2014 Basic Science

Question 1

A 74-year-old man reports progressive left hip pain with weight-bearing activities. A radiograph is shown in Figure 1. What is the most likely underlying diagnosis?

1. Infection
2. Lymphoma
3. Paget disease
4. Massive bone infarct
5. Old pelvic trauma

Answer 1

PREFERRED RESPONSE: 3

DISCUSSION: The radiograph shows enlargement of the bone, coarse trabeculation, a blastic appearance, and thickening of the cortex, revealing the classic appearance of Paget disease in the sclerotic phase, the most common presentation. While lymphoma may present as a blastic lesion, it will not have the same enlargement, coarse trabeculation of bone, and the significant sclerosis seen here.

Friedlaender GE, Katz LD, Flynn SD: Paget’s disease and Paget’s sarcoma, in Menendez LR, ed: Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 211-215.

Resnick D, ed: Diagnosis of Bone and Joint Disorders. Philadelphia, PA, WB Saunders, 2002, pp 1947-2000.

Question 2

You are interested in learning a new technique for minimally invasive total knee arthroplasty. The Keyhole Genuflex system seems appealing to you because the instrumentation comes with wireless controls. Which of the following represents an acceptable arrangement?

1. The local Keyhole representative has invited you and your spouse out to dinner at a local restaurant to discuss your interest in their new minimally invasive total knee system, the Keyhole Genuflex knee.
2. Keyhole has offered to pay your tuition to attend a CME course sponsored by the American Association of Hip and Knee Surgeons where both the Genuflex and the competing Styph total knee are discussed and demonstrated.
3. Keyhole will pay your expenses to attend a workshop, in Phoenix at their company headquarters, to learn how to implant the Genuflex knee and to see how the implant is manufactured and tested.
4. Keyhole will pay you $500 for each knee that you implant if you switch from your current total knee system.
5. After you have implanted 25 Genuflex knees, Keyhole will list you on their website as a consultant, pay you a consulting fee of $5,000 per year, and invite you to a golf tournament for their consultants at a resort.

Answer 2

PREFERRED RESPONSE: 3

DISCUSSION: Both the American Academy of Orthopaedic Surgeons (AAOS) and AdvaMed, the medical device manufacturer’s trade organization, have written guidelines that address potential conflicts of interest regarding interactions between physicians and manufacturer’s representatives when it comes to patients’ best interest. The AAOS thinks that the orthopaedic profession exists for the primary purpose of caring for the patient and that the physician-patient relationship is the central focus of all ethical concerns. When an orthopaedic surgeon receives anything of significant value from industry, a potential conflict of interest exists. The AAOS believes that it is acceptable for industry to provide financial and other support to orthopaedic surgeons if such support has significant educational value and has the purpose of improving patient care. All dealings between orthopaedic surgeons and industry should benefit the patient and be able to withstand public scrutiny. A gift of any kind from industry should in no way influence the orthopaedic surgeon in determining the most appropriate treatment for his or her patient. Orthopaedic surgeons should not accept gifts or other financial support with conditions attached. Subsidies by industry to underwrite the costs of educational events where CME credits are provided can contribute to the improvement of patient care and are acceptable. A corporate subsidy received by the conference’s sponsor is acceptable; however, direct industry reimbursement for an orthopaedic surgeon to attend a CME educational event is not appropriate. Special circumstances may arise in which orthopaedic surgeons may be required to learn new surgical techniques demonstrated by an expert or to review new implants or other devices on-site. In these circumstances, reimbursement for expenses may be appropriate.

REFERENCES: AAOS Standard of Professionalism -Orthopaedist -Industry Conflict of Interest (Adopted 4/18/07), Mandatory Standard numbers 6, 9, 12-15. http://www3.aaos.org/member/profcomp/SOPConflictsIndustry.pdf.

The Orthopaedic Surgeon’s Relationship with Industry, in Guide to the Ethical Practice of Orthopaedic Surgery, ed 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2007. http://www.aaos.org/about/papers/ethics/1204eth.asp.

AdvaMed Code of Ethics on Interactions with Health Care Professionals, 2005. http://www.advamed.org/MemberPortal/searchresults.htm?query=Advamed%20Code%20of%20Ethics%20on%20Interactions%20with%20Health%20Care%20Professionals%202005.

Question 3

A 20-year-old woman with a history of subtotal meniscectomy has a painful knee. What associated condition is a contraindication to proceeding with a meniscal allograft?

1. Grade I posterior cruciate ligament tear
2. Grade II medial collateral ligament tear
3. Lateral meniscal tear
4. 5° of genu varum
5. 5 × 5– mm patellar chondral lesion

Answer 3

PREFERRED RESPONSE: 4

DISCUSSION: Patients with substantial joint malalignment place increased stresses on the allograft, and this malalignment must be corrected to decrease the likelihood of meniscal allograft failure. None of the other options would lead to failure of the allograft.

REFERENCE: Bush-Joseph C, Carter TR, Miller MD, Rokito AS, Stuart MJ: Knee and leg: Soft-tissue trauma, in Koval KJ, ed: Orthopaedic Knowledge Update, ed 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, p 499.

Question 4

Figures 2A through 2C show the radiograph and MRI scans of a 16-year-old patient who has a painful hip. Examination reveals a significant limp, limited abduction and internal rotation, and severe pain with internal rotation and adduction. A photomicrograph from a biopsy specimen is shown in Figure 2D. What is the deposited pigment observed in this condition?

1. Hemoglobin
2. Myoglobin
3. Melanin
4. Copper
5. Hemosiderin

Answer 4

PREFERRED RESPONSE: 5

DISCUSSION: Pigmented villonodular synovitis (PVNS) is a synovial proliferative disorder that remains difficult to diagnose. The most common clinical features are mechanical pain and limited joint motion. On radiographs, the classic finding is often a large lesion, associated with multiple lucencies. Other findings may include a normal radiographic appearance, loss of joint space, osteonecrosis of the femoral head, or acetabular protrusion. MRI is the imaging modality of choice and will show the characteristic findings of a joint effusion, synovial proliferation, and bulging of the hip. The synovial lining has a low signal on T1- and T2-weighted images, secondary to hemosiderin deposition. Copper deposition occurs in patients with Wilson disease, which mainly affects the liver.

Bhimani MA, Wenz JF, Frassica FJ: Pigmented villonodular synovitis: Keys to early diagnosis. Clin Orthop 2001;386:197-202.

Cotten A, Flipo RM, Chastanet P, et al: Pigmented villonodular synovitis of the hip: Review of radiographic features in 58 patients. Skeletal Radiol 1995;24:1-6.

Question 5

Titanium and its alloys are unsuitable candidates for which of the following implant applications?

1. Fracture plates
2. Femoral heads in a hip prosthesis
3. Bone screws
4. Intramedullary nails
5. Porous coatings for bone ingrowth

Answer 5

PREFERRED RESPONSE: 2

DISCUSSION: Titanium alloy is highly biocompatible, has higher strength than stainless steel, and is highly resistant to corrosion. It is particularly suited for use in fracture plates, bone screws, and intramedullary nails because of its low modulus of elasticity (low stiffness), which can reduce stress shielding. It is also widely used for porous-ingrowth coatings. However, clinical experience has shown that titanium alloy bearing surfaces such as a femoral ball are highly susceptible to severe metallic wear, particularly in the presence of third-body abrasive particles (such as polymethyl methacrylate fragments, bone chips, or metal debris).

