2009 Basic Science

Question 1

Titanium, an extremely reactive metal, is one of the most biocompatible implant materials because 1. nothing in the biologic environment reacts with titanium. 2. physiologic conditions inhibit titanium reactions. 3. proteins coat the titanium and “insulate” it from the body. 4. titanium spontaneously forms a stable oxide coating. 5. titanium alloys are less reactive than pure metal.

Answer 1

PREFERRED RESPONSE: 4 DISCUSSION: Titanium rapidly forms an adherent oxide, TiO2, when exposed to oxygen. This process of self-passivation effectively covers the surface of titanium and titanium alloys with a nonreactive ceramic coating and makes these materials extremely biocompatible. REFERENCES Black J: Orthopaedic Biomaterials in Research and Practice. New York, NY, Churchill Livingstone, 1988, pp 57-81. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 467-474.

Question 2

Which of the following cell membrane proteins convey chemotherapeutic resistance to tumor cells? 1. CD44 glycoproteins 2. P-glycoproteins 3. Paracrine peptides 4. Matrix metalloproteinases (MMPs) 5. Stromelysins

Answer 2

PREFERRED RESPONSE: 2 DISCUSSION: One of the mechanisms of chemotherapeutic resistance of cancer cells is through the expression of the multidrug resistance gene 1 (MDR1). MDR1 codes for a membrane phosphoglycoprotein (p-glycoprotein). P-glycoprotein is an energy-dependent efflux pump that is associated with resistance to hydrophobic agents. The presence of p-glycoprotein in chondrosarcoma has been hypothesized to contribute to its chemotherapeutic resistance. CD44 glycoprotein is a cell surface cytokine found on metastatic tumor cells that binds to subendothelial basement membranes. Paracrine peptides are growth factors found in the local tissue environment, rather than tumor cell-produced growth factors (autocrine peptides) that promote metastatic tumor growth. MMPs are proteases produced by malignant cells that degrade tissue basement membranes to assist in metastasis. Stromelysins are MMPs that degrade proteoglycan core protein, laminin, fibronectin, and nonhelical portions of basement membrane collagens. REFERENCES Terek RM, Schwartz GK, Devaney K, et al: Chemotherapy and p-glycoprotein expression in chondrosarcoma. J Orthop Res 1998;16:585-590. Pastan I, Gottesman M: Multiple-drug resistance in human cancer. N Engl J Med 1987;316:1388-1393.

Question 3

Bone destruction as a result of multiple myeloma is primarily caused by which of the following cell types? 1. Myeloma cells 2. Macrophages 3. Osteoclasts 4. Plasma cells 5. Pericytes

Answer 3

PREFERRED RESPONSE: 3 DISCUSSION: Myeloma is commonly associated with bone destruction. Osteoclasts appear to be the major cell type involved in bone osteolysis. Osteoclasts have been reported to cluster on bone-resorbing surfaces adjacent to collections of myeloma cells. In addition, cultures of human myeloma cells in vitro produce several osteoclast activating factors, including lymphotoxin, interleukin-l, and interleukin-6. Myeloma cells have not been reported to directly destroy bone. Osteoblast function is inhibited by the presence of myeloma cells. Pericytes derive from the vascular endothelium and are hypothesized to function as osteoblast progenitor cells. REFERENCES Mundy GR, Yoneda T: Facilitation and suppression of bone metastasis. Clin Orthop Relat Res 1995;312:34-44. Mundy GR: Mechanisms of osteolytic bone destruction. Bone 1991;12(suppl 1): S1-6.

Question 4

Which of the following antibiotics is bacteriostatic at therapeutic serum concentrations? 1. Penicillin 2. Cefoxitin 3. Clindamycin 4. Vancomycin 5. Bacitracin

Answer 4

PREFERRED RESPONSE: 3 DISCUSSION: Penicillin and cephalosporins such as cefoxitin, vancomycin, and bacitracin are all bactericidal by causing loss of bacterial cell wall viability, either by activating enzymes that disrupt cell walls or by inhibiting synthesis of cell walls. Clindamycin is bacteriostatic and acts by inhibiting protein synthesis. REFERENCES Sande MA, Kapusnik-Uner JE, Mandell GL: Antimicrobial agents, in Gilman AG (ed): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York, NY, McGraw, 1990, p 1019. Pruitt BA, McManus WF, McManus AT, et al: Infections: Bacteriology, antibiotics and chemotherapy, in Jupiter JB (ed): Flynn’s Hand Surgery, ed 4. Baltimore, MD, Williams & Wilkins, 1991, p 713.

Question 5

The administration of ciprofloxacin is contraindicated in which of the following patient populations? 1. Diabetics 2. Alcoholics 3. Intravenous drug abusers 4. Patients with renal failure 5. Children

Answer 5

PREFERRED RESPONSE: 5 DISCUSSION: Quinolone antibiotics such as ciprofloxacin have produced arthropathy in immature mammals and, although these lesions have not been reported in humans, these drugs are not recommended for use in children. The two major drug interactions to be aware of with ciprofloxacin are the significant decrease in absorption of the drug when taken orally with magnesium or aluminum-containing antacids, and the increase in serum concentration when theophylline is administered with ciprofloxacin. REFERENCES Frymoyer JW (ed): Orthopaedic Knowledge Update 4: Home Study Syllabus. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1993, p 157. Sande MA, Kapusnik-Uner JE, Mandell GL: Antimicrobial agents, in Gilman AG (ed): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York, NY, McGraw, 1990, p 1059.

