Uh/ Tamc Millers Basic Science 1

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Contents of haversian canals

Back 1

Arterioles, Venules, Capillaries, Nerves, Lymphatics

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Contents of canals/canaliculi

Back 2

Osteocyte cell processes

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Cement lines

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Define border of osteon

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Characteristics of cortical bone

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Slow turnover, high Young modulus, higher resistance to torsion and bending

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Characteristics of cancellous bone

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Less dense, more remodeling according to Wolff's law, higher turnover, smaller Young modulus, more elastic

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Characteristics of woven bone

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Random organization (not oriented according to stress), increased turnover, weak, flexible. Can be immature or pathologic

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Osteoblasts

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Form bone by generating organic, non-mineralized matrix. Mesenchymal origin. More active cells line bone, less active trapped in resting regions- maintain ionic mileiu of bone.

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Growth factor effects on osteoblasts

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Differentiation increased by PDGF/ IDGF

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PTH effects on osteoblasts

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Secondary messenger-->activates adenyl cyclase-->Produce ALK Phos, type I collagen, osteocalcin, bone sialoprotein

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Osteoblast receptors

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1. PTH 2. 1,25- dihydroxyvitamin D 3. glucocorticoids 4. prostagalndins 5. estrogen

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Osteocytes

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Maintain bone. Most common cell in mature bone. Made from osteoblasts. Important for control of calcium/phosphorous balance. Stimulated by calcitonin/ inhibited by PTH

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Osteoclasts

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Resorb bone. Multinucleated giant cells. Monocyte origin. Ruffled brush border used for bone resorption. Osteoclast formation inhibited by IL-10

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RANKL

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On surface of osteoblasts and tumor cells. Stimulate RANK on osteoclasts--> differentiation into mature osteoclasts/ increases bone resorption. Inhibited by osteoprotegrin

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Osteoclast bone resorption

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Occurs in Howship's lacunae. Carbonic anhydrase creates H+ ions--> lower pH-->increases solubility of hydroxyapatite. Organic matrix removed via proteolytic digestion. Stimuated by IL-1.

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Bisphosphonate effects

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Inhibit osteoclast resorption. Prevents formation of ruffled border.

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Osteoprogenitor differentiation in different environments

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low strain/ high O2--> osteoblasts. Intermediate strain/low O2--> cartilage. High strain--> fibrous tissue

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Calcitonin

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From parafollicular cells of thyroid. Stimulated by high Ca+. Inhibits osteoclastic bone resorption-> transient decreased Ca+. Analgesic properties in pathologic fractures

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Vitamin D3 effects on osteoblasts

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stimulates matrix and ALK Phos synthesis/ bone protein synthesis

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Glucocorticoid effects on bone

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inhibits synthesis of DNA/ collagen production/protein synthesis by osteoblast. Cancellous affected more than cancellous.

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Prostaglandin effects on osteoblasts

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activates adenylyl cyclase--> stimulates resorption of bone

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Estrogen effects on bone

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Anabolic/ anticatabolic. Increases mRNA levels for ALK Phos and inhibits adenyly cyclase activation. Side effect: inc risk of heart disease/ breast CA

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Collagen structure

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Triple helix of one alpha 2/ 2 alpha 1 chains. Hole zone: within fibril between ends of molecules. Pores between sides of parallel molecules

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Collagen cross-linking

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decreases solubility/ increases strength

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Most abundant non-collageneous protein in bone

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Osteocalcin. Note: VERY popular question on OITE

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Osteocalcin

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Most abundant protein in bone (except collagen). Attracts osteoclasts, regulates bone density. Marker of bone turnover. Inhibited by PTH/ stimulated by vit D

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Proteoglycans in bone

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Compressive strength. Composed of GAG complexes. Inhibit mineralization

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Osteonectin

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Secreted by platelets and osteoblasts. Role in regulating calcium/ matrix

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Osteopontin

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Cell-binding protein similar to an integrin

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Ca hydroxyapatite

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Compressive strength. Most of inorganic matrix.

