Calcium Homeostasis

Question 1

What are the major organs involved in calcium homeostasis?

Answer 1

Skeleton

Small Intestine

Kidneys

Parathyroid Glands

Question 2

What is the distribution of calcium in the plasma?

Answer 2

50% is freely ionized Ca, the biologically active form

40% is bound to plasma proteins - pH sensitive

10% in the form of soluble complexes with citrate, phosphate or other compounds

Question 3

What is the distribution of phosphate in the plasma?

Answer 3

Mostly ionized and in the form of phosphoric acid, referred to as inorganic phosphate

Question 4

What is a negative calcium balance associated with?

Answer 4

Immobilization of a limb

Prolonged bed rest

Weightlessness during space flight

Certain forms of cancer

Question 5

What is positive calcium balance associated with?

Answer 5

Skeletal growth

Question 6

What gives bone its rigidity?

Answer 6

Minerals impregnated in the bone matrix, accounts for about 2/3 of bone weight

Question 7

What are the organic constituents of bone?

Answer 7

The principal organic molecule in the bone matrix is type I collagen

Provides tensile strength

Question 8

How do the bones play a role in calcium homeostasis?

Answer 8

Contains a substantial calcium reserve

Question 9

What is compact bone?

Answer 9

Densely packed matrix that forms the shaft of long bones and covers the ends and surfaces of long bones and other bones

Question 10

What is cancellous bone?

Answer 10

Sponge-like bone that makes up the inner portion of flat bones, vertebral bodies and the epiphyses and interior diaphysis of long bones

Question 11

What is bone remodeling?

Answer 11

The resoprtion (breakdown) of discrete packets of old bone by osteoclasts and the subsequent formation of new bone at the resorption sites

Question 12

What are osteoblasts?

Answer 12

Play a major role in both the regulation of bone resorption and in promoting the formation of new bone

Question 13

What type of bone has the higher annual turnover rate?

Answer 13

Cancellous (Trabecular) at about 20% per year

Question 14

How does the rate of bone modeling change in response to use and disuse?

Answer 14

Low levels of loading leads to bone loss (more resorption)

High levels of loading leads to an increase in bone mineral density

Question 15

What are osteoclast precursor cells and what are they derived from?

Answer 15

Derived from monocyte/macrophage lineage cells

Differentiate into osteoclasts

Question 16

What is the OPG/RANK-L/RANK System?

Answer 16

Primary mechanism through which osteoblasts and osteoblast lineage cells regulate osteoclastogenesis and bone resorption

Question 17

What is RANK-L?

Answer 17

Cell surface ligand expressed by osteoblast lineage cells

Stimulate osteoclast precursor cells via direct cell-to-cell contact

Question 18

What is RANK?

Answer 18

Receptors expressed by osteoclast precursors that bind to RANK-L

Question 19

What occurs when RANK-L stimulates RANK?

Answer 19

Activation of signaling pathways in osteoclast precursors that promote their differentiation, fusion into multinucleated cells and activation

Also prolongs the life-span of the osteoclast by inhibiting apoptosis

Question 20

What is osteoprotegerin (OPG)?

Answer 20

Soluble protein released by osteoblasts that binds RANK-L and prevents it from activating RANK

Question 21

What stimulates and inhibits RANK-L expression?

Answer 21

Stimulates - PTH and 1,25(OH)2D3

Inhibits - estradiol

Question 22

What stimulates and inhibits OPG production?

Answer 22

Stimulates - Estradiol

Inhibits - PTH

Question 23

What is M-CSF?

Answer 23

Macrophage colony stimulating factor

Promotes the early differentiation of monocyte/macrophage lineage cells and works in concert with RANK-L to promote osteoclastogenesis

Question 24

How is bone resoprtion initiated?

Answer 24

By hormones, cytokines or other factors that bind receptors expressed by osteoblasts

This causes the osteoblasts to:

Degrade unmineralized osteoid

Increase their expression of RANK-L

Synthesize and release M-CSF

Question 25

What are osteoclasts and what occurs when they’re activated?

Answer 25

Large multinucleated cells formed by the fusion of mononucleated precursors of monocyte/macrophage lineage

When activated, attach to bone to form sealing zones which effectively seal off an area of bone surface

Question 26

What is the ruffled border formed by osteoclast plasma membrane?

Answer 26

Secretes H+ onto the bone surface via membrane-associated H+-ATPases

The low pH dissolves the hydroxyapatite crystal

At the same time proteases secreted by the osteoclast digest the matrix proteins

Question 27

What are Bone turnover markers?

Answer 27

Products of matrix degradation that indicate bone resorption rate

CTX and NTX

Question 28

What do osteoblasts express receptors for?

Answer 28

PTH

1,25(OH)2D3

Estorgens

Glucocorticoids

Question 29

What two proteins can be used as clinical indicators of bone formation?

Answer 29

Alkaline phosphatase

Osteocalcin

Question 30

What occurs to osteoblasts after matrix formation?

Answer 30

50-70% undergo apoptosis

Some remaining osteoblasts become lining cells that cover newly formed bone

Others become osteocytes

Question 31

What are canaliculi?

Answer 31

Canals that allow the communication of osteocytes with lining cells

This network supports bone metabolism and functions to detect changes in mechanical strain

Question 32

How does bone mass change with age?

Answer 32

Modeling of bone continues through early adulthood, afterwhich the skeleton remains in a homeostatic state

Starting in the 4th decade of life, more bone is resorbed than produced, causing a gradual decline in bone mass with increasing age