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What are the mechanisms of wear

third body


What are the 5 forms of lubrication

  • elastohydrodynamic
    • main mechanism during dynamic joint function
    • elastic deformation of articular surfaces
    • thin films of lubricant separate the surfaces 
  • boundary (slippery surfaces)
    • bearing surface is non-deformable
    • lubricant only partially separates surfaces
    • superficial zone proteins have a role in this lubrication mechanism
  • boosted (fluid entrapment)
    • concentration of lubricating fluid in pools 
    • trapped by regions of bearing surfaces that are making contact
  • hydrodynamic
    • fluid separates surfaces when one surface is sliding on the other
  • weeping 
    • fluid shifts out of articular cartilage in response to load
    • surfaces separated by hydrostatic pressure


What changes occur in aging cartilage

  • increases in
    • chondrocytes size
    • protein content
    • stiffness (passive glycation leads to increased stiffness of collagen) 
    • increase in ratio of proteoglycan keratin sulfate to chondroitin sulfate
  • decrease in
    • absolute number of cells (becomes hypocellular, despite the fact that individual chondrocytes are increasing in size)
    • water content (differentiates from osteoarthritis where water content actually increases)
    • solubility
    • proteoglycan size
    • elasticity


What are the 5 forms of articular cartilage

hyaline or articular cartilage
fibroelastic cartilage (meniscus)
fibrocartilage (at tendon and ligament insertion into bone)
elastic cartilage (trachea)
physeal cartilage (growth plate)


What is the function of cartilage

  • decreases friction
  • distributes loads
  • cartilage exhibits stress-shielding of the solid matrix components
    • high water content
    • incompressibility of water
    • structural organization of the proteoglycan and collagen molecules


What are the extracellular components of cartilage

  • water
    • makes up 65% to 80% of mass of the cartilage 
    • accounts for 80% of the weight near the surface 
    • 65% at the deep zone
  • collagen
    • makes up 10 to 20% of total cartilage mass
    • type II collagen accounting for 90% to 95% of the total collagen content. 
    • functions to provide cartilagenous framework and tensile strenth
    • small amounts of types V, VI, IX, X, and XI collagen are also present
  • proteoglycans 
    • makes up 10 to 15% of cartilage 
    • functions to provide compressive strength and attract water   
    • produced by chondrocytes
    • composed of GAG subunits 
      • chondroitin sulfate
      • keratin sulfate
  • noncollagenous protein


What are the zones of articular cartilage

  • Superficial zone (tangential zone) 
    • Type II collagen orientation is parallel to joint 
    • Has flattened chondrocytes, condensed collagen fibers, and sparse proteoglycans
    • only zone where articular cartilage progenitor cells have been found 
  • Intermediate zone
    • Type II collagen has an oblique or random organization
    • Is the thickest layer with round chondrocytes, and abundant proteoglycan content
  • Deep layer (basal layer) 
    • Type II collagen is perpendicular to joint and crosses tidemark;  has the highest concentration of proteoglycans
    • Round chondrocytes arranged in columns                     
  • Tidemark
    • Is deep to the basal layer and separates the true articular cartilage from the deeper cartilage that is a remnant of the cartilage anlage, which participated in endochondral ossification during longitudinal growth in childhood.
    • The tidemark divides
      • the superficial uncalcified cartilage from the deeper calcified cartilage
      • division between nutritional sources for the chondrocytes  
    •  The tidemark is found only in joints 
    •  Most prominently in the adult and nongrowing joint
  • Subchondral Bone  


What nurishes cartilage

surface - synovial fluid

subchondral bone at base


What are the 8 components of SF-36

physical functioning
bodily pain
general health perceptions
physical role functioning
emotional role functioning
social role functioning
mental health

36 questions; SF17 is a more condested version


What are the 4 components of the HHS

  • pain
    • no pain given 44 points
  • function
    • no limp, walks without aid, and can walk more than six blocks given 33 points
  • function activities
    • no disabilities given 14 points
  • physical exam  
    • based on range of motion with max score of 9

out of 100


What are the components of the WOMAC score




total score

30 questions on a likert scale; scored out of 100


Compare observational and experimental designs for research studies

  • observational 
    • researchers observe patient groups without allocation of intervention
    • may be either prospective or retrospective
    • may be descriptive or analytic 
      • descriptive 
        • useful for obtaining background information for more advance studies
        • examples 
          • case reports
          • case series
          • cross-sectional studies
      • analytic 
        • explores the association between a given outcome and a potentially related variable
        • examples 
          • case-control
          • cohort
          • meta-analysis
  • experimental 
    • researchers allocate treatment
    • allows the evaluation of efficacies of therapeutic interventions
    • examples 
      • double-blinded, prospective, randomized clinical trial is the gold standard for evidence based medicine