Question 6

What antibiotic works by inhibiting peptidoglycan synthesis? 1. Penicillin 2. Gentamicin 3. Rifampin 4. Tetracycline 5. Clindamycin

Answer 6

PREFERRED RESPONSE: 1 DISCUSSION: The beta-lactam antibiotics such as penicillin are thought to work by inhibiting peptidoglycan synthesis by binding to the bacterial cell membrane surface penicillin-binding proteins. Rifampin inhibits bacterial RNA synthesis. Gentamicin, clindamycin, and tetracycline act via different mechanisms to interfere with bacterial RNA function. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, p 505. Saude MA, Kapusnik-Uner JE, Mandell GL: Antimicrobial agents, in Gilman AG (ed): Goodman and Gilman’s The Pharmacological Basis of Therapeutics, ed 8. New York, NY, McGraw, 1990, p 1019.

Question 7

Which of the following organisms is (are) most likely to cause hematogenous osteomyelitis in hemodialysis patients? 1. Escherichia coli and Klebsiella pneumoniae 2. Staphylococci 3. Candida species 4. Anaerobic oral organisms 5. Anaerobic enteric organisms

Answer 7

PREFERRED RESPONSE: 2 DISCUSSION: Hemodialysis patients are at increased risk for hematogenous osteomyelitis because indwelling intravenous catheters used over the long term serve as a source of infection. Staphylococcus aureus and S epidermidis are the organisms most commonly isolated. The ribs and thoracic vertebrae are the most frequently affected bones. REFERENCE Gupta M, Frenkel LD: Acute osteomyelitis, in Jauregui LE (ed): Diagnosis and Management of Bone Infections. New York, NY, Marcel Dekker, 1995, p 15.

Question 8

The pharmacologic effect of warfarin is caused by what mechanism? 1. Inhibition of platelet aggregation 2. Inhibition of hepatic enzymes that activate vitamin K 3. Binding to vitamin K-dependent clotting factors II, VII, IX, and X 4. Binding to antithrombin III, which increases its affinity for activated Factor X and thrombin 5. Direct binding to vitamin K

Answer 8

PREFERRED RESPONSE: 2 DISCUSSION: Warfarin acts by inhibiting hepatic enzymes, vitamin K epoxide, and possibly vitamin K reductase. This inhibition leads to reduced carboxylation of vitamin K-dependent proteins (prothrombin and factors VII, IX, and X). The therapeutic effect of warfarin on the clotting cascade is delayed by the time necessary for normal clotting factors to be turned over and replaced by decarboxylated factors. Factor VII, with a half-life of 6 to 7 hours, is the first to be affected. The early onset of therapeutic anticoagulation may be limited by the simultaneous suppression of the antithrombogenic factor, Protein C, which is also a carboxylated vitamin K-dependent protein. Warfarin does not act by binding directly to vitamin K or to clotting factors. REFERENCES Zimlich RH, Fulbright BM, Friedman RJ: Current status of anticoagulation therapy after total hip and total knee arthroplasty. J Am Acad Orthop Surg 1996;4:54-62. Colwell CW, Spiro TE, Trowbridge AA, et al: Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep vein thrombosis after elective hip replacement: A clinical trial comparing efficacy and safety. J Bone Joint Surg Am 1994;76:3-14. RD Heparin Arthroplasty Group: RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg Am 1994;76:1174-1185.

Question 9

A brittle material such as a ceramic femoral head prosthesis undergoes what type(s) of deformation when loaded to failure? 1. Elastic and plastic 2. Elastic 3. Plastic 4. Viscoelastic 5. Viscoelastic and plastic

Answer 9

PREFERRED RESPONSE: 2 DISCUSSION: Brittle materials undergo only fully recoverable (elastic) deformation prior to fracture. Brittle materials have little or no capacity to undergo permanent (plastic) deformation prior to fracture. The properties of brittle materials are neither temperature nor rate dependent (viscoelastic). REFERENCES Burstein AH, Wright TM: Fundamentals of Orthopaedic Biomechanics. Baltimore, MD, Williams & Wilkins, 1994, pp 95-129. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 449-452.

Question 10

The risk of human immunodeficiency virus (HIV) transmission via a processed musculoskeletal allograft obtained from an American Association of Tissue Banks (AATB) certified bone bank is estimated to be 1. 1 in 50,000. 2. 1 in 100,000. 3. 1 in 500,000. 4. 1 in 1.5 million. 5. 1 in 5 million.

Answer 10

PREFERRED RESPONSE: 4 DISCUSSION: In a recent review, the risk of HIV transmission in patients receiving processed musculoskeletal allografts from reputable bone banks was estimated to be 1 in 1.5 million. The following precautions are important: Bone banks certified by the AATB screen all donors by taking a social and medical history and performing serology for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, syphilis, human T cell leukemia virus antibody, HIV-I and -II antibody and HIV-I antigen (P24). Some banks examine donor tissues for HIV using polymerase chain reaction technology. Using this technology, one infected cell can be reliably detected in a population of 106 uninfected cells. Additionally, the interval between inoculation of a person with the virus and detection of the virus is shorter than with antibody tests. When the tissue or bone is processed (debrided, washed, soaked in ethanol or antibiotics), the risk is further reduced. To date there has been no documented case of disease transmission by processed musculoskeletal allografts. REFERENCE Tomford WW: Transmission of disease through transplantation of musculoskeletal allografts. J Bone Joint Surg Am 1995;77:1742-1754.