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Location of mineralization of bone

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Primary mineralizatin occurs in collagen gaps. Secondary at periphery

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Osteocalcium phosphate

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Remainder of inorganic matrix of bone

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Wolff's Law

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Bone remodels in response to mechanical stress. Increased stress--> increased bone density. Immobilization--> loss of bone mass

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Ionic properties of bone

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Compression side: electronegative--> stimulates osteoblasts. Tension side: electropositive--> stimulates osteoclasts

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Hueter-Volkman law

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remodeling occurs in basic multicellular units (BMU's) modulated by hormones/ cytokines. Compression inhibits growth/ tension facilitates growth

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Cortical bone remodeling

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Osteoclastic tunneling (cutting cones)--> layering of osteoblasts and deposition of laemllae. Head of cutting cone made of osteoclasts followed by capillaries/osteoblasts

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Cancellous bone remodeling

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Osteoclastic resorption--> osteoblastic formation

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Blood flow to bone

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5-10% of cardiac output

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Nutrient artery

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branch from major arteries--> diaphyseal cortex through nutrient foramen--> medullary canal-->arterioles in endosteal cortex. Suplly inner 2/3 of diaphyseal cortex. High pressure

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Periosteal blood supply

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Primarily capillaries--> outer 1/3 diaphyseal cortex. Low pressure

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Direction of blood flow in bone

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Normal bone: centifugal (in to out). Displaced fracture: centripetal (in to out)- disrupt high flow endosteal supply and flow reverses. Immature bone: centripetal (highly vascularized periosteum). Venous flow: centripetal

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Physiologic states that increase blood flow to bone

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hypoxia, hypercapnia, sympathectomy (SCI)

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Effect of fracture on blood flow to bone

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immediate: decreased. Hours-days: increases. 2wks: peak blood flow. 3-5 months: normal

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Effect of reaming on endosteal blood supply

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devascularizes inner 50-80%

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Periosteum

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Inner layer: cambium- loose/vascular/contains cells capable of becoming osteoblasts. Responsible for increaseing diameter o f bone/ forming callus. Outer layer: fibrous/less cellular/contiguous with joint capsules

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Bone marrow

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Red: Hematopoietic (40% H20/40%fat/20% protein). Changes to yellow marrow. Yellow marrow: inactive: 80% fat

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Enchondral ossification

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Replaces cartilage model. Locations: embryonic long bones. Physis. Callus. Disrupted in achondroplasia

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Intramembranous ossification

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Aggregates of undifferentiated mesenchymal cells become osteoblasts--> bone. Locations: embryonic flat bones. Distraction osteogenesis. Blastema bone. Disrupted in cledicranial dysostosis

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Appositional ossification

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Osteoblasts lay new bone on old bone. Locations: periosteal bone enlargement. Bone remodeling.

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Physeal nutrition

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primarily from perichondrial artery

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Physis physiology: reserve zone

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cells store material. Low O2 tension. Effected by lysosomal storage diseases

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Physis physiology: proliferative zone

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longitudinal growth. Increased O2 tension. Inc PG--> inhibits calcification. Effected by achondroplasia

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Physis physiology: hypertrophic zone

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Three zones. Maturation/degeneration/provisional calcification. Matrix mineralization occurs. Low O2 tension. Low PG. Widened in rickets

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Indian hedgehog

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produced by physeal chondrocytes. Regulates expression of PTHrP

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Physeal layer affected by SCFE

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Hypertrophic zone- idiopathic. Metaphyseal spongiosa- renal failure

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Groove of Ranvier

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supplies chondrocytes to periphery of growth plate--> increased width

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Perichondrial ring of LaCroix

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Dense fibrous tissue. Anchors and supports physeal periphery. Affected in Salter Harris VI injuries

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Stages of fracture repair

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Inflammation, repair, remodeling

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Inflammatory phase of fracture healing

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Hematoma--> cells release growth factors--> attract cells-->granulation tissue at fracture ends-->osteoblasts/fibroblasts proliferate

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Repair phase of fracture healing

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primary callus within 2wks. Soft callus replaced by hard callus by enchondral ossification. Cellular differentation depends on local strain and O2 tension.

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Effects of ultrasound on fracture healing

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Low intensity/ pulsed- accelerates healing and improves callus strength.

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Electrical stimulation effects on bone

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DC: stimulates inflammatory like response. AC: affects cAMP/colalgen synthesis/calcification during repair stage. Pulsed electromagnetic fields: initiate calcification of fibrocartilage

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Location with highest risk of pathologic fracture

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Subtrochanteric femur

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Osteoconductive

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scaffold for bone formation

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Osteoinductive

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Growth factures- stimulate bone formation

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Osteogenic

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Cells that make bones

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Bone graft antigenicity

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mediated by cell surface glycoproteins. Method of rejection: cellular

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Cortical bone graft

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Slower incorporation through remodeling of haversian systems. Resorption occurs first--> weakens graft.