What are the key aspects of a randomized control trial

  • Definition
    • a study in which patients are randomly assigned to the treatment or control group and are followed prospectively 
    • provides the most compelling evidence that the study treatment causes the expected effect on human health 
    • randomization minimizes study bias 
  • Crossover design
    • administration of two or more therapies, one after the other, in a random order
    • susceptible to bias if washout period is inadequate   
    • single blinded study vs. double blinded study 
      • double = participant and administrator
  • Analysis 
    • intent-to-treat analysis
      • outcomes based on the group into which they were randomized, regardless of whether the patient actually received the planned intervention
      • minimizes non-responder bias
    • per protocol 
      • excludes patients who were not compliant with the protocol guidelines 


What are the key aspects of a cohort study

  • Definition
    • a study in which patient groups are separated non-randomly by exposure or treatment, with exposure occurring after (prospective), or before (retrospective), the initiation of the study
  • Evidence
    • Level II or III evidence
  • Analysis
    • results usually reported as relative-risk
  • Example
    • you want to determine if smoking is a risk factor for the development of lung cancer.  You identify a group of smokers and a group of non-smokers, and follow them over time measuring the desired outcome, in this case, lung cancer.


What are the key aspects of a case control study

  • Definition
    • a study in which patient groups are separated by the current presence (cases) or absence (controls) of disease and examined for the prior exposure of interest
  • Evidence
    • Most are Level III evidence
  • Analysis
    • usually reported as odds-ratio
  • Example
    • you want to determine if smoking is a risk factor for the development of lung cancer.  You compare the smoking history of individuals with lung cancer (cases) and those without (controls).


What is a cross-sectional study

  • Definition 
    • study group is analyzed at a given time ("snapshot") with no follow-up
  • Example 
    • you want to determine the prevalence of baseball injuries during the 2003 little-league season

Example of an observational study


What are the levels of evidence

  • Level 1
    • Randomized controlled trial (RCT) 
    • Meta-analysis of randomized trials with homogeneous results 
  • Level 2   
    • Prospective comparative study (therapeutic) 
    • Meta-analysis of Level 2 studies or Level 1 studies with inconsistent results 
  • Level 3
    • Retrospective cohort study
    • Case-control study 
    • Meta-analysis of Level 3 studies 
  • Level 4
    • Case series
  • Level 5
    • Case report (a report of a single case) 
    • Expert opinion
    • Personal observation


What are some of the most common surgical medical errors

  • Communication errors are the leading cause of wrong-side surgeries, medication errors, diagnostic delays or loss to follow-up     
  • Wrong site surgery
    • involve the patient in identifying correct side 
    • response when performed
      • address by immediate discussions with family revealing errors 
      • apologize and accept responsibility, but not blame   
  • Surgical "time-out" should include the following according to JCAHO     
    • identify correct side, site, and patient
    • verify the correct procedure
    • surgeon is most effective OR team member at reducing complications when using surgical checklist and "time-out"
  • Medication prescribing errors
    • reduced when physicians use computerized order entry 
  • errors in medical documentation
    • It is illegal to alter the medical record for any reason 
    • no one has the authority to authorize a physician to alter the medical record
    • errors can be noted and addendums can be added


What is the definition of medical negligence

  • Negligence is the failure to provide the standard of health care resulting in medical injuries
  • A second-opinion physician has an ethical obligation, but not legal obligation, to disclose if the standard of care has been breached by a treating physician. 
  • A successful patient-plaintiff lawsuit for medical negligence against a physician requires that the following FOUR elements be alleged and proven in a court of law 
    • duty
      • the duty of the physician is to provide care equal to the same standard of care ordinarily executed by surgeons in the same medical specialty.
    • breach of duty
      • breach of duty occurs when action or failure to act deviates from the standard of care.
    • causation
      • causation is present when it is demonstrated that failure to meet the standard of care was the direct cause of the patient’s injuries.
    • damages
      • damages are monies awarded as compensation for injuries sustained as the result of medical negligence


Definition of workers compenstation

  • A workmans' compensation patient is determined to reach maximum medical improvement when further restoration of function is no longer anticipated and can then settle his/her claim.   
  • Ability for worker's compensation patients to choose their own physician varies by the statutes of each state. 
  • Legal definitions
    • impairment
      • loss of function resulting from an anatomic or physiologic derangement. 
    • disability
      • limitation of an individual’s capacity to meet certain personal social or occupational demands.


What are factors that contribute to radiation exposure from flouro in the OR

  • Factors which increase radiation exposure levels during use of fluoroscopy   
    • imaging large body parts
    • positioning extremity closer to the x-ray source 
    • use of large c-arm rather than mini c-arm 
    • radiation exposure is minimal during routine use of mini-c-arm fluoroscopy unless the surgical team is in the direct path of the radiation beam 
  • Factors to decrease radiation exposure to patient and surgeon 
    • maximizing the distance between the surgeon and the radiation beam
    • minimizing exposure time
    • manipulating the x-ray beam with collimation (coning)
    • orienting the fluoroscopic beam in an inverted position relative to the patient 
    • strategic positioning of the surgeon within the operative field to avoid direct path of beam
    • use of protective shielding during imaging