Question 11

Which of the following methods or parameters would best determine the percentage of aneuploid cells in a malignant tumor? 1. Immunohistochemistry 2. Histiologic mapping 3. Degree of necrosis 4. Presence of dedifferentiation 5. Flow cytometry

Answer 11

PREFERRED RESPONSE: 5 DISCUSSION: Flow cytometry is a method by which the amount of DNA in cells is quantified. Thousands of cell nuclei, normal and neoplastic, are passed through a machine that uses a fluorescent dye as a marker of the DNA content. The pattern generated can be characterized as either normal or abnormal based on the cell ploidy. By convention, the amount of DNA in an ovum or sperm is haploid, and normal cells are diploid (euploid) in the G0 phase of the cell cycle, twice the amount of DNA (tetraploid) is seen during cell division. Normal flow cytometry patterns demonstrate a large diploid spike with a much smaller tetraploid spike representing those few cells undergoing division. Abnormal amounts of DNA (aneuploid) show patterns outside of these two spikes. Immunohistochemical analysis can assist in histiologic classification of tumors but does not measure aneuploidy. The degree of necrosis and presence of dedifferentiation may signify a high-grade lesion, but does not relate to the aneuploid nature of malignant cells. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 219-276. Mankin HJ, Conner JF, Schiller AL, et al: Grading of bone tumors by analysis of nuclear DNA content using flow cytometry. J Bone Joint Surg Am 1985;67:404-413.

Question 12

Which of the following variables most influences the volumetric wear of polyethylene occurring on secondary surfaces (backside wear) in modular total hip and total knee components? 1. Total contact area 2. Roughness of the metal surface 3. Composition of the metal surface 4. Magnitude of the load 5. Relative motion

Answer 12

PREFERRED RESPONSE: 5 DISCUSSION: Wear is the removal of material that occurs as the result of relative motion between two opposed surfaces. All of these factors can influence the volume of backside polyethylene wear; however, the most important factor is relative motion. Surfaces in contact without relative motion do not wear. REFERENCE McKellop HA, Campbell P, Park SH, et al: The origin of submicron polyethylene wear debris in total hip arthroplasty. Clin Orthop Relat Res 1995;311:3-20.

Question 13

What factor is most likely to decrease the rigidity of an external fixation system? 1. Increased pin diameter 2. Increased pin number 3. Decreased pin separation 4. Decreased pin group separation 5. Increased distance of the side bar to the bone

Answer 13

PREFERRED RESPONSE: 5 DISCUSSION: An increase in pin length (bone surface to frame) significantly increases the deformability to load, and reduces the construct rigidity. The longer the length of a rod or pin, the greater the deformation under a given load. As the point of attachment of the sidebar is moved further from the bone surface, the effective pin length is increased. REFERENCES Chao EYS, Aru HT: Biomechanics of fracture fixation, in Mow VC, Hayes WC (eds): Basic Orthopaedic Biomechanics. New York, NY, Raven Press, 1991, pp 309-315. Chao EYS, Kasman RA, An KN: Rigidity and stress analysis of external fracture fixation devices: A theoretical approach. J Biomech 1982;15:971-983.

Question 14

Which of the following functions primarily as an osteoconductive as opposed to an osteoinductive material? 1. Autogenous cortical bone 2. Demineralized bone matrix 3. Freeze-dried cortical allogeneic bone 4. Autogenous cancellous bone 5. Bone morphogenetic protein

Answer 14

PREFERRED RESPONSE: 3 DISCUSSION: Freeze-dried cortical allografts are almost exclusively osteoconductive. All of the above materials have been used to augment bone repair. Osteoconduction is a property of bone graft materials, which provide a three-dimensional trellis for the ingrowth of host capillaries and osteoprogenitor cells. Osteoinduction involves the recruitment and differentiation of undifferentiated mesenchymal stem cells from the surrounding host tissues to osteoblasts. Osteoinductive substances can promote bone formation in ectopic sites. Autogenous bone grafts are osteogenic, which means they possess the intrinsic potential to form new bone. They also are osteoconductive. Allografts are not considered osteoinductive because this property is lost through processing to eliminate immunologic barriers. Bone morphogenetic proteins are purely osteoinductive. REFERENCES Burchardt H: The biology of bone graft repair. Clin Orthop Relat Res 1983;174:28-42. Goldberg VM, Stevenson S: The biology of bone grafts. Semin Arthroplasty 1993;4:58-63. Damien CJ, Parsons JR: Bone graft and bone graft substitutes: A review of current technology and applications. J Appl Biomater 1991;2:187-208.

Question 15

What antibiotic works by inhibiting DNA gyrase? 1. Penicillin 2. Gentamicin 3. Vancomycin 4. Ciprofloxacin 5. Clindamycin

Answer 15

PREFERRED RESPONSE: 4 DISCUSSION: The quinolone antibiotics such as ciprofloxacin function by inhibiting DNA gyrase. Gentamicin and clindamycin act via different mechanisms to interfere with bacterial RNA function. Penicillin binds to bacterial surface membrane proteins. inhibiting peptidoglycan synthesis. Vancomycin interferes with the insertion of glycan subunits into the cell wall. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, lL, American Academy of Orthopaedic Surgeons, 1994, p 505. Frymoyer JW (ed): Orthopaedic Knowledge Update 4: Home Study Syllabus. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1993, p 157.

