3 - Principles of Bone Healing Flashcards
Bone
- A type of mineralized connective tissue , the blend made up of organic and inorganic components
Organic components of bone
Organic component (35% of bone)
o Cells = Osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts
o Matrix proteins
– 95% collagen type I (PRIMARY ORGANIC COMPONENT)
– 5% non-collagenous proteins (adhesion proteins, calcium binding proteins, mineralization proteins, enzymes, growth factors, etc.)
Inorganic component of bone
Inorganic component (65% of bone) o Minerals (e.g. calcium hydroxyapatite) o Bone stores 95% of body’s calcium, 80% of phosphorus, and 65% of sodium and magnesium
Osteoid
Un-mineralized bone is called OSTEOID ***
o This is an immature form of organic matrix of bone which may be lined by osteoblasts
Osteoprogenitor cells
o Pluripotential mesenchymal cells which can mature to form osteoblasts
Osteoblasts
o Synthesize and transport protein (like type 1 collagen) and osteoprotegerin,
o Initiate mineralization
o Have receptors for parathyroid hormone, Vit. D and estrogen, cytokines
o Produce many growth factors (like Interleukin-1), and RANK-L (Receptor Activator of Nuclear factor-Kappa B) which combines with RANK receptor on osteoclasts to stimulate osteoclastic bone resorption
o Osteoblasts live on bone surfaces and surround woven bone
o Usually found in large groups (up to 400 cells) to form normal bone units
o Activity of osteoblasts is coordinated; become osteocytes when surrounded by matrix
Osteocytes
o Matured osteoblasts, found within the osseous matrix
o Regulate daily serum Ca++ and P
o Communication with other osteocytes via canaliculi
o Allow surface membrane potential and substrate transfer
Osteoclasts
o Responsible for bone resorption**
o Multiple nuclei
o Live in Howship lacunae
o Contain RANK receptors* – can be blocked by osteoprotegerin
Osteoclast processes
- Osteoclasts found on bone surface in small pits (Howship lacunae)
- Responsible for bone resorption and initiate constant bone remodeling
- Derived from hematopoietic progenitor cells → monocytes/macrophages; fuse into multinucleated giant cells, osteoclasts; contain many lysosomes rich in enzymes
- Differentiation & maturation controlled by cytokines (NOT going to test cytokines)
- Activity initiated by binding to surface matrix adhesion proteins
- Do NOT resorb bone lined by osteoid or un-mineralized cartilage
Hormonal influences and receptors
NOT going to test the specifics of this
- Estrogen ↑ (increases) bone formation by ↑ (increasing) collagen synthesis by osteoblasts
- Estrogen prevents bone resorption by inhibiting osteoclast differentiation (osteoprotegerin)
- Absence of estrogen (post-menopausal
o Increased secretions of cytokines which stimulate osteoclasts and bone resorption
o Decrease osteoprotegerin, which leads to further bone resorption
Microscopic organization of bone tissue
- Type I collagen forms the backbone; 90% of protein
- Collagen deposited in random weave (woven bone) or in parallel arrangement (lamellar bone)
- Woven bone = normally present in fetal skeleton, at growth plates, and in processes where there is very rapid bone production; almost always pathologic in adults
- Lamellar bone = gradually replaces woven bone during growth; stronger than woven bone; only type of normal bone in adults
Woven bone
IMMATURE BONE
- Haphazard arrangement (“random weave”) intermixed with fibrous tissue found in:
o Fetal skeleton and growth plates
o Callus (reparative bone, healing fracture)
o Fibrous dysplasia
o In areas surrounding tumor or infection
- Woven bone in adults always indicative of a pathologic state, but not diagnostic
- First type of bone laid down during growth and repair
o Grows rapidly, low strength, matures into lamellar bone
Lamellar bone
TRABECULAR BONE
- Highly orderly, layered, strong, parallel arrangement of type I collagen with few osteocytes
- Lamellae in compact bone are arranged concentrically around central vascular Haversian canals
- Lamellae in cancellous bone are arranged in linear, parallel plates
Bone regions
- Epiphysis = end of long bone
- Epiphyseal plate = growth plate
- Metaphysis = next to growth plate
- Diaphysis = shaft
- Periosteum = covering (blood vessels, nerves)
Cartilage components
No blood vessels, nerves or lymphatics
Inorganic phase
o Calcium hydroxyapatite crystals similar to bone
Organic matrix
o 80% water (↑ resilience & lubrication of joints), with remainder type II collagen and proteoglycans (chondroitin sulfates most abundant)
Bone modeling and remodeling
THIS IS IMPORTANT FOR HEALING
- At maturity, breakdown and renewal of bone is equal –> it balances out
- Beginning in the 4th decade, resorption begins to outweigh deposition
- Rate of resorption is dependent on many factors:
o Load on joints, age, nutrition, hormones (estrogen)
o Calcium and Vitamin D intake, Vit. D receptor type - Bone will also do some remodeling depending on stress
- The functional ‘basic multicellular’ unit is comprised of osteoblasts and osteoclasts
o This tightly couples bone formation (modeling) and bone resorption and renewal (remodelling)
Control of bone resorption and bone formation
** NEED TO KNOW **
- Here you can see osteoclasts breaking down bone
- Surface osteoblasts become activated by 3 factors
o Mechanical, hormones, cytokines - Activated osteoblasts start laying down osteoid
o Collagen type I, which eventually becomes mineralized
o This is the remodeling process
Bone remodeling cycle
- Osteoclast precursors recruited to bone surface, where they fuse, differentiate, and mature.
- Osteoclasts resorb both organic and inorganic bone matrix
- Resorption phase ends with osteoclast apoptosis
- In reversal phase, osteoblasts differentiate from mesenchymal precursors, under influence of factors from osteoclasts, and secrete new bone matrix (osteoid)
- At the end of the cycle, some osteoblasts have been incorporated into bone as osteocytes and others remain on the surface as quiescent bone-lining cells
Cycle of bone turnover
KNOW THIS
- Lining cells on bone become activated (mechanical/chemical)
- Lining cells retract and the underlying membrane is removed by
matrix metalloproteinases - Osteoclasts are then attracted to this cleared site, fuse then
become activated - Osteoclast digestion of underlying bone occurs
- Osteoblasts then move into the resorption cavity and form new
osteoid, which is subsequently calcified
Cycle of bone turnover continued
KNOW THIS*
- Not testing specific cytokines, but know that bone turnover
occurs due to mechanical stress as well as systemic factors
(endocrine, metabolic, nutritional) - Osteoclasts and osteoblasts act in a coordinated manner to
form or resorb bone - Osteocytes act as mechanosensory cells and play a critical role
in regulating bone remodeling
Vitamin C
- Maintenance of normal connective tissue
- Synthesizes collagen
- Responsible for bone formation –> synthesizes organic matrix
- Inorganic calcified portion of capillary walls
Vitamin C deficiency
- Scurvy is a distinctive clinical syndrome related to problems with osteoid synthesis and collagen support of the blood vessels
- In children, the osteoblasts lay down scanty, poor-quality osteoid
- Radiographs and deformities similar to Rickets
- In both children and adults, the capillaries weaken
- Patients bruise easily, and bleed spontaneously, bleeding gums, petechiae around hair follicles
- Bleeding into joints
- Body hairs often become curled like “corkscrews”
- Hemorrhages found around “corkscrew” hairs (perifollicular)
- Hemorrhages beneath the periosteum develop
o Subperiosteal hemorrhage
o Most painful of the deficiency diseases - Wounds heal poorly and old ones reopen