What are the risk of HIV and hepatitis transmission in orthopedics

  • Risk of HIV transmission
    • needlestick  
      • seroconversion from a contaminated needlestick is ~ 0.3% 
        • exposure to large quantities of blood increases risk
      • seroconversion from exposure to HIV contaminated mucous membranes is ~0.09%
    • frozen bone allograft 
      • risk of transmission is <1 per million
      • donor screening is the most important factor in prevention
      • no reported cases of transmission from frozen bone allograft since 2001
    • blood transfusion
      • risk of transmission from blood transfusion is 1/500,000 per unit transfused
      • seronegative blood may still transmit virus due to delay between HIV infection and antibody development
  • Risk of Hepatitis B transmission
    • needlestick
      • 37% to 62% eventually seroconvert following needlestick
      • 22 to 31% develop clinical Hepatitis B infection following needlestick
  • Risk of Hepatitis C transmission
    • needlestick
      • 0.5 to 1.8% risk of transmission


What are the major and minor criteria for fat emboli syndrome

  • Major (1) 
    • hypoxemia (PaO2 < 60)
    • CNS depression (changes in mental status)
    • petechial rash
    • pulmonary edema
  • Minor (4) 
    • tachycardia
    • pyrexia
    • retinal emboli
    • fat in urine or sputum
    • thrombocytopenia
    • decreased HCT
  • Additional 
    • PCO2 > 55
    • pH < 7.3
    • RR > 35
    • dyspnea
    • anxiety


What is virchows triad DVT

venous stasis
hypercoagulable state
intimal injury


What is the pathophysiology of clot formation

  • stasis
  • fibrin formation 
    • thromboplastin (aka Tissue Factor (TF), platelet tissue factor, factor III, or CD142) is released during dissection which leads to activation of the extrinsic pathway and fibrin formation 
  • clot retraction
  • propagation


What are primary hypercoagulopathies

factor V Leiden mutation   
antithrombin III deficiency 
protein C deficiency
protein S deficiency
activated protein C resistance


What are secondary factors that contribute to DVT


  • malignancy 
    • recently been associated with up to 20% of all new diagnoses of VTE
  • elevated hormone conditions 
  • recombinant erythropoeitin 
  • hormone replacement
  • oral contraceptive therapy
  • late pregnancy
  • elevated antiphospholipid antibody conditions 
  • lupus anticoagulant
  • anticardiolipin antibody
  • history of thromboembolism
  • obesity
  • aging
  • CHF
  • varicose veins
  • smoking
  • general anesthesics (vs. epidural and spinal)
  • immobilization
  • increased blood viscosity


What are aquired risk factors for DVT in athletes

  • Hemoconcentration
    • dehydration, trauma, immobilization, travel, blood hyperviscosity, OCPs
      • Recent travel >4 h have 4x risk of VTE; however, varying results of studies…
  • Marathon running + air travel >4h
    • acute hypercoagulable state exaggerated with increasing age >35
    • add in a thrombophilia and you have even higher risks
  • Hypoxia at high altitude
    • body increases RBC production
    • hyperviscocity – risk in climbers
  • Females on OCPs have 4x the risk
    • those with inherited thrombophilias and on the OCP have even higher risk (up to over 30 fold, they say..)


What are the increased risk for DVT with various thrombophilic diseases

  • Factor V Leiden mutation
    • Heterozygous 7×
    • Homozygous 80×
  • Prothrombin G20210A mutation 2.8×
  • Antithrombin III deficiency 5–20×
  • Protein C deficiency 2–10×
  • Protein S deficiency 2–10×
  • Hyperhomocysteinemia 2.5×
  • Elevated factor VIII 5×
  • Elevated factor XI 2.2× 


What are prevention strategies for DVT in athletes

  • screening
    • prior to race
    • family history
    • previous VTE
    • medications (OCP)
  • Prevention
    • LMWH for high risk situation
    • hydration
    • early mobilization after surgery
    • avoidace of high risk situations


What is the wells criteria to predict PE

  • Clinical signs and symptoms of DVT (3)
    • (ie, minimum leg swelling, pain on palpation of deep veins)
  • An alternative diagnosis is less likely than PE (3)
  • Heart rate >100 BPM (1.5)
  • Immobilization or surgery in previous 4 weeks (1.5)
  • Previous DVT/PE (1.5)
  • Hemoptysis (1)
  • Malignancy (1)
    • (on treatment, treated in last 6 months, or palliative) 


Ca requirements per population

children - 600

adolescents - 1300

adults - 750

pregnant women - 1500

Lactating women - 2000


Contraindications to bisphosphanates

  • severe renal disease 
    • primary mode of excretion is renal
  • following lumbar fusion 
    • decreased spinal fusion rates in lab animal models (increased fusion mass size, but decreases the actual fusion rate)


side effects of bisphosphonates

Jaw osteonecrosis   
Atypical subtrochanteric and femoral stress fractures     
Radiographic changes consistent with osteopetrosis


What are considerations for antibiotics prior to dental procedures in patients who have undergone TJA

  • TJA patients at increased risk of hematogenous seeding should be given prophylactic antibiotics prior to dental procedures. This includes
    • all patients for the first two years after TJA
    • immunocompromised patients
    • drug induced immunosuppression
    • radiation induced immunosuppression
    • inflammatory arthropathies including SLE and RA
    • comorbidities including
      • previous prosthetic joint infection
      • Type I (insulin-dependent) diabetes
      • malnourishment
      • hemophilia
      • HIV
      • malignancy
  • AAOS and ADA recognizes there is limited or inconclusive evidence to support the recommendations above and practitioners should use clinical judgment