Question 16

In some cases of osteopetrosis, bone resorption and remodeling are impaired because of a defect in carbonic anhydrase. The function of this enzyme in bone is to 1. promote maturation of mononuclear phagocytes into osteoclasts. 2. degrade osteoid. 3. generate hydrogen ions at the ruffled border. 4. promote coupling between osteoblasts and osteoclasts. 5. initiate stress-related remodeling.

Answer 16

PREFERRED RESPONSE: 3 DISCUSSION: Osteoclasts are attached to underlying bone via integrin receptors in the clear zone. This effectively seals the space below the osteoclasts. Hydrogen ions produced by carbonic anhydrase are pumped into the space across the ruffled border of the osteoclasts. In the ruffled border space, the underlying hydroxyapatite is solubilized in the low pH and calcium ions are released. Patients who are deficient in carbonic anhydrase cannot resorb bone by this mechanism. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 185-217. Poss R (ed): Orthopaedic Knowledge Update 3: Home Study Syllabus. Park Ridge, IL, American Academy of Orthopaedic Surgeons, 1990, pp 29-45.

Question 17

The structure of cartilage proteoglycans can be described as 1. multiple hyaluronate molecules bound to core protein, which is subsequently bound to a glycosaminoglycan chain. 2. multiple glycosaminoglycan chains bound to hyaluronate, which is subsequently bound to core protein. 3. multiple glycosaminoglycans bound to core protein, which is subsequently bound to hyaluronate via a link protein. 4. multiple link proteins bound to core protein, which is subsequently bound to glycosaminoglycan. 5. multiple hyaluronate chains bound to link protein, which is subsequently bound to glycosaminoglycan.

Answer 17

PREFERRED RESPONSE: 3 DISCUSSION: Cartilage proteoglycans are large negatively charged molecules with a molecular weight of several million and a spatial configuration reminiscent of a test tube brush. The core of the brush is the hyaluronate (a complex sugar), to which are attached many proteoglycan core proteins through an interaction with link protein. On each core protein are many glycosaminoglycan chains. REFERENCES Bullough PO, Vigorita VJ: Atlas of Orthopaedic Pathology. Baltimore, MD, University Press, 1984, p 34. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 9-11.

Question 18

A newly discovered gene (retinoblastoma gene) is expressed in normal cells. Loss of this gene results in a malignant phenotype. What type of gene is being described? 1. Dominant oncogene 2. Recessive oncogene 3. Proto-oncogene 4. Suppressor gene 5. Transgene

Answer 18

PREFERRED RESPONSE: 4 DISCUSSION: The retinoblastoma (RB) gene encodes for a protein that regulates a specific oncogene that, if absent, results in oncogene expression. The RB gene is termed a tumor suppressor gene. Onco-genes, when expressed, result in a malignant phenotype. A proto-oncogene is a normal gene. A transgene is not normally found in an organism, but it can be artificially placed into the single-celled embryo and therefore will be present in all cells of that organism. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 219-276. Lewin B: Genes, ed 3. New York, NY, John Wiley & Sons, 1987, pp 698-715.

Question 19

What component of frozen allograft bone has the least amount of immunogenicity? 1. Bone marrow cells 2. Proteoglycans 3. Hydroxyapatite 4. Cytokines 5. Cell surface proteins

Answer 19

PREFERRED RESPONSE: 3 DISCUSSION: Large frozen allografts are composite materials and contain a variety of potential antigens. Allografts are primarily subjected to cellular mechanisms, as opposed to humoral rejection mechanisms. Class I and class II cellular antigens, which are encoded by the major histocompatibility complex (MHC) contained within the allograft, are the major alloantigens that are recognized by host T-lymphocytes. Cellular populations that contribute to this antigen pool include marrow adipose tissue, microvascular endothelium, and retinacular activating cells, with those of granulocytic origin being the most inflammatory. The extracellular matrix in the graft elicits a measurable antigenic response, but this response is greatly diminished when compared with the cellular components. Type I collagen, which represents nearly 90% of the organic matrix of bone, has been shown to stimulate both humoral and cell-mediated responses in vivo. The noncollagenous portion of organic bone matrix, consisting of large proteoglycan molecules as well as osteocalcin, osteopontin, and other glycoproteins, has been reported to stimulate immune responsiveness. Hydroxyapatite, the mineral component of bone, has not been shown to elicit an immune response. The failure of allograft incorporation is associated with the degree of allograft cellularity, as well as the MHC incompatibility between allografts and host tissues. REFERENCES Horowitz MC, Friedlaender GE: Induction of specific T-cell responsiveness to allogeneic bone. J Bone Joint Surg Am 1991;73:1157-1168. Muscolo DL, Caletti E, Schajowicz F, Araujo ES, Makino A: Tissue-typing in human massive allografts of frozen bone. J Bone Joint Surg Am 1987;69:583-595. Trentham DE, Townes AS, Kang AH, David JR: Humoral and cellular sensitivity to collagen and type II collagen induced arthritis in rats. J Clin Invest 1978;61:89-96.

