Basic Sciences

 Tissues

1     Bone

 Take-Home Message

•      Bone regeneration depends on an osteoinductive stimulus, osteoconduc-tive matrix, source of responding cells, and suffi cient vascular supply.

•      T he mechanical environment will infl uence bone grown in accordance with Wolff’s Law.

•      I f one or more of these factors is lacking, new bone formation is signifi cantly decreased.

 Osteoinduction

•      Characterized by the process of recruitment of immature  pluripotent cells.

•      Subsequent stimulation causes differentiation into pre-osteoblasts.

•      Several growth factors have been identifi ed as critical components in osteoinduc-tion (Table  1 and Figure  1 ).

•      The most widely studied are those in the bone morphogenetic protein (BMP) family, of which over 20 have been identifi ed.

•      B MPs are members of the TGF-β[beta] superfamily of growth hormones with BMP-2 and BMP-7 having the most development for therapeutic applications.

•      B MP supplementation is FDA-approved to augment spinal arthrodesis and to treat nonunion or open fractures of long bones.

•      Absorbable collagen sponges have been commercialized as a method of local delivery of BMP to surgical sites; endogenous BMP molecules are also naturally released during trauma to bone and during bone remodeling.

•      Infl ammatory cytokines and damage to the bone ECM can liberate matrix-bound growth factors which induce differentiation and proliferation of osteoprogenitor cells.

 Table 1  Mediators of bone formation

 Sources: Refs. [2, 3, 7, 10–18, 23]

 TGF transforming growth factor,  MSC mesenchymal stem (stromal) cell,  ECM extracellular matrix,  TNF tumor necrosis factor

•      Under the infl uence of an osteoinductive environment, these cells terminally dif-ferentiate into osteoblasts and begin to deposit calcifi ed extracellular matrix (ECM).

 Osteoconduction

•      T he process of bone growth on a surface or scaffold, the initial deposit of osteoid and its conversion to woven and lamellar bone, is an example of this process.

•      Implantation of bone grafts and scaffolds are other examples of osteoconduction.

•      There are many characteristics of a scaffold that optimize its ability to aid bone regeneration such as compressive strength, biocompatibility, adhesive properties, and pore size.

•      It has been previously reported that osteoconduction does not occur on some materials such as copper and silver, with increasing success on materials of higher biocompatibility such as titanium.

•      Due to stress shielding, bone growth around and within a scaffold is optimized when the Young’s modulus (stiffness) of the scaffold closely correlates to that of bone; pore size of the scaffold can be adjusted to meet this requirement in nonabsorbable scaffolds.

•      Increased porosity allows for a greater surface area upon which recruited cells may grow, too much of which makes the matrix unstable.

•      S caffolds are also often coated with or made from biologic agents to encourage cell recruitment and adhesion or provide extended release of osteoinductive compounds.

•      M aterials such as chitin, Gelfoam, hydroxyapatite, polyethylene glycol, or  collagen have been investigated.

•      With rapidly absorbable scaffolds, the rate of degradation should correlate with the rate of new bone growth, presenting a challenge in the design of novel material implants.

 Responding Cells

•      There are four primary cell types in bone tissue: osteocytes, osteoblasts, osteo-clasts, and osteoprogenitor cells.

•      A source of responding cells is required to provide a renewable source of pri-mary osteoblasts and osteoclasts that will aid in the continuous formation and remodeling of bone.

•      C ells can either be delivered through a cell-based strategy or endogenously confi ned through binding epitopes. Each strategy is designed to offer a long-term source of osteogenic activity.

•      Cell-based therapies often require concomitant regeneration of vasculature in addition to bone and therefore osteogenic and vasculogenic cell types have been grown in coculture to promote heterotypic interactions.

•      During an acute fracture, bone marrow is the main source of stem cells for bone repair. Mesenchymal cells under the infl uence of chemotactic agents are recruited

to the site of injury, where local osteoinductive effects encourage differentiation of these cells into pre-osteoblasts.

•      These osteoprogenitor cells further differentiate into osteoblasts and after a period of months may terminally differentiate into osteocytes.

•      Osteoblasts are responsible for bone formation by depositing osteoid and  mineralizing it. The absolute number of osteoblasts tends to decrease with age.

•      O steocytes are long-lived stellate cells that are trapped within the matrix they secrete.

•      Osteoclastic cells are derived from hematopoietic progenitor cells which  differentiate under infl uence from mesenchymal stromal cells. The balance between osteoblast and osteoclast activity is responsible for the continuous remodeling of bone tissue.

 Vascular Supply

•      Bone is a highly vascular tissue, receiving 10–20 % of the resting cardiac output.

•      Fracture healing is a delicate physiological process dependent on adequate  vascular supply to damaged tissue.

•      P reservation of tissue planes during surgical exposure is an important tenet to avoid disrupting the existing blood supply to the area.

•      O steocytes receive nutrition via cell–cell communication through bone canaliculi, while Volkmann and Haversian canals allow routes for blood vessels to penetrate through bone tissue.

•      The ultimate strength of bony repair hinges on the vascular supply to the ana-tomic area. For example, fractures which occur in a rich vascular environment (distal radius metaphysis) have a much higher healing rate than those with poor circulation (scaphoid).

•      Avascular necrosis (AVN) of bone tissue has been well described (femoral head AVN, Kienbock’s disease). It is also well known that poor vascular supply is associated with unfavorable outcomes following surgery.

•      V EGF has been shown to be the most important growth factor for angiogenesis and bone healing at a fracture site. Hypoxia has been shown to enhance angiogenic response and levels of VEGF in rodent bone marrow cells.

•      L ocal delivery of these factors may lead to enhanced angiogenesis which may affect outcomes. Vascular tissue is an important source not only for nutrition and a route for responding cells, but also for osteoinductive stimuli.  

 Fig. 1  Factors infl uencing bone formation

    2     Peripheral Nervous System

 Take-Home Message

•      Axons are surrounded by three layers of connective tissue including the endoneurium, the perineurium (blood–nerve barrier), and the epineurium.

•      Seddon’s classifi cation of nerve injury: neurapraxia, axonotmesis, neurotmesis.

•      E arly tension-free nerve repair in young patients results in best chances for functional recovery.

 Defi nitions   The primary cellular components of peripheral nerves are axons from neurons and glial cells. Neurons are polarized cells with dendrites and axons that process and transmit information through electrochemical signals.

I n the peripheral nervous system (PNS), the primary glial cell is the Schwann cell which serves to ensheathe axons in myelin and provides trophic support through release of important neurotrophic factors.

 Peripheral nerves are part of the PNS that convey signals between the spinal cord to the limbs and organs. Nerves are composed of cellular processes from multiple different neurons including motor, sensory, and autonomic. The efferent neurons (motor and autonomic) receive signals from the central nervous systems (CNS) and transmit messages to their target end organs. Afferent nerves receive signals from specialized cell types, such as Pacinian corpuscles for fi ne sensation, and relay this information to the CNS.

 Embryology   The PNS are primarily derived from neural crest cells. Neural crest cells are groups of ectodermal cells that delaminate from the dorsal neural tube in early development. These cells then migrate throughout the body and develop into neurons, glia, and neurosecretory cells of the PNS.

 Histology/Physiology   A neuron usually ranges from 5 to 150 μm in diameter and contains a cell body and at least two cellular processes, the dendrite and the axon (Fig.  2 ). Impulses from the dendrites are directed toward the cell body, which in turn generate an action potential which is directed down the axon toward the synapse, or a target end organ such as a neuromuscular junction (NMJ). Axons can be myelinated (large fi bers such as motor) or unmyelinated (small fi bers such as type C pain fi bers) (Table  2) . Myelin, produced by the Schwann cells, acts as insulation surrounding the axon and serves to reduce the dissipation of action potential into the surrounding environment. Within myelinated axons, there are gaps without myelin called nodes of Ranvier, which allows propagation of action potential via saltatory conduction so as to increase nerve conduction velocity without increasing the diameter of an axon.

 Cross-Sectional Anatomy  T he peripheral nerve is surrounded by three layers of connective tissue (Fig.  3) . The innermost layer is the endoneurium and consists of loose collagenous matrix that nourishes and protects each axon. The middle layer is

                   Dendrite

Nucleus

 Fig. 2  Neuron morphology

 Table 2  Nerve fi ber types and function

 Fig. 3  Cross-sectional anatomy of the peripheral nerve (Adapted with permission from Lundborg G. Nerve injury and repair. New York: Churchill Livingstone; 1988. p. 33.)

the perineurium and consists of fl attened fi broblasts that surround a fascicle of axons so as to act as a blood–nerve barrier via tight and gap junctions. The perineural layer is the major contributor to nerve tensile strength and has high resistance to compression and longitudinal traction. The outermost connective tissue layer is the epineurium and consists of an inner and outer layer. The outer layer surrounds and protects the nerve from external stresses while the inner layer pads the nerve’s multiple fascicles and perineurium.

N eural blood supply is derived from a complex network of blood vessels. There are two major arterial systems and one minor longitudinal system that are linked together by anastomoses. The major systems consist of vessels that lie superfi cially on the nerve and within the interfascicular epineurium while the minor blood vessel system consists of blood vessels located in the endoneurium and perineurium.

 Injury   Injury to peripheral nerve can be acute or chronic.

 Acute peripheral nerve injuries were initially described by Seddon and later refi ned by Sunderland. Seddon classifi ed nerve injuries into three groups: neurapraxia, axonotmesis, and neurotmesis. A neurapraxia is characterized by myelin damage without neuronal injury so that distal neural degeneration does not occur. Axonotmesis is characterized by loss of axonal continuity with the preservation of connective tissue elements so as to provide a framework for healing. Importantly, the distal axon does undergo a series of cellular and molecular changes known as Wallerian degeneration to prepare for neural regeneration. Neurotmesis is the physiologic disruption of entire nerve with the ensuing distal axon undergoing degeneration without a framework for healing unless surgical repair is performed.

 Sunderland further divided axonotmetic injuries into three types depending on severity of injury to connective tissues (Table  3 ).

 After injury, axonal growth from proximal stump occurs with the growth cone regenerating at a rate of approximately 1–3 mm/day.

C hronic nerve compression (CNC) injuries such as carpal tunnel syndrome are common conditions that are acquired over long duration and involve ischemia and fi brosis. Unlike acute nerve injuries, CNC injuries are Schwann cell-mediated and lack axonal involvement early in the disease process and thereby do not undergo Wallerian degeneration or changes in the NMJ.

 Table 3  Classifi cation of nerve injuries

 Treatment   Acute nerve injury can result in motor and sensory defi cits with  life- altering outcomes for patients. Reconstruction of nerve after transection or segmental loss is essential to achieve functional reinnervation. Prerequisites for nerve repair are clean wound, good vascular supply, and adequate tissue coverage. Microscope, capable surgeons and team, and patient participation are essential for success. Early surgical repairs tend to have better functional recovery as there is diminished neural retraction and reduced requirement for grafting. If tension-free repair cannot be achieved, nerve grafting must be performed with an autograft (same donor), an allograft (donor from same species), or a nerve conduit. The current gold standard for grafting remains the autograft.

 Nerve repair can be performed via suturing the epineurium or group of fascicles (Fig.  4) . Epineural repair establishes continuity of the nerve without tension and properly aligns the fascicles.  

 a

 Fig. 4  ( a ) Group fascicular repair (Adapted with permission from Lundborg G. Nerve injury and repair. New York: Churchill Livingstone; 1988. p. 199). ( b ) Group fascicular repair (Adapted with permission from Lundborg G. Nerve injury and repair. New York: Churchill Livingstone; 1988. p. 200)

b

Fig. 4 (continued)

 Group fascicle repair aligns proper fascicles (sensory–sensory, motor–motor) and allows proper reinnervation. In theory, group fascicular repair should produce a better clinical outcome; however, multiple studies have not shown improved functional outcomes.

 Prognosis   Meaningful functional recovery (M3-against gravity, S3-pain and touch with >15 mm 2-point discrimination) can be achieved in approximately 60 % of patients with best results achieved with median nerve repair and worst outcomes with ulnar nerve repair.

Y oung patient, early repair, single function nerve, distal repairs, and short or no nerve graft are important prognostic factors for improving results. Future directions for improving functional neural recovery include developing strategies to improve the rate of regeneration, to improve the specifi city of regeneration, to create novel allografts, and to prevent target end-organ degeneration of the neuromuscular junction.

    3     Skeletal Muscle

 Take-Home Message

•      Muscle > fascicle > muscle fi ber (single cell) > myofi bril > myofi lament >sarcomere

•      Actin-binding site for myosin are blocked by tropomyosin.

•      Contraction: sliding of actin and myosin.

•      Bands: A, I, H, M, and Z. Bands H and I shorten during contraction.

•      Maximal force is proportional to physiologic cross-sectional area (PCSA). Maximal excursion and velocity are proportional to length.

•      Eccentric contraction generates highest tension and risk of injury.