Load, stress, strain

  • Load
    • a force that acts on a body
  • Stress
    • intensity of an internal force
    • calculation - force / area
    • Pascal's (Pa) or N/m2
  • Strain
    • relative measure of the deformation of an object
    • change in length / original length


toughness, creep, load relaxation

  • toughness
    • amount of energy per volume a material can absorb before failure (fracture)
    • area under the stress/strain curve 
    • joules per meter cubed, J/m3
  • creep 
    • increased load deformation with time under constant load
  • load relaxation 
    • decrease in applied stress under conditions of constant strain


hysteresis, finite element analysis

  • hysteresis (energy dissipation)
    • characteristic of viseoelastic materials where the loading curve does not follow the unloading curve
    • the difference between the two curves is the energy that is dissipated 
  • finite element analysis 
    • breaking up a complex shape into triangular or quadrilateral forms and balancing the forces and moments of each form to match it with its neighbor


Important concepts of a stress-strain curve

  • Elastic zone
    • the zone where a material will return to its original shape for a given amount of stress
    • "toe region" 
      • applies to a ligaments stress/strain curve
      • represents straightening of the crimped ligament fibrils 
  • Yield point
    • the transition point between elastic and plastic deformation 
  • Yield strength 
    • the amount of stress necessary to produce a specific amount of permanent deformation 
  • Plastic zone
    • the zone where a material will not return to its orginal shape for a given amount of stress
  • Breaking point
    • the object fails and breaks
  • Ultimate (Tensile) strength
    • defined as the load to failure
  • Hooke's law
    • when a material is loaded in the elastic zone, the stress is proportional to the strain
  • Young's modulus of elasticity 
    • measure of the stiffness (ability to resist deformation) of a material in the elastic zone
    • calculated by measuring the slope of the stress/strain curve in the elastic zone
    • a higher modulus of elasticity indicates a stiffer material


Young's modulus of materials


Ceramic (Al2O3)
Alloy (Co-Cr-Mo)
Stainless steel
Cortical bone
Matrix polymers
Cancellous bone
Tendon / ligament


Brittle, ductile, viscoelastic

  • Brittle material 
    • a material that exhibits linear stress stain relationship up until the point of failure
    • undergoes elastic deformation only, and little to no plastic deformation
    • ie; PMMA
  • Ductile Material 
    • undergoes large amount of plastic deformation before failure
    • ie; metal
  • Viscoelastic material
    • a material that exhibits a stress-strain relationship that is dependent on the load and the rate by which the load is applied
    • a function of the internal friction of a material 
    • ie; ligaments, bone


isotropic vs anisotropic

  • Isotropic materials
    • possess the same mechanical properties in all directions 
  • Anisotropic materials
    • possess different mechanical properties depending on the direction of the applied load
    • ie; ligaments, bone


What are the three types of corrosion

  • galvanic corrosion 
    • dissimilar metals leads to electrochemical destruction   
    • mixing metals 316L stainless steel and cobalt chromium (Co-Cr) has highest risk of galvanic corrosion 
    • can be reduced by using similar metal
  • crevice corrosion 
    • occurs in fatigue cracks due to differences in oxygen tension
    • 316L stainless steel most prone to crevice corrosion 
  • fretting corrosion 
    • occurs at contact sites between two materials that are subject to micromotion
    • common at the head-neck junction in hip arthroplasty 


Fatigue failure, endurance limit

  • Fatigue failure
    • failure at a point below the ultimate tensile strength secondary to repetitive loading     
    • depends on magnitude of stress and number of cycles
  • Endurance limit
    • defined as the maximal stress under which an object is immune to fatigue failure regardless of the number of cycles


Mechanical properties of ligaments and tendons

  • Characteristics 
    • viscoelastic with nonlinear elasticity 
    • displays hysteresis (see definition above)
  • Advantages 
    • strong in tension (can withstand 5-10% as opposed to 1-4% in bone)
  • Disadvantages 
    • demonstrate creep and stress relaxation


What is the working length of a plate


  • defined as the length from the fracture to the closest screw on either side of the fracture
  • decreasing the working distance increases the stiffness of the fixation construct


Advantages and indications for locking plates

  • advantages of locking plates 
    • locked plate/screw constructs compared to non-locked plate/screw constructs result in less angulation in comminuted metaphyseal fractures 
  • indications for locking plate technology     
    • indirect fracture reduction
    • diaphyseal/metaphyseal fractures in osteoporotic bone
    • bridging severely comminuted fractures
    • plating of fractures where anatomical constraints prevent plating on the tension side of the bone (e.g. short segment fixation).