Question 20

What portion of the knee meniscus has the greatest concentration of mechanoreceptors? 1. Peripheral one third 2. Central one third 3. Inner two thirds 4. Anterior horn 5. Posterior horn

Answer 20

PREFERRED RESPONSE: 5 DISCUSSION: The neural elements are found in greatest concentration in the horns of the meniscus, and particularly in the posterior horns. The presence of these mechanoreceptors may play a role in sensory feedback of the knee. REFERENCES 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 532-545. O’Connor BL: The mechanoreceptor innervation of the posterior attachments of the lateral meniscus of the dog knee joint. J Anat 1984;138:15-26.

Question 21

Figure 1 shows the radiograph of a 6-year-old girl who has a right thoracic scoliosis that measures 60°. Examination shows multiple cafe-au-lait spots, and family history reveals that the child’s mother has the same disorder. The gene responsible for this disorder codes for 1. dystrophin. 2. frataxin. 3. neurofibromin. 4. peripheral myelin protein. 5. sulfate transport protein. Fig. 1.

Answer 21

PREFERRED RESPONSE: 3 DISCUSSION: The patient has the dystrophic type of scoliosis seen in patients with neurofibromatosis type I (NF-1). The NF-1 gene is located on chromosome 17 and codes for neurofibromin, believed to be a tumor-suppresser gene. Abnormalities in the dystrophin gene are seen in Duchenne muscular dystrophy and Becker muscular dystrophy. A mutation in the frataxin gene is responsible for Friedreich ataxia. The most common type of hereditary motor and sensory neuropathy (Charcot-Marie-Tooth), HMSN type IA is caused by a complete duplication of the peripheral myelin protein gene. A defect in the cellular sulfate transport protein results in undersulfation of proteoglycans seen in diastrophic dysplasia. REFERENCE Beaty JH: Orthopaedic Knowledge Update 6. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1999, pp 225-234.

Question 22

In children, scurvy has the greatest effect on bone formation in the 1. physis. 2. diaphysis. 3. epiphysis. 4. metaphysis. 5. articular surface.

Answer 22

PREFERRED RESPONSE: 4 DISCUSSION: Deficiency of vitamin C produces a decrease in chondroitin sulfate synthesis, and a deficiency in collagen cross-linking is seen in the metaphysis. The microscopic appearance of the cartilaginous portion of the growth plate is normal but the metaphysis is quite abnormal. It appears that the deficiency in the metaphysis is related to the large amount of type I collagen normally found in this region. Radiographic findings may include the accumulation of calcified cartilage at the metaphysis-growth plate junction that results in a white line on the radiograph (white line of Fraenkel). The trabeculae are sparse and there is a generalized osteoporosis. The metaphyseal bone is weakened with microfractures and marginal spurs (Pelkin sign). Displacement of the growth plate may occur. The epiphyseal nucleus is also markedly radiolucent, but the calcified cartilage is unaffected, producing an appearance of ringed epiphyses (Wimberger sign). REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 185-217. Ramar S, Sivaramakrishnan V, Manoharan K: Scurvy: A forgotten disease. Arch Phys Med Rehabil 1993;74:92-95.

Question 23

Warfarin limits the risk of deep venous thrombosis (DVT) by which of the following actions? 1. Competitive inhibition of vitamin K-dependent clotting factors 2. Inhibition of the posttranslational modification of vitamin K-dependent clotting factors 3. Reversible inhibition of platelet function 4. Irreversible inhibition of platelet function 5. Potentiation of antithrombin III

Answer 23

PREFERRED RESPONSE: 2 DISCUSSION: Warfarin is an oral anticoagulant that inhibits the posttranslational carboxylation of clotting factors II, VII, IX, and X (the so-called “vitamin K-dependent clotting factors”) in the liver. When these factors are not carboxylated, they cannot bind calcium or function in the clotting cascade. Therefore, warfarin does not competitively inhibit the factors, but rather reduces their active concentration. Aspirin and its analogues inhibit platelet function. The potentiation of antithrombin III is the mechanism by which heparin functions as an anticoagulant. REFERENCE Gilman AG, et al: The Pharmacological Basis of Therapeutics. New York, NY, MacMillan Publishing.

Question 24

What is the most common bacterium found in an infection caused by a human bite? 1. Eikenella 2. Pasturella multocida 3. Borrelia burgdorferi 4. Salmonella typhosa 5. Methicillin-resistant Staphylococcus aureus

Answer 24

PREFERRED RESPONSE: 1 DISCUSSION: The human bite is the most common source for Eikenella, and a cat bite is a source of Pasturella multocida. Lyme disease is caused by a tick bite (either Ixodes dammini or Io pacificus) that carries the bacteria Borrelia burgdorferi. Staphylococcus and Streptococcus remain the most common bacteria that cause orthopaedic infections and must always be assumed present until cultures or response (or lack of response) prove otherwise. REFERENCES Beaty JH (ed): Orthopaedic Knowledge Update 6. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1999, pp 191-203. Kasser JR (ed): Orthopaedic Knowledge Update 5. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1996, pp 149-161, 295-309. 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 240-259.

Question 25

The rate of chondrocyte maturation in the growth plate is directly regulated by an interaction between systemic hormones and 1. electric fields. 2. local growth factors. 3. oxygen tension. 4. mechanical forces. 5. calcium concentrations.