McKellop HA, Sarmiento A, Schwinn CP, et al: In vivo wear of titanium-alloy hip prostheses. J Bone Joint Surg Am 1990;72:512-517.

Salvati EA, Betts F, Doty SB: Particulate metallic debris in cemented total hip arthroplasty. Clin Orthop 1993;293: 160-173.

Evans BG, Salvati EA, Huo MH, et al: The rationale for cemented total hip arthroplasty. Orthop Clin North Am 1993;24:599-610.

Question 6

A 30-year-old man reports pain and weakness in his right arm. Examination reveals grade 4 strength in wrist flexion and elbow extension, decreased sensation over the middle finger, and decreased triceps reflex. These symptoms are most compatible with impingement on what spinal nerve root?

1. C5
2. C6
3. C7
4. C8
5. T1

Answer 6

PREFERRED RESPONSE: 3

DISCUSSION: Motor impulses to the triceps, wrist flexion and elbow extension, and sensation to the middle finger are associated most commonly with the C7 root.

Hoppenfeld S: Physical Examination of the Spine and Extremities. Upper Saddle River, NJ, Prentice Hall, 1976, p 125.

Lauerman WC, Goldsmith ME: Spine, in Miller MD, ed: Review of Orthopaedics, ed 3. Philadelphia, PA, WB Saunders, 2000, pp 353-378.

Question 7

Why is tendon considered an anisotropic material?

1. Young modulus is greater than that of bone.
2. Young modulus is greater than that of ligament.
3. Mechanical properties change with preconditioning.
4. Intrinsic mechanical properties vary depending on the direction of loading.
5. Intrinsic mechanical properties vary depending on the rate of loading.

Answer 7

PREFERRED RESPONSE: 4

DISCUSSION: Anisotropic materials have mechanical properties that vary based on the direction of loading. The relative values of Young modulus for tendon, ligament, and bone are not relevant to isotropy. The mechanical properties of tendon do change with preconditioning, but this change is related to viscoelasticity. The intrinsic mechanical properties of tendon do vary with the rate of loading, but this variance is related to viscoelasticity.

Mow VC, Flatow EL, Ateshian GA: Biomechanics, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 134-180.

Lu L, Kaufman KR, Yaszemski MJ: Biomechanics, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 49-64

Question 8

Which of the following changes to heart rate, blood pressure, and bulbocavernosus reflex are typical of spinal shock?

1. Tachycardia, hypertension, intact bulbocavernosus reflex
2. Tachycardia, hypotension, intact bulbocavernosus reflex
3. Tachycardia, hypotension, absent bulbocavernosus reflex
4. Bradycardia, hypotension, absent bulbocavernosus reflex
5. Bradycardia, hyperthermia, intact bulbocavernosus reflex

Answer 8

PREFERRED RESPONSE: 4

DISCUSSION: The term spinal shock applies to all phenomena surrounding physiologic or anatomic transection of the spinal cord that results in temporary loss or depression of all or most spinal reflex activity below the level of the injury. Hypotension and bradycardia caused by loss of sympathetic tone is a possible complication, depending on the level of the lesion. The mechanism of injury that causes spinal shock is usually traumatic in origin and occurs immediately, but spinal shock has been described with mechanisms of injury that progress over several hours. Spinal cord reflex arcs immediately above the level of injury also may be depressed severely on the basis of the Schiff-Sherrington phenomenon. The end of the spinal shock phase of spinal cord injury is signaled by the return of elicitable abnormal cutaneospinal or muscle spindle reflex arcs. Autonomic reflex arcs involving relay to secondary ganglionic neurons outside the spinal cord may be affected variably during spinal shock, and their return after spinal shock abates is variable. The returning spinal cord reflex arcs below the level of injury are irrevocably altered and are the substrate on which rehabilitation efforts are based.

REFERENCE: Ditunno JF, Little JW, Tessler A, et al: Spinal shock revisited: A four-phase model. Spinal Cord 2004;42:383-395.

Question 9

What is the primary intracellular signaling mediator for bone morphogenetic protein (BMP) activity?

1. Interleukin-1 (IL-1)
2. Runx2
3. NFK-B
4. SMADs
5. P53

Answer 9

PREFERRED RESPONSE: 4

DISCUSSION: BMPs signal through the activation of a transmembrane serine/threonine kinase receptor that leads to the activation of intracellular signaling molecules called SMADs. There are currently eight known SMADs, and the activation of different SMADs within a cell leads to different cellular responses. The other mediators are not believed to be directly involved with BMP signaling.

Lieberman J, Daluiski A, Einhorn TA: The role of growth factors in the repair of bone: Biology and clinical applications. J Bone Joint Surg Am 2002;84:1032-1044.

Li J, Sandell LJ: Transcriptional regulation of cartilage-specific genes, in Rosier RN, Evans C, eds: Molecular Biology in Orthoapedics, Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 21-24.

Zuscik MJ, Drissi MH, Reynolds PR, et al: Molecular and cell biology in orthopaedics, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp3-23.

Question 10

Which of the following properties primarily provides the excellent corrosion resistance of metallic alloys such as stainless steel and cobalt-chromium-molybdenum?

1. High surface hardness
2. High levels of nickel
3. Adherent oxide layer
4. Low galvanic potential
5. Metallic carbides

Answer 10

PREFERRED RESPONSE: 3

DISCUSSION: All of the metals and metallic alloys used in orthopaedic surgery obtain their corrosion resistance from an adherent oxide layer. For stainless steel and cobalt alloy, the addition of chromium as an alloying element ensures the formation of a chromium oxide passive layer that forms on the surface and separates the bulk material from the corrosive body environment. Titanium alloy achieves the same result without chromium by forming an adherent passive layer of titanium oxide. Although these layers can indeed be hard, hardness does not in and of itself provide corrosion resistance. Adding nickel to both metallic alloys adds to strength but does not influence corrosion resistance appreciably. Galvanic potential can influence corrosion but does so by differences in potential between two contacting materials; for example, stainless steel and cobalt alloy have substantially different potentials, and if they were in contact within an aqueous environment, corrosion would commence with the stainless steel becoming the sacrificial anode. Metallic carbides are important in strengthening the alloys but have no role in providing corrosion resistance.

Williams DF, Williams RL: Degradative effects of the biological environment on metal and ceramics, in Ratner BD, Hoffman AS, Shoen FJ, et al, eds: Biomaterials Science. San Diego, CA, Academic Press, 1996, pp 260-265.

Wright TM, Li S: Biomaterials, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 190-193.

Wright TM, Maher SA: Biomaterials, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 65-85.

Question 11

Immobilization of human tendons leads to what changes in structure and/or function?

1. Decrease in tensile strength
2. Decrease in the likelihood of rupture
3. Increase in cellularity
4. Increase in aggrecan
5. Increase in collagen fibril diameter

Answer 11

PREFERRED RESPONSE: 1

DISCUSSION: Recent in vivo and in vitro experiments demonstrate that immobilization of tendon decreases its tensile strength, stiffness, and total weight. Microscopically, there is a decrease in cellularity, overall collagen organization, and collagen fibril diameter.