How to increase stability of a locking plate construct

bicortical locking screws
increased number of screws
screw divergence from screw hole < 5 degrees
longer plate

a unicortical locking screw has less pullout strength than a bicortical non-locking screw


How to increase stability of external fixation

contact of ends of fracture 
larger diameter pins (most important) 
additional pins
decreased bone to rod distance
pins in different planes
increasing size or stacking rods
rods in different planes
increased spacing between pins


Indications and advantages to myoelectric prosthesis

  • indications
    • best candidate is a  patient with a transradial amputation 
    • best for sedentary work
    • can be used for overhead activities
  • advantages
    • better cosmesis
    • allows more proximal coverage
  • disadvantages
    • heavier and more expensive prosthesis
    • less sensory feedback
    • requires more maintenance


What are the advantages and disadvantages of a body-powered prosthesis

  • indications
    • best for heavy labor with less maintenance needed
  • techniques
    • activate terminal device with shoulder flexion and abduction
    • center the harness ring just off the midline of C7 towards the non-amputated side  
  • advantages 
    • moderate cost and weight
    • most durable prosthesis
    • higher sensory feedback
  • disadvatnages 
    • poorer cosmesis
    • requires more gross upper limb movement for proper function


Causes of hypercalcemia

  • malignancy - caused by parathyroid-related hormone protein (PTHrP)

    • characterized by: 
      • hypercalcemia, hypophosphatemia, low PTH
    • examples of malignancies:
    •  Paget's Disease
    •  Multiple Myeloma
    • Squamous cell cancer of the lung
    • ectopic production of PTH
    • Multiple endocrine neoplasia (type I and II)
    • Pituitary adenoma
  • medical conditions
    • primary hyperparathyroidism
    • sarcoidosis
    • Familial hypocalciuric hypercalcemia
    • hyperthyroidism
    • Addison's disease
    • Zollinger-Ellison syndrome
    • drugs
    • thiazide diuretics
    • dietary
    • calcium ingestion (milk-alkali syndrome)
    • hypervitaminosis D
    • hypervitaminosis A


Presentation and treatment of hypercalcemia

  • Presentation
    • CNS 
      • confusion
      • stupor
      • weakness
    • gastrointestinal 
      • constipation
      • anorexia
      • nausea
      • vomiting
    • kidney 
      • polyuria
      • kidney stones
      • polydipsia
  • Treatment
    • Hydration
      • saline diuresis
    • Drug therapies
      • loop diuretics
      • bisphosphonates
      • mithramycin
      • calcitonin
      • galium nitrate
    • Dialysis (severe)


Presentation of hypocalcemia

  • Symptom
    • symptoms of hypocalcemia
      • paresthesia 
      • fingertip, toes, perioral
      • abdominal pain, biliary colic
      • muscle cramps, tetany
      • dyspnea (laryngospasm, bronchospasm)
      • convulsions
      • mental status changes 
      • anxiety, fatigue, mood swings
  • Physical exam 
    • findings of tetany
      • Trousseau's Sign  
        • carpopedal spasm after blood pressure readings
        • inflate BP cuff 20mmHg above systolic BP x 3-5min
        • hand adopts a MCP flexed, DIP and PIP extended position
        • more sensitive than Chvostek's sign 
      • Chvostek's Sign 
        • facial muscle contractions after tapping on the facial nerve
    • dermatologic 
      • fungal nail infections
      • hair loss
      • blotchy skin
      • pigment loss, vitiligo
  • ECG - prolonged QT potential


What is the presentation of Hyperparathyroidism

  • Symptoms 
    • often asymptomatic
    • weakness
    • kidney stones ("stones")
    • bone pain ("bones")
    • constipations ("groans")
    • uncommon cause of secondary hypertension
  • Imaging
    • Brown's tumor


Complications of hyperparathyroidism

  • Peptic ulcer disease
    • ↑ gastrin production stimulated by ↑ Ca2+
  • Acute pancreatitis
    • ↑ lipase activity stimulated by ↑ Ca2+
  • CNS dysfunction
    • anxiety, confusion, coma
    • result of metastatic calcification of the brain
  • Osteoporsis
    • Bone loss occurs as result of bone resorption due to excess PTH


Compare primary, secondary and tertiary hyperparathyroidism

  • Primary 
    • typically the result of hypersecretion of PTH by a parathyroid adenoma/hyperplasia
    • may result in osteitis fibrosa cystica
      • breakdown of bone, predominently subperiosteal bone
      • commonly involves the jaw
  • Secondary 
    • secondary parathyroid hyperplasia as compensation from hypocalcemia or hyperphosphatemia
      • ↓ gut Ca2+ absorption
      • ↑ phosphorous
    • associated conditions 
      • chronic renal disease
        • renal disease causes hypovitaminosis D 
        • leads to ↓ Ca2+ absorption
      • renal osteodystrophy
  • Tertiary 
    • parathyroid glands become dysregulated after secondary hyperparathyroidism
    • secrete PTH regardless of Ca2+ level


Treatment of hyperparathyroidism

  • Acute hypercalcemia 
    • IV fluids
    • Loop diuretics
  • Symptomatic hypercalcemia is treated surgically 
    • treat with parathyroidectoy
      • complications include post-op hypocalcemia
      • manifests as numbness, tingling, and muscle cramps
      • should be treated with IV calcium gluconate 