 Muscle Morphology   Muscle fi ber: single multinucleated cell.

 Muscle fi bers are made from myofi brils that are divisible into myofi laments (functional units composed of sarcomeres arranged in series) (Fig.  5).  

 Myofi brils are surrounded by sarcoplasmic reticulum (SR) and its transverse tubules (T tubules). The SR is an endoplasmic reticulum specialized in storing and pumping Ca ²⁺ions. T tubules are continuous with the sarcolemma (cell membrane), extending the extracellular space into the muscle fi ber.

 No syncytial bridges as opposed to cardiac muscle.

 Endomysium: connective tissue (CT) surrounding individual fi bers.

 Perimysium: CT surrounding collections of fi bers.

 Epimysium: CT covering entire muscle.

C ross-striations are identifi ed by letters. A sarcomere is the area between two Z lines in a myofi bril. Contraction results in H- and I-band shortening. A-band remains the same.

 Contractile proteins

•      Thick fi laments

 Myosin-II: long tail and two globular heads that contain an actin-binding site and a catalytic site that hydrolyzes ATP.

•      Thin fi laments             

 Actin: long double helix

 Tropomyosin: fi laments located in the groove between chains of actin  Troponin: located along tropomyosin molecules. Three subunits:

                                                            Muscle Morphology

 Fig. 5  Morphology (Adapted. Permission license BAS59347 McGraw-Hill Education)

 T binds to tropomyosin.

Cbinds to Ca ²⁺ producing a conformational change affecting subunit I.  I inhibits the interaction of myosin with actin.

 Structural proteins

 Actinin binds actin to Z lines.

 Titin connects Z lines to M lines and provides scaffolding and passive elasticity of the muscle. Largest known protein (3,800,000 Da). When stretched (unfolding

of folded domains), quickly increases resistance protecting sarcomere structure.

 Desmin binds Z lines to plasma membrane.

Dystrophin: scaffolding for fi brils and connection with the extracellular environment. One of the longest known genes, therefore susceptible to mutation.

 Pathologies affecting dystrophin:

 If absent, produces Duchenne muscular dystrophy, X-linked frame-shift mutation, fatal by 30.

 If altered or reduced, produces Becker muscular dystrophy, X-linked mutated gene.

 Muscle Physiology   Impulse transmission and contraction (Fig.  6)

•      Action potential – > voltage-gated Ca ²⁺channels – > intracellular Ca ²⁺causes release of acetylcholine (ACh).

2+

2+

 Fig. 6 M uscle contraction (Adapted from Muskel-molekular.png. Wikimedia Commons. Hank van Helvete. 2006 licensed with Cc-by-sa-2.5)

•      A ctivation of nicotinic ACh receptor (nAChR) leads to depolarization of the motor end plate (muscle cell).

•      Depolarization spreads along muscle cell and T tubules.

•      V oltage-sensitive dihydropyridine receptor on the T tubules couples with ryanodine receptor (also Ca ²⁺sensitive) on SR, inducing Ca ²⁺release. Effect amplifi ed by calcium-induced Ca ²⁺release.

•      Ca ²⁺binds to troponin C, causing conformational change, exposing binding site on actin, allowing myosin–actin crossbridges.

•      M yosin releases bound adenosine diphosphate (ADP) and bends at the junction of the head and neck, sliding actin over myosin, shortening the sarcomere (power stroke).

•      ATP binds to now-exposed site on myosin, detaching it from actin.

•      ATP is hydrolyzed into ADP. Myosin head returns to resting position.

 Each power stroke shortens the sarcomere by 1 % (10 nm). Muscles shorten 35–50 %. Myosin crossbridge action  repeats several times during contraction, if ATP available and Ca ²⁺present.

 Electronic response of the muscle fi ber is similar to that of the nerve (5 ms). Contraction and relaxation are slower (100 ms), making temporal summation of contractions possible. Repeated stimulations before relaxation produce a response added to the contraction already present. When frequency is high enough to produce a continuous contraction without relaxation, it is called tetanic contraction.

 Types of muscle fi bers:  a continuum. Classifi cations are made for research

(Table  4).

 Table 4  Types of muscle fi bers

    3.1     Contraction Types

•      Isometric: muscle remains the same length, muscular strength matches load.

•      Isotonic: muscle contracts, maintaining constant tension.

•      Isovelocity (isokinetic): contraction velocity remains constant; force may vary.

Rare in natural state. Primarily an analysis method.

•      Concentric: muscle force overcomes resistance, muscle shortens.

•      Eccentric: resistance overcomes muscle force, muscle lengthens. Higher risk of injury.

    3.2     Contraction Physiology

 Excursion and velocity are proportional to muscle fi ber length, yielded by sarcomeres arranged in series (Fig.  7 ).  

 Maximum tetanic tension is proportional to the physiologic cross-sectional area (PCSA) (Fig.  7 ). PCSA is dependent on anatomic cross-sectional area, pennation (angle of fi bers), muscle density, and fi ber length.

 Force – length relationship , also called length–tension curve (Fig.  8). Muscles operate with greatest active force when close to an ideal length (often resting length). Based on the amount of overlapping molecules of myosin and actin that can interact at a specifi c length. Due to the presence of elastic proteins within a muscle (such as titin), when muscle is stretched beyond a given length, entirely passive forces oppose lengthening.  

 Force – velocity relationship (Fig.  9 ): Under experimental conditions, contraction speed (regulated by load) affects force. Force is inversely proportional in a hyperbolic fashion to velocity.  

 Max velocity: zero force

 Zero velocity: isometric max force

N egative velocity (eccentric contraction): force above isometric maximum (absolute maximum)

 Fig. 7  Sarcomeres arrangement tension, excursion and velocity

Sarcomere length (µm)

 Fig. 8  Force-length relationship curve

             0                                                                                                                              0

              -3             -2            -1              0              1              2              3              4             5

Velocity (lengths/second)

 Fig. 9  Force-velocity relationship

P ower: Product of force and velocity. The muscle does not generate power at isometric force (due to zero velocity) nor maximal velocity (due to zero force). Optimal shortening velocity for power generation is approximately one-third of maximum shortening velocity (Fig.  9 ).

 Training

S trength training: high load, low repetition. Produces hypertrophy of all fi ber types, especially type 2B

E ndurance training: low load, high repetition. Muscle increases effi ciency. Increase in capillarity, mitochondrial size, number, and density. Increase in oxidative capacity in all fi ber types, especially type 2A

 Bibliography

1. B arrett KE, Boitano S, Barman SM, Brooks HL, editors. Ganong’s review of medical physiology. 24 ed. New York: McGraw-Hill; 2010.

2. H erzog W, editor. Skeletal muscle mechanics. From mechanisms to function. West Sussex: Wiley; 2000.

 3.  Lieber RL. Skeletal muscle, structure, function, and plasticity. The physiological basis of rehabilitation. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2002.  4.  Lieberman JR, editor. AAOS comprehensive orthopaedic review. Rosemont: AAOS; 2009.

 5.  Nigg BM, Herzog W, editors. Biomechanics of the musculo-skeletal system. 3rd ed. West Sussex: Wiley; 2007.

    4     Tendon

 Matthew  T.  Provencher,  Daniel  J.  Gross,  Amun  Makani,  and  Petar  Golijanin 

 Take-Home Message

•      T endons are produced by tenocytes and primarily formed from water. The dry weight is primarily formed of type I collagen. The collagen polypeptides form a triple helix, which then cross-link to form fi brils.

•      Collagen’s parallel fi bril arrangement with cross-linking contributes to ten-sile strength.

•      Type III collagen is found in the endotenon and epitenon and is important during early healing and remodeling.

•      Nutrition is derived from synovial fl uid for intrasynovial tendons, where as extrasynovial tendons are able to remain metabolically active regardless of environment.

•      The transition zone for tendon insertion consists of four layers: tendon, unmineralized fi brocartilage, mineralized fi brocartilage (Sharpey’s fi bers), and bone.

•      T endons follow a stress–strain relationship, and its characteristics can be illustrated on a load–elongation curve.

•      Tendon healing follows four stages of repair: infl ammation, proliferation, matrix formation, and remodeling.

•      Tendons are weakest at 7–10 days during infl ammation stage and generally reach maximum strength at 6 months.

 Anatomy

•      Composition:

–     Primarily composed of collagen (approximately 85 % of dry weight) with a high concentration of proteoglycans (and elastin)

•      Collagen:

–     Basic structural unit of tendon

•      Type I collagen is predominant.

•      Type III collagen is found in the endotenon and epitenon and increases during the early phase of healing and remodeling.

–     C  ollagen polypeptides form a triple helix which then combines to form fi brils with cross-linking.

•  This parallel fi bril arrangement with cross-linking contributes to the tensile strength of tendon.

–     Produced by tenocytes.

•      Proteoglycans:

–     I  nteract with the collagen fi brils, helping to form a matrix that disperses load between fi brils.

–     Composed of subunits known as glycosaminoglycans (GAGs).

–     Negatively charged, hydrophilic molecules resist compressive force.

–     Responsible for viscoelasticity.

•      Viscoelasticity:

–     Describes a rate-dependent response to load.

–     Is a function of the internal friction of the material. –  Tendons are less viscoelastic than ligaments.

•      Histology and Microanatomy:

–     Fibroblasts (tenocytes) are the predominant cell type.

–     Tendons are composed of bundles of collagen called fascicles (See Fig.  10 ).

 Fig. 10  Architecture of tendon

•      Fascicles are groups of collagen fi brils running in parallel to the long axis of the tendon.

•      Resist tensile force.

•      Grouped into individual fascicles that are surrounded by endotenon.

•      Groups of fascicles are surrounded by epitenon.

•      E pitenon is a synovial-like outer membrane containing blood vessels, nerves, and lymphatics.

•      Blood supplies two types of tendons:

–     Paratenon-covered (vascular): patellar tendon, Achilles tendon

•      Vascular tendons with capillary system contained within paratenon

•      Greater healing potential than avascular tendons

–     Sheathed (avascular) tendon: hand fl exor tendons

•      V incula (vascular mesotenons) carry a vessel that supplies only one tendon segment.

•      A vascular areas receive nutrition via diffusion from vascularized segments including musculotendinous and tendon–bone junction.

•      Nutrition:

–     Intrasynovial: tendons are dependent on the synovial fl uid for nutrition.

•  Regenerative ability is decreased when removed from this environment.

–     Extrasynovial: able to remain metabolically active regardless of environment.

•      Nutrition is derived from several sources including perimysium, periosteal attachments, and surrounding tissues.

•      Insertion:

–     Two types of insertion: direct and indirect

–     Fibrocartilaginous (Direct): transition zone consisting of four layers:

•      Tendon

•      Unmineralized fi brocartilage

•      Mineralized fi brocartilage (Sharpey’s fi bers)

•      Bone

–     Transition zone allows gradual dissipation of force.

–     “Direct” refers to the absence of periosteum.

–     Present in distal insertion of medial collateral ligament (MCL) on prox-imal tibia.

–     F  ibrous (Indirect): collagen fi bers of the tendon enter bone via perforating collagen fi bers (periosteum).

•  Present in proximal insertion of MCL on distal femur

 Biomechanics

•      Tendons are oriented along lines of stress.

•      Load transmission:

–     Stress-strain relationship: Time-dependent, nonlinear viscoelastic proper-ties with stress being force per unit area and strain being the change in length.

–     Stress-relaxation:

•      Stress (or deformation) decreases with time if the strain is held constant.

–     Creep:

•      S train increases with time if the stress is held constant (increased deformation under a constant load).

•      Load–elongation curve: Four distinct regions (See Fig.  11):

–     Toe region: greatest amount of deformation for given load

•  Relaxed (crimped) fi bers of a tendon are straightened and oriented to take up load.

–     Linear region: constant load-elongation behavior

•  Tendon fi bers are oriented parallel to the direction of the load, and tissue stiffness is represented by the slope.

–     Yield Point: tendon transitions from elastic (reversible) to plastic (irreversible). –  Failure: curve beings to decline

•      Hysteresis: energy dissipation

–     L  oading and unloading curves differ due to energy dissipated during loading of tendon.

 Injury and Repair   Tendon–bone healing (Fig.  12):

–     B  ony avulsion of tendon insertions heals more rapidly than midsubstance tears.

•      Tendon healing follows four stages of repair:

–     Infl ammation: 0–5 days

•      Primary cells: neutrophils and macrophages.

•      Initial production of type III collagen.

•      Tendon is at its weakest during this stage of healing (weakest at 7–10 days).

–     Proliferation: 4–14 days

•      Five growth factors shown to be signifi cantly upregulated during healing (TGF-β[beta], BMPs (−12, −13, −14), PDGF, IGF-1, VEGF, bFGF) promote differentiation and proliferation of fi broblasts.

–     Matrix formation: >14 days

•      Increased angiogenesis

•      Deposition of large amounts of disorganized collagen

–     Remodeling: up to 18 months

•      Fibrosis

•      Tissue may continue to remodel for approximately 1 year, but it generally reaches maximum strength by 12 months.