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Cancellous bone grafts

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Revascularize and incorporate quickly. Osteoblasts lay down new boneon old trabeculae (creeping substitution)

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Silicate grafts

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bioactive glasses

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Ca-phosphate based grafts

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capable of osseoconduction/ osseointegration. Biodegrade at very slow rate. Ceramics

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BMP effects on bone

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Osteoinductive. Induces metaplasia of mesenchymal cells into osteoblasts. Target cesll: undifferentiated perivascular mesenchymal cells. Signal via serine/threonine kinase

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TGF-beta effects on bone

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induces production of type II collagen/ PG. Induces osteoblasts to synthesize collagen. Regulates cartilage/bone formation in fracture callus. Serine/threonine kinase signalling

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IGF-II effects on bone

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Stimulates type I collagen/ cellular proliferation/cartilage matrix and bone formation. Tyrosine kinase signalling

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PDGF effects on bone

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Chemotactic for inflammatory cells to fracture site. Released by platelets. Tyrosine kinase signalling

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Distraction osteogenesis phaes

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Latency: 5-7 days. Distraction: 1mm/day. Consolidation: 2x duration of distraction phase

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Most osteoconduction bone graft

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cancellous autograft

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Most osteogenic bone graft

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cancellous autograft

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Best structuaral bone graft

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cortical autograft

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Effects of bisphosphonates on HO

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inhibits mineralization but does not prevent osteoid matrix. Will mineralize when medication stopped

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Calcium metabolism

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Absorbed in duodenum (active transport-regulated by vit D3) and passive diffusion in jejunum. Kidney resorbs most Ca @ proximal tubules.

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Calcium intake needs

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600mg/day- kids. 1300 mg/day- adolescents. 750mg/day- adults. 1500mg/day-pregnant. 2000mg/day- lactating. 1500mg/day- healing fracture

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PTH

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Secreted by chief cells in parathyroid glands. Stimulated by low Ca conc. Inhibited by high Ca/ high 1,25(OH)2 vit D. Directly activates osteoblasts/modulates renal phosphate filtration. Stimulates 1,25(OH)2 vit D production in kidney, increaes renal Ca resorption, increases excretion of Phos. Net: inc Ca/dec Phos

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1,25(OH)2 vit D

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Secreted by proximal tubule of kidney. Stimulated by PTH. Inhibited by low PTH/high Ca/high phos. Stimulates intestinal absorption of Ca/phos. Stimulates osteoclastic resorption of bone.

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Phenytoin effects on bone

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impairs vitamin D metabolizms

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Effects of menopause on calcium

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decreased intestinal absorption/ increased urinary excretion

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Markers of bone resorption.

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Urinary hydroxyproline, pyridinoline cross-links.

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Markers of bone formation

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Serum alk phos.

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Hypercalcemia symptoms

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polyuria/polydipsia/nephrolithiasis/osteotis fibrosa cystica/confusion/constipation/anorexia/nausea

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Primary hyperparathyroidism

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Usually due to parathyroid adenoma. Result: inc Ca/dec phos. Increased bone resorption/ poor mineralization. Labs: high ca/PTH/urinary phos. Bony changes: osteopenia/fibrous replacement of marrow/brown tumors- destructive metaphyseal lesiosn.

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Pseudohypoparathyroidism

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PTH receptor abnormality. Decreased levels of active form of vitamin D. Normal serum Ca

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hypoparathyroidism

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low ca/ high phos. Low 1,25(OH)2 vit D. Usually iatrogenic

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Renal osteodystrophy- high turnover

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Decreased renal phos excretion-->hyperphosphatemia--> low Ca/ high PTH--> secondary hyperparathyroidism. Osteitis fibrosa cystica/amyloidosis. Tx: treat renal dz, restrict dietary phos, phosphate biding antacids, 1,25(OH)2 vit D supplementation

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Renal osteodystrophy- low turnover

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secondary to aluminum toxicity. No hyperparathyroidism

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Hypophosphatemic rickets

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Most common type. Inborn error in phosphate transport--> renal phosphate loss. Ca nml/PTH nml/vit D nml. Classic triad: hypophosphatemia/lower limb deformities/ stunted growth

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Hypophosphatasia

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Inborn error in alkaline phosphatase. High Ca/phos. Low serum alk phos. Osteomalacia. Early loss of teeth. Dx: elevated urinary phosphoethanolamine. Tx: none available

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Nutritional rickets

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low or nml ca/high phos. Hihg alk phos/PTH. Sx: Osteomalacia/hypotonia/weakness/tetany. Bowing of long bones. Tx: vitamin D/Ca/Phos supplementation depending on etiology