Treatment of hypocalcemia

  • calcium gluconate infusion
    • with cardiac monitoring to prevent hypercalcemia
  • activated vitamin D (calcitriol)


What is the presentation and treatment of hypoparathyroidism

  • Usually iatrogenic
  • presents with hypocalcemia
  • treatment
    • Ca and Vit D supplements
    • follow closely


What is the pathophysiology of hypophosphatasia

  • Pathophysiology 
    • low levels of alkaline phosphate result in decreased synthesis of inorganic phosphate necessary for bone matrix formation
    • osteoid that forms in the hypertrophic zone of the growth plate fails to mineralize
    • the zone of provisional calcification never forms and growth is inhibited
  • Genetics 
    • inheritance pattern 
    • autosomal recessive 
    • caused by a mutation in the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP)


What is are the orthopedic associations and presentation of hypophosphatasia

  • Associated conditions
    • orthopaedic manifestations
      • similar to rickets
      • bow legs
      • short stature
    • non-orthopaedic manifestations 
      • abnormal tooth formation
      • loss of teeth
  • Clinical findings 
    • presentation similar to rickets 
    • genu varum
    • short stature
    • abnormal dentition
  • Radiographs 
    • abnormal bone formation 
    • "deossification of bone" adjacent to growth plate 
    • physeal widening


What it the treatment of hypophosphatasia

none known


Differential diagnosis for hypocalcemia

  • decreased PTH that can be caused by 
    • hypoparathyrodism 
    • renal osteodystrophy 
    • pseudohypoparathyroidism (this topic)
    • pseudopseuodohypoparathyroidism
  • decreased vitamin D3


What is the most common cause of hypoparathyroidism

thyroidectomy most common cause


What is the pathophysiology and conditions associated with renal osteodystrophy

  • Pathophysiology 
    • hypocalcemia
      • due to the inability of the damaged kidney to convert vitamin D3 to calcitrol (the active form)
      • because of phosphate retention (hyperphosphatemia)
    • hyperparathyroidism and secondary hyperphosphatemia
      • caused by hypocalcemia and lack of phosphate excretion by damaged kidney
    • uremia related phosphate retention 
      • is a key pathological step
  • Associated conditions
    • carpal tunnel syndrome 
    • tendinitis and tendon rupture
    • AVN
    • osteomalacia (adults) and growth retardation (children)
    • deposition of amyloid (β2 microglobulin)
    • pathologic fracture   
      • from brown tumors (hyperparathyroidism) or amyloid deposits
    • osteomyelitis and septic arthritis


What are the radiographic findings associated with renal osteodytrophy

  • Looser's zones   
  • brown tumor   
  • osteosclerosis         
    • from mineralization of osteomalacic bone 
    • rugger jersey spine   
  • widened growth plate and zone of provisional calcification (children)
  • varus deformity of the femurs (children) 
  • fracture   
  • soft-tissue calcification   
  • osteopenia


What is the pathology and conditions associated with rickets

  • A defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate
    • prior to closure of physis known as rickets
    • after physeal closure called osteomalacia
  • Pathophysiology
    • disruption of calcium/phosphate homeostasis
    • poor calcification of cartilage matrix of growing long bones
    • occurs at zone of provisional calcification
      • leads to increased physeal width and cortical thinning and bowing
      • Vitamin D and PTH  play an important role in calcium homeostasis 
  • Associated conditions 
    • brittle bones with physeal cupping/widening
    • bowing of long bones 
    • ligamentous laxity
    • flattening of skull
    • enlargement of costal cartilage (rachitic rosary) 
    • kyphosis (cat back) 


What is the differential for looser zones

  • Insufficient nutritional quantities or faulty metabolism of vitamin D or phosphorus
  • Renal tubular acidosis
  • Malnutrition during pregnancy
  • Malabsorption syndrome
  • Hypophosphatemia
  • Chronic renal failure
  • Tumor-induced osteomalacia


Differential for rickets

familial hypophosphatemic (vitamin D-resistant) (see below)
vitamin D-deficient (Nutritional)
vitamin D-dependent (type I & type II)
renal osteodystrophy 


What is the pathophysiology of familial hypophosphatemic rickets

  • Also known as 
    • Vitamin D resistant Rickets
    • X-linked hypophosphatemic
  • Most common form of heritable rickets  
    • caused by inability of renal tubules to absorb phosphate
    • GFR is normal
      • impaired vitamin D3 response
  • Genetics 
  • X-linked dominant
  • Presentation 
    • tibial bowing as result of widened proximal tibia physis 
  • Labs   
    • low serum phosphorous
    • elevated alkaline phosphatase 
    • serum calcium is usually normal or low normal
  • Treatment with Pi has shown poor results; at this point in time treatment is supportive


Risk factors for rickets


rare now that Vitamin D is added to milk
still seen in 

premature infants
patients with malabsorption syndromes (celiac sprue) or chronic parenteral nutrition
Asian immigrants
Patients with out of the ordinary dietary choices