Answer 25

PREFERRED RESPONSE: 2 DISCUSSION: Local growth factors directly regulate the rate of chondrocyte maturation in the growth plate. A signaling loop involving parathyroid-related peptide (PTHrP), which is a potent inhibitor of chondrocyte maturation, and indian hedgehog has been well described. Indian hedgehog is produced by growth plate chondrocytes and regulates the expression of PTHrP. Systemic factors, such as vitamin D and growth hormone, also have important effects on chondrocyte differentiation, but indirectly regulate this process. While electric fields may influence fracture healing, a role in physeal chondrocyte maturation has not been identified. Mechanical forces are important for normal growth, but the nature of their effects is not known. Calcification of the cartilaginous matrix is essential for primary bone formation, but external calcium concentrations do not affect differentiation. In the past, a low oxygen tension was considered responsible for chondrocyte hypertrophy and differentiation, but that is now known to be incorrect. REFERENCES Grimsrud CD, Romano PR, D'Souza M, et al: BMP-6 is an autocrine stimulator of chondrocyte differentiation. J Bone Miner Res 1999;14:475-482. Erickson DM, Harris SE, Dean DD, et al: Recombinant bone morphogenetic protein (BMP)-2 regulates costochondral growth plate chondrocytes and induces expression of BMP-2 and BMP-4 in a cell maturation-dependent manner. J Orthop Res 1997;15:371-380.

Question 26

A genetic defect in type X collagen is most likely to result in which of the following conditions? 1. Multiple early fractures 2. Osteoporosis 3. Chondrodysplasia 4. Joint laxity 5. Inflammatory arthritis

Answer 26

PREFERRED RESPONSE: 3 DISCUSSION: Type X collagen is a short-chain, nonfibrillar collagen that is produced only by hypertrophic chondrocytes during the process of endochondral ossification. This collagen is found in the matrix in association with hypertrophic chondrocytes in all areas of endochondral bone formation, including growth plate, fracture callus, and heterotopic bone formation. Although a specific role for type X collagen has not been identified in endochondral bone formation, a genetic defect in this collagen is associated with Schmid metaphyseal chondrodysplasia, which is characterized by short limbs and bowing of the legs that is aggravated by walking. Similar to defects in type I collagen, which give rise to osteogenesis imperfecta, multiple separate mutations have been identified in patients with Schmid metaphyseal chondrodysplasia. More than 10 separate mutations have been identified thus far and all involve the noncollagenous globular region of the type X collagen molecule. Multiple early fractures are associated with osteogenesis imperfecta, a genetic defect in type I collagen. Joint laxity is associated with diseases such as Ehlers-Danlos syndrome, which results from a genetic defect in lysyl oxidase, an enzyme involved in collagen cross-linking and which also leads to hyperdistensible skin. Inflammatory arthritis is not associated with collagen disorders. Osteoporosis results from a decrease in bone density, and whereas most cases are idiopathic, some individuals with osteoporosis have been identified as having mild and previously unrecognized disorders of type I collagen consistent with osteogenesis imperfecta. REFERENCE Warman ML, Abbott M, Apte SS, et al: A type X collagen mutation causes Schmid metaphyseal chondrodysplasia. Nat Genet 1993;5:79-82.

Question 27

Most natural biologic materials are anisotropic, meaning that their stress-strain curve exhibits 1. different moduli for compressive and tensile tests. 2. a high degree of nonlinearity. 3. a high sensitivity to the size of the test specimen. 4. dependence on the rate of loading. 5. dependence on the direction of load application.

Answer 27

PREFERRED RESPONSE: 5 DISCUSSION: Isotropic materials have the same elastic properties in three orthogonal directions; anisotropy means that the properties are different when loading in at least one direction. A ligament that is very stiff in the direction of the collagen fibers, but much more compliant in the two transverse directions, is a simple example. Knowing and reporting the direction of load on a test sample is extremely important in measuring the properties of anisotropic materials. The tensile and compressive properties of ligaments are also very different, but this is not anisotropy; isotropic materials can also behave in this manner (eg, cement). Stress-strain curves that vary with the test rate are a hallmark of viscoelastic materials; those sensitive to sample size indicate heterogeneity. Nonlinearity can result from many compositional and structural features. REFERENCES Ratner B, Hoffman AS, Schoen FJ, et al: Biomaterials Science. San Diego, CA, Academic Press, 1996, pp 16-17. 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 182-215.

Question 28

Which of the following factors is most commonly associated with late aseptic loosening of cemented acetabular components? 1. Increased frictional torque 2. Recurrent neck-socket impingement 3. Fatigue failure of cement 4. Poor initial component fixation 5. Polyethylene wear

Answer 28

PREFERRED RESPONSE: 5 DISCUSSION: Surgical and autopsy specimens consistently document the presence of macrophages containing many submicron polyethylene wear particles in cement-bone interfacial tissue. Progressive disruption of the cement-bone interface by this inflammatory process results in late component loosening. REFERENCE Schmalzried TP, Kwong LM, Jasty M, et al: The mechanism of loosening of cemented acetabular components in total hip arthroplasty: Analysis of specimens retrieved at autopsy. Clin Orthop Relat Res 1992;274:60-78.