REFERENCE: Garrett WE, Speer KP, Kirkendall DT, eds: Principles & Practice of Orthopaedic Sports Medicine. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, p 687.

Question 12

Human menisci are made up predominantly of what collagen type?

1. I
2. II
3. III
4. V
5. VI

Answer 12

PREFERRED RESPONSE: 1

DISCUSSION: Type I collagen accounts for more than 90% of the total collagen content. Other minor collagens present include types II, III, V, and VI.

Mow VC, Arnoczky SP, Jackson DW, eds: Knee Meniscus: Basic and Clinical Foundations. New York, NY, Raven Press, 1992, p 41.

Kawamura S, Rodeo SA: Form and function of the meniscus, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 175-189

Question 13

What changes in muscle physiology would be expected in an athlete who begins a rigorous aerobic program for an upcoming marathon?

1. Hypertrophy of type I muscle fibers
2. Reduced fatigue resistance
3. Decreased capillary density
4. Decreased VO2 max
5. Decreased mitochondrial density per muscle cell

Answer 13

PREFERRED RESPONSE: 1

DISCUSSION: Muscle fibers can be categorized grossly into two types. Type I muscle, also known as slow-twitch muscle, is responsible for aerobic, oxidative muscle metabolism. It has a much lower strength and speed of contraction than fast-twitch type II muscle but is significantly more fatigue resistant. With training for endurance sports, the type I muscle undergoes adaptive changes to the increased stress. Increases in capillary density, oxidative capacity, mitochondrial density, and subsequent fatigue resistance are all observed changes. Hypertrophy of type IIb muscle is seen in strength training.

Garrett WE Jr, Best TM: Anatomy, physiology, and mechanics of skeletal muscle, in Simon SR, ed: Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 89-125.

Thayer R, Collins J, Noble EG, et al: A decade of aerobic endurance training: Histological evidence for fibre type transformation. J Sports Med Phys Fitness 2000;40:284-289.

Question 14

A 16-year-old girl has had anterior leg pain and a mass for the past 8 months. Figures 3A and 3B show a radiograph and a hematoxylin and cosin stained histologic specimen. Which of the following disorders is believed to be a precursor of this lesion?

Nonossifying fibroma
Fibrous dysplasia
Unicameral bone cyst
Osteogenesis imperfecta
Osteofibrous dysplasia

Answer 14

PREFERRED RESPONSE: 5

DISCUSSION: The radiograph and pathology are consistent with adamantinoma. Although the mechanism underlying adamantinoma has not been identified, it is believed to be closely related to osteofibrous dysplasia, which may represent a precursor. The other diagnoses are not known to give rise to adamantinoma.

REFERENCE: Springfield DS, Rosenberg AE, Mankin HJ, et al: Relationship between osteofibrous dysplasia and adamantinoma. Clin Orthop 1994;309:234-244.

Question 15

Acetaminophen is an antipyretic medication. It exerts its pharmacologic effects by inhibiting which of the following enzymes?

1. Cyclooxygenase-2
2. Interleukin-1 beta (IL-1 Β)
3. Tumor necrosis factor-alpha (TNF-α)
4. 5-Hydroxytryptamine
5. Matrix metalloproteinases

Answer 15

PREFERRED RESPONSE: 2

DISCUSSION: Acetaminophen inhibits prostaglandin E2 production via IL-1Β, without affecting cyclooxygenase-2 enzymatic activity. The therapeutic concentrations of acetaminophen induce an inhibition of IL-1Β– dependent nuclear factor of kappa B nuclear translocation. The selectivity of this effect suggests the existence of an acetaminophen-specific activity at the transcriptional level that may be one of the mechanisms through which the drug exerts its pharmacologic effects. Acetaminophen does not affect any of the other enzymes named above.

REFERENCE: Mancini F, Landolfi C, Muzio M, et al: Acetaminophen down-regulates interleukin-1beta-induced nuclear factor-kappaB nuclear translocation in a human astrocytic cell line. Neurosci Lett 2003;353:79-82.

Question 16

Nutritional rickets is associated with which of the following changes in chemical blood level?1.

1. Low vitamin D levels
2. High to normal calcium levels
3. High phosphate levels
4. Decreased parathyroid hormone (PTH)
5. Decreased alkaline phosphatase levels

Answer 16

PREFERRED RESPONSE: 1

DISCUSSION: Nutritional rickets is associated with decreased dietary intake of vitamin D, resulting in low levels of vitamin D that result in decreased intestinal absorption of calcium and low to normal serologic levels of calcium. To boost serum calcium levels, there is a compensatory increase in PTH and bone resorption, leading to increased alkaline phosphatase levels.

Brinker MR: Cellular and molecular biology, immunology, and genetics in orthopaedics, in Miller MD, ed: Review of Orthopaedics, ed 3. Philadelphia, PA, WB Saunders, 2001, pp 81-94.

Pettifor J: Nutritional and drug-induced rickets and osteomalacia, in Farrus MJ, ed: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, ed 5. Philadelphia, PA, Lippincott Williams and Wilkins, 2003, pp 399-466.

Einhorn TA: Metabolic bone disease, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 415-426.

Question 17

What assay most directly assesses gene expression at the posttranslational level?

1. Real-time polymerase chain reaction (PCR)
2. Standard PCR
3. Northern blot
4. Western blot
5. Microarray expression profile analysis

Answer 17

PREFERRED RESPONSE: 4

DISCUSSION: Gene expression at the posttranslational level refers to proteins, as opposed to DNA or RNA. The only assay listed that targets protein expression directly is the Western blot. Standard PCR is amplification of targeted DNA segments, regardless of whether or not they are actively expressed. Real-time PCR, Northern blot, and microarray expression profile analysis all quantify RNA as a means to determine posttranscriptional gene expression.

Brinker MR: Cellular and molecular biology, immunology, and genetics in orthopaedics, in Miller MD, ed: Review of Orthopaedics, ed 3. Philadelphia, PA, WB Saunders, 2001, pp 81-94.

Rosier RN, Reynolds, PR, O’Keefe RJ: Molecular and cell biology in orthopaedics, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 19-76.

Question 18

What is the relative amount of type II collagen synthesis in disease-free adult articular cartilage compared to that in developing teenagers?

1. Less than 5%
2. 25%
3. 50%
4. 75%
5. 90%

Answer 18

PREFERRED RESPONSE: 1

DISCUSSION: Adult articular cartilage has less than 5% of the synthesis rate of type II collagen than that seen in developing teenagers. Both synthesis and degradation of type II collagen in normal adult articular cartilage is very low compared to that in children. In osteoarthrosis, both synthesis and degradation are increased, but the collagen does not properly incorporate into the matrix.

Lippiello L, Hall D, Mankin HJ: Collagen synthesis in normal and osteoarthritic human cartilage. J Clin Invest 1977;59:593-600.

Nelson F, Dahlberg L, Laverty S, et al: Evidence for altered synthesis of type II collagen in patients with osteoarthritis. J Clin Invest 1998;102:2115-2125.

Question 19

What gene is expressed the earliest during the differentiation of a chondrocyte during endochondral ossification?

