Physiology of Bone Flashcards
What are the physiological functions of bone tissue?
Support, movement, protection, mineral storage, energy storage and metabolism, blood cell formation
What are the main bone cell types?
Osteoclasts, osteoblasts, osteocytes, osteogenic cells
What do osteoclasts do?
Secrete acid and lytic enzymes to resorb bone (break down and releases minerals)
Where will you find osteoclasts?
Bone surfaces and sites of old/injured bone
What do osteogenic cells do?
Stem cells that will differentiate into osteoblasts
Where will you find osteogenic cells?
Inner layer of periosteum
What do osteoblasts do?
Build bone by directly regulating bone matrix synthesis and mineralization
Indirectly control bone resorption via controlling osteoclasts
Where will you find osteoblasts?
Growing portions of bone including periosteum and endosteum
Describe the differentiation process for osteoblasts
Mesenchymal stem cells
Preosteoblasts
Osteoblasts
Osteocytes
What do osteocytes do?
Maintain bone tissue by being a terminally differentiated osteoblast AND
Respond to mechanical loading by releasing paracrine factors that stimulate bone remodeling and Ca++ release
Where will you find osteocytes?
Trapped within newly deposited bone matrix
What 2 divisions is the ECM of bone divided into?
Organic and inorganic
What is the job of the organic ECM?
(35%) - mostly collagen, contributes to tensile strength and flexibility of bone
What is the job of the inorganic ECM?
(65%) - mostly inorganic hydroxyapatites or mineral salts (calcium phosphate), contribute to the hardness and compressive strength of bone
What is Wolff’s law?
If loading on a particular bone increases, the bone will remodel itself over a period of time to withstand greatest strength with the least amount of material by changing its architecture
Why is bone remodeling an ongoing process?
In order to repair microdamage, maintain strength, maintain calcium serum levels
Describe the bone remodeling process
Osteoclasts progenitors bind to RANKL on osteoblasts using a RANK receptor and then differentiate into osteoclasts to degrade bone (resorption)
OPG then is secreted by osteoblasts and binds RANKL to prevent further osteoclast activation
Osteoblasts then differentiate from mesenchymal cells to build and remodel the bone
Transforming growth factor beta (TGFbeta)
Stimulate proliferation of osteoblasts, OPG and bone formation
Bone morphogenic proteins (BMPs)
Stimulates proliferation of osteoblasts and bone formation, regulates matrix production, used clinically for fracture healing and spinal fusion
OPG
Prevents osteoclast activation
Fibroblast growth factors (FGF)
Increase proliferation of osteoblasts and enhance callus formation during fracture repair
Insulin-like growth factors (IGFs)
Increase bone collagen matrix synthesis and inhibits degradation
Platelet derived growth factor (PDGF)
Increase collagen synthesis
RankL
Secreted from osteoblasts, activates osteoclasts to resorb bone and is inhibited by OPG
Interleukins (IL-1 = most potent)
Stimulate bone resorption
IL-1 is decreased by estrogen… may be a cause of bone resorption increase in post-menopausal women because IL-1 is increased when their estrogen is decreased
Parathyroid hormone (PTH)
Low blood calcium levels signals to parathyroid gland to release PTH which then tells osteoclasts to degrade bone to increase calcium levels
What does fracture healing depend on?
Amount of movement and space between bone fragments
What constitutes indirect bone healing?
Limited movement of bones, gaps greater than 500 nm
What constitutes direct bone healing?
NO MOVEMENT, rigid internal fixation, no gaps or gaps between 200 and 500 nm
What are the steps of indirect fracture healing?
Tissue injury and hematoma Inflammatory phase (1 week) Soft callus formation (2-3 weeks) - unmineralized cartilage Hard callus formation (4-12 weeks) Remodeling of bone (years)
Is a callus formed in direct fracture healing?
NOOOOOOOO
What are some Anti-resorption treatments for bone?
Bisphosphonates (inhibit osteoclasts by inducing their apoptosis), hormone replacement (estrogen), selective estrogen receptor modulators, denosumab (Ab against RANKL)
What are some Anabolic Agents (build bone)?
BMP-2 (induces osteoblast formation)
PTH: continual admin = catabolic for bone
PTH: intermittent admin (daily) = anabolic for bone… weird
How do glucocorticoids increase bone resorption?
They inhibit calcium absorption in the gut, which signals for PTH which then increases osteoclastic bone resorption
