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肌肉骨骼系统 骨 骼 Content 骨骼大体解剖 骨组织学 骨组织新陈代谢 骨组织生物力学 骨折愈合 骨骼疾病 骨折愈合（不愈合） 骨坏死 骨折疏松 器械、生物材料，药物，细胞，因子 骨骼的大体解剖 206 bones make up the adult skeleton (20% of body mass) 80 bones of the axial skeleton 126 bones of the appendicular skeleton The actual number of bones in the human skeleton varies from person to person By age 25 the skeleton is completely hardened 4 Functions of Skeletal System Provides support and framework for body Protects delicate internal organs Also provides attachment sites for organs such as skeletal muscles Bones serve as mineral storage for Calcium and phosphorus Bones are also the site of red blood cell formation in their marrow Bone as a signalling centre 314 | NATURE | VOL 481 | 19 JANUARY Osteocalcin, a bone-derived multifunctional hormone 314 | NATURE | VOL 481 | 19 JANUARY SKELETON should be familiar with all major bones(脊柱、骨 盆、四肢长骨） Bone Shapes • Long – Upper and lower limbs • Short – Carpals （腕骨） and tarsals（跗骨） • Flat – Ribs, sternum（胸骨 ）, skull, scapulae（肩 胛骨） • Irregular – Vertebrae, facial Divisions of the Skeleton Copyright © The McGraw-Hill Companies, Inc. 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Cranium • Axial Skeleton • Skull • Spine • Rib cage Skull Face Hyoid Clavicle Scapula Sternum Humerus Ribs Vertebral column • Appendicular Vertebral column Hip bone Skeleton • Upper limbs • Lower limbs • Shoulder girdle • Pelvic girdle Carpals Sacrum Radius Coccyx Ulna Femur Metacarpals Phalanges Patella Tibia Fibula Tarsals Metatarsals Phalanges (a) (b) 10 Skull •cranium (brain case) and the facial bones Parietal bone Squamous suture Lambdoid suture Occipital bone Temporal bone External acoustic meatus Mastoid process Mandibular condyle Styloid process Zygomatic process of temporal bone Coronoid process Coronal suture Frontal bone Sphenoid bone Ethmoid bone Lacrimal bone Nasal bone Zygomatic bone Temporal process of zygomatic bone Maxilla Mental foramen Mandible Infantile Skull • Fontanels – fibrous membranes Frontal suture (metopic suture) Frontal bone Anterior fontanel Sagittal suture Posterior fontanel Vertebral Column The vertebral column, or spinal column, consists of many vertebrae separated by cartilaginous intervertebral discs. 13 Vertebral Column Cervical vertebrae (7) Thoracic vertebrae (12) Copyright © The McGraw-Hill Companies, Inc. 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Cervical vertebrae Cervical curvature Vertebra prominens Lumbar vertebrae (5) Rib facet Sacral (4-5 fused segments) Thoracic vertebrae Thoracic curvature • Sacrum is fused bone Intervertebral Coccygeal (3-4 fused segments) Intervertebral foramina Lumbar curvature Lumbar vertebrae • Coccyx is fused bone Sacrum Sacral curvature Coccyx (a) (b) 14 Typical Vertebrae Includes the following parts: • Vertebral body （椎体） • Pedicles （椎弓根） • Lamina（椎板） • Transverse processes（横突） •Spinous process （棘突） • Vertebral foramen （椎孔） • Facets（关节突） Cervical Vertebrae Atlas – 1st; supports Posterior head(寰椎） Facet that articulates with occipital condyle Vertebral foramen Axis – 2nd; dens pivots to turn head （枢椎） Transverse foramina Bifid spinous Transverse process Facet that articulates Anterior with dens (odontoid process) of axis Atlas (a) Spinous process processes Dens Anterior articular facet for atlas Spinous process Superior articular facet Transverse foramen Vertebral prominens – useful landmark Transverse foramen Body Inferior articular Transverse process process (b) (c) Axis Dens (odontoid process) Thoracic Vertebrae • Long spinous processes