•      Type I collagen begins replacing type III collagen.

•      I n bone–tendon healing, bone grows into the fi brovascular scar tissue over time. While this coincides with signifi cant increase in strength, this scar tissue at the site of repair will limit the ultimate strength.

•      Known factors that impede healing:

–     NSAIDs

–     Smoking

–     EtOH

–     Diabetes

–     Vitamin D defi ciency

–     Stress overload

 Current Knowledge and Trends   Post-injury mechanics:

–     Early range of motion (ROM) and cyclic loading after surgical tendon repair have been shown to help avoid postoperative stiffness, reduce adhesions, and regain maximal ROM.

–     It has also been shown to increase the infl ammatory response at the repair site, which may affect the terminal strength of the tendon–bone interface.

–     P  ostoperative immobilization has been shown to modulate the early infl ammatory response, but its end effect on terminal strength of the tendon–bone interface is inconclusive, and potential complications include postoperative stiffness as well as reduced fi nal ROM.

•      Biological augmentation for tendon healing and repair:

–  Growth factors and stem cells:

•      Various growth factors and stem cells have been shown to be effective at augmenting tendon–bone healing, but delivery to the site continues to be the limiting factor to their effectiveness.

•      Investigators continue to look toward bioscaffolds and gene therapy to improve delivery, as well as optimal combinations of both growth factors and stem cells to improve effectiveness.

 Bibliography

1 . B rophy RH, Kovacevic D, Imhauser CW, Stasiak M, Bedi A, Fox AJS, et al. Effect of short-duration low-magnitude cyclic loading versus immobilization on tendon-bone healing after ACL reconstruction in a rat model. J Bone Joint Surg Am. 2011;93(4):381–93.

2.   Isaac C, Gharaibeh B, Witt M, Wright VJ, Huard J. Biologic approaches to enhance rotator cuff healing after injury. J Shoulder Elbow Surg. 2012;21(2): 181–90.

3.   Lui PP, Wong OT. Tendon stem cells: experimental and clinical perspectives in tendon and tendon-bone junction repair. Muscles Ligaments Tendons J.

2012;2(3):163–8. Print 2012 Jul.

 Orthopaedic Diseases

1     Genetics

 Take-Home Message

•  Genetic anomalies can result in signifi cant musculoskeletal issues and perioperative complications and risks.

1.1     Modes of Inheritance

 Autosomal Dominant   A single copy of the mutated gene is suffi cient to create the disorder; if the gene is present, the disorder will occur.

 5

 Autosomal Recessive   Two copies of the mutated gene are for this person to be affected with the disease; single copy of the gene creates a gene carrier but that will not have the disease

 X-Linked Dominant  A  disorder of a gene on the X chromosome causes a disorder to be expressed in all individuals (both males and females)

 Females more frequently affected; no male-to-male transmission.

 X-Linked Recessive  D isorder in a gene on the X chromosome, but the disorder will only occur in males and females with two mutated copies of the gene; no maleto- male transmission

 Variable Inheritance (Penetrance)   Spectrum of disease severity from a genetic mutation known to cause disease, ranging from no obvious disease to mild to severe. Even within the same family with the same gene mutation, signifi cant variation in disease severity can occur.

 Chromosomal Abnormalities  A  structural anomaly in the chromosomes resulting in missing, abnormal, or excess DNA compared to normal chromosomes; can occur in all cells in the body or only in select cells (mosaicism)

1.2     Down Syndrome

 Defi nition   Chromosomal anomaly associated with cognitive delay, muscle hypotonia, and other birth defects

 Etiology   Trisomy 21 (extra copy of chromosome 21 from one parent), more common from egg but can be from sperm  Rate: 1 per 691 births in the USA.

C an also occur from unbalanced translocation of chromosome 21 and another chromosome. One or both parents may not be affected due to a balanced translocation, but this translocation can become unbalanced in their child(ren), leading to disease.

 Pathophysiology   Distinctive facial appearance, 50 % have heart defect, joint instability (hip, patella, neck, and foot), muscle hypotonia in infants, and cataracts

 Treatment   Supportive treatment for symptomatic defects, physical therapy, and surveillance

1.3     Turner Syndrome

 Defi nition   Chromosomal anomaly in females that affects development

 Etiology   Single X chromosome (50 % of cases) or severely dysfunctional second

X chromosome in females

 Rate: 1 per 2,500 in females, can present as mosaicism with only some cells affected

 SHOX gene on X chromosome most associated with musculoskeletal anomalies in the syndrome

 Pathophysiology   Normal intelligence, early ovarian failure (most do not undergo puberty and are infertile), webbed neck (30 %), low hairline, lymphedema of limbs (70 %), skeletal anomalies, renal defects, heart defects (30–50 %), and hypothyroid (10–30 %)

I ncreased risk of congenital hip dislocation, scoliosis (10 %), delayed skeletal maturation (85 %), short 4th metacarpal, and osteoporosis

 Treatment   Hormone therapy to induce puberty, supportive care, physical therapy, and surveillance

1.4     Von Willebrand Disease

 Defi nition   Bleeding disorder with slowed clotting process resulting in easy bruising and prolonged bleeding after injury

 Etiology   Most common genetic bleeding disorder

 Estimated incidence: 1 per 100 to 1 per 10,000 people

 Diagnosis   Bleeding time, tests for von Willebrand factor (quantity and quality)

 Pathophysiology  M utations in the VWF gene reducing the amount of von Willebrand factor produced.

V on Willebrand factor essential for platelet adhesion and stabilizes other clotting proteins preventing their breakdown.

 Impaired function prevents clots from forming normally.

C linical Manifestations   Easy bruising, heavy or prolonged menstrual bleeding, prolonged bleeding after injury, nosebleeds, and excessive bleeding after dental work  Classifi cation   

 Type I: decreased von Willebrand factor levels, most common type (75 % of patients), mildest form, variable quantities of von Willebrand factor in bloodstream, and autosomal dominant inheritance.

 Type II: abnormally functioning von Willebrand factor, intermediate in severity, and autosomal recessive inheritance.

 Type III: most severe form with no von Willebrand factor produced, extremely rare (1 per 500,000), autosomal recessive inheritance; mutation creates short nonfunctional protein.

 Treatment   Desmopressin nasal spray stimulates release of von Willebrand factor from vascular endothelium.

 For severe cases: von Willebrand factor and factor VIII transfusions

 For surgery/procedures: may need to have blood products including von Willebrand factor available

1.5     Hemophilia

 Defi nition   Factor defi ciency that slows blood clotting process; its classic form is factor VIII defi ciency.

 Etiology   X-linked recessive mutation in F8 gene; rate: 1 in 5000 males

 Produces abnormal version of coagulation protein  Leads to prolonged prothrombin time (PTT)

 Pathophysiology   Continuous bleeding after injury, surgery, or dental work, sometimes spontaneous bleeding (joints, muscles, brain)

 Treatment  I V replacements with recombinant factor VIII preoperatively, continue 5 days postoperatively, 21 days for bone procedures

 Hemophilic Arthropathy   Synovitis and cartilage destruction in a joint due to repeated bleeds

 Treatment   Factor replacement, physical therapy, bracing, arthroscopic synovectomy, or total knee replacement for more severe cases

1.6     Christmas Disease

 Defi nition   Clotting disorder defi ciencies in factor IX

 Etiology   X-linked defect in F9 gene liposomal protein production, second most common form of hemophilia; rate: 1 per 20,000 in males

 Pathophysiology  F orm of hemophilia, similar effects and treatments as common hemophilia

 Treatment  I V infusion factor IX (plasma or recombinant), desmopressin applied directly small wounds

1.7     Gaucher’s Disease

 Defi nition   Cell storage disorder that affects beta-glucocerebrosidase enzyme activity and allows accumulation of glucocerebroside within cells to toxic levels.

 Etiology   Autosomal recessive mutations in GBA gene; rate: 1 per 50,000–100,000  In people of Ashkenazi Jewish descent; rate: 1 per 500–1000

P athophysiology  H epatosplenomegaly, anemia, thrombocytopenia, bone pain and pathologic fractures, abnormal bone remodeling, delayed healing, arthritis, and lung disease

 Increased perioperative bleeding and infection risk

 Classifi cation  

 Type I: most common form, non-neuropathic, more frequent with Ashkenazi Jewish descent

 Type II: added effect on the central nervous system and brain, begins in infancy, with brain damage, seizures, and abnormal eye movements

 Type III: also affect the central nervous system, slower progression than type II

 Treatment   IV enzyme replacement for types 1 and 3

1.8     Sickle Cell Anemia

 Defi nition   Disorder that affects hemoglobin protein and causes red blood cells to distort into crescent/sickle shape

 Etiology   Autosomal recessive mutations in HBB gene affect beta-globin subunit of hemoglobin (hemoglobin S form)

 Hemoglobin has four subunit: two alpha-globins and two beta-globins

M ost common in those of African descent; rate: one for 70,000 in the USA, one in 500 African-Americans, and one in 1,000 Hispanic Americans

 Classifi cation   

 Sickle cell trait: at least one beta-globin subunit replaced by hemoglobin S  Sickle cell disease: globulin subunit replaced I hemoglobin S

 Pathophysiology   Symptoms of sickle cell disease seen in early childhood

A nemia, pain episodes, repeated infection, shortness of breath, fatigue, delayed growth and development, osteonecrosis, and pulmonary hypertension

 Pain episodes occur when cells undergoes cyclic and have trouble passing through blood vessels.

 Treatment   Decitabine or hydroxyurea (induces production of fetal hemoglobin), pain medications, fl uids, rest, oxygen if levels are low, and blood transfusion for severe anemia or perioperatively

1.9     Thalassemias

 Defi nition  D isorder that reduces hemoglobin production resulting in diffi culties carrying oxygen to cells of the body

 Etiology   Defect in quantity in either the alpha or beta subunit of hemoglobin production resulting in low hemoglobin levels

 Can occur as major form (both genes for the subunit effected, got one from each parent) or minor form (one gene for the subunit effected, other is normal)

 Classifi cation   

A lpha thalassemia: involves the alpha subunit of hemoglobin, losses from two genes involved (HBA 1/HBA 2); two forms: HbBart (severe, with loss of all 4 alleles of HBA genes) and HbH (milder, loss of 3 of the 4 alleles; more common in Southeast Asia and Mediterranean countries; complex inheritance because it involves gene copy number

 Beta thalassemia: involves the beta subunit of hemoglobin, common globally but most frequent with Mediterranean decent, involves mutations in the HBB gene that range from complete loss of beta-globin production to decreased quantity, generally autosomal recessive inheritance/rare autosomal dominance

 Pathophysiology   Decrease oxygen delivery to tissues. Anemia, weakness, fatigue, increased risk of blood clots, jaundice, hepatosplenomegaly, osteoporosis and fragility fractures, and growth retardation

 Treatment  B lood transfusions, folate supplementation, iron chelation, and perioperative caution with increased clotting risk

2     Calcium and Phosphate Metabolism

 Kate  Edwards

 Take-Home Message

•      Calcium is an important mineral in the body that is tightly regulated by intact parathyroid hormone, vitamin D, and calcitonin. It is involved in many physiologic processes. Both too much and too little calcium can be pathologic.

•      R ickets – failure of osteoid to calcify in children resulting in bony abnormalities

•      Osteomalacia – incomplete mineralization of osteoid following growth plate closure

2.1     Calcium

 Calcium is the most abundant mineral in the body with 98–99 % housed in the bone and teeth as hydroxyapatite. In the plasma, 50 % is ionized and active, while 45 % is protein bound (albumin) and 5 % is bound to phosphate and citrate. The total amount of calcium in the extracellular fl uid is approximately 1 g. In contrast, the bone contains 1 kg of calcium!

 Serum calcium concentration is 8.5–10.2 mg/dL.

T o correct for a low albumin, use the following equation: ([4-plasma albumin in g/dL] × 0.8 + serum calcium).

 Calcium is required for many physiologic processes including: muscle contraction, enzyme cofactor for hormonal secretion, vascular contraction and dilation, membrane stability, intracellular signaling, bone structure and mineralization, and nerve conduction.

R ecommended amount of dietary calcium per the Institute of Medicine is 700– 1,300 mg/day based on age with an upper limit of 1,000–3,000 mg/day.

T he gut absorbs only 30–40 % of ingested calcium. In contrast, the kidneys are quite effi cient and absorb 97–98 % of circulating calcium. Approximately 500 mg of calcium is exchanged daily in the bone with remodeling.

 pH is important in calcium regulation. In states of acidemia, there is decreased calcium binding to albumin which increases ionized calcium, while the reverse is true for alkalemia.

 Calcium is closely regulated by parathyroid hormone (PTH), vitamin D, and calcitonin. Calcium levels are also affected by magnesium and phosphorous.