1. Aggrecan
2. Sox-9
3. Collagen type II
4. Collagen type IV
5. Collagen type XI

Answer 19

PREFERRED RESPONSE: 2

DISCUSSION: Transcription factors regulate the activation or repression of cartilage-specific genes. Sox-9, considered a major regulator of chondrogenesis, regulates several cartilage-specific genes during endochondral ossification, including genes for collagen types II, IV, and XI and aggrecan.

Li J, Sandell LJ: Transcriptional regulation of cartilage-specific genes, in Rosier RN, Evans C, eds: Molecular Biology in Orthoapedics, Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 21-24.

Sandell LJ: Genes and gene expression. Clin Orthop 2000;379:S9-S16.

Question 20

The vascular supply to the medial meniscus comes primarily from what artery?

1. Lateral genicular
2. Lateral branch of the superior genicular
3. Medial branch of the superior genicular
4. Medial branch of the inferior genicular
5. Medial genicular

Answer 20

PREFERRED RESPONSE: 4

DISCUSSION: The vascular supply to the medial and lateral menisci originates predominantly from the medial and lateral genicular arteries. The popliteal artery splits into the superior genicular, which splits into medial and lateral branches supplying the patellar cartilage and the posterior cruciate ligament. The middle genicular artery also supplies the anterior curciate ligament, posterior cruciate ligament, and collateral ligaments. The inferior genicular splits into medial and lateral branches and supplies the menisci and other knee ligaments. Despite propagation of incorrect terminology, there is no superior or lateral genicular artery.

REFERENCE: Mow VC, Arnoczky SP, Jackson DW, eds: Knee Meniscus: Basic and Clinical Foundations. New York, NY, Raven Press, 1992, p 4.

Question 21

What term best describes the process involved when a growth factor produced by an osteoblast stimulates the differentiation of an adjacent undifferentiated mesenchymal cell during fracture repair?

1. Mechanical
2. Autocrine
3. Paracrine
4. Endocrine
5. Systemic

Answer 21

PREFERRED RESPONSE: 3

DISCUSSION: Growth factors are proteins secreted by cells that can act on target cells to produce certain biologic actions. These actions can be described as autocrine, paracrine, and endocrine. Autocrine actions are those in which the growth factor influences an adjacent cell of its origin or identical phenotype. Paracrine actions are those in which the protein influences an adjacent cell that is different in its origin or phenotype. Endocrine actions are those in which the factor influences a cell located at a distant anatomic site.

Lieberman J, Daluiski A, Einhorn TA: The role of growth factors in the repair of bone: Biology and clinical applications. J Bone Joint Surg Am 2002;84:1032-1044.

Zuscik MJ, Drissi MH, Reynolds PR, et al: Molecular and cell biology in orthopaedics, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 3-23.

Question 22

What additional percentage of energy expenditure above baseline is required for ambulation after an above-the-knee amputation?

1. 0%
2. 5%
3. 20%
4. 65%
5. 90%

Answer 22

PREFERRED RESPONSE: 4

DISCUSSION: Patients with an above-the-knee amputation have a 65% increase in energy expenditure. A patient with a transtibial amputation requires 25% more energy above baseline values; however, bilateral transtibial amputations are associated with a 40% increase in energy expenditure.

Otis JC, Lane JM, Kroll MA: Energy cost during gait in osteosarcoma patients after resection and knee replacement and after above-the-knee amputation. J Bone Joint Surg Am 1985;67:606-611.

Pinzur MS, Gold J, Schwartz D, et al: Energy demands for walking in dysvascular amputees as related to the level of amputation. Orthopedics 1992;15:1033-1036.

Question 23

Ceramic bone substitutes have which of the following properties?

1. There is vascular ingrowth and subsequent graft resorption with host bone ingrowth.
2. Their interconnectivity is similar to that of cancellous bone.
3. They are brittle with significant tensile strength.
4. They are resorbed at a fairly constant rate.
5. Because of their strength, rigid stabilization of the surrounding bone is not necessary.

Answer 23

PREFERRED RESPONSE: 1

DISCUSSION: Ceramics have the following properties: They are resorbed at varying rates, and the chemical composition of the ceramic significantly affects the rate of resorption. For example, tricalcium phosphate (TCP) undergoes biologic resorption 10 to 20 times faster than hydroxyapatite. The partial conversion of TCP to hydroxyapatite once it is in the body significantly reduces the rate of resorption. Some segments of hydroxyapatite can remain in place in the body for 7 to 10 years. In clinical trials, TCP more readily remodels because of its porosity, but it is weaker. The success of converted corals as a bone graft substitute relies on a complex sequence of events of vascular ingrowth, differentiation of osteoprogenitor cells, bone remodeling, and graft resorption occurring together with host bone ingrowth into and on the porous coralline microstructure or voids left behind during resorption.

REFERENCES: Lane JM, Bostrom MP: Bone grafting and new composite biosynthetic graft materials. Instr Course Lect 1998;47:525-534.

Walsh WR, Chapman-Sheath PJ, Cain S, et al: A resorbable porous ceramic composite bone graft substitute in a rabbit metaphyseal defect model. J Orthop Res 2003;21:655-661.

Wright TM, Maher SA: Biomaterials, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science:Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 65-85.

Question 24

Human tendons are made up primarily of what collagen type (~95%)?

1. I
2. II
3. III
4. IV
5. V

Answer 24

PREFERRED RESPONSE: 1

DISCUSSION: Tendons are dense, primarily collagenous tissues that attach muscle to bone. Collagen content of the dry weight is slightly greater than that found in ligaments and is predominantly type I. Type III collagen makes up the remaining ~5% of total collagen content.

Kasser JR, ed: Orthopaedic Knowledge Update, ed 5. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1996, pp 10-12.

Garrett WE, Speer KP, Kirkendall DT, eds: Principles & Practice of Orthopaedic Sports Medicine. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, pp 21-37.

Frank CB, Shrive NG, Lo IK, et al: Form and function of tendon and ligament, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 191-222.

Question 25

The therapeutic effect of etanercept in the treatment of rheumatoid arthritis is primarily mediated through

1. antagonism of tumor necrosis factor-alpha (TNF-α).
2. antagonism of matrix metalloproteinases.
3. inhibition of cyclooxygenase-2 (COX-2).
4. stimulation of interleukin-1 (IL-1).
5. stimulation of tissue inhibitors of metalloproteinases.

Answer 25

PREFERRED RESPONSE: 1

DISCUSSION: Etanercept is a fusion protein that combines the ligand-binding domain of the TNF-α receptor to the Fc portion of human immunoglobulin G. Protein serves as a competitive inhibitor of TNF-α signaling. COX-2 is the target of NSAIDs, including newer formulations that are more COX-2– specific. The remaining responses are not direct targets of etanercept.

Weinblatt ME, Kremer JM, Bankhurst AD, et al: A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253-259.

Recklies AD, Poole AR, Banerjee S, et al: Pathophysiologic aspects of inflammation in diarthrodial joints, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 489-530.

Question 26

A 21-year-old woman has a nontraumatic rupture of the Achilles tendon. Which of the following commonly prescribed medications has been associated with this condition?