Superior • Rib facets articular process Transverse process Facet for tubercle of rib Superior articular process Transverse process Pedicle Body Intervertebral notch Body Spinous process Inferior articular process (a) Inferior articular process Intervertebral disc Spinous process Lamina Transverse process Facet for tubercle of rib Superior articular process Vertebral foramen Pedicle Anterior Spinous process Body (b) Posterior (c) Lumbar Vertebrae • Large bodies • Thick, short spinous processes Spinous process Lamina Superior articular process Transverse process Pedicle Vertebral foramen Body (c) Lumbar vertebra 18 Sacrum Superior articular process Sacral canal Sacral promontory • 4-5 fused segments • Median sacral crest • Posterior sacral foramina • Posterior wall of pelvic cavity • Sacral promontory aka base • Area toward coccyx is the apex Sacrum Anterior sacral foramen Coccyx (a) (b) Auricular surface Tubercle of median sacral crest Posterior sacral foramen Sacral hiatus Coccyx • Aka tailbone • 3-4 fused segments Sacral promontory Superior articular process Sacrum Anterior sacral foramen Coccyx (a) (b) Sacral canal Auricular surface Tubercle of median sacral crest Posterior sacral foramen Sacral hiatus Thoracic Cage • The thoracic cage includes the ribs, the thoracic vertebrae, the sternum, and the costal cartilages that attach the ribs to the sternum. 21 Thoracic Cage • Ribs (12) • Sternum • Thoracic vertebrae (12) • Costal cartilages • Supports shoulder girdle and upper limbs • Protects viscera • Role in breathing Jugular notch (suprasternal notch) Sternal angle Thoracic vertebra Clavicular notch 1 2 Manubrium 3 True ribs 4 (vertebrosternal 5 ribs) Body Sternum 6 7 Xiphoid process 8 Ribs Vertebrochondral 9 False ribs ribs 10 11 Floating ribs (vertebral ribs) Costal cartilage 12 (a) 22 (b) b: © Victor B. Eichler, PhD Pectoral Girdle Acromial end Sternal end Acromion process • Also Clavicle Head of humerus known as the shoulder girdle • Clavicles • Scapulae • Supports upper limbs • True shoulder joint is simply the articulation of the humerus and scapula Coracoid process Sternum Scapula Humerus Ulna Radius (a) Rib Costal cartilage Upper Limb • Humerus Humerus • Radius • Ulna (Interosseous membrane) • Carpals • Metacarpals • Phalanges Humerus Olecranon process Olecranon fossa Head of radius Neck of radius Ulna (c) Radius Ulna Ulna Carpals Metacarpals Phalanges (a) Hand (palm anterior) (b) Hand (palm posterior) (d) Humerus • Head • Greater tubercle • Lesser tubercle • Anatomical neck • Surgical neck • Deltoid tuberosity • Capitulum • Trochlea • Coronoid fossa • Olecranon fossa Greater tubercle Head Intertubercular groove Anatomical neck Lesser tubercle Surgical neck Greater tubercle Deltoid tuberosity Coronoid fossa Lateral epicondyle Olecranon fossa Lateral epicondyle Medial epicondyle Capitulum Trochlea (a) (b) Radius Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Lateral forearm bone • Head • Radial tuberosity • Styloid process Trochlear notch Olecranon process Coronoid process Head of radius Olecranon process Radial tuberosity Trochlear notch Coronoid process Radial notch Radius (b) Ulna Head of ulna Styloid process (a) Styloid process Ulnar notch of radius 26 Ulna • Medial forearm bone • Trochlear notch • Olecranon process • Coronoid process • Styloid process Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Trochlear notch Olecranon process Coronoid process Head of radius Olecranon process Trochlear notch Radial tuberosity Coronoid process Radial notch Radius (b) Ulna Head of ulna Styloid process (a) Styloid process Ulnar notch of radius 27 Pelvic Girdle Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sacral canal • Coxal Bones (2) • Supports trunk of body • Protects viscera • Forms pelvic cavity Ilium Sacrum Sacral hiatus Coccyx Ischium (b) Pubis Obturator foramen Sacroiliac joint Ilium Sacral promontory Sacrum Acetabulum Pubis Symphysis pubis Pubic tubercle Ischium Pubic arch (a) 28 c: © Martin Rotker (c) Hip Bones • Also known as the coxae: • Acetabulum • There are three (3) Iliac crest bones: Iliac fossa 1. Ilium Anterior superior • Iliac crest iliac spine • Iliac spines Anterior • Greater sciatic inferior iliac spine notch 2. Ischium Obturator foramen • Ischial spines • Lesser sciatic notch Pubis • Ischial tuberosity 3. Pubis • Obturator foramen • Symphysis pubis (a) • Pubic arch Iliac crest Posterior superior iliac spine Ilium Ilium Posterior inferior iliac spine Greater sciatic notch Acetabulum Obturator foramen Ischium Ischial spine Lesser sciatic notch Ischial tuberosity (b) Pubic crest Ischium Pubis Pubic tubercle Greater and Lesser Pelves • Greater Pelvis • Lumbar vertebrae posteriorly • Iliac bones laterally • Abdominal wall anteriorly • Lesser Pelvis • Sacrum and coccyx posteriorly • Lower ilium, ischium, and pubic bones laterally and anteriorly Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Flared ilium Sacral promontory Pelvic brim Symphysis pubis (a) Female pelvis Pubic arch Sacral promontory Sacral curvature (b) Male pelvis Pubic arch 30 Differences Between Male Female Pelves • Female pelvis • Iliac bones more flared • Broader hips • Pubic arch angle greater • More distance between ischial spines and ischial tuberosities • Sacral curvature shorter and flatter • Lighter bones Flared ilium Sacral promontory Pelvic brim Symphysis pubis (a) Female pelvis Pubic arch Sacral promontory Sacral curvature (b) Male pelvis Pubic arch 31 Lower Limb Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Femur Femur • Patella Patella Femur Fibula • Tibia Tibia (c) Lateral view • Fibula Patella • Tarsals Fibula Femur Tibia Lateral condyle Medial condyle • Metatarsals Fibula Tibia • Phalanges Tarsals Metatarsals Phalanges (b) (d) Posterior view 32 Femur Fovea capitis • Longest bone of body • Head • Fovea capitis • Neck • Greater trochanter • Lesser trochanter • Linea aspera • Condyles • Epicondyles Neck Head Greater trochanter Gluteal tuberosity Lesser trochanter Linea aspera Lateral epicondyle (a) Patellar surface Medial epicondyle Medial Lateral condyle condyle Intercondylar fossa (b) Patella Femur • Aka kneecap • Anterior surface of the knee joint • Flat sesamoid bone located in the quadriceps tendon Patella Femur Fibula Tibia (c) Lateral view Patella Fibula Femur Tibia Lateral condyle Medial condyle Fibula Tibia Tarsals Metatarsals (d) Posterior view Phalanges (b) 34 Tibia Lateral condyle • Aka shin bone • Medial to fibula • Condyles • Tibial tuberosity • Anterior crest • Makes the medial malleolus Head of fibula Intercondylar eminence Medial condyle Tibial tuberosity Anterior crest Fibula Tibia Lateral malleolus Medial malleolus Fibula Lateral condyle • Lateral to tibia • Long, slender • Head • Makes the lateral malleolus • Non-weight bearing Head of fibula Intercondylar eminence Medial condyle Tibial tuberosity Anterior crest Fibula Tibia Lateral malleolus Medial malleolus Foot • Tarsal Bones (14) • Calcaneus • Talus • Navicular • Cuboid • Lateral (3rd) cuneiform • Intermediate (2nd) cuneiform • Medial (1st) cuneiform Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fibula Tibia