2.2     PTH

•      Stimulates bone resorption

•      Stimulates calcium reabsorption at the distal tubule of the kidney

•      Stimulates phosphate excretion

•      Stimulates conversion of 25 hydroxyvitamin D2 to 1,25 dihydroxyvitamin D3

•      Indirectly increases gut absorption due to the increased vitamin D

 PTH has a very short half-life of 5 min.

 PTH receptors are found on osteoblasts. It is thought that PTH inhibits osteoblast function and increases osteoclastic activity via cell-to-cell communication.

T he parathyroid gland is extremely sensitive to changes in ionized calcium as detected by calcium-sensing receptors (CaSR) which ultimately regulates the release of PTH.

2.3     Calcitonin

 Is a hormone released by the thyroid parafollicular cells in response to elevated calcium levels.

I n the bone, it inhibits resorption of calcium, and in the kidney, it inhibits reabsorption of both calcium and phosphate.

2.4     Vitamin D

•      Stimulates calcium absorption in the gut

•      Stimulates bone resorption

•      Stimulates renal reabsorption of calcium

•      Regulates PTH release

 Check serum 25(OH) level, desired level is >30 ng/dL

 25(OH) has a longer half-life than the active form, 1,25 dihydroxyvitamin D3 (15 days vs. 4 h), and its concentration is 1,000-fold greater.

A s far as oral supplementation, D2(ergocalciferol) and D3(cholecalciferol) are traditionally regarded as equivalents.  

             24, 25-dihydroxy Vitamin D-2

    resorption                   reabsorption               absorption                                                         

2.5     Phosphorous

 Most phosphorous in the body is present as phosphate.

 80–90 % of ingested phosphorous is absorbed by the gut.

 Serum levels are primarily maintained by the rate of kidney excretion.

 Serum concentration is 3–4 mg/dL.

 Helps maintain physiologic pH.

 Defi ciency is uncommon except in genetic disorders of phosphate metabolism.  Calcium and phosphate are both deposited and resorbed from bone together.

2.6     Hypocalcemia

 Defi nition   Serum calcium <10.5 mg/dL or ionized calcium <1.0 mmol/L

 Causes  R enal failure, vitamin D defi ciency, magnesium defi ciency, acute pancre-

atitis, hypoparathyroidism, hyperphosphatemia, and medication effect  Very common in hospitalized patients

 Symptoms   

 Acute – syncope, perioral numbness, fatigue, muscle cramps, and congestive heart failure

 Chronic – psoriasis, dry skin, coarse hair, brittle nails, poor dentition, and cataracts

S evere hypocalcemia can but rarely causes tetany, arrhythmias, hypotension, and seizures as well as other signs/symptoms of neuromuscular irritability.

 Diagnosis   Ionized calcium level

 Check liver function test, albumin, iPTH, magnesium, BUN, and creatinine to assess for secondary causes.

 Treatment is with oral versus IV supplementation.

2.7     Hypercalcemia

 Defi nition   Serum calcium >10.5 mg/dL or ionized calcium >2.5 mmol/L  Causes  

 90 % caused by malignancy or hyperparathyroidism

1 0 % caused by increased vitamin D levels, thiazide diuretics, renal failure, rapid bone turnover, and familial causes

 Symptoms   Anxiety, depression, coma, somnolence, arrhythmia, nephrolithiasis, hypertension, nausea, vomiting, anorexia, and osteoporosis (“stones, bones, abdominal groans, psychiatric moans”)

 Treatment   IV fl uids, loop diuretics, IV bisphosphonates, calcitonin, dialysis, and glucocorticoids

2.8     Rickets

 Defi nition   Disease of growing bone affecting children

 Causes   Failure of osteoid to calcify typically from prolonged vitamin D defi ciency.

 Vitamin D defi ciency → decreased serum calcium →+PTH →increased renal phosphorous loss → decreased deposition of calcium in the bone

 Demographics   More common in exclusively breastfed babies and those with little sunlight exposure. Also present in conditions that cause malabsorption such as celiac disease and seen in severe renal disease.

 Physical Exam   Skeletal deformity (bow leg, knock knee, rachitic rosary), short stature, dental defects, kyphoscoliosis, and delay in closure of fontanels

CLINICAL SIGNS OF RICKETS

Soft spot on baby’s head is slow to close.

bony necklace

curved bones

big, lumpy joints

bowed legs

(knees bent out)

 Laboratory   

 Low calcium, phosphorous, and vitamin D levels  Elevated alkaline phosphate and PTH

 Radiography   Anterior view of the knee will show cupping and widening of the metaphyses

 Treatment   Vitamin D and calcium supplementation, may need surgical intervention for skeletal deformities

2.9     Osteomalacia

 Similar to rickets but occurs in adults

 Defi nition   Incomplete mineralization of osteoid following growth plate closure. Normal amount of collagen, too little calcium.

 Not to be confused with osteoporosis, which is a decrease in bone mass with NORMAL mineralization

 Causes   Most commonly from vitamin D defi ciency.

C an also be caused by celiac disease, anticonvulsants, kidney and liver disease, surgeries that remove part of the stomach or small intestine, low phosphorous intake, and cancer

 Symptoms   Bone pain, muscle weakness, and fractures

 Physical Exam   Patients may exhibit a waddling gait.

 Workup   Low levels of serum calcium, vitamin D, and phosphorous

 Radiology   Radiography may show Looser’s transformation zones (pseudofractures)

 Diagnosis  B one biopsy can defi nitively make the diagnosis, usually blood work, and radiography is suffi cient for diagnosis.

 Treatment   Vitamin D and calcium supplementation, braces, and surgical intervention in severe cases

3     Joint Arthridites: Osteoarthritis and Infl ammatory Arthritis

 Amanda  Marshall

 Osteoarthritis  D egenerative joint disease affecting the articular cartilage of synovial joints; infl ammation is not the major component of the disorder.

 Primary (most common) – develops in the absence of a known cause, aka idiopathic

 Secondary – results from hereditary, developmental, metabolic, traumatic, infectious, or neurologic condition

 Infl ammatory Arthritis   Infl ammatory process from various triggers mediating synovial proliferation and infl ammation ultimately resulting in soft tissue and bone destruction. The most common type is rheumatoid arthritis (affecting 0.5–1 % of US adults), but other conditions include systemic lupus erythematosus (SLE),  ankylosing spondylitis, and psoriatic arthritis.

 Pathophysiology  

O steoarthritis: sequence of changes within the matrix affecting the structure and function of the articular cartilage.

S tage I, matrix alteration – increased water content, decreased proteoglycan aggregation, and decrease in glycosaminoglycan chain length, but no change in type II collagen concentration.

 Stage II, chondrocyte response – increase in matrix synthesis, turnover, and chondrocyte proliferation. Matrix metalloproteinases (MMPs) destroy aggrecan and activate collagenase.

S tage III, decline in chondrocyte response – accumulation of molecules within the matrix.

 The bone responds to the degeneration of articular cartilage by increasing subchondral bone density, formation of cysts, and development of bony and cartilaginous outgrowths later forming osteophytes. End-stage disease represented by complete loss of cartilage and resultant denuded bone.

 Infl ammatory arthritis: migration of mononuclear cells via induction of IL-8, and IL-1β incites infl ammatory response directed at periarticular tissues. Midkine (heparin-binding growth factor) upregulates osteoclast differentiation.

 Diagnostic Criteria     

A nkylosing Spondylitis   Manifests frequently during second decade of life. It usually presents as back pain characterized as insidious in onset, present for greater than 3 months; morning stiffness improves with exercise, worsens with rest. Extraspinal features include enthesitis, dactylitis, and uveitis. Radiographic changes include early squaring of the vertebral bodies progressing to bamboo spine chronically. MRI most sensitive for sacroiliac involvement. +HLA-B27

 Psoriatic Arthritis   Occurs in 15–20 % of patients with psoriasis. Skin lesions (scaly erythematous plaques) appear prior to onset of arthritic symptoms in 80 % of patients. Most common presentation is asymmetrical oligoarthritis (50 %). Spondylitis present in up to 40 % of patients. Synovial fl uid analysis WBC 5,000– 15,000. Radiographic features include mild erosive disease. Arthritis mutilans = “pencil in cup” deformity of hands.

 Biochemical Markers   

 Osteoarthritis: Several biochemical markers have been investigated, but none have proven suffi ciently discriminatory in the diagnosis and/or prognosis of OA. Recent studies show promise for serum, urine, and synovial fl uid biomarkers such as uCTX-II (urinary cross-linked C-telopeptide of collagen), sCOMP (serum cartilage oligomeric matrix protein) fragment, sfNT (synovial fl uid nitrotyrosine), and CXCL12 (serum and synovial fl uid stromal cellderived factor).

 Rheumatoid arthritis: The serum biochemical markers associated with RA are “infl ammation”-based and include IL-6, leptin, resistin, CRP, MMP-1 and MMP- 3, and YKL-40 (chitinase-3-like protein 1 aka CH13L1). A commercially available kit is available for use in clinical practice.

 Treatment   Physical therapy

 NSAIDS

 Disease-modifying antirheumatic drugs (DMARDS)

 Biologic agents: Apremilast, Phosphodiesterase-4 inhibitor, ustekinumab  Surgery:

 Arthroscopic synovectomy

 Joint replacement

 Arthrodesis

 Bibliography

 1.  Lafeber FPJG, Van Spil WE. Osteoarthritis year 2013 in review: biomarkers; refl ecting before moving forward, one step at a time. Osteoarthritis Cartilage.

2013;21:1452–64.

4     Infection, Septic Arthritis, and Osteomyelitis

 Brian  A.  Mosier,  Daniel  T.  Altman

 Take-Home Message

•      S. aureus      is the most common species involved in bone infections.

•      Intravenous drug users have a predilection for  Pseudomonas aeruginosa and gram-negative infections.

•      Defi nitive diagnosis is based on cultures from bone and soft tissue specimens.

•      Biofi lms can exist on orthopedic devices in a sessile state and contribute to chronic bacterial infections.

 Defi nitions   

•      Biofi lm: Communities of microorganisms encased within an extracellular poly-meric slime matrix.

•      Osteomyelitis

–     Sequestra: Dead infected bone seen in acute osteomyelitis. Serves as a sub-strate for biofi lm formation

–     I  nvolucrum: New periosteal bone that forms in chronic osteomyelitis encasing and supporting the weakened area of dead infected bone

 Etiology   Septic Arthritis

•      Adult Septic Arthritis

–     Mechanisms of inoculation are hematogenous seeding, direct inoculation, and contiguous spread.

–     Most frequently involved joints: Knee, hip, elbow, and ankle. –  Two major patient groups:

•      <40: the most common organism is  N. gonorrhoeae .

•      Elderly: the most common organism is  S. aureus .

•      Pediatric Septic Arthritis

–     Source is dependent on age and blood vessel fl ow patterns.

•      Neonates: adjacent osteomyelitis due to vessels crossing the physis

•      I nfants/children: hematogenous spread most common. May have spread from adjacent portions of intracapsular metaphyseal areas such as in the wrist, hip, and knee and humerus.

•      Adult Osteomyelitis

–     Most common mechanisms are contiguous spread and direct inoculation.

–     S  taphylococcus is the most common organism involved due to its inherent adherence mechanisms.

•      Pediatric Osteomyelitis

–  Most common organism is  S. Aureus .

•      In neonates, suspect group A streptococci.

–     Mechanism usually via hematogenous spread.

–     D  ue to robust blood supply in the metaphyseal region of children, acute osteomyelitis may prelude septic arthritis.

 Pathophysiology   

Septic Arthritis

P roteolytic enzymes produced by PMNs cause irreversible destruction of articular cartilage.

 Osteomyelitis

 Acute suppurative infection can disrupt the vascular supply to the bone leading to areas of necrosis. The sequestra serve as a medium for biofi lm formation with chronic infection ensuing unless an intervention occurs.

 Biofi lms

•      C an develop on implanted orthopedic devices or dead bone and may mature over months or years with few signs of infl ammation.

•      Imparts resistance to host immunity, responds poorly to antibiotics, is chronic in nature, and is often culture negative.

•      Detection and management are diffi cult and evolving.

 Radiology  

 Septic Arthritis

 Radiographs:

•      Useful for assessing bony involvement or presence of hardware  MRI:

•      Convenient to rule out periarticular soft tissue infection or abscess

 Ultrasound

•      P referred method for determining deep joint distension/effusion in pediatric septic arthritis

 Radiographs:

•      Early osteomyelitis: adjacent soft tissue swelling and joint effusions. Most useful for ruling out presence of fractures, implant loosening.

•      L ate osteomyelitis: bone destruction and necrosis within the sequestrum signifi ed by periosteal reactions, bone cysts, and focal areas of resorption.

Demonstrates mixed destructive-sclerotic lesions.

 MRI:

•      F indings are seen 2–3 weeks before any changes are observed on plain radiographs.

•      Low signal on T1 study, edema on T2 study, and enhancement on post- gadolinium study.