1. Ibuprofen
2. Fluoroquinolones
3. Bisphosphonates
4. Metoprolol
5. Simvistatin

Answer 26

PREFERRED RESPONSE: 2

DISCUSSION: Fluoroquinolones have been associated with increased rates of tendinitis, with special predilection for the Achilles tendon. Tenocytes in the Achilles tendon have exhibited degenerative changes when viewed microscopically after fluoroquinolone administration. Recent clinical studies have shown an increased relative risk of Achilles tendon rupture of 3.7. The other drugs listed have no known increase in tendon rupture rates nor tendinitis.

van der Linden PD, van de Lei J, Nab HW, et al: Achilles tendinitis associated with fluoroquinolones. Br J Clin Pharmacol 1999;48:433-437.

Bernard-Beaubois K, Hecquet C, Hayem G, et al: In vitro study of cytotoxicity of quinolones on rabbit tenocytes. Cell Biol Toxicol 1998;14:283-292.

Maffulli N: Rupture of the Achilles tendon. J Bone Joint Surg Am 1999;81:1019-1036.

Question 27

Bioabsorbable polymers are used in a wide range of orthopaedic devices, including anchors, staples, pins, plates, and screws. What is the primary drawback for bioabsorbable implants?

1. High cost
2. Increased rates of infection
3. High elastic modulus
4. Brittleness
5. Foreign body reaction

Answer 27

PREFERRED RESPONSE: 5

DISCUSSION: A number of bioabsorbable polymers are used in orthopaedic applications, and all have in common reports of foreign body reactions, which occur in more than 50% of patients in some series. In general, the high cost of these polymers is offset by the elimination of a second surgery to remove the implant. Bioabsorbable polymers are low strength in comparison to metallic alloys but of sufficient strength for many orthopaedic applications. The elastic modulus is not as high as many other orthopaedic biomaterials, making them suitable for applications where lower stiffness is an asset.

Ambrose CG, Clanton TO: Bioabsorbable implants: Review of clinical experience in orthopedic surgery. Ann Biomed Eng 2004;32:171-177.

Bergsma JE, de Bruijn WC, Rozema FR, et al: Late degradation tissue response to poly (L-lactide) bone plates and screws. Biomaterials 1995;16:25-31.

Question 28

What ligament is the primary restraint to applied valgus loading of the knee?

1. Posteromedial capsule
2. Posterior cruciate ligament (PCL)
3. Superficial medial collateral ligament (MCL)
4. Deep MCL
5. Medial meniscus

Answer 28

PREFERRED RESPONSE: 3

DISCUSSION: The superficial portion of the MCL contributes 57% and 78% of medial stability at 5° and 25° of knee flexion, respectively. The deep MCL and posteromedial capsule act as secondary restraints at full knee extension. The anterior cruciate ligament and PCL also provide secondary resistance to valgus loads.

REFERENCE: Garrett WE, Speer KP, Kirkendall DT, eds: Principles & Practice of Orthopaedic Sports Medicine. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, p 767.

Question 29

What region of the thoracic curve is most dangerous for pedicle screw insertion while performing a posterior fusion for adolescent idiopathic scoliosis?

1. Concave side at the stable vertebra
2. Concave side at the apex of the curve
3. Convex side at the stable vertebra
4. Convex side at the apex of the curve
5. Thoracolumbar junction

Answer 29

PREFERRED RESPONSE: 2

DISCUSSION: Morphologic and anatomic studies confirm the pedicle is smaller on the concave side of thoracic curves. The dura is also closer to the pedicle on the concave side of the curves.

Liljenqvist U, Allkemper T, Hackenberg L, et al: Analysis of vertebral morphology in idiopathic scoliosis with use of magnetic resonance imaging and multiplanar reconstruction. J Bone Joint Surg Am 2002;84:359-368.

Parent S, Labelle H, Skalli W, et al: Thoracic pedicle morphometry in vertebrae from scoliotic spines. Spine (Phila Pa 1976) 2004;29:239-248.

Question 30

What mechanism is associated with the spontaneous resorption of herniated nucleus pulposus?

1. Macrophage infiltration and phagocytosis
2. Granuloma formation
3. Antibody-mediated destruction
4. Complement cascade activation
5. Major histocompatibility complex-mediated pathways

Answer 30

PREFERRED RESPONSE: 1

DISCUSSION: Nonsurgical modalities remain the mainstay for treatment of herniated disks. Spontaneous resorption of herniated disks frequently is detected by MRI. Marked infiltration by macrophages and neovascularization are observed on histologic examination of herniated disks, and the resorption is believed to be related to this process. Many cytokines such as vascular endothelial growth factor, tumor necrosis factor-α, and matrix metalloproteinases have been implicated in this process, but none has been found to be singularly responsible.

Haro H, Kato T, Kamori H, et al: Vascular endothelial growth factor (VEGF)-induced angiogenesis in herniated disc resorption. J Orthop Res 2002;20:409-415.

Doita M, Kanatani T, Ozaki T, et al: Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption. Spine (Phila Pa 1976) 2001;26:1522-1527.

Question 31

Clinical evidence suggests that grafts for replacing a torn anterior cruciate ligament often stretch after surgery. What is the most probable mechanism for this behavior?

1. Gross failure at the attachment sites
2. Fatigue failure of the ligament tissue
3. Creep of the graft material
4. Water absorption by the graft material
5. Elastic stretch of collagen fibers

Answer 31

PREFERRED RESPONSE: 3

DISCUSSION: The stretching of the graft occurs over time as the graft is loaded. Time-dependent deformation under load is called creep and is common in viscoelastic materials such as ligament tissue. Creep can occur under both static and cyclic load conditions; time-dependent deformation will occur as long as load is applied to the tissue. Similarly, when a graft is initially tensioned to a given deformation at surgery, the load generated in the graft will decrease over time; this behavior is called stress relaxation and also is indicative of a viscoelastic material. Water content may affect the viscoelastic properties by changing the friction between collagen fibers, but studies have shown little difference in water content between grafts and normal ligaments. Fatigue failures may manifest themselves through damage to the ligament tissue, but this would require higher loads than are routinely experienced by grafts. Elastic stretch is recoverable and, therefore, does not contribute to a permanent stretch. Similarly, gross failure at the attachment would not cause a stretch, but rather a catastrophic instantaneous instability.

Boorman RS, Thornton GM, Shrive NG, et al: Ligament grafts become more susceptible to creep within days after surgery. Acta Orthop Scand 2002;73:568-574.

Woo SL-Y, An K-N, Frank CB, et al: Anatomy, biology, and biomechanics of tendon and ligament, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 596-609.

Lu L, Kaufman KR, Yaszemski MJ: Biomechanics, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp49-64.

Question 32

Which of the following clinical disorders is the result of a mutation in fibroblast growth factor recepter 3 (FGFR3)?

1. Cleidocranial dysplasia
2. Schmid metaphyseal chondrodysplasia
3. Achondroplasia
4. Fibrous dysplasia
5. Camptomelic dysplasia

Answer 32

PREFERRED RESPONSE: 3

DISCUSSION: Camptomelic dysplasia is caused by a heterozygous loss of function of the Sox9 gene. The alternatives have genetic causes, but are not linked to Sox9. Cleidocranial dysplasia is related to a defect in Cbfa-1 (Osf-2, Runx2). Schmid metaphyseal chondrodysplasia is related to type X collagen. Fibrous dysplasia is related to a defect in the alpha subunit of stimulatory guanine-nucleotide-binding protein (Gs). Achondroplasia is related to a defect in fibroblast growth factor receptor 3.

