix, releasing calcium and phosphorus into blood.

47
Q

Why is raloxifene no longer a recommended treatment?

A

Recent evidence indicates that raloxifene significantly increases risk of thromboembolism and is no longer a recommended treatment for osteoporosis according to the American College of Physicians.

48
Q

What do bisphosphonates do?

A

Block bone resorption with immediate effect.

Bone formation continues for 6 – 12 months after start of treatment.

Minerals are more densely packed and so the bone density increases.

49
Q

What two classes are there of bisphosphonates?

A

Class I: Bisphosphonates that do not contain nitrogen
Class II: Bisphosphonates that contain nitrogen

50
Q

What happens when a Class I bisphosphonate attaches to a mineral in bone tissue?

A

They are metabolised in osteoclast to compounds that compete with ATP in energy metabolism.
Induces apoptosis and osteoclast death.

51
Q

What happens when a Class II bisphosphonate attaches to a mineral in bone tisuse?

A

Inhibit modification of proteins essential to key osteoclast processes such as adhesion, migration, vesicular trafficking, formation of ruffled border.
Can also lead to osteoclast apoptosis.

52
Q

Parathyroid hormone (PTH) a polypeptide with __ amino acids

A

84

53
Q

Parathyroid hormone regulates…

A

calcium in our bodies

MNSR - MCQ (5 decks)

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