 Radionuclide Imaging

 Technetium Bone Scan

•      Sensitive to tumor, infection, arthritis, or trauma

•      Combination of indium ( ¹¹¹In) and technetium ( ⁹⁹T n) labeling provides the most sensitive and specifi c imaging in acute bone infections.

 PET Scan

•      Expensive

•      PET scans with FDG (fl uorodeoxyglucose) labeling are valuable and have increased utility in diagnosing periprosthetic joint infections.

 Diagnosis   

Septic Arthritis

 Serum Blood Tests:

•      CBC: leukocyte count usually elevated.

•      ESR/CRP: CRP always elevated; ESR is sometimes normal.

•      Blood cultures required.

 Joint Fluid Aspirate:

•      Mandatory for diagnosis and identifi cation of the inciting organism

•      Send for cell count with differential, gram stain, glucose level, crystal analy-sis, and culture (aerobic/anaerobic, fungal, mycobacterial).

•      Characteristics of a likely infected aspirate:

–     Cloudy or purulent

–     Glucose <60 % serum level

–     >75 % PMNs

–     50,000 cells/mm ³

•      CBC: leukocyte count elevated or normal in acute osteomyelitis. Most often nor-mal in chronic osteomyelitis

•      ESR/CRP: Elevated in both acute and chronic osteomyelitis

–     Monitor CRP level to determine effectiveness of treatment.

–     CRP dissipates after 1 week of effective treatment.

–     ESR is elevated in 90 % of cases and peaks after 3–5 days.

 Defi nitive diagnosis is based on cultures obtained from bone biopsies.

C lassifi cation  O steomyelitis: Cierny-Mader Staging System for Osteomyelitis (Fig.  1 )

                                Medullary                                                          Superficial

                                 Localized                                                            Diffuse

 Fig. 1  Cierny anatomic classifi cation of adult osteomyelitis (Cierny III G, Mader JT, Pennink

JJ. A clinical staging system for adult osteomyelitis. Contemo Orthop. 1985;10:17–37)

•      Based on anatomic site of infection and physiologic class of the host including systemic and local factors.

•      Relates medical context of the host to their ability to respond to an infection.

•      Weak hosts require more aggressive treatment.

 Treatment  

 Septic Arthritis

M ain goal of treatment is the preservation of articular cartilage by eliminating proteolytic enzymes that rapidly destroy the articular cartilage.

•      S erial aspirations: monitor joint fl uid polymorphonuclear cell count to assess adequacy of treatment.

•      Open debridement: Highest chance of clearing offending agents.

 Osteomyelitis

 Acute Osteomyelitis:

•      Almost always requires debridement of abscesses in bone and soft tissues.

•      Soft tissue loss requires coverage with a muscle fl ap transfer.

•      C utaneous oxygen tension measurements are the best method to evaluate local tissue perfusion.

•      Antibiotics are generally continued for 4–6 weeks.

 Chronic Osteomyelitis

•      D ebridement of all devascularized tissues and dead bone to areas of punctate bleeding with removal of all implanted devices that may harbor biofi lms.

•      Stabilization is achieved by splint/cast or external fi xation with pins placed away from the infection site.

•      Antibiotic-impregnated polymethylmethacrylate may be used to temporarily fi ll bone voids.

•      Muscle fl ap coverage for areas defi cient of soft tissue coverage.

 Prevention   

Surgical Site Infection( SSI )

•      Most common nosocomial infection

•      P roper skin preparation, strict sterile technique, decreased surgical duration, and limiting traffi c fl ow decrease infection rate and bacterial load.

5     Complex Regional Pain Syndrome

 Take-Home Message

•      S ymptom complex of pain, allodynia, vasomotor instability, swelling, and dystrophic skin changes and motor dysfunction.

•      Peripheral and central nervous system is involved.

•      Treatment is multidisciplinary and should start as early as possible.

•      Treatment is directed toward improving limb function and pain symptoms.

 Defi nition   Regional pain with autonomic dysfunction, atrophy, and functional impairment affecting musculoskeletal, neural, and vascular structures.

 Diagnostic criteria include hyperalgesia (often non-anatomic), allodynia, vasomotor instability, motor dysfunction, and trophic symptoms.

 Etiology   Common cause is trauma to an extremity.

 Peripheral and central nervous system sensitization.

C ausative mechanisms may differ across patients and within a patient over time.

 Risk factors include prolonged immobilization, smoking, substance abuse, genetic, and psychological factors (anxiety, depression).

 Pathophysiology  

 Unknown, multifactorial; begins with initial trauma

•      Upregulation of alpha 1-adenoreceptor in the peripheral nervous system and in the spinal cord.

•      Primary afferent nociceptive mechanisms demonstrate abnormally heightened sensation, including spontaneous pain and hyperalgesia.

•      Infl ammatory response increases in interleukin (IL) – 1β[beta], 2, 6; tumor necrosis factor (TNF) – α [alpha]; calcitonin gene-related peptide (CGRP); bradykinin; and substance P. Decrease in IL-10.

•      Brain plasticity causes decreased representation of the affected limb in the in somatosensory cortex causing greater pain intensity and hyperalgesia, impaired tactile discrimination, and perception of sensations outside of the nerve distribution.

 Imaging   X-rays: show regional osteopenia in 80 % of patients

 Triple phase bone scan: diffusely increased periarticular uptake involving multiple joints in the affected extremity; imaging modality with greatest sensitivity and negative predictive value for ruling out CRPS type 1

M RI: may show bone marrow edema, skin edema, uptake of the skin, joint effusion, and intra-articular uptake

 Total digital microvascular fl ow: analyzed by digital temperature measurements, laser Doppler fl uxmetry, and vital capillaroscopy

 Classifi cation   

T ype 1: initiated by minor trauma to an extremity compounded by external forces

(tight cast, dependant positioning, excessive swelling). “Classic RSD”

 Type 2: associated with an identifi able peripheral nerve injury or “causalgia”

 Type 3: nontraumatic cause producing extremity pain such as myofascial syndrome

 Warm vs. cold CRPS describes temperature changes of limb.

 Cold – more chronic state, poorer prognosis.

 Historical stages – times and stages are not absolute.

 Stage 1 (lasts 1–3 months):

•      Changes in skin temperature, switching between warm and cold

•      Faster growth of nails and hair

•      Muscle spasms and joint pain

•      Severe burning, aching pain that worsens with slight touch or breeze • S kin becomes blotchy, purple, pale, or red; thin and shiny; swollen; sweatier

 Stage 2 (lasts 3–6 months):

•      Continued changes in the skin

•      Nails that are cracked and break more easily

•      Pain that is becoming worse

•      Slower hair growth

•      Stiff joints and weak muscles

 Stage 3 (irreversible changes can be seen)

•      Limited movement – contracted muscles and tendons

•      Muscle atrophy

•      Pain in the entire limb

 Treatment  M ultidisciplinary treatment is key (PCP, therapy, pain management, support groups, psychotherapy, etc.).

I dentify reversible causes (injured nerve), and correct if possible, especially in CRPS type 2.

S tart physical and occupational therapy as early as possible – improve mobility and strength.  Medications

•      Antidepressants – relieve post-traumatic depression; provide analgesia and  modulate sympathetic hyperactivity in the peripheral nervous system and CNS (tricyclic antidepressants, tetracyclic antidepressants, atypical antidepressants, and selective serotonin reuptake inhibitors)

•      Anticonvulsants – treat hyperpathic pain; thought to stabilize excitable nerve membranes, limit neuronal hyperexcitability, and inhibit trans-synaptic neuronal impulses in the CNS

•      L ocal and oral anesthetic agents – only used in severe, refractory cases due to signifi cant side effects

•      A drenergic medications – peripheral vasodilation, increases nutritional blood fl ow, and affects α[alpha]1 and α[alpha]2 receptors

•      Calcium channel blockers decrease sympathetic tone

•      B isphosphonates – provide analgesia by preventing bone resorption; some act on infl ammatory mediators, including IL-1, IL-6, lactic acid, and TNF-α[alpha].

 Parenteral Medications

•      Intravenous regional infusions – pain management specialists may use; bretylium tosylate (only FDA-approved medication) and corticosteroids most common

•      Percutaneous neural or ganglionic blockade

•      Sympathetic blockade – continuous infusion of a local anesthetic around stellate ganglion or paravertebral ganglia, along the brachial plexus, or within the epidural space

 Implantable Devices

•      P eripheral nerve stimulator – for gray matter, the dorsal column, the spinal cord, and peripheral nerves; improve pain relief, improve sleep, decrease the use of addictive pain medication, and improve health-related quality of life

•      S pinal cord stimulator – invasive, high complication rate, results diminish with time, but can help in carefully selected patients

C entral nervous system ablative techniques – sympathectomy; only short-term palliation; may make some patients worse

 Biofeedback/acupuncture – useful in properly selected patients

 Complications   

•      Cognitive impairment

•      Depression

•      Loss of muscle size or strength in the affected limb

•      Worsening of the affected limb

•      Complications from surgical procedures

 Prognosis   Varies

 Children and teenagers – good recovery

 Early intervention and rehabilitation can limit severity and duration on symptoms.

 Some patients will develop unremitting pain and crippling, irreversible changes despite treatment.

 Prevention  

•      Vitamin C following wrist fracture. 500 mg daily for 45–50 days

•      Early mobilization and ambulation following a stroke or other extremity trauma  Bibliography

1. B ruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010;113:713–25.

2. C appello ZJ, Kasdan ML, Louis DS. Meta-analysis of imaging techniques for the diagnosis of complex regional pain syndrome type I. J Hand Surg Am. 2012;37A:288–96.

 3.  Marinus J, Moseley GL, Birklein F, Baron R, Maihöfner C, Kingery WS, van Hilten JJ. Clinical features and pathophysiology of complex regional pain syndrome. Lancet Neurol. 2011;10(7):637–48.

6     Connective Tissue Disorders

 Michael  Pensak,  Jennifer  Moriatis  Wolf

 Take-Home Message

•      Ehlers-Danlos is a connective tissue disorder of collagen metabolism char-acterized by skin elasticity, fragility, and hypermobile joints.

•      Marfan’s syndrome is a connective tissue disorder resulting from autoso-mal dominant mutation in fi brillin-1 gene – aortic root dilation/dissection, joint laxity, and scoliosis.

•      Neurofi bromatosis-1 is an autosomal dominant disorder characterized by neurofi broma masses, congenital pseudarthrosis, café au lait spots, and axillary/groin freckling.

•      Homocystinuria is an inborn error of methionine metabolism, with typical laxity, and scoliosis; diagnosed by urine sulfur amino acid and treated with pyridoxine.

6.1     Ehlers-Danlos

 Defi nition   

•  Connective tissue disorder characterized by skin elasticity, fragility, and joint hypermobility due to abnormal collagen metabolism resulting from a variety of mutations.

 Etiology   

•      Multiple mutations identifi ed, though common feature to all subtypes involves abnormal collagen in connective tissues

–     Mutations in type V collagen (40–50 %)

–     Mutations in type III collagen

–     Mutation in collagen cross-linking enzyme, lysyl hydroxylase

 Pathophysiology   Laxity in multiple joints – shoulders, patellae, and ankles

•      Kyphoscoliosis

•      Loose, fragile skin with poor wound healing capability

 Radiography  

•      Joint specifi c x-rays to rule out subluxations/dislocations

•      PA/lateral spine radiographs to follow kyphoscoliosis

 Classifi cation   

 Villefranche (1998)

•      Type I – Classic. Autosomal dominant. Mutations in type V collagen but no known universal cause. Major features: skin elasticity, wide scars, and joint hypermobility. Minor features: smooth skin, velvety skin, molluscoid pseudotumors, subcutaneous spheroids, muscle hypotonia, easy bruising, and positive family history

•      T ype II – Hypermobility. Autosomal dominant. Major features: skin involvement and joint hypermobility. Minor features: joint dislocations, chronic joint/limb pain, and positive family history

•      T ype III – Vascular. Autosomal dominant. Major features: thin, translucent skin and arterial/intestinal or uterine rupture, extensive bruising, and characteristic facial features (pinched nose, thin lips, tight skin, hollow cheeks). Minor features: small joint hypermobility, muscle/tendon rupture, clubfoot, varicose veins, pneumothorax, AV or carotid-cavernous sinus fi stula, gingival recession, and positive family history

–  Col3A1 mutation results in abnormal procollagen III synthesis

•      T ype IV – Kyphoscoliosis. Autosomal recessive. Defect in lysyl hydroxylase, involved in collagen cross-linking. Major features: joint laxity, hypotonia at birth, progressive scoliosis, and globe ruptures. Minor features: tissue fragility, easy bruising, arterial rupture, microcornea, osteopenia, and positive family history

•      Type V – Arthrochalasis. Autosomal dominant. Major features: extreme hyper-laxity, recurrent subluxations, and congenital hip dislocations. Minor features: hyperextensible skin, fragile tissues, atrophic scars, easy bruising, hypotonia, kyphoscoliosis, and osteopenia. Col1A1 or Col1A2

•      Type VI – Dermatosparaxis. Autosomal recessive. Major features: skin fragility, sagging, or redundant skin. Minor features: soft skin, easy bruising, premature rupture of fetal membranes, and hernias

 Treatment  

 No cure for underlying metabolic abnormalities of collagen production

•      Nonoperative – mainstay of management

–     Reduce and immobilize joint dislocations

–     Physical therapy and orthotics

•      Operative

–     Joint fusions for recalcitrant dislocations; soft tissue procedures alone have low success rate.