Wagner T, Wirth J, Meyer J, et al: Autosomal sex reversal and camptomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 1994;79:1111-1120.

Dietz FR, Murray JC: Update on the genetic basis of disorders with orthopaedic manifestations, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 111-131.

Dietz FR, Murray JC: Genetic basis of disorders with orthopaedic manifestations, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 25-47.

Question 33

What is the main mechanism for nutrition of the adult disk?

1. Capillary network from the adjacent segmental arteries
2. Capillary network from the arterioles in the vertebral body
3. Diffusion through the anulus fibrosus
4. Diffusion through pores in the end plates
5. Diffusion through nerves in the dorsal root ganglion

Answer 33

PREFERRED RESPONSE: 4

DISCUSSION: Disk nutrition occurs via diffusion through pores in the end plates. The disk has no direct blood supply, and the anulus fibrosus is not porous to allow diffusion. The dorsal root ganglion does not provide blood supply to the disk.

Biyani A, Andersson GB: Low back pain: Pathophysiology and management. J Am Acad Orthop Surg 2004;12:106-115.

Urban JG, Holm S, Maroudas A, et al: Nutrition of the intervertebral disc: Effect of fluid flow on solute transport. Clin Orthop 1982;170:296-302.

Park AE, Boden SD: Form and function of the intervertebral disk, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 259-264.

Question 34

A knockout mouse for the vitamin D receptor has which of the following phenotypes?

1. Osteopetrosis
2. Renal failure
3. Rickets
4. Jansen-type metaphyseal dysplasia
5. Compensatory hyperparathyroidism and no skeletal phenotype

Answer 34

PREFERRED RESPONSE: 3

DISCUSSION: A knockout mouse to the vitamin D receptor would cause loss of vitamin D function, resulting in rickets. Renal failure would not occur; although vitamin D is converted from 25 (OH) D to 1,25 (OH) D in the kidney, the active hormone acts on the gut and bone. Osteopetrosis can be seen as the phenotype for the c-fos knockout mouse; the Jansen-type metaphyseal dysplasia phenotype results from overactivation of the parathyroid hormone (PTH)/receptor protein receptor. Although compensatory hyperparathyroidism would occur, excessive PTH would not be able to rescue the skeletal loss and instead phosphaturia and phosphatasia would result.

Glowacki J, Hurwitz S, Thornhill TS, et al: Osteoporosis and vitamin-D deficiency among postmenopausal women with osteoarthritis undergoing total hip arthroplasty. J Bone Joint Surg Am 2003;85:2371-2377.

Rosier RN, Reynolds PR, O’Keefe RJ: Molecular and cell biology in orthopaedics, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, p 51.

Question 35

Intramembranous ossification during fracture repair is characterized by absence of which of the following elements?

1. Alkaline phosphatase
2. Osteonectin
3. Osteopontin
4. Collagen type I expression
5. Collagen type II expression

Answer 35

PREFERRED RESPONSE: 5

DISCUSSION: Intramembranous ossification occurs through the direct formation of bone without the formation of a cartilaginous intermediate. Clinically, both intramembranous and endochondral ossification occur simultaneously during fracture healing; however, the latter is characterized by the differentiation and maturation of chondrocytes, vascular invasion of a hypertrophic cartilage matrix, and bone formation. Collagens type II and X are cartilage specific and would be characteristic of endochondral ossification, not intramembranous ossification.

Li J, Sandell LJ: Transcriptional regulation of cartilage-specific genes, in Rosier RN, Evans C, eds: Molecular Biology in Orthoapedics, Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 21-24.

Buckwalter JA, Einhorn TA, Bolander ME: Healing of the musculoskeletal tissues, in Rockwood CA Jr, Green DP, Bucholz RW, et al, eds: Rockwood and Green’s Fractures in Adults, ed 4. Philadelphia, PA, Lippincott-Raven, 1996, pp 261-276.

Question 36

Patients with rheumatoid arthritis may exhibit an increase in viral load for which of the following viruses?

1. HIV
2. Papilloma virus
3. Epstein-Barr virus (EBV)
4. Hepatitis C virus (HCV)
5. Hepatitis B virus (HBV)

Answer 36

PREFERRED RESPONSE: 3

DISCUSSION: Rheumatoid arthritis (RA) is a complex multisystem disorder. It has been suggested that patients with RA have an impaired capacity to control infection with EBV. EBV has oncogenic potential and is implicated in the development of some lymphomas. Recent publications provide evidence for an altered EBV-host balance in patients with RA who have a relatively high EBV load. Large epidemiologic studies confirm that lymphoma is more likely to develop in patients with RA than in the general population. The overall risk of development of lymphoma has not risen with the increased use of methotrexate or biologic agents. Histologic analysis reveals that most lymphomas in patients with RA are diffuse large B cell lymphomas, a form of non-Hodgkin lymphoma. EBV is detected in a proportion of these. Patients with RA do not have prevalence for infection with any of the other mentioned viruses.

Callan MF: Epstein-Barr virus, arthritis, and the development of lymphoma in arthritis patients. Curr Opin Rheumatol 2004;16:399-405.

Baecklund E, Sundstrom C, Ekbom A, et al: Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma. Arthritis Rheum 2003;48:1543-1550.

Question 37

Osteopenia is defined by the World Health Organization (WHO) as a bone mineral density (BMD) that is

1. within 1 standard deviation of age-matched normals.
2. within 1 and 2.5 standard deviations below age-matched normals.
3. within 1 standard deviation of young normals.
4. within 1 and 2.5 standard deviations below young normals.
5. more than 2.5 standard deviations below age-matched normals.

Answer 37

PREFERRED RESPONSE: 4

DISCUSSION: Osteopenia, decreased bone mass without fracture risk as defined by the WHO criteria for diagnosis of osteoporosis, is when a woman’s T-score is within -1 to -2.5 SD. The T-score represents a comparison to young normals or optimum peak density. The Z-score represents a comparison of BMD to age-matched normals. Measurements of bone mineral density (BMD) at various skeletal sites help in predicting fracture risk. Hip BMD best predicts fracture of the hip, as well as fractures at other sites.

REFERENCE: Kanis JA, Johnell O, Oden A, et al: Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone 2000;27:585-590.

Question 38

Which of the following best describes the mechanism of action of gentamycin?

1. Inhibits cell wall synthesis by inhibiting peptidyl traspeptidase
2. Increases cell membrane permeability
3. Binds to the 30S ribosome subunit interfering with protein synthesis
4. Inhibits DNA gyrase
5. Forms oxygen radicals leading to loss of helical structure and breakage of DNA strands

Answer 38

PREFERRED RESPONSE: 3

DISCUSSION: Gentamycin and the aminoglycosides (streptomycin, tobramycin, amikacin, and neomycin) work by binding to the 30S ribosome subunit, leading to the misreading of mRNA. This misreading results in the synthesis of abnormal peptides that accumulate intracellularly and eventually lead to cell death. These antibiotics are bactericidal. Cephalosporins, vancomycin, and penicillins interfere with cell wall synthesis by inhibiting the transpeptidase enzyme. Polymyxin, nystatin, and amphotericin increase cell membrane permeability by disrupting the functional integrity of the cell membrane. The quinolones inhibit the enzyme, DNA gyrase. Metronidazole forms oxygen radicals that are toxic to anaerobic organisms because they lack the protective enzymes, superoxide dismutase and catalase.