Talus Medial cuneiformNavicular Metatarsals (metatarsus) • Metatarsal Bones (10) • Phalanges (28) • Proximal • Middle • Distal Calcaneus Phalanges Calcaneal tuberosity (b) Tarsals (tarsus) 37 骨骼的组织学 Long bone Diaphysis: long shaft of bone Epiphysis: ends of bone Epiphyseal plate: growth plate Metaphysis: b/w epiphysis and diaphysis Articular cartilage: covers epiphysis Periosteum: bone covering (pain sensitive) Sharpey’s fibers: periosteum attaches to underlying bone Medullary cavity: Hollow chamber in bone - red marrow produces blood cells - yellow marrow is adipose. Endosteum: thin layer lining the medullary cavity Periosteum (review) Outer layer: protective, fibrous dense irregular connective tissue Inner layer: osteogenic stem cells that differentiate (specialize) into bone cells like osteoblasts (bone forming) or osteoclasts (bone dissolving) cells. Periosteum: double-layered membrane on external surface of bones Histology of bone tissue Cells are surrounded by matrix. - 25% water - 25% protein - 50% mineral salts Abundant inorganic mineral salts: - Tricalcium phosphate in crystalline form -- hydroxyapatite Ca3(PO4)2(OH)2 -Calcium Carbonate: CaCO3 -Magnesium Hydroxide: Mg(OH)2 -Fluoride and Sulfate These salts are deposited on the collagen fiber framework (tensile strength) and crystallization occurs.- calcification or mineralization Bone cells Osteoclasts 4 cell types make up osseous tissue Osteoprogenitor cells Osteoblasts Osteocytes The different stages of osteoblast lineage cell differentiation 28 | JANUARY 2012 | VOLUME 13 nat Developmental signals regulating key steps of osteoblast differentiation 28 | JANUARY 2012 | VOLUME 13 nat The different stages of osteoclast lineage cell differentiation NATURE | VOL 423 | 15 MAY 200 Bone Matrix 6-47 Structure of Bone Tissue • Compact bone – Hard, densely calcified “typical bone” – Living tissue with blood supply, nerves – Organized of osteons Structure of Bone Tissue • Compact bone – Osteon（骨单元） • Central (Haversian) canal at center • Osteocytes in lacunae surrounding Haversian canal • Lamellae of bone matrix between rings of osteocytes Cancellous Bone • Consists of trabeculae – Oriented along lines of stress 6-51 Structure of Spongy Bone • Spongy bone – Trabeculae（小梁） • Irregular thin plates & struts of hydroxyapatite with osteocytes – Spaces between filled with marrow (yellow or red) Compact vs. spongy bone Compact bone – External layer – Arranged in osteons – Lamellae are found around periphery and between osteons – Central canals connected to each other by perforating canals Spongy bone – No osteons – Arranged in trabeculae – Major type of tisse in short, flat, irregular bones – Much lighter than compact bone – Supports red bone marrow 骨骼的发育 Formation of Bone: Ossification Two mechanisms – Intramembranous ossification – Endochondral ossification No difference in final result. 55 Endochondral ossification Perichondrium becomes periosteum Mesenchyme cells become osteoblasts Form primary ossification center Cartilage under bone collar calcifies & dies Endochondral ossification Invasion of nutrient blood vessel, Continued deterioration of cartilage, Formation of spongy bone 57 Endochondral ossification Primary ossification center grows, elongates, Formation of marrow cavity, Formation of secondary ossification centers at ends, Ossification of epiphyses. 