–     Posterior spinal fusion for kyphoscoliosis with long constructs.

 Complications  

•      Joint dislocations

•      Kyphoscoliosis

•      Aortic dilatation

–     Cardiology consult

–     Echocardiogram

•      Easy bruising and scarring

•      Chronic pain

6.2     Marfan’s Syndrome

 Defi nition  C onnective tissue disorder with multiple manifestations: joint laxity, long limbs, scoliosis, cardiac valve abnormalities, aortic dilatation, etc.

 Etiology   Autonomic dominant mutation in fi brillin-1 gene and chromosome 15q21

 Pathophysiology  

 Abnormal fi brillin-1 may also indirectly lead to increases in TGF-β which is implicated in the deleterious effects seen on heart valves and the aorta.

•      M usculoskeletal fi ndings – scoliosis, protrusio acetabula, pes planovalgus, tall, thin stature with long limbs (dolichostenomelia), and long fi ngers (arachnodactyly)

–     Steinberg sign – with the fi ngers clenched in a fi st over an adducted thumb, the thumb tip protrudes out the ulnar aspect of the hand.

–     Walker sign – overlap of the thumb and little fi nger when attempting to encir-cle the contralateral wrist.

•      Non-musculoskeletal fi ndings

–     Cardiac abnormalities

•      Aortic root dilatation

•      Aortic dissection

•      Mitral valve prolapse

–     Pectus excavatum

–     Spontaneous pneumothoraces

–     Ectopia lentis – superior lens dislocation

 Radiography   Scoliosis (PA and lateral spine fi lms)

 Classifi cation   

Revised Ghent system 2010

•      E mphasizes presence of cardinal features of aortic root dilatation/dissection and ectopia lentis

 Treatment    

 Diagnostic criteria for Marfan’s syndrome

 In the absence of family history:

1. Aortic dilatation/dissection AND ectopia lentis

2. Aortic dilatation/dissection AND FBN1 mutation

3. Aortic dilatation/dissection AND systemic score >7                4. Ectopia lentis AND FBN1 AND aortic dilatation/dissection  In the presence of family history:

5. Ectopia lentis AND positive family history

6. Systemic score ≥7 AND positive family history

7. Aortic dilatation/dissection AND positive family history

 Systemic features

 Assigned various points from 1 to 3, maximum score of 20, score greater than or equal to 7 indicates systemic involvement

 Wrist AND thumb sign, pectus carinatum, pes planovalgus, pneumothorax, dural ectasia, protrusio acetabuli, scoliosis or thoracolumbar kyphosis, reduced elbow extension, facial features, skin striae, myopia, mitral valve prolapse

 Adapted from revised Ghent nosology (2010)

•      Nonoperative

–     Scoliosis – early bracing

–     Cardiac issues – beta-blockers for cardiac involvement

•      Operative – scoliosis

–     Long posterior spinal fusion

–     Mandatory preoperative MRI

–     Cardiac consultation and echocardiogram

•      Pes planovalgus – fl atfoot reconstruction

•      Protrusio acetabula – epiphysiodesis of triradiate cartilage (pediatric popu-lation); total hip arthroplasty for advanced joint degeneration

 Complications   

Scoliosis

•      Higher complication rate than in adolescent idiopathic scoliosis

•      10–20 %, including pseudarthrosis, hardware failure, loss of correction, and infection

6.3    Neurofi bromatosis-1

 Defi nition   Autosomal dominant disorder leading to hamartomatous proliferations  Etiology  

•      Mutation on chromosome 17 affecting the NF-1 gene.

•      NF-1 is a tumor suppressor gene whose coded protein is implicated in cell growth and differentiation.

 Pathophysiology   

•      Skeletal fi ndings

–  Scoliosis

•      Thoracic spine involvement – short, sharply angled curves

•      Dystrophic subtype – likely to progress, risk of neurologic defi cit

•      Non-dystrophic subtype – resembles AIS

–     C  ongenital pseudarthrosis of the tibia – anterolateral bowing of tibia often is present at birth

–     Hemihypertrophy – uncommon, unilateral, may involve bone and soft tissue

•      Nonskeletal fi ndings

–     Café au lait spots – hyperpigmented lesions with rounded borders

–     Axillary and inguinal freckling

–     Cutaneous neurofi bromas – composed of axons and Schwann cells

–     L  isch nodules – pathognomonic dome-shaped elevations of the surface of the iris

–     Plexiform neurofi bromas – subcutaneous lesions with “bag of worms” feel

•      25% of patients with NF-1

•      1 –4 % risk of malignant degeneration – remove if lesions enlarge or become painful

•      Can lead to overgrowth of an extremity

–     V  errucous hyperplasia – thick overgrowth of skin with a soft, velvety feel that can form crevices predisposing to infections

–     Optic glioma – low-grade CNS tumor, present in 15–20 %

 Diagnosis   

 Two of seven criteria as delineated by the NIH

 Clinical assessment and the presence of two of any of the above fi ndings are diagnostic for NF-1

 Radiography  

•      Tibia/fi bula x-rays to monitor anterolateral bowing

•      PA/Lateral spine radiographs to evaluate scoliosis

–     Sharp vertebral end plates

–     Rib penciling – central narrowing of rib shafts

•      Preoperative spine MRI to rule out dural ectasia or intraspinal anomaly  Classifi cation  

•      Neurofi bromatosis-1

–     Autosomal dominant mutation of chromosome 17

–     Incidence 1/2,500–4,000

•      Neurofi bromatosis-2

–     Autosomal dominant mutation of chromosome 22

–     Incidence 1/25,000–40,000

 Treatment  

•      Scoliosis

–     Attempt trial of bracing for non-dystrophic form

–     Posterior spinal fusion for management of dystrophic form and non- dystrophic form that has failed bracing

•      Anterolateral bowing of tibia/Congenital pseudarthrosis

–     Brace with total contact orthosis prior to fracture

–     Surgical fi xation once fracture or pseudarthrosis is present

–     Amputation for persistent pseudarthroses

 Complications  

•      Scoliosis

–     Pseudarthrosis

•      Anterolateral bowing of tibia/Congenital pseudarthrosis

–     Recurrent fracture in up to 50 % of individuals

6.4     Homocystinuria

 Defi nition   Inborn error of methionine metabolism resulting in mental retardation, thromboembolic events, inferior lens dislocation and skeletal manifestations similar to Marfan’s syndrome

 Etiology  

 Autosomal recessive mutation causing a defi ciency in cystathionine synthetase

•      L ack of cystathionine synthetase prevents conversion of homocysteine to cystathionine leading to homocystine accumulation.

•      Homocystine is converted to homocystine.

•      Homocystine accumulates in tissues and is excreted in the urine.

•      Plasma methionine also becomes elevated.

 Pathophysiology  

•      Skeletal manifestations

–     Tall, thin stature with long limbs (dolichostenomelia) and moderate arachnodactyly

–     Severe pes planovalgus

–     Thoracolumbar scoliosis

–     Osteoporosis

–     Pectus carinatum

•      Nonskeletal manifestations

–     Venous/arterial thrombotic events

–     Inferior lens dislocations (ectopia lentis) from defective suspensory ligament

 Radiography  

•      P A/lateral spine radiographs for thoracolumbar scoliosis with biconcave endplates and fl attening (platyspondyly)

•      Knee fi lms – wide metaphyses and enlarged epiphyses

 Diagnosis   Screen for sulfur amino acid concentrations in urine (homocysteine)

 Treatment   Oral pyridoxine – 50 % of patients may respond.  Operative, scoliosis – posterior spinal fusion.

 Complications  

•      Scoliosis

•      Osteoporosis

•      Pes planovalgus

•      Blood clots

•      Inferior lens dislocation

 Bibliography

1 . B ravo JF, Wolff C. Clinical study of hereditary disorders of connective tissues in a Chilean population: joint hypermobility syndrome and vascular Ehlers-Danlos syndrome. Arthritis Rheum. 2006;54(2):515–23.

2.    Herring JA. Orthopaedic-related syndromes. In: Herring JA, editor. Tachdjian’s pediatric orthopaedics. Dallas: Saunders Elsevier; 2008. p. 1795–913.

3.    Kobayasi T. Dermal elastic fi bres in the inherited hypermobile disorders. J Dermatol Sci. 2006;41(3):175–85.

4.    Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet.

2010;47(7):476–85.

Materials and Biomechanics

Brett D. Crist, Ajay Aggarwal, Charles Lewis, Ferris M. Pfeiffer, and Trent M. Guess

1     Biomaterials

Brett D. Crist and Ajay Aggarwal

1.1     Fracture Implants

Take-Home Message

•      Modulusofelasticityforcorticalboneis~20GPa,stainlesssteel≈200GPa, and titanium ≈100 GPa

•      Bending stiffness of plates ≈ thickness of the plate³

•      Bending stiffness of intramedullary nails ≈ radius⁴

Modulus of Elasticity

•      Stress = force/area

•      Strain = change in length/original length

•      Modulus of elasticity (Young’s modulus) = stress/strain. Most solid material has a linear portion of its stress-strain curve (Fig. 1). This portion is the slope of the

B.D. Crist, MD (*) • A. Aggarwal, MD    

F.M. Pfeiffer, PhD (*) • T.M. Guess, PhD

Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri, USA e-mail: cristb@health.missouri.edu; aggarwala@health.missouri.edu;  pfeifferf@health.missouri.edu; guesstr@health.missouri.edu

C. Lewis, BSc, MSc, FRCS (*)

Taranaki District Health Board, New Plymouth, New Zealand e-mail: charliealewis7@gmail.com

© Springer-Verlag France 2015                                                                                              129

C. Mauffrey, D.J. Hak (eds.), Passport for the Orthopedic Boards  and FRCS Examination, DOI 10.1007/978-2-8178-0475-0_6

Fig. 1Stress–strain curve                                          Ultimate Strength

curve and the elastic modulus (E). Hooke’s law of elasticity indicates that no permanent deformation/damage occurs within the linear area of the curve.

Yield and Ultimate Strength

•      Once a material is loaded past the elastic portion of the stress-strain curve and there is permanent damage to the material (plastic deformation), it reaches its yield point.

•      If loading continues past the yield point, the material will eventually catastrophically fail and that is the ultimate strength.

•      Ductility: amount of plastic deformation tolerated before ultimate failure.

•      Brittle materials: high elastic modulus, low ductility = stiff but fail at yield point

•      Ductile materials: lower elastic modulus, larger area of plastic deformation before ultimate failure = flexible and deform prior to ultimate failure. Fatigue Strength or Endurance Limit

•      Materials can withstand cyclic loading until microdamage accumulates causing rapid failure. The fatigue strength/endurance limit is the maximum stress the material can withstand without failure after 10–100 million cycles.

Plates

•      Extramedullary, usually load-bearing devices

•      Bending stiffness ≈ to plate thickness³

– Ex: Increasing the thickness of a plate by 2 mm increases the bending stiffness eight times the original.

Intramedullary Nails

•      Intramedullary, usually load-sharing devices

•      Bending stiffness = π × radius⁴

– Ex: Increasing the radius of an IM nail by 2 mm increases the bending stiffness by 16 times.

Common Fracture Implant Materials

•      Stainless steel: elastic modulus ~200 GPa, plates, and screws

–     Stiff and more brittle

–     Risk of rejection if patient has a nickel allergy

•      Titanium: elastic modulus ~100 GPa, intramedullary nails, and plates and screws

–     Flexible and more ductile.

–     Titanium resists corrosion.

–     Titanium forms passivation layer to inhibit bacterial colonization.

–     Used in nickel-allergic patients.

–     Risk of cold welding that makes implant removal difficult.

1.2     Arthroplasty

Take-Home Message

•      Highly cross-linked polyethylene liners have performed well in vivo. Wear is significantly lower compared to conventional polyethylene. Fracture of highly cross-linked polyethylene occurs and is multifactorial.

•      Metal-on-metal (MOM): Worldwide reduction in utilization of MOM is due to concerns about adverse local tissue reactions (ALTR) secondary to wear and/or corrosion of cobalt-chromium-based components. Elevated metal ions can cause pseudotumors and aseptic lymphocytic vasculitisassociated lesion (ALVAL).

•      Ceramic-on-ceramic: Is an attractive option for young and active patients. The most significant disadvantage is the potential for fracture and squeaking.

