Bone: Normal Physiology and Response to Injury

Wongworawat

August 3, 2010

Structure

• Cortical vs. Trabecular

• Woven vs. Lamellar

• Vascular supply– Nutrient artery—intramedullary– Periosteal– Periarticular plexus

Extracellular Matrix

• Mineral: 2/3– Hydroxyapatite Ca10(PO4)6(OH)2

• Organic– Type I collagen: 90%– Noncollagenous protein: 10%

• Osteocalcin, most abundant

• Proteoglycans

• Others

Collagen Problems

• OI: Type I collagen

• Scurvy: Ascorbic acid dependent prolyl hydroxylase and lysyl hydroxylase

• Ehlers-Danlos: Lysyl oxidase for crosslinking

• Urinary detection of turnover: pyridinoline, telopeptide, and hydroxyproline

Bone Cells

• Osteoblasts– Receptor for PTH– Roles

• Form bone

• Regulate osteoclasts

– Lipoprotein receptor-related protein 5 (LRP5)• Transmembrane protein for osteoblast proliferation

regulation

• Signaling important for maintenance of bone mass

Bone Cells

• Osteoblast differentiation– Stem cell– Mesenchymal stem cell– Osteoprogenitor– Pre-osteoblast– Mature osteoblast– Osteocyte– Cell deth

Osteoblastic Problems

• Fibrodysplasia ossificans progressiva– Activating mutation in BMP receptor ACVR1

• Cleidocranial dysostosis– Loss of runx 2 gene (formerly CBFA 1)

– Runx 2: transcription factor, “master regulator” of osteoblast differentiation

Osteoclasts

• Lineage: related to hematopoietic cells, macrophages

• Receptors– Calcitonin– RANKL, (osteoprotegrin)– Integrin

• Half-life: 10 days

Form and Function

• Remodeling– Trabecular– Cortical

• Molecular coupling– PTH– RANKL– BMP

Mechanical Regulation

• Wolff’s Law

Mechanical Properties

• Anisotropic– Stronger in compression than tension

• Viscoelastic– Higher stiffness and strength at higher loading

rates

Aging

• Osteoporosis: 2.5 SD < young standard

• Increase in both inner and outer diamters

• More anisotropy

Bone Injury and Repair

• Osteonecrosis

• Fracture

• Fixation

• Adjunctive therapies

Osteonecrosis

• Histo changes 10-14 days after event

• Empty lacunae

• MRI findings

• Bone remodeling: creeping substitution– Vascularization from fibrous tissue– Differentiation of bone cells– Cutting cones– Remodeling

Fracture Healing

• External factors– Micromotion: endochondral ossification– Rigid fixation: direct intramembranous

ossification

Fracture Healing

• Inflammatory response

• Cell differentiation– sox9 upregulates cartilage genes (col2)– Hypertrophic chondrocytes: type X collagen

• Ossification

• Remodeling

Chondrogenesis Pathology

• Camptomelic dysplasia: sox9 mutation

• Cleidocranial dysplasia: runx2 mutation

• Multiple epiphyseal dysplasia (MED): cartilage oligomeric matrix protein (COMP)

• Diastrophic dysplasia: sulfate transport protein

Fixation Biomechanics

• Intramedullary device

• Plates– Rigidity: thickness3

• External fixation– Rigidity

• Pin diameter, number, bone to rod distance, pin group separation, ½ pins separated 45°

Bone Grafts

• Osteoconductive

• Osteoinductive

• Osteogenic

• Gold Standard: Autograft

Allograft

• Structural

• Particulate

• Demineralized

Minerals and Other

• Calcium sulfate

• Tricalcium phosphate ceramics

• Calcium phosphate cements

• Polymers

BMP

• TGF- β family

• Bind cell curface receptors– Serine/threonine kinase receptors

• Phosphorylate SMADs

• SMADs translocates into nucleus to activate genes for osteoblast differentiation

Adjunctive Therapies

• Inductive coupling (magnetic)– Upregulation TGF-β1, FGF-2, BMP

• Capacitative coupling (electrodes)– Transmembrane calcium translocation– Upregulation of TGF- β1, BMP

• Ultrasound– Increased TGF- β1, PGE2, PDGF