Question 29

Which of the following processes will most greatly increase the wear damage to an ultrahigh molecular weight polyethylene articulating surface? 1. Ethanol sterilization 2. Third body inclusion 3. Cold flow deformation 4. Gamma radiation sterilization 5. Ion implantation on the mating metallic surface

Answer 29

PREFERRED RESPONSE: 2 DISCUSSION: While recent data suggest that both storage and sterilization techniques affect the wear properties of ultrahigh molecular weight polyethylene, the most dramatic increase in wear is associated with third body inclusion on the articular surface. REFERENCES Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 449-486. McKellop HA, Campbell P, Park SH, et al: The origin of submicron polyethylene wear debris in total hip arthroplasty. Clin Orthop Relat Res 1995;311:3-20.

Question 30

What is the function of a transcription factor? 1. Bind to DNA and influence gene expression 2. Bind to cell membrane receptors and induce phosphorylation 3. Package DNA 4. Unwind DNA 5. Dehydrate cellular proteins

Answer 30

PREFERRED RESPONSE: 1 DISCUSSION: Transcription factors bind to DNA and initiate gene transcription. A variety of transcription factors have been identified and some have a specific role in bone and cartilage physiology. Many transcription factors are present in the cell in an inactive form, but are activated by a series of phosphorylation reactions that follow the binding of a growth factor or other ligand to a specific cellular receptor. Cancers are frequently associated with the abnormal activation of transcription factors. Histones are molecules that bind and package DNA, but are not involved in transcription. Helicases unwind DNA and are involved in DNA synthesis, while metalloproteinases are enzymes that are involved in tissue catabolism and are involved in the pathogenesis of arthritis. REFERENCES Schmitt JM, Hwang K, Winn SR, Hollinger JO: Bone morphogenetic proteins: An update on basic biology an clinical relevance. J Orthop Res 1999;17:269-278. Reddi AH: Initiation of fracture repair by bone morphogenetic proteins. Clin Orthop Relat Res 1998;355:S66-S72. 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 20-76.

Question 31

What is the most common bacterium found in an infection caused by a tick bite? 1. Eikenella 2. Vibrio vulnificus 3. Borrelia burgdorferi 4. Clostridium perfringens 5. Methicillin-resistant Streptococcus

Answer 31

PREFERRED RESPONSE: 3 DISCUSSION: Lyme disease is caused by a tick bite (either Ixodes dammini or Io pacificus) that carries the bacterium Borrelia burgdorferi. The human bite is the most common source for Eikenella, and a cat bite is a source of Pasturella multocida. Brackish water can cause a devastating infection of Vibrio vulnificus. Staphylococcus and Streptococcus remain the most common bacteria that cause orthopaedic infections and must always be assumed present until cultures or response (or lack of response) prove otherwise. REFERENCES Beaty JH (ed): Orthopaedic Knowledge Update 6. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1999, pp 191-203. Kasser JR (ed): Orthopaedic Knowledge Update 5. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1996, pp 149-161, 295-309. 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 240-259.

Question 32

Methicillin-resistant Staphylococcus aureus can be treated effectively with an oral quinolone and which of the following antibiotics to achieve synergy? 1. Penicillin 2. Probenecid 3. Rifampin 4. Cefoxitin 5. Amoxicillin

Answer 32

PREFERRED RESPONSE: 3 DISCUSSION: Rifampin has been shown to have synergy with quinolones in the treatment of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis. Each of the two antibiotics lessens the development of resistant mutants. REFERENCES Chambers HF: Methicillin resistance in staphylococci: Molecular and biochemical basis and clinical implications. Clin Microbiol Rev 1997;10:781-791. Drancourt M, Stein A, Argenson JN, et al: Oral rifampin plus ofloxacin for treatment of Staphylococcus-infected orthopaedic implants. Antimicrob Agents Chemother 1993;37:1214-1218.

Question 33

A fully differentiated osteoclast has receptors for which of the following proteins? 1. Parathyroid hormone (PTH) 2. Calcitonin 3. Cholecalciferol 4. Bone morphogenetic protein (BMP) 5. Interleukin-2 (IL-2)

Answer 33

PREFERRED RESPONSE: 2 DISCUSSION: Osteoclasts resorb bone in response to specific systemic and intracellular signals. Regulation of osteoclastic bone resorption depends on the way its physiologic function is regulated through receptor mediated pathways. Calcitonin is a peptide hormone that directly binds to a cell surface receptor on osteoclasts to inhibit osteoclast function. Although PTH is frequently regarded as an agent that stimulates bone resorption, osteoclasts do not possess receptors for this hormone; instead, they are signaled to resorb bone by osteoblasts, the cells that possess receptors to PTH. IL-2 is an immunomodulatory cytokine that does not directly influence osteoclast function. BMP is the name for a family of osteoinductive proteins, many of which have receptors in osteoblast progenitor cells, but not in fully differentiated osteoclasts. Although osteoclast precursors do directly respond to 1,25 dihydroxycholecalciferol, they do not have a receptor for cholecalciferol itself (vitamin D). REFERENCES Suda T, Udagawa N, Takahashi N: Cells of bone: Osteoclast generation, in Bilezikian JP, Raisz LG, Rodan GA (eds): Principles of Bone Biology. San Diego, CA, Academic Press, 1996, pp 87-102. Mundy GR: Bone resorbing cells, in Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, ed 3. Philadelphia, PA, Lippincot-Raven, 1996, pp 16-24.