REFERENCE: Morris CA, Einhorn TA: Principles of orthopaedic pharmacology, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 217-236.

Question 39

What type of muscle contraction occurs while the muscle is lengthening?

1. Isometric
2. Isotonic
3. Concentric
4. Isokinetic
5. Eccentric

Answer 39

PREFERRED RESPONSE: 5

DISCUSSION: A muscle that lengthens as it is activated is an eccentric contraction. Isometric contraction involves no change in length. Concentric contraction occurs while the muscle is shortening. In isotonic contraction, the force remains constant through the contraction range. Isokinetic muscle contraction occurs at a constant rate of angular change of the involved joint.

Garrett WE, Speer KP, Kirkendall DT, eds: Principles & Practice of Orthopaedic Sports Medicine. Philadelphia, PA, Lippincott Williams & Wilkins, 2000, pp 12-13.

Lieber RL: Form and function of skeletal muscle, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 223-243.

Question 40

Osteoclasts originate from which of the following cell types?

1. Fibroblasts
2. Monocytes
3. Megakaryocytes
4. Plasma cells
5. Osteoprogenitor cells

Answer 40

PREFERRED RESPONSE: 2

DISCUSSION: Osteoclasts originate from the monocyte/macrophage lineage. Fibroblasts and osteoprogenitor cells originate from mesenchymal stem cells and do not form osteoclasts. Plasma cells reside in the bone marrow and are derivatives of the hematopoietic system. Megakaryocytes are also in the bone marrow and synthesize platelets.

Zaidi M, Blair HC, Moonga BS, et al: Osteoclastogenesis, bone resorption, and osteoclast-based therapeutics. J Bone Miner Res 2003;18:599-609.

Brinker MR: Bone (Section 1), in Miller M, ed: Review of Orthopaedics, ed 2. Philadelphia, PA, WB Saunders, 1996, pp 1-35.

Zuscik MJ, Drissi MH, Reynolds PR, et al: Molecular and cell biology in orthopaedics, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 3-23.

Question 41

A study is being designed to compare the effectiveness of an antibiotic. The choice of the number of patients (the sample size) depends on several factors. What type of calculation assesses the potential of the study to successfully address the effectiveness of the antibiotic?

1. Regression analysis
2. Power analysis
3. Correlation analysis
4. Nonparametric analysis
5. Analysis of variance

Answer 41

PREFERRED RESPONSE: 2

DISCUSSION: Power analysis is used to determine the minimum number of specimens (sample size) such that, if a difference is found that is large enough to be clinically important, the associated level of statistical reliability will be high enough (ie, the P-value will be small enough) for the investigators to conclude that the difference observed in the study also holds in general. For the statistician to do a power analysis, the investigators must first decide on the minimum difference that they consider to be clinically important, for example, a reduction of 3% in the rate of infection. It is important to recognize that the choice of what constitutes the minimum difference in the rate of infection that is clinically (medically) important cannot and should not be done by the statistician. Rather, this is a clinical-medical issue and must be done by the physician researcher based on a comprehensive assessment of the medical risks and benefits. The power analysis also requires an estimate of the variance in the data, which may be based on previous similar studies, if available. A statistician can then calculate the minimum sample size (number of patients) required such that, if a clinically important difference does, in fact, exist between the full populations, there is a reasonable probability or power (typically 80% to 90%) that a difference this large also will occur between the sample populations at the desired level of statistical significance (usually, but not necessarily, P < 0.05). The other answers refer to types of analyses that are usually conducted after the data are collected.

REFERENCE: Ebramzadeh E, McKellop H, Dorey F, et al: Challenging the validity of conclusions based on P-values alone: A critique of contemporary clinical research design and methods. Instr Course Lect 1994;43:587-600.

Question 42

What is the most common cause of mechanical failure of an orthopaedic biomaterial during clinical use?

1. Fatigue
2. Tension
3. Compression
4. Shear
5. Torsion

Answer 42

PREFERRED RESPONSE: 1

DISCUSSION: In most orthopaedic applications, the materials are strong enough to withstand a single cycle of loading in vivo. However, these loads may be large enough to initiate a small crack in the implant that can grow slowly over thousands or millions of cycles, eventually leading to gross failure. Such fatigue failure has occurred with virtually every type of implant, including stainless steel fracture plates and screws, bone cement in joint arthroplasty, and polyethylene inserts in total knee arthroplasty.

Lewis G: Fatigue testing and performance of acrylic bone-cement materials: State-of-the-art review. J Biomed Mater Res Br 2003;66:457-486.

Stolk J, Verdonschot N, Huiskes R: Stair climbing is more detrimental to the cement in hip replacement than walking. Clin Orthop 2002;405:294-305.

Wright TM, Maher SA: Biomaterials, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 65-85.

Question 43

Which of the following body positions is associated with the highest intradiskal pressure?

1. Standing, bending forward
2. Standing, bending back
3. Sitting, bending forward
4. Sitting, bending back
5. Supine, lateral decubitus

Answer 43

PREFERRED RESPONSE: 3

DISCUSSION: Intradiskal pressure is lowest when the patient is in the supine position. Sitting is associated with higher intradiskal pressures than standing. Flexion also increases intradiskal pressure. The combination of flexion and sitting produces the highest intradiskal pressure. Nachemson and Morris found that intradiskal pressure increases as position changes from lying supine, lying prone, standing, leaning forward, sitting, and sitting leaning forward. Twisting or straining in positions of relatively high intradiskal pressure may predispose patients to herniation of the intervertebral disk. Patients with a herniated disk may also notice their pain worsens with activities that increase the disk pressure, including the positions mentioned, or activities that increase intra-abdominal pressure (coughing, sneezing, straining).

Nachemson A, Morris JM: In vivo measurements of intradiscal pressure. J Bone Joint Surg Am 1964;46:1077-1092.

Buckwalter JA, Mow VC, Boden SD, Eyre DR, Weidenbaum M: Intervertebral disk structure, composition, and mechanical function, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 547-556.

Question 44

Stiffness relates the amount of load applied to a structure like a long bone or an intramedullary nail to the amount of resulting deformation that occurs in the structure. What is the most important material property affecting the axial and bending stiffness of a structure?

1. Elastic modulus
2. Ductility
3. Ultimate stress
4. Yield stress
5. Toughness

Answer 44

PREFERRED RESPONSE: 1

DISCUSSION: The amount of deformation resulting in response to an applied load depends on the stress distribution that the load creates in the structure and the stress versus strain behavior of the material that makes up the structure. Axial and bending loads create stress distributions that involve normal stresses and normal strains. Although all five responses are indeed material properties, only one, elastic modulus, relates normal stresses to normal strains. In fact, axial and bending stiffness are directly proportional to modulus, so that a nail made from stainless steel will have nearly twice the stiffness of a nail made from titanium alloy (because their respective elastic moduli differ by about a factor of two).