What are the clinical findings and treatment of rickets

  • Clinical findings 
    • rachitic rosary (enlargement of costochondral junction)
    • bowing of knees
    • codfish vertebrae 
    • retarded bone growth (widened osteoid seams, physeal cupping) 
    • muscle hypotonia
    • dental disease
    • pathologic fractures
    • waddling gate
  • Laboratory values 
    • low to normal serum calcium
    • low serum phosphate
    • elevated alkaline phosphatase
    • elevated parathyroid hormone
    • low vitamin D
  • Treatment 
    • Vitamin D (5000 IU daily)


What is the cause of hereditary vitamen D dependant rickets

  • Rare disorder 
    • Clinical features similar to Vitamin D-Deficient Rickets but more severe
    • May have alopecia
  • Type I  
    • caused by defect in renal 25-(OH)-vitamin D1 alpha-hydroxylase 
    • defect prevents conversion of inactive form of vitamin D to active form
    • responsible gene on chromosome 12q14
  • Type II  
    • caused by a defect in intracellular receptor for 1,25-(OH)2-vitamin D
  • Genetics 
    • type I  
      • autosomal recessive
      • Laboratory values
        • type II is distinguished from type I by markedly elevated levels of 1,25-(OH)2-Vitamin D
  • Treatment
    • physiologic doses (1-2 micrograms/day) of 1,25-(OH)2-Vit D
      • type I 
    • daily high dose Vitamin D + elemental calcium
      • type II


Compare T-test, Chi Square, ANOVA and Linear Regression

  • Continuous data
    • potentially infinite possible values (ie. Height, HEAD SIZE)
  • Categorical data
    • variables are a given number of categories (ie. Gender, fracture classification)
  • T-test
    • used to compare TWO independent CONTINUOUS variables
  • Chi square
    • used to compare two or more CATEGORICAL variables
    • used to compare three or more CONTINUOUS Variables
  • Linear Regression
    • used to investigate whether a variable can be predicted by another single variable (simple linear regression) or by a combination of other variables (multiple linear regression)


What is the kaplan meier survivorship curve?

Total number failed

Total number still being followed


What are the institute of medicine clinical practice guidelines

  • The process for how the guideline is developed and funded is transparent.
  • Conflicts of interest should be declared, minimal to no conflicts should exist (chair and co-chair should have no conflicts of interest). 
  • The guideline should be composed of methods experts, clinicians, representatives of stakeholders, and affected populations. 
  • must meet the IOM’s methodologic standards.
  • Level of evidence should be rated, and have reasoning behind each recommendation.
  • describe the action recommended by the guideline and when it should be used
  • External review should include a full spectrum of stakeholders; reviewers should not be identified by name
  • guideline should be updated and include dates of the guideline, systematic review, and                                                             any planned update. 


What is the equation for power


an estimate of the probability a study will be able to detect a true effect of the intervention     


power = 1 - (probability of a type-II, or beta error)


What are type I and type II error

  • Type 1
    • null hypothesis is rejected even though it is true   
    • by definition, alpha-error rate is set to .05, meaning there is a 1/20 chanc a type-I error has occured
    • Bonferroni correction
      • post-hoc statistical correction made to P values when several dependent or independent statistical tests are being performed simultaneously on a single data set 
  • Type 2
    • a false negative difference that can occur by detecting no difference when there is a difference or accepting a null hypothesis when it is false and should be rejected   
    • power = 1 - (type-II error)
    • Clinical significance 
      • a study that fails to find a difference may be because 
        • there actually is no difference or
        • the study is not adequately powered


What is the criteria for causation

  • Analogy: The effect of similar factors may be considered.
  • Consistency: Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect.
  • Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations"
  • Experiment: "Occasionally it is possible to appeal to experimental evidence"
  • Strength: A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal
  • Specificity: Causation is likely if a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship
  • Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge)
  • Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay).
  • Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence


When does intramembranous healing occur

  • embryonic flat bone formation
    • skull, maxilla, mandible, pelvis, clavicle, subperiosteal surface of long bone
  • distraction osteogenesis bone formation
  • blastem bone (occurs in children with amputations)
  • fracture healing with rigid fixation (compression plate)
  • one component of healing with intramedullary nailing


Conditions associated with disruption of intramembranous healing

cleidocranial dysplasia  

caused by defect in intramembranous ossification 
caused by mutation in CBFA1 (also know as Runx2) located on chromosome 6