Question 34

Cephalosporins are effective antibiotic agents because of their action on what aspect of bacterial metabolism? 1. DNA gyrase 2. Cell wall 3. mRNA 4. Cell membrane 5. Protein

Answer 34

PREFERRED RESPONSE: 2 DISCUSSION: The mechanism of action has been defined for seven antibiotic classes. The cephalosporin action is to inhibit cell wall synthesis. Quinolones inhibit DNA gyrase. Beta-lactam antibiotics bind to the surface of the cell membrane. Aminoglycosides inhibit protein synthesis by binding to ribosomal RNA. Rifampin inhibits RNA synthesis in bacteria. REFERENCE Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, pp 489-517.

Question 35

Repair of the peripheral one third of the meniscus is sometimes possible because it has which of the following characteristics? 1. Increased blood supply 2. Appropriate viscoelasticity 3. High glycoprotein concentration 4. High type II collagen concentration 5. Large size

Answer 35

PREFERRED RESPONSE: 1 DISCUSSION: The outer one third of the meniscus is well vascularized, and this characteristic allows for an excellent healing potential. REFERENCES 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, pp 2000, 532-545. Arnozczky SP: Gross and vascular anatomy of the meniscus and its role in meniscal healing, regeneration and remodeling, in Mow VC, Arnozczky SP, Jackson DW (eds): Knee Meniscus Basic and Clinical Foundations. New York, NY, Raven Press, 1992, pp 1-14.

Question 36

During the first 2 years of life, which of the following actions is most responsible for increasing structural stability of the physis? 1. The change from a flat to an undulating physis 2. The growth of the zone of Ranvier 3. Increased strength of the points of insertion of muscles onto bone 4. Increased penetration of proprioceptive nerve endings about the physis 5. Increased capillary penetration about the physis

Answer 36

PREFERRED RESPONSE: 2 DISCUSSION: The zone of Ranvier provides the earliest increase in strength of the physis. 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. The zone also helps the physis grow latitudinally. In turn, the increased width of the physis helps the physis further resist mechanical forces. The change in shape of the physis to its progressively more undulating form is also a factor in increasing physeal strength, but this occurs over a longer period of time, as the child's activity level increases. The undulations of the physis seen in some growth plates also add to stability but to a lesser extent. The other changes contribute little toward increasing physeal strength. REFERENCES Burkus JK, Ogden JA: Development of the distal femoral epiphysis: A microscopic morphological investigation of the zone of Ranvier. J Pediatr Orthop 1984;4:661-668. Shapiro F, Holtrop ME, Glimcher MJ: Organization and cellular biology of the perichondrial ossification groove of Ranvier: A morphological study in rabbits. J Bone Joint Surg Am 1977;59:703-723.

Question 37

Virtually all biological materials are viscoelastic, which means that their mechanical behavior is dependent on what factor? 1. Load applied 2. Cross-sectional area 3. Rate of loading 4. Mode of loading 5. Direction of loading

Answer 37

PREFERRED RESPONSE: 3 DISCUSSION: Viscoelastic materials exhibit both viscous and elastic behavior. Elastic materials have the same stress-strain relationship regardless of the rate at which the load is applied. Viscoelastic behavior is dependent upon the strain rate; the modulus increases as the strain rate increases. The faster a load is applied to such materials the more elastic they behave. Many materials, both elastic and viscoelastic (including bone), have different properties in tension and compression. Ligaments are an excellent example, stiff in tension but not in compression. Materials that have different mechanical properties in different directions are called anisotropic. REFERENCES Black J: Orthopaedic Biomaterials in Research and Practice. New York, NY, Churchill Livingstone, 1988, pp 57-81. Simon SR (ed): Orthopaedic Basic Science. Rosemont, IL, American Academy of Orthopaedic Surgeons, 1994, p 456.

Question 38

When a long bone is subjected to a bending moment, the greatest tensile stresses are located 1. within the cortex. 2. at the neutral axis. 3. at a periosteal surface. 4. at an endosteal surface. 5. along the bending axis.

Answer 38

PREFERRED RESPONSE: 3 DISCUSSION: The greatest tensile stresses are on the convex outer surface of the bone. In bending, the neutral axis is where the transition occurs from tension to compressive stress, and stresses are at a minimum. In a symmetrical structure, the neutral axis and the benign axis align, but in an asymmetric structure such as a long bone, the axes do not align. REFERENCES Timoshenko S, Young DH: Elements of Strength of Materials, ed 5. New York, NY, Van Nostrand Reinhold, 1968, pp 70-74. Burstein AH, Wright TM: Fundamentals of Orthopaedic Biomechanics. Baltimore, MD, Williams and Wilkins, 1994.

Question 39

What is the dominant component of articular cartilage extracellular matrix by weight? 1. Water 2. Collagen 3. Keratan sulfate 4. Chondroitin sulfate 5. Nerve and lymphatic tissue

Answer 39

PREFERRED RESPONSE: 1 DISCUSSION: Articular cartilage is a highly organized viscoelastic material, and load transmission depends on the specific composition of the extracellular matrix. Articular cartilage is devoid of neural, lymphatic, and blood vessel tissue. The extracellular matrix consists of water, proteoglycans, and collagen. Water comprises most of the wet weight (65% to 80%). Type II collagen comprises 95% of the collagen. The collagen and proteoglycan (keratan sulfate and chondroitin sulfate) matrix and its high water content are responsible for the mechanical properties of the articular cartilage. REFERENCES Buckwalter JA, Mankin HJ: Articular cartilage: Degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect 1998;47:487-504. Koval KJ (ed): Orthopaedic Knowledge Update 7. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 3-18.