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Vitamin D dependent rickets- type I

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Pseudo vitamin D deficiency. Defect in renal 25-(OH) vatimin D 1alpha hydroxylase-->inhibits activation of vitamin D. More severe than vit D deficiency rickets

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Vitamin D dependent rickets- type II

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intracellular receptor deficit for 1,25 (OH)2. Very very high levels of vitamin D diagnostic

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treatment of hypercalcemia

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1. Saline hydration 2. loop diuretics 3. dialysis-severe

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Hypocalcemia sx

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increased neuromuscular irritability (tetany/seizures/Chvostek's sign). Cataracts. Onychomycosis. Prolonged QT.

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pseudo-pseudohypoparathyroidism

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looks like pseudoparathyroidism except Ca normal and normal response to PTH

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Amyloidosis

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Accumulation of beta-2-microglobulin. Assocaited with carpal tunnel syndrome, arthropathy, pathologic fractures.

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Definition of osteoporosis/osteopenia

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WHO: L2-L4 density at least 2.5 SD below peak bone mass of 25yo. Osteopenia- 1.0-2.5 SD

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Risk factors osteoporosis

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sedentary thin caucasian female age smokers heavy drinkers northern european h/o breast feeding poor diet phenytoin use

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Strongets predictor of future vertebral fracture

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2+ prior vertebral fractures

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Type I osteoporosis

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Postmenopausal. Primarily affects trabecular bone. Vertebral/distal radius fractures

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Type II osteoporosis

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Age related. >75yo. Affects trabecular and cortical bone. Related to poor calcium absorption. Hip/pelvic fractures.

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Degree of osteoporosis necessary to be visible on XR

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>30%

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Idiopathic transient osteoporosis of hip

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third trimester of pregnancy. Presents with groin pain/ dec ROM/ localized osteopenia. Tx: PWB. Resolves after 6-8mo.

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Osteomalacia

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Defect in mineralization. Qualitative deficit. Associated with Vit d deficiency/ GI disorders/ phenytoin/alcoholism. RA: Looser's zones, biconcave vertebral bodies, trefoil pelvis. Bx: widened osteoid seams. Tx: high dose vitamin D theraphy

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Scurvy

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Vitamin C deficiency-->dec chondroitin sulfate synthesis--> defective collagen growth/impaired hydroxylation of collagen. Sx: gum bleeding/ecchymosis/joint effusion/iron deficiency. RAD: thin cortices. Histo: widened zone of provisional calcification. Metaphyseal bone affected first

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Osteopetrosis

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Decreased osteoclast/chondroclast function-->failure in bone resorption. Histo: osteoclasts lack ruffled border/clear zone. Marrow filled with necrotic calcified cartilage.

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Infantile AR form of osteopetrosis

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Most severe form. Bone within bone appearance. Hepatosplenomegoly. Aplastic anemia. Fatal during infancy. Tx: BMT. High dose calcitriol +/- steroids

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AD form of osteopetrosis

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Albers-Schonberg disease. Generalized osteosclerosis. Rugger jersey spine. Pathologic fractures

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Osteopoikolosis

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Spotted bone disease. Islands of deep cortical bone within medullary cavity and cancellous bone. Asymptomatic. No malignant degeneration

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Paget's disease

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Dx: Elevated alk phos/urinary hydroxyproline/ virus-like inclusion bodies in osteoclasts. Active phase: intense resorption. Mixed phase. Sclerotic phase: osteoblastic formation. Inactive phase.

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Caisson's disease

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osteonecrosis secondary to dysbarism (SCUBA)

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Osteonecrosis

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Bony necrosis due to loss of blood supply. Hip commonly affected. Associated with steroid use/alcoholism/blood dyscrasias/radiation. Path: grossly necrotic bone. Bilateral in hip in 50% (80% if associated with steroids). MRI best study- most sens/spec and positive earliest. Pressure measurements: >30mmHg abnormal

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Legg-Calve-Perthe's disease

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osteonecrosis of femoral head

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Osgood-Schlatter disease

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Osteochondrosis of tibial tuberosity

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Sinding-Larsen-Johannson disease

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Osteochondrosis of inferior pole of patella

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Blount disease

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Osteochondrosis of proximal tibial epiphysis

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Sever's disease

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Osteochondrosis of calcaneus

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Kohler's disease

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Osteochondrosis of tarsal navicular

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Freiberg's infarction

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Osteochondrosis of metatarsal head

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Kienbock's disease

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osteochondrosis of lunate