58 Growth in Bone Length • Appositional growth – New bone on old bone or cartilage surface • Epiphyseal plate zones – – – – Resting cartilage Proliferation Hypertrophy Calcification Physiology of bone growth: - epiphyseal plate (bone length) - 4 zones of bone growth under hGH. 1- Zone of resting cartilage: - no bone growth - located near the epiphyseal plate - scattered chondrocytes - anchors plate to bone 2- Zone of proliferating cartilage - chondrocytes stacked like coins - chondrocytes divide 3- Zone of hypertrophic (maturing) cartilage - large chondrocytes arranged in columns - lengthwise expansion of epiphyseal plate 4- Zone of calcified cartilage - few cell layers thick - occupied by osteoblasts and osteoclasts and capillaries from the diaphysis - cells lay down bone - dead chondrocytes surrounded by a calcified matrix. Extracellular signals regulating growth plate development on August 28, 2013 - Published by Cold Spring Harbor Laboratory Age 18-21: Longitudinal bone growth ends when epiphysis fuses with the diaphysis. - epiphyseal plate closure - epiphyseal line is remnant of this - last bone to stop growing: clavicle Intramembranous ossification Begins in embryonic mesenchyme membranes Mesenchyme cells become osteoblasts Begin laying down matrix (osteoid) 65 Intramembranous ossification Layer of “woven bone” and periosteum Remodeling to form compact bone on surfaces Cranial & facial bones, mandible, clavicles. 66 Growth in Bone Width Osteoclast and osteoblast lineage cells 28 | JANUARY 2012 | VOLUME 13 nat 骨骼的维持 Bone Remodeling Wolff’s Law bone is laid down where needed and resorbed where not needed shape of bone reflects its function tennis arm of pro tennis players have cortical thicknesses 35% greater than contralateral arm (Keller & Spengler, 1989) osteoclasts resorb or take-up bone osteoblasts lay down new bone Bone is Dynamic! Bone is constantly remodeling and recycling Coupled process between: Bone deposition (by osteoblasts) Bone destruction/resorption (by osteoclasts) 5-7% of bone mass recycled weekly All spongy bone replaced every 3-4 years. All compact bone replaced every 10 years. Prevents mineral salts from crystallizing; protecting against brittle bones and fractures Bone Resorption Osteoclasts are related to macrophages: secrete lysosomal enzymes and HCl acid Move along surface of bone, dissolving grooves into bone with acid and enzymes Dissolved material passed through osteoclasts and into bloodstream for reuse by the body Bone Remodeling Sequence Osteocytes Activation Quiescence Resorption Formation & Mineralization Reversal Bone Mass (g of Ca) Age, Bone Mass and Gender 1000 500 0 25 50 Age (yr) From: Biomechanics of Musculoskeletal Injury, Whiting and Zernicke 75 100 Effects of Aging on Skeletal System • • • • Bone Matrix decreases Bone Mass decreases Increased bone fractures Bone loss causes deformity, loss of height, pain, stiffness – Stooped posture – Loss of teeth Changes in Bone Over Time Older Adults • 30 yrs males and 40 yrs females – BMD peaks (Frost, 1985; Oyster et al., 1984) – decrease BMD, diameter and mineralization after this • activity slows aging process Osteopenia Reduced BMD slightly elevated risk of fracture Osteoporosis Hormonal Factors Nutritional Factors 28 million Americans affected – 80% of these are women 10 million suffer from osteoporosis 18 million have low bone mass Severe BMD reduction very high risk of fracture (hip, wrist, spine, ribs) Physical Activity Osteoporosis • age – women lose 0.5-1% of their bone mass each year until age 50 or menopause – after menopause rate of bone loss increases (as high as 6.5%) Hormonal control of bone resorption Hormonal control of bone resorption NATURE | VOL 423 | 15 MAY 200 Hormonal control of bone resorption NATURE | VOL 423 | 15 MAY 200 骨骼的生物力学 Biomechanical Characteristics of Bone - Bone Tissue Organic Components (e.g. collagen) Inorganic Components (e.g., calcium and phosphate) 65-70% (dry wt) H2O (25-30%) 25-30% (dry wt) Ductile延展性 one of the body’s hardest structures Brittle易脆性 Viscoelastic粘弹性 Mechanical Loading of Bone Compression Tension Shear Torsion Bending Tensile Loading Main source of tensile load is muscle tension can stimulate tissue growth fracture due to tensile loading is usually an avulsion撕裂 other injuries include sprains, strains, inflammation, bony deposits when the tibial tuberosity experiences excessive loads from quadriceps muscle group develop condition known as Osgood-Schlatter’s disease Compressive Loading Vertebral fractures cervical fractures spine loaded through head e.g., football, diving, gymnastics once “spearing” was outlawed in football the number of cervical injuries declined dramatically lumbar fractures weight lifters, linemen, or gymnasts spine is loaded in hyperlordotic (aka swayback) position Shear Forces created by the application of compressive, tensile or a combination of these loads Bending Forces Usually a 3- or 4-point force application Torsional ForcesCaused by a twisting force produces shear, tensile, and compressive loads tensile and compressive loads are at an angle often see a spiral fracture develop from this load Bone geometry Exam I Periostial Endosteal Bone area Area I Force Stress 2 0.5 2.95 0.78 20 256 Exam III 2 2.5 0 2 3.14 1.77 0.79 1.13 20 20 253 221 I Exam II Increase in stiffness without adding mass Why not solid bones? II d= 2.0 III d = 2.5 Material Properties Comparison Material Compressive Strength (MPa) Modulus (GPa) Cortical 10-160 4-27 Trabelcular 7-180 1-11 Concrete ~4 30 Steel 400-1500 200 Wood 100 13 Elastic & Plastic responses plastic region fracture/failure Stress (Load) elastic region •elastic thru 3%deformation •plastic response leads to fracturing Dstress •Strength defined by failure point Dstrain •Stiffness defined as the slope of the elastic portion of the curve Strain (Deformation) Elastic Biomaterials (Bone) •Elastic/Plastic characteristics Brittle material fails before permanent deformation Ductile material deforms greatly before failure Load/deformation curves elastic limit ductile material brittle material bone Bone exhibits both properties deformation (length) Fatigue of Bone Microstructural damage due to repeated loads below the bone’s ultimate strength – Occurs when muscles become fatigued and less able to counter-act loads during continuous strenuous physical activity – Results in Progressive loss of strength and stiffness Cracks begin at discontinuities within the bone (e.g. haversian canals, lacunae) – Affected by the magnitude of the load, number of cycles, and frequency of loading Fatigue of Bone (Cont’) • 3 Stages of fatigue fracture – Crack Initiation • Discontinuities result in points of increased local stress where micro cracks form – Often bone remodeling repairs these cracks – Crack Growth (Propagation) • If micro cracks are not repaired they grow until they encounter a weaker material surface and change direction – Often transverse growth is stopped when the crack turns from perpendicular to parallel to the load – Final Fracture • Occurs only when the fatigue process progresses faster than the rate of remodeling http://www.orthoteers.co.uk/Nrujp~ij33lm/Orthbonemech.htm Simon, SR. Orthopaedic Basic Science. Ohio: American Academy of Orthopaedic Surgeons; 1994. Fatigue Fracture A fatigue fracture may be caused by: – Abnormal muscle stress • Loss of shock absorption • Strenuous or repeated activity – Associated with new or different activity • Abnormal loading • Abnormal stress distribution Fatigue Theory – During repeated efforts (as in running) • Muscles become unable to support during impact • Muscles do not absorb the shock • Load is transferred to the bone • As the loading surpasses the capacity of the bone to adapt • A fracture develops 骨折愈合 • Fractures: Any bone break. - blood clot will form around break - fracture hematoma - inflammatory process begins - blood capillaries grow into clot - phagocytes and osteoclasts remove damaged tissue - procallus forms and is invaded by osteoprogenitor cells and fibroblasts - collagen and fibrocartilage turns procallus to fibrocartilagenous (soft) callus - broken ends of bone are bridged by callus - Osteoprogenitor cells are replaced by osteoblasts and spongy bone is formed - bony (hard) callus is formed - callus is resorbed by osteoclasts and compact bone replaces spongy bone. Remodeling : the shaft is reconstructed to resemble original unbroken bone. Bone Repair 6-101 Fractures MUST have a blood supply to heal Bone blood supply • Endosteal – Inner 2/3rds • Periosteal – Outer 1/3rd • Disrupted by a fracture • Further damaged by surgery Bone blood supply Plates • Damage periosteal blood supply • Causes underlying necrosis Bone blood supply - plates • Can be reduced by – LCDCP – Locking plate Augmentation of fracture healing Bone Grafts Bone Graft Substitutes Osteo-inductive agents Mechanical methods Ultrasound Electromagnetic fields Bone Graft Properties Osteoconduction 3D scaffold Osteo-induction Biological stimulus Osteogenic Contains living cells that can differentiate to from bone Mesenchymal cells Osteoprogenitor cells Structural Osteo-inductive agents • Transforming growth factor Superfamily – BMPs – GDFs (growth differentiation factors) – Possibly TGF-β 1, 2, and 3. Demineralized bone matrix • Acid extraction of allograft – type-1 collagen – non-collagenous proteins – osteoinductive growth factors: BMP, GDFs, TGF1,2 + 3 Different companies , processing different ALLOGRAFT, no reported infection transmission BMP 7 (OP-1) • Tibial non-unions – RCT OP1 v autogenous graft – No difference in union rate – Less infections – Friedlaender et al J Bone Joint Surg Am. 2001;83 Suppl 1(Pt 2):S151-8. • Open Tibia – OP1 v control – Less secondary interventions – McKee et al Proceedings of the 18th Annual Meeting of the Orthopaedic Trauma Association; 2002 Oct 11-13 • OP 1 • 653 cases, overall success rate 82% Injury, Int. J. Care Injured (2005) 36S, S47—S50 • BMP £ 3000 per vial • Mean number of operations • Pre BMP 4.16 • Post BMP 1.2 • Hospital stay and cost • Pre BMP 26.84 days and £ 13,844.68 • Post BMP 7.8 days and £ 7338.40 • Overall cost using BMP-7 - 47.0% less. Injury, Int. J. Care Injured (2007) 38, 371—377 BMP 2 • BESTT • Open tibial fractures – Control v 6mg v 12mg – Higher dose • • • • Fewer secondary procedures accelerated time to union improved wound-healing Reduced infection rate Govender et al Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84:2123-34. Osteoconductive Making the break. Karin Hing's fellowship has brought independence to pursue her work on bone graft substitutes. Osteoconductive RCT’s osteoconductive materials Vs autograft encouraging. – Calcium sulfate • Predictable resorption • Resorbs a little too fast – Calcium phosphates • Tricalcium phosphate TCP • Hydroxyapatite • TCP is more rapidly absorbed than hydroxyapatite, TCP inadequate when structural