What are the zones of the growth plate

  • Reserve Zone   
    • Cells store lipids, glycogen, and proteoglycan aggregates for later growth and matrix production
    • Low oxygen tension
  • Proliferative Zone   
    • Proliferation of chondrocytes with longitudinal growth and stacking of chondrocytes
    • Highest rate of extracellular matrix production
    • Increased oxygen tension in surroundings inhibits calcification
  • Hypertrophic Zone   
    • Zone of chondrocyte maturation, chondrocyte hypertrophy, and chondrocyte calcification.
    • Three phases occur in the hypertrophic zone 
      • Maturation zone: preparation of matrix for calcification, chondrocyte growth
      • Degenerative zone: further preparation of matrix for calcification, further chondrocyte growth in size (5x)
      • Provisional calcification zone: chondrocyte death allows calcium release, allowing calcification of matrix
    • Chondrocyte maturation regulated by local growth factors (parathyroid related peptides, expession regulated by Indian hedgehog gene)
    • Type X collagen produced by hypertrophic chondrocytes important for mineralization    
  • Primary Spongiosa (metaphysis)   
    • Vascular invasion and resportion of transverse septa.
    • Osteoblasts align on cartilage bars produced by physeal expansion. 
    • Primary spongiosa mineralized to form woven bone and then remodels to become secondary spongiosa (below)
  • Secondary spongiosa (metaphysis)
    • Internal remodeling (removal of cartilage bars, replacement of fiber bone with lamellar bone) 
    • External remodeling (funnelization)
  • Groove of Ranvier
    • During the first year of life, the zone spreads over the adjacent metaphysis to form a fibrous circumferential ring bridging from the epiphysis to the diaphysis. 
    • This ring increases the mechanical strength of the physis and is responsible for appositional bone growths
    • supplies chondrocytes to periphery
  • Perichondrial fibrous ring of La Croix
    • Dense fibrous tissue that is the primary limiting membrane that anchors and supports the physis through peripheral stability 


What are syndromes associated with each area of the growth plate

  • Resting Zone
    • Gaucher's
    • diastrophic dysplasia
    • Kneist*
    • Pseudoachondroplasia*
  • Proliferative Zone   
    • Achondroplasia 
    • Gigantism 
    • MHE 
  • Hypertrophic Zone   
    • SCFE (not renal) 
    • Rickets (provisional calcification zone)
    • Enchondromas
    • Mucopolysarcharide disease
    • acromegaly
    • SED
    • MED
    • Schmids
    • Kneist*
    • Pseudoachondroplasia*
    • Fractures most commonly occur through the zone of provisional calcification, specifically Salter-Harris I fractures   
  • Primary Spongiosa (metaphysis)   
    • Metaphyseal "corner fracture" in child abuse
    • Scurvy
  • Secondary spongiosa (metaphysis)
    • Renal SCFE
  • Groove of Ranvier
    • Osteochondroma
  • Perichondrial fibrous ring of La Croix


Stages of fracture healing

  • Inflammation
    • Hematoma forms and provides source of hemopoieitic cells capable of secreting growth factors.
    • Osteocytes undergo apoptosis, macrophages, neutrophils and platelets release several cytokines
      • this includes PDGF, TNF-Alpha, TGF-Beta, IL-1,6, 10,12
      • lack of TNF-Alpha (ie. HIV) results in delay of both enchondral/intramembranous ossification
    • Fibroblasts and mesenchymal cells migrate to fracture site and granulation tissue forms around fracture ends  
    • during fracture healing granulation tissue tolerates the greatest strain before failure 
    • Osteoblasts and fibroblasts proliferate
    • inhibition of COX-2 (ie NSAIDs) causes repression of runx-2/osterix, which are critical for differentiation of osteoblastic cells
  • Repair
    • Primary callus forms within two weeks
      • the mechanical enviroment drives differentiation of either osteoblastic (stable enviroment; <2% strain) or chondryocytic (unstable environment; 2-10% strain) 
      • cartilage production provides provisional stabilization 
      • Type II collagen (cartilage) is produced early in fracture healing and then followed by type I collagen (bone) expression
      • Amount of callus is inversely proportional to extent of immobilization  
  • Remodeling
    • Begins in middle of repair phase and continues long after clinical union
    • chondrocytes undergo terminal differentiation 
    • complex interplay of signaling pathways including, indian hedgehog (Ihh), parathyroid hormone related peptide (PTHrP), FGF and BMP
    • type X collagen types is expressed by hypertrophic chondrocytes as the extraarticular matrix undergoes calcification 
    • proteases degrade the extracellular matrix 
    • cartilaginous calcification takes place at the junction between the maturing chondrocytes and newly forming bone
    • subsequently, chondrocytes become apoptotic and VEGF production leads to new vessel invasion
    • newly formed bone (woven bone) is remodeling via organized osteoblastic/osteoclastic activity 
    • Shaped through 
      • Wolff's law: bone remodels in response to mechanical stress
      • piezoelectic charges : bone remodels is response to electric charges: compression side is electronegative and stimulates osteoblast formation, tension side is electropostive and simulates osteoclasts


Phases of healing bone graft

1. Inflammation: Necrotic debris stimulates chemotaxis
2. Osteoblast differentiation: Differentiates from mesenchymal precursor cells
3. Osteoinduction: Stimulation of osteoblast and osteoclast function
4. Osteoconduction: Bone forms around the new scaffold
5. Remodeling: Continual process for years



What are the comlications associated with Iliac crest grafting

  • Anterior - 13mL
  • Posterior - 30mL
  • RIA - 90mL
  • Minor 10%-40%
    • Pain - Most Common
    • Fracture
    • Sensory Nerve Injury
    • LFCN – anterior
    • S. Cluneal – posterior (7cm)
  • Major 2%-10%
    • Infection
    • Hematoma
    • Hematoma
    • Superficial Infection
    • Hernia
    • Permanent Nerve Injury
    • Vascular Injury
    • Ureteral Injury