Polyethylene Processing

Polyethylene is a long-chain hydrocarbon. When exposed to radiation, carbon–carbon and carbon–hydrogen bonds can be broken. As a result, chain scission or free radical formation can occur. Oxygen can bind at a free radical site, leading to oxidation. Both chain scission and oxidation have negative consequence for wear and mechanical properties.

Cross-linking involves formation of carbon–carbon bonds between two adjacent polyethylene polymers. Irradiation is the first step and produces free radicals. Free radicals then react and cross-link the polymer chains. The amount of cross-linking is proportional to the radiation dose. Doses of 50–100 kGy (5–10 mrads) are typically used. Heating is the second step, and it reduces the free radicals and thus decreases the risk of oxidation.

Conventional Polyethylene

•    Radiation dose between 2.5 and 4.0 mrads.

– Disadvantage: Higher linear and volumetric wear leading to increased incidence of osteolysis and loosening.

Highly Cross-Linked Polyethylene

•    Radiation dose between 5.0 and 10.0 mrads.

–     Advantage: Markedly decreased linear (<0.004–0.25 mm/year) and volumetric wear. Smaller wear particles decrease the risk of osteolysis and loosening.

–     Disadvantage: Decreased mechanical properties leading to reduced strength, fatigue resistance, and fracture toughness. Fracture of polyethylene has been associated with suboptimal positioning of components, implant design with sharp corners at the locking mechanism, and thin polyethylene.

Vitamin E Polyethylene

Vitamin E helps in stabilizing the free radicals without postradiation melting and maintains the mechanical properties of polyethylene. Vitamin E highly cross-linked polyethylene demonstrates oxidative resistance, good strength, and low wear.

Metal-on-Metal (MOM)

MOM is characterized by higher wear during the run-in period (1–2 years) followed by substantially lower steady-state wear. Smaller <50 nm wear particles.

•      Advantages: Low wear secondary to lower surface roughness and higher sphericity. Positioning of the acetabular component can influence wear and ion production. Wear decreases with increased head size and clearance decreases.

•      Disadvantages: Local and systemic accumulation of metallic debris and ions.

Elevated ions can cause ALVAL and pseudotumors.

Factors associated with increased metal ions

•      Small-diameter components implanted at higher abduction (>50–55°) and higher combined version are at increased risk of edge wear, elevated ions, and ALTR.

•      Large diameter >36 mm MOM heads are at increased risk of head and neck taper and fretting corrosion.

•      Serum ion levels (CO, Cr):

–     Low risk <3 ppb – Moderate risk 3–10 ppb – Higher risk >10 ppb.

–     Cross-sectional imaging with MARS MRI is indicated for symptomatic patients with elevated ions. CRP can be elevated.

Ceramic-on-Ceramic

Ceramics are stable, dense, and hard surfaces. They are scratch resistant and hydrophilic, have a low coefficient of friction, and create less reactive debris, making them an attractive option for young and active patients.

•      Advantages: Low wear, hard, and scratch resistant.

•      Disadvantages:

–     Brittle

–     Stripe wear due to localized edge loading in deep flexion.

–     Fracture in ceramics can be due to poor material, large grain size, small head size, incorrect component positioning, residual internal stress, and poor taper design.

–     Squeaking (incidence = 0.45–10.7 %)

–     Factors associated with squeaking include implant (stem) design, component malposition, edge loading, wear debris, disruption of lubrication film increasing the coefficient of friction, micro-separation, and stripe wear.

Bibliography

 1. O’Keefe RJ, Jacobs JJ, Chu CR, Einhorn TA editors. Orthopaedic basic science.

4th ed. Rosemont: American Academy of Orthopaedic Surgeons; 2013.

2     Biomechanics: Free Body Analysis

Charles Lewis

Take-Home Message

•      Force – is a load that acts on a body.

•      JRF = force generated within a joint as a response to all forces acting on a joint.

•      Moment – the effect of a force at a perpendicular distance from an axis.

2.1     Basic Definitions

Newton’s Laws First Law (Inertia)

If there is no net force on an object, its velocity will remain constant. Second Law (Action)

Force = mass × acceleration

Third Law (Reaction)

For every action, there is an equal and opposite reaction.

(This is important for the understanding of free body analysis.)

Force A push or pull on an object.

1 Newton = force required to give 1 kg mass an acceleration of 1 m/s².

Moment The tendency of a force to rotate a body around an axis

Moment = force × distance (perpendicular)

Torque Is the magnitude of a moment

Work When force acts upon an object to create displacement

Work = force × distance

Energy Ability of an object to perform work. Kinetic energy = ½ mv²

Potential energy = mass × gravity × height

Vector A quantity having direction as well as magnitude, especially as determining the position of one point in space relative to another.

2.2     Hip Biomechanics and Free Body Analysis

Static Analysis A method of determining forces and moments that act on a body by isolating that body part and ensuring it is in static equilibrium.

Forces and moments are vectors; they must = zero in all three perpendicular directions.

Free body analysis makes certain assumptions:

•    Weight of the leg is 1/6 of total body weight See Fig. 2below:

W = gravitational force

M= abductor muscle force R = joint reaction force

Fig. 2Free body diagram for the human hip

To calculate JRF (R)

Sum of all moments = 0

                                                         (A´My)+(B´W)=0

Assume A = 5 cm and B = 12.5 cm

My = 2.5W

Calculating Ry

Ry=My+W

Ry = 2.5W W+

Ry +3.5W

Calculate R

                                                         R= Ry(cosine30°)

                                                                    R=-4W

2.3     Strategies to Reduce JRF

Reduce Body weight

Decrease lever arm

Medialize axis or rotation

Trendelenburg gait

Help Abductors

Provide cane in opposite hand (reduces abductor muscle pull and decreases moment arm)

Carrying load in ipsilateral hand

Increase abductor lever arm by increasing offset/osteotomy/varus angulation of stem.

Bibliography

1.    Nordin M, Frankel VH, editors. Basic biomechanics of the musculoskeletal system. 2nd ed. Philadelphia: Lea and Febriger; 1989.

2.    Ramachandran M. Basic orthopaedic sciences – the Stanmore guide. 1st ed.

London, UK: Edward Arnold Publishers Ltd; 2007.

3     Gait Cycle

Ferris M. Pfeiffer and Trent M. Guess

Definitions

Stance phase: period of gait when the foot is on the ground, 60 % of gait cycle

Heel strike: start of the gait cycle, body’s center of mass at lowest position

Foot flat: plantar foot surfaces touch the ground, body weight shifted from contralateral leg

Midstance: swinging contralateral foot passes the stance foot, body’s center of mass at highest position

Heel-off: heel loses contact with ground, toes begin pushing off

Toe-off: toe loses contact with ground, ends the stance phase

Swing phase: period of gait when foot is not in contact with the ground, 40 % of gait cycle

Acceleration: leg is accelerating forward

Midswing: swing foot passes directly below the body

Deceleration: muscles slow limb in preparation for heel strike

Stride length: distance travelled in one gait cycle (heel strike to heel strike)

Double support: period when both feet are in contact with the ground

Single limb stance: period when only one foot is in contact with the ground Etiology

Abnormal gait

Insufficiencies in nervous system – motor control, proprioception

Insufficiencies in musculoskeletal system – muscle, tendon, ligament, bone

Pathophysiology

Neuromuscular diseases affecting gait can arise from pathologies which affect the nerves, nervous junctions, and/or muscles. The effect of such pathologies on gait is often defined by the location of the pathology. Disorders such as cerebral palsy, traumatic brain injury, stroke, Parkinson’s disease, and multiple sclerosis primarily affect upper motor neuron function. Injuries/insufficiencies in the spinal nerves more often affect lower motor neuron function.

Musculoskeletal diseases such as muscular dystrophy, rheumatoid and osteoarthritis, tendon/ligament insufficiencies, and degenerative disc disease affect the ability of muscles and joints to stabilize and move the body in a controlled normal gait. This can be due to biomechanical limitations such as insufficient muscle force development (as is seen in muscular dystrophy) and excessive joint laxity (as is seen in ACL rupture).

Gait analysis: often performed with motion capture, force plates, and electromyography (EMG) sensors

Kinematic measures (motion) – joint rotations during movement (e.g., knee flexion/ extension angle)

Kinetic measures (forces) – joint moments (e.g., hip adduction moment)

EMG – measures timing and magnitude of muscle activations

Classification

Phenomenologically classified as [1]:

Hemiparetic: extension and circumduction of unilateral leg

Paraparetic: extension, stiffness, adduction, scissoring of bilateral legs

Sensory: unsteady gait with lack of visual input

Steppage: foot drop, excessive hip and/or knee flexion to clear ground

Cautious: careful, wide based, and slow

Freezing: difficulty initiating steps, feet “stuck to floor”

Propulsive or retropulsive: center of gravity in front of (pro) or behind (retro) feet

Ataxic: wide based, uncoordinated

Waddling: wide based with swaying, symmetric bilaterally

Dystonic: hyperflexed hips

Choreic: irregular, spontaneous flexion of knees with raising of legs Antalgic: limp

Vertiginous: unsteady with tendency to fall to one side Hysteric: nonphysiologic

Anatomically classified as [1]:

Frontal gait disorders, corticobasal gait disorders, pyramidal gait disorders, cerebellar gait disorders, and cortical-subcortical gait disorders

Treatment

Surgical or medical intervention to remove pathology when possible. Physical therapy to improve balance, muscle function, and joint range of motion.

Bibliography

1.    Jankovic J, Nutt JG, Sudarsky L. Classification, diagnosis, and etiology of gait disorders. Adv Neurol. 2001;87:119–33.

2.    Saunders JB, Inman VT, Eberhardt HD. The major determinants in normal and pathological gait. J Bone Joint Surg Am. 1953;35-A(3):543–58.

3.    Whittle M. Gait analysis: an introduction. 2nd ed. Oxford: ButterworthHeinemann; 1996.

 Statistics and Research & Diagnostic Imaging

 David  A.  Volgas and  Julia  R.  Crim

1     Statistics and Research

 David  A.  Volgas

1.1    Defi nitions

 Confounding Variable   

 a factor (such as educational level) not specifi cally assessed by a study, but which may infl uence outcome.

B ias  

i ntentional or unintentional errors in assigning patients to treatment groups (selection bias) or in evaluating exposures or outcomes. These errors make the likelihood of making a type I or type II error more likely and thus diminish the value of a study.

 Sensitivity   

 the probability that a test is positive when there is disease present (true positive/(true positive + false negative)).

 Specifi city  

 the probability that if a test is negative, then the disease will not be present (true negative/(true negative + false positive)).

 D. A.  Volgas ,  MD (*)

 Department of Orthopaedic Surgery,  University of Missouri,  Missour,  Columbia, USA  e-mail: volgasd@health.missouri.edu

 J. R.  Crim ,  MD

 Department of Radiology,  University of Missouri,  Missour,  Columbi, USA

© Springer-Verlag France 2015                                                                                              139

C. Mauffrey, D.J. Hak (eds.), Passport for the Orthopedic Boards and FRCS Examination, DOI 10.1007/978-2-8178-0475-0_7

 Relative Risk  

 the probability that a patient who has a risk factor also has a disease or condition, compared to the probability that a patient who has the disease does not have the risk factor.  Given the following:

                                               RR ⁼(a a b/( + ))/(x x y/( + ))                                               

 Odds Ratio  

 if a patient has a disease or condition, what is the probability of having a given risk factor? (more commonly used in orthopedic literature than relative risk)

                  OR =(a x/ ) (/ b y/ )oray bx/                                             

 Type I Error  

 an error in which the null hypothesis is true, but the statistics rejects this. Also known as “α” or false-positive rate. For example, a spam fi lter fl ags an email as spam, but in fact it is not.

N ot to be confused with the signifi cance level of a test, which is set by the researcher at a predetermined level (.05) and refl ects the threshold at which he/she is willing to accept the likelihood of a type I error.

 Type II Error  

c onversely, an error in which the null hypothesis is false, but the test statistics accepts it as true. Also known as “β” or false negative. For example, when a spam fi lter fails to catch a spam email.

 P -Value  

 the probability of the difference between two means is due to chance assuming that the null hypothesis is true.

 Power  

t he ability of a study to correctly identify that the null hypothesis is false. Expressed as 1-β.

 Effect Size   magnitude of the difference between the experimental group and the control group. Related to the concept of clinical signifi cance in contrast to the statistical signifi cance of a test.

 Confi dence Interval   

 a range which is likely to include the mean of a population for which the mean is unknown.

 Incidence  

t he rate of having a given condition during a given time, e.g., the incidence of having a revision arthroplasty within 10 years from the index operation is 5 %.

 Prevalence  

a  “snapshot” at a given point in time of how many subjects have a given condition, e.g., the prevalence of people of Asian ethnicity in San Francisco in the 1990 census was 29.1 %.

1.2     Statistical Inference

 Statistical inference is the use of statistical tests to estimate the characteristics of the entire population based on the known characteristics of a limited sample.