Hayes WC, Bouxsein ML: Analysis of muscle and joint loads, in Mow VC, Hayes WC, eds: Basic Orthopaedic Biomechanics, ed 2. New York, NY, Lippincott-Raven, 1997, pp 74-82.

Mow VC, Flatow EL, Ateshian GR: Biomechanics, in Buckwalter JA, Einhorn TA, Simon SR, eds: Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 159-165.

Wright TM, Maher SA: Biomaterials, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 65-85.

Question 45

Osteoclasts are primarily responsible for bone resorption of malignancy. Which of the following stimulates osteoclast formation?

1. Receptor activator of nuclear factor-κB ligand gene (NF-κB ligand)
2. Osteoprotegerin (OPG)
3. Interleukin-5 (IL-5)
4. Matrix metalloproteinase-2 (MMP-2)
5. Collagen type I

Answer 45

PREFERRED RESPONSE: 1

DISCUSSION: Bone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Increasing evidence suggests that RANKL is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, OPG inhibits osteoclast development. IL-8 but not IL-5 is known to play a role in osteoclastogenesis. MMP-2 and collagen type I do not have a direct role in osteoclastogenesis.

Kitazawa S, Kitazawa R: RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol 2002;198:228-236.

Einhorn TA: Metabolic bone disease, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 415-426.

Question 46

Collagen orientation is parallel to the joint surface in what articular cartilage zone?

1. Diagonal
2. Middle
3. Deep
4. Superficial
5. Calcified

Answer 46

PREFERRED RESPONSE: 4

DISCUSSION: The collagen orientation changes from parallel in the superficial zone to a more random pattern in the middle zone and finally to perpendicular in the calcified zone.

Bush-Joseph C, Carter TR, Miller MD, Rokito AS, Stuart MJ: Knee and leg: Soft-tissue trauma, in Koval KJ, ed: Orthopaedic Knowledge Update, ed 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 498-499.

Mankin HJ, Grodzinsky AJ, Buckwalter JA: Articular cartilage and osteoarthritis, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 161-174.

Question 47

Which of the following agents increases the risk for a nonunion following a posterior spinal fusion?

1. Ibuprofen
2. Intranasal calcitonin
3. Simvastatin
4. Gentamycin
5. Tamoxifen

Answer 47

PREFERRED RESPONSE: 1

DISCUSSION: NSAIDs have been shown to increase the risk of pseudarthrosis. In a controlled rabbit study, nonunions were reported with the use of toradol and indomethacin. NSAIDs are commonly used medications with the potential to diminish osteogenesis. Studies clearly have demonstrated inhibition of spinal fusion following the postoperative administration of several NSAIDs, including ibuprofen. Cigarette smoking is another potent inhibitor of spinal fusion.

Glassman SD, Rose SM, Dimar JR, et al: The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine (Phila Pa 1976)1998;23:834-838.

Martin GJ Jr, Boden SD, Titus L: Recombinant human bone morphogenetic protein-2 overcomes the inhibitory effect of ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), on posterolateral lumbar intertransverse process spine fusion. Spine (Phila Pa 1976)1999;24:2188-2193.

Question 48

A study was conducted in 500 patients to measure the effectiveness of a new growth factor in reducing healing time of distal radial fractures. The authors reported that average healing time was reduced from 9.2 to 8.9 weeks (P < 0.0001). Because the difference was highly statistically significant, they recommended routine clinical use of this drug despite its high cost. A more appropriate interpretation of these results is that they are

1. clinically significant.
2. statistically significant but perhaps not clinically significant.
3. statistically and clinically significant.
4. not statistically or clinically significant.
5. nonconclusive.

Answer 48

PREFERRED RESPONSE: 2

DISCUSSION: The results are statistically significant (at the arbitrary level of P < 0.05). That is, they indicate a probability of only 1/10,000 that the observation that the drug is effective in reducing healing time by 0.3 weeks occurred by chance selection of the study subjects. However, because the statistical power of a study increases with the number of subjects included (sample size), a difference that is trivial clinically can occur with a very high level of statistical significance (a very small P-value) if enough patients are included in the study. Because of this, the P-value alone, no matter how small, does not establish clinical significance or importance. Rather, the clinical significance of the observed difference must be assessed taking into consideration the medical importance of the difference if it is, in fact, true in the general population. In this example, the reduction in healing time of only a few days is probably clinically unimportant, particularly if the use of the new growth factor is expensive, complex, and/or has substantial side effects.

REFERENCE: Ebramzadeh E, McKellop H, Dorey F, et al: Challenging the validity of conclusions based on P-values alone: A critique of contemporary clinical research design and methods. Instr Course Lect 1994;43:587-600.

Question 49

What type of multiple lesions is associated with Maffucci syndrome?

1. Nonossifying fibromas
2. Enchondromas
3. Langerhans cell histiocytosis
4. Osteochondromas
5. Giant cell tumors

Answer 49

PREFERRED RESPONSE: 2

DISCUSSION: Maffucci syndrome is a form of enchondromatosis associated with subcutaneous and deep hemangiomas. Similar to Ollier disease, the risk of malignant transformation of the enchondromas is much higher than that of a solitary enchondroma. Multifocal nonossifying fibromas associated with other clinical findings such as mental retardation and café-au-lait spots is known as Jaffe-Campanacci syndrome. There are two types of multifocal forms of histiocytosis: Letterer-Siwe and Hand-Schüller-Christian disease.

Schwartz HS, Zimmerman NB, Simon MA, et al: The malignant potential of enchondromatosis. J Bone Joint Surg Am 1987;69:269-274.

Frassica F: Orthopaedic pathology, in Miller M, ed: Review of Orthopaedics, ed 2. Philadelphia, PA, WB Saunders, 1996, pp 292-335.

Yuan J, Fuchs B, Scully SP: Molecular basis of cancer, in Einhorn TA, O’Keefe RJ, Buckwalter JA, eds: Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, pp 379-393.

Question 50

Joint contact pressure in normal or artificial joints can best be minimized by what mechanism?

1. Increasing joint force and contact area
2. Increasing joint force and decreasing contact area
3. Decreasing joint force and contact area
4. Decreasing joint force and increasing contact area
5. Decreasing joint force only

Answer 50

PREFERRED RESPONSE: 4

DISCUSSION: Joint contact pressure is a stress and as such is defined as the load transferred across the joint divided by the contact area between the joint surfaces (the area over which the joint load is distributed). Therefore, any mechanism that decreases the load across the joint (for example, a walking aid) will decrease the stress. Similarly, any mechanism that increases the area over which the load is distributed (for example, using a more conforming set of articular surfaces in a knee joint arthroplasty) will also decrease the stress. Other mechanisms that influence joint contact pressure include the elastic modulus of the materials (cartilage in the case of natural joints and polyethylene in joint arthroplasty) and the thickness of the structures through which the joint loads pass.

Bartel DL, Bicknell VL, Wright TM: The effect of conformity, thickness, and material on stresses in UHMWPE components for total joint replacement. J Bone Joint Surg Am 1986;68:1041-1051.

Wright TM: Biomechanics of total knee design, in Pellicci PM, Tria AJ Jr, Garvin KL, eds: Orthopaedic Knowledge Update: Hip and Knee Reconstruction, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 265-274.