Calcium Homeostasis Flashcards
What are the major organs involved in calcium homeostasis?
Skeleton
Small Intestine
Kidneys
Parathyroid Glands
What is the distribution of calcium in the plasma?
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
What is the distribution of phosphate in the plasma?
Mostly ionized and in the form of phosphoric acid, referred to as inorganic phosphate
What is a negative calcium balance associated with?
Immobilization of a limb
Prolonged bed rest
Weightlessness during space flight
Certain forms of cancer
What is positive calcium balance associated with?
Skeletal growth
What gives bone its rigidity?
Minerals impregnated in the bone matrix, accounts for about 2/3 of bone weight
What are the organic constituents of bone?
The principal organic molecule in the bone matrix is type I collagen
Provides tensile strength
How do the bones play a role in calcium homeostasis?
Contains a substantial calcium reserve
What is compact bone?
Densely packed matrix that forms the shaft of long bones and covers the ends and surfaces of long bones and other bones
What is cancellous bone?
Sponge-like bone that makes up the inner portion of flat bones, vertebral bodies and the epiphyses and interior diaphysis of long bones
What is bone remodeling?
The resoprtion (breakdown) of discrete packets of old bone by osteoclasts and the subsequent formation of new bone at the resorption sites
What are osteoblasts?
Play a major role in both the regulation of bone resorption and in promoting the formation of new bone
What type of bone has the higher annual turnover rate?
Cancellous (Trabecular) at about 20% per year
How does the rate of bone modeling change in response to use and disuse?
Low levels of loading leads to bone loss (more resorption)
High levels of loading leads to an increase in bone mineral density
What are osteoclast precursor cells and what are they derived from?
Derived from monocyte/macrophage lineage cells
Differentiate into osteoclasts
What is the OPG/RANK-L/RANK System?
Primary mechanism through which osteoblasts and osteoblast lineage cells regulate osteoclastogenesis and bone resorption
What is RANK-L?
Cell surface ligand expressed by osteoblast lineage cells
Stimulate osteoclast precursor cells via direct cell-to-cell contact
What is RANK?
Receptors expressed by osteoclast precursors that bind to RANK-L
What occurs when RANK-L stimulates RANK?
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
What is osteoprotegerin (OPG)?
Soluble protein released by osteoblasts that binds RANK-L and prevents it from activating RANK
What stimulates and inhibits RANK-L expression?
Stimulates - PTH and 1,25(OH)2D3
Inhibits - estradiol
What stimulates and inhibits OPG production?
Stimulates - Estradiol
Inhibits - PTH
What is M-CSF?
Macrophage colony stimulating factor
Promotes the early differentiation of monocyte/macrophage lineage cells and works in concert with RANK-L to promote osteoclastogenesis
How is bone resoprtion initiated?
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
What are osteoclasts and what occurs when they’re activated?
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
What is the ruffled border formed by osteoclast plasma membrane?
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
What are Bone turnover markers?
Products of matrix degradation that indicate bone resorption rate
CTX and NTX
What do osteoblasts express receptors for?
PTH
1,25(OH)2D3
Estorgens
Glucocorticoids
What two proteins can be used as clinical indicators of bone formation?
Alkaline phosphatase
Osteocalcin
What occurs to osteoblasts after matrix formation?
50-70% undergo apoptosis
Some remaining osteoblasts become lining cells that cover newly formed bone
Others become osteocytes
What are canaliculi?
Canals that allow the communication of osteocytes with lining cells
This network supports bone metabolism and functions to detect changes in mechanical strain
How does bone mass change with age?
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