 Parametric tests are those which assume a normal population distribution.  Nonparametric tests do not assume a normal population distribution.

 Continuous data is numerical data which includes non-integer values. This data may be analyzed using a Student’s  t -test (parametric) or Mann–Whitney test (nonparametric).

 Categorical data is data which has a limited set of values, e.g., male or female. This data may be analyzed using a chi-square test or, when there are less than fi ve observations in a category, a Fisher’s exact test. Proportions may also be analyzed with these methods.

 Multiple regression analysis is a generic term encompassing several statistical methods which attempt to quantify the contribution of each of several variables to the observed outcome.

1.3     Study Design

 Experimental studies are those in which two (or more) treatment or exposure groups are selected by the investigator, usually assigned in a random fashion. These studies are potentially the most powerful studies since they may eliminate selection bias.

However, many clinical studies are not amenable to randomization because of ethical considerations (amputation vs. limb salvage) or group size considerations (rare diseases).

 Observational studies are those in which the treatment or exposure is not selected by the researcher. This type of study may be very powerful if the researcher is careful to eliminate as many confounding variables and biases as possible prior to  beginning the study.

 Prospective Study   the outcome cannot occur until after the patient is enrolled.

 Retrospective Study   

t he outcome has already occurred before the study begins. Generally is considered more prone to bias than prospective studies.

 Cohort Study  

 a given outcome is correlated with a given treatment or exposure. A cohort study can be prospective or retrospective.

 Case–Control Study  

a  retrospective study which has two groups, cases (subjects which received a given treatment) and controls (subjects which did not). These groups are compared for the presence or absence of risk factors.

 Cross-sectional  

a  retrospective study which reports the prevalence of a condition. May be useful to determine if a condition warrants further study.

 Case Series  

 a retrospective report of a group of patients who had the same treatment or exposure.

 Meta-analysis  

 a study which combines similar outcomes from multiple studies. Meta-analyses often defi ne study inclusion criteria very narrowly and exclude a large percentage of studies.

1.4     Levels of Evidence

L evels of evidence vary in precise defi nition from journal to journal, but the general characteristics of each level are listed below:

•      High-quality randomized, prospective studies or high-quality meta-analyses with consistent results

•      Lesser-quality randomized studies, high-quality prospective observational study, meta-analyses based on primarily level II studies

•      Case–control study, retrospective cohort study

•      Case series

•      Expert opinion

 Readers should be aware that levels of evidence do not necessarily take into consideration effect size, generalizability, assessment of bias, or handling of missing data.

1.5     Outcome Measures

 Test Validity   the degree to which a test measures what it purports to measure.

 Construct Validity  

t he degree to which test questions measure the outcome of interest completely but exclusively, a test which is designed to measure reading comprehension but is written in a foreign language would have poor construct validity.

 Content Validity  

t he degree to which all aspects of the quality being measured are included, e.g., a scale measuring foot and ankle function should account for all aspects of function of the foot or ankle such as range of motion, pain, stability, etc.

 Criterion-Based Validity  

 measures the degree to which a test agrees with other external measures of the same outcome.

2     Diagnostic Imaging

 Julia  R.  Crim 

 Take-Home Message

•      C T scan has advantages over MRI in rapidity of exam and visualization of fractures and their complications.

•      T riple-phase technetium MDP bone scan is often viewed as a test specifi c for osteomyelitis, but yields positive results in cases of trauma, infl ammatory, or crystal arthritis.

•      M RI offers the most complete evaluation of soft-tissue and bony abnormalities.

•      Ultrasound is increasingly used for targeted evaluation of the musculoskel-etal system.

 Fig. 1Sagittal reformatted CT of distal radius hardware malposition. Hardware obscured the fracture line on routine radiographs (not shown). Sagittal reformatted CT scan shows the volar fi xation plate and screws. One fi xation screw ( black arrow ) is intraarticular, and there is separation of the fracture fragments. Three months after fi xation, there is no central callus, although a small amount of peripheral callus is visible. Hardware was subsequently revised.  White arrow shows artifact adjacent to the fi xation plate. In most cases, artifact does not compromise CT diagnosis of fracture evaluation

 CT (Computed Tomography) Scan  

 Current CT scanners obtain high-resolution images at submillimeter slices which can be reformatted in any plane. CT scan offers rapid evaluation of the trauma patient and has largely replaced trauma radiography of the cervical spine. CT scan can be performed with metallic hardware in place, although there is some degradation of image quality. CT scan is the modality of choice for evaluation of potential nonunion when radiographs and symptoms are inconclusive (Fig.  1 ). It is also useful to evaluate tumor matrix. It can be used to evaluate bone and soft-tissue infection, but is less sensitive than MRI. CT is used for guidance of biopsies and aspirations when fl uoroscopy and ultrasound are not suffi cient.

 Coronal and sagittal reformatted images are standard in orthopedic imaging. Trauma imaging should never be considered complete unless reformatted images are obtained, since malalignment and fractures in the axial plane may be missed on axial images. 3D reformatted images are a useful adjunct in explicated complex fractures, especially in the pelvis.

 Iodinated contrast agents are used with CT scan to assess vascularity of abnormalities. The contrast agent collects in areas of increased vascularity, a process known as tissue enhancement. Enhancement is seen in all vascularized tissues and is a very nonspecifi c process. Absence of enhancement can be used as a sign of necrosis. Contrast agents are not used in the setting of renal failure unless hemodialysis is planned.

T he lifetime increased risk of cancer due to diagnostic imaging is widely debated. If there is a slight risk associated with low-dose radiation, it is a long-term increased risk of sarcoma, with a prolonged latency. Therefore, it is recommended that CT scans be limited in children and young adults when other imaging methods (primarily MRI and ultrasound) can be used instead.

 Nuclear Medicine Scans  

A  variety of radionuclides are used to evaluate abnormalities of the musculoskeletal system. The most common is technetium 99 m-MDP, an agent which is injected intravenously and deposited in the soft tissues based on blood fl ow and osteoblastic activity. The triple-phase bone scan consists of an arterial phase obtained with multiple short images over the area of concern, a blood-p ool phase several minutes after injection, and a delayed phase 4–6 h when the concentration of radionuclide is dependent primarily on osteoblastic activity. Although the triple-phase bone scan is often considered to be specifi c for osteomyelitis, it is also positive in infl ammatory arthritis, gout and pseudogout, trauma, and neuropathic arthropathy. In the past, bone scans have been used to diagnose radiographically occult fractures in osteopenic patients. However, they have about a 10 % false-negative rate in the fi rst 24 h after a fracture occurs and have been superseded by MRI for occult fracture. The primary use of bone scans currently is in the evaluation of metastatic disease (Fig.  2). Ninety percent of metastases and 50 % of myeloma lesions are positive on bone scans.

G allium-67 scans and indium-111 scans are both performed for infection. Gallium scans can be false positive in noninfected nonunions. Indium scans may be false negative in chronic infections. Both are still used when MRI is not feasible because of metallic implants (Fig.  3 ).  

 Positron emission tomography (PET) scan is currently used primarily for tumor evaluation. Positron-labeled fl uorodeoxyglucose (FDG) is injected intravenously and distributes in the body according to metabolic activity. Due to poor spatial resolution, PET scanning is almost always performed in conjunction with CT or MRI scan. It is important to know that not all sarcomas are FDG-avid. Infl ammatory and infectious processes may also be PET-avid.

 Magnetic Resonance Imaging (MRI)  

M RI is the modality of choice for evaluation of internal derangements of joints, infection, and bone marrow abnormalities. It is more sensitive and specifi c than radionuclide scanning for diagnosis of stress fracture or occult fracture. Although metal causes MRI artifacts due to distortion of the magnetic fi eld, diagnostic imaging quality can often be obtained adjacent to prostheses (Fig.  4 ).

 MRI exploits the polarity of the hydrogen ion. In the normal resting state, hydrogen ions are randomly oriented. When the patient is placed in a strong magnetic fi eld (0.3–3.0 tesla (T)), the hydrogen ions (protons) tend to align with the fi eld. In MRI, various magnetic pulses are applied after the patient is placed in the static magnetic fi eld. The magnetic signals emitted by protons are measured as the protons return to their resting state. The magnetic signal depends on the type of pulse applied, the number of free protons, and the characteristics of different tissue types. The pulses are described in terms of echo time (TE), repetition time (TR), inversion time (TI), and fl ip angle (FA). Many different types of MRI sequences are used. The most common sequences are fast spin echo (FSE). A T1-weighted FSE image (at 1.5 T,

 Fig. 2Technetium bone scan in patient with metastatic prostate carcinoma. Multiple areas of increased radionuclide uptake are seen and are characteristic of metastases. The radionuclide is excreted by the kidneys, and activity in the kidneys and bladder is normal

TE < 20, TR < 600) shows fat and blood as white (high signal intensity). Cortical bone, tendons, calcifi cations, fl uid, and fi brous tissue are black (low signal intensity). Muscle and many internal organs are gray (intermediate signal intensity.) Fluidsensitive sequences show fl uid as high signal intensity. They include T2-weighted (TE > 60, TR > 2,500), proton density (TE 20–60, TR > 1,500), STIR (TE 30–45, TE 3,000–4,000, TI 110–150), and T2*gradient echo (variable parameters). Fat will also be

 Fig. 3Indium scan in patient with several years’ history of aching hip pain after fracture. Extensive hardware precluded MRI. CT scan showed healed fracture and bone sclerosis. Indium scan showed increased radionuclide activity centered on the ischium. Surgery confi rmed osteomyelitis

     Fig. 4  T1-weighted coronal image shows metal artifact ( white arrows ) and focus of metallosis ( black arrow ). Metal artifact on MRI is larger than the metallic implant

high signal intensity, unless a fat suppression (also known as fat saturation or FS) technique is used. Fat suppression is important in musculoskeletal MRI because most abnormal fl uid occurs in areas where fat is present. If fat suppression is not

 Fig. 5Sagittal STIR image through the foot shows an elongated, nonanatomic region of high signal intensity ( arrows ). Gadolinium contrast (Fig.  6 ) is useful to distinguish phlegmon from abscess

     Fig. 6  Sagittal Gd-enhanced image through the foot in the same patient as Fig.  5

shows large deep abscess

( arrows )

used, abnormalities are often masked by adjacent fat. Proton density sequences are intermediate between T1 and T2. STIR sequences use an inversion recovery (IR) pulse to suppress signal intensity from fat; fl uid is high signal intensity on these sequences, and fat signal is more uniformly suppressed than on T2-weighted images with fat suppression (Fig.  5) . Almost every disease process is characterized by increased tissue fl uid. On MRI, the morphology and distribution of the fl uid are analyzed together with anatomic features in order to reach a diagnosis.  

 Gadolinium is a rare earth which in chelated compounds is used to assess vascularity of tissues. Any process with increased vascularity will show increased signal intensity on T1-weighted images (“enhancement”) following gadolinium administration. Abscesses and necrotic tumors show an enhancing rim around a central, nonenhancing rim (Fig.  6 ). Gadolinium is contraindicated in patients with poor renal function, as it can cause nephrogenic systemic fi brosis (NSF).  

 Ultrasound  

 Ultrasound is increasingly used in orthopedic imaging for evaluation of tendon and ligament injuries, as well as the initial evaluation of soft-tissue masses, and to guide aspiration and biopsy. It has considerable advantages over MRI in terms of cost and is accurate in experienced hands. Tissues are characterized on ultrasound based on their echogenicity. Simple fl uid contains no echoes (anechoic, Fig.  7) , while complex fl uid contains low-level echoes. Tendons have a uniform, fi ne echotexture, while muscle has a looser architecture. A tendon tear on ultrasound shows both altered echogenicity and altered anatomy.

 Fig. 7Ultrasound can be used for both diagnosis and treatment. Image shows a painful cyst which has been punctured by a needle ( arrow ) for aspiration and steroid injection

 Bone Densitometry  

T here are 2 methods of bone density measurement in common use today. Dual energy X-ray absorptiometry (DEXA) is more popular because of signifi cantly lower cost. However, bone density as measured by DEXA can be artifi cially elevated in the presence of degenerative disc disease or chronic fractures.

 Electrodiagnostic Studies  

N erve conduction studies are useful to assess the level and severity of nerve impingement. They are widely used to evaluate radiculopathies and nerve compression syndromes such as carpal tunnel syndrome. A transcutaneous electrode creates an action potential in the nerve, and velocity and signal amplitude is measured and compared to other nerves in the same region. Nerve velocity is measured as distance traveled/latency of pulse. Decreased nerve velocity and signal amplitude are a sign of nerve dysfunction, and the level of nerve injury can be fairly accurately determined. However, the sensitivity and specifi city of nerve conduction studies for nerve compression compared to clinical exam is debated.

E lectromyography utilizes an intramuscular electrode to evaluate electrical impulses at rest and during muscle contraction. It can determine acuity of neurogenic dysfunction and also distinguish between neurogenic and myopathic disease.