support is desired – Injectable osteoconductive cements • Several variations Concentrated bone marrow aspirate • Non union – 75-95% success • Aseptic non-unions – Only works if adequate cell concentration – Hernigou Pet al Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am. 2005;87:1430 -7 • Concentrated BM aspirate – Ongoing multicentre RCT in France – Open tibial fractures Composite synthetic graft • Prospective multicenter RCT • 249 long-bone #, min two years FU • Bone graft v biphasic calcium phosphate mixed with bovine collagen + autogenous bone marrow • No sig. diff. – More infections with bone graft (22 v 9 p=0.008) • Chapman MW et al. Treatment of acute fractures with a collagen-calcium phosphate graft material. A randomized clinical trial. J Bone Joint Surg Am. 1997;79:495-502. Mechanical Controlled axial micromotion Compression Distraction LIPUS Electromagnetic Controlled axial micromotion • Prospective RCT 102 tibial fractures – 1.0 mm at 0.5 Hz /30 minutes per day • Sig. reduction – Time to union – Secondary surgery • Kenwright J, Goodship AE. Controlled mechanical stimulation in the treatment of tibial fractures. Clin Orthop 1988;241:36-47. Low Intensity Ultrasound • Several RCTs • Reduced time to union – Non-op tibia (No benefit in nailed #) – Scaphoids – Impacted distal radius – Jones • May reduce time to healing • JW Busse et al. The effect of low-intensity pulsed ultrasound therapy on time to fracture healing: a meta-analysis. Canadian Medical Association Journal 2002 166: 437-441 Sonic Accelerated Fracture Healing System (SAFHS®) Exogen 2000® • Acute fractures with ultrasound • Inconsistency in evidence ? Type II failure • Available evidence supports the use of ultrasound in the treatment of acute fractures of tibia and radius treated with plaster immobilization. (non op) • No benefit of LIPUS in the treatment of fractures of the tibia managed with intramedullary fixation. J Trauma. 2008 Dec;65(6):1446-52 • Current evidence on the efficacy of low-intensity pulsed ultrasound to promote fracture healing is adequate to show that this procedure can reduce fracture healing time and gives clinical benefit, particularly in circumstances of delayed healing and fracture nonunion. • There are no major safety concerns. • Therefore this procedure may be used with normal arrangements for clinical governance, consent and audit Electromagnetic devices • In vivo – Osteoblasts BMP,TGFs, IGF • Small RCT – 66% vs 0 healing of tibial non-union Scott G, King JB. A prospective double blind trial of electrical capacitive coupling in the treatment of nonunion of long bones. J Bone Joint Surg [Am] 1994;76-A:8206. • Several series – 64-87% union of tibial non-union 浙大案例 自体PRP浓集治疗骨折不愈合临床研究 浙江省男排主力（二传） 戴**， 男， 20岁 骨折不愈合11月余 术前 术后3周 骨髓干细胞治疗 骨髓干细胞治疗 治疗前 治疗两年后 两年后股骨头坏死区体积比 较。骨髓干细胞移植治疗组 （实线），对照组（虚线） PRP联合生物材料治疗 • Wei等进行了一项长达7年的PRP联合异体骨移植治疗跟骨关节内骨折移位临 床试验。 • 将254例患者随机分成自体骨移植组、PRP联合异体骨移植组和异体骨移植组 ，通过影像学、三维立体扫描断层技术和足踝功能评分评估治疗结果，发现 在12个月，24个月和72个月时PRP联合异体骨移植组和自体骨移植组明显优 于单纯异体骨移植组，显示PRP对跟骨关节内骨折移位治疗有促进作用。 术前 术后12月 国际现状---《2009年 世界再生医学调查报告》 国际上2008-2009 已市场化的组织工程和再生医学产品 目标 组织 关节 软骨 皮肤 骨 牙科 眼科 美容 其他 总 计 产品 数 15 28 34 11 4 1 4 97 产业化 较成熟 2008-2009年 已进入临床实验期的组织工程和再生医学产品 目标 组织 关节 软骨 骨 产品 数 12 17 皮肤 心 伤口愈合 血管 27 41 糖 尿 病 肝 脏 中枢神 经系统 总 计 4 3 1 105 更新活跃 我国组织工程和再生医学技术的开发和临床转化 明显严重滞后！！！ 知识要点 能够描述脊柱组成，胸廓组成，骨盆组成 能够绘画肱骨，尺骨，桡骨，股骨，胫骨大体结构 能够描述骨的细胞和组织成分 能够绘画骨单位结构 能够描述骨组织发育主要阶段 能够描述osteoblast 和osteoclast的分化阶段 能够描述骨组织的主要生物力学特性 能够描述骨愈合主要过程 能够描述骨质疏松疾病中相应“骨的宏观/微观结构-力学性能osteoblast/osteoclast-主要信号通路”每一层面的改变和相互联系， 并能思考针对每一个层面改变可能采取的干预措施。 谢 谢！
