ORTHOPEDICS HYPERGUIDE MCQ 901-950

901. (3289) Q2-4133:

The receptor activator of nuclear factor-kB ligand (RANKL) is expressed on the surface of which of the following cells:

1) Osteoclasts

3) Platelets

2) Osteoblasts and marrow stromal cells

5) Vascular endothelial cells

4) Macrophages

The RANKL is the final common denominator of osteoclast activation and is expressed on the surface of osteoblasts and marrow stromal cells.

Numerous conditions such as bone metastases, multiple myeloma, osteoporosis, hyperparathyroidism, and others result in osteoclast activation. In these conditions, there is an increased expression and release of the RANKL from the surface of the osteoblasts and marrow stromal cells. The RANKL then binds to the RANK receptor on the osteoclast precursor cells, differentiating into active osteoclasts.

C orrect Answer: Osteoblasts and marrow stromal cells

902. (3290) Q2-4134:

In transgenic mice, the overproduction of osteoprotegerin (OPG) results in which of the following conditions:

1) Multiple hereditary exostoses

3) Secondary hyperparathyroidism

2) Primary hyperparathyroidism

5) Osteopetrosis

4) Primary osteoporosis

Osteoprotegerin is a competitive decoy inhibitor that binds the receptor activator of nuclear factor-kB ligand (RANKL), thereby preventing the RANKL from attaching to the RANK receptor on osteoclast precursor cells. The ratio of the RANKL to OPG determines whether osteclast activation occurs.

When overproduction of OPG occurs, there is a marked reduction in osteoclast activation. In this scenario, osteopetrosis develops. In osteopetrosis, a lack of osteoclasts results in dense bone with virtually no marrow cavity.

C orrect Answer: Osteopetrosis

903. (3291) Q2-4135:

Which of the following factors are essential for osteoblast differentiation:

1) Dihydrofolate reductase

3) Insulin-like growth factor 1

2) C ore binding factor alpha 1 (C BFA1 or Runx2)

5) Osteoprotegerin (OPG)

4) Receptor activator of nuclear factor-kB ligand (RANKL)

Osteoblasts arise from mesenchymal stem cells. C ore binding factor alpha (C BFA1 or Runx2) is a transcription factor that induces most genes that are associated with osteoblast differentiation.C orrect Answer: C ore binding factor alpha 1 (C BFA1 or Runx2)

904. (3292) Q2-4136:

Which of the following factors most likely has a role in the production of osteoblastic bone metastases:

1) Receptor activator of nuclear factor-kB ligand (RANKL)

3) Osteoprotegerin (OPG)

2) Parathyroid hormone-related protein (PTHrP)

5) Macrophage inflammatory protein (MIP) 1 alpha

4) Endothelin-1

Endothelin-1 likely plays a major role in blastic metastases in breast and prostate cancers. Endothelin-1 stimulates bone formation and the proliferation of osteoblasts.

The mechanism of bone formation is not nearly as well defined as bone destruction in metastatic bone disease. Correct Answe Endothelin-1

905. (4059) Q2-4137:

Which of the following is a marker for osteoclastic activity:

1) Serum bone specific alkaline phosphatase

3) Serum type 1 procollagen C -propeptide

2) Serum osteocalcin

5) Serum endothelin-1

4) Urine type 1 collagen cross-linked N-telopeptides

The markers of osteoclastic activity are:

Serum C -terminal telopeptide of type 1 collagen

Serum tartrate resistant acid phosphatase

Urine type 1 collagen cross-linked N-telopeptides

Urine C -terminal telopeptide of type 1 collagen

The markers of osteoblastic activity are:

Serum bone specific alkaline phosphatase

Serum osteocalcin

Serum type 1 procollagen C -propeptide

Serum endothelin-1

C orrect Answer: Urine type 1 collagen cross-linked N-telopeptides

906. (4060) Q2-4138:

Which of the following is a marker for osteoblastic activity:

1) Serum C -terminal telopeptide of type-1 collagen

3) Urine type-1 collagen cross linked N-telopeptides

2) Serum tartrate resistant acid phosphatase

5) Serum osteocalcin

4) Urine C -terminal telopeptide of type 1 collagen

The markers of osteoclastic activity are:

Serum C -terminal telopeptide of type 1 collagen

Serum tartrate resistant acid phosphatase

Urine type 1 collagen cross-linked N-telopeptides

Urine C -terminal telopeptide of type 1 collagen

The markers of osteoblastic activity are:

Serum bone specific alkaline phosphatase

Serum osteocalcin

Serum type 1 procollagen C -propeptide

Serum endothelin-1

C orrect Answer: Serum osteocalcin

907. (3293) Q2-4139:

Which of the following is a marker for osteoblastic activity:

1) Serum C -terminal telopeptide of type 1 collagen

3) Urine type 1 collagen cross-linked N-telopeptides

2) Serum tartrate resistant acid phosphatase

5) Serum endothelin-1

4) Urine C -terminal telopeptide of type 1 collagen

The markers of osteoclastic activity are:

Serum C -terminal telopeptide of type 1 collagen

Serum tartrate resistant acid phosphatase

Urine type 1 collagen cross-linked N-telopeptides

Urine C -terminal telopeptide of type 1 collagen

The markers of osteoblastic activity are:

Serum bone specific alkaline phosphatase

Serum osteocalcin

Serum type 1 procollagen C -propeptide

Serum endothelin-1

C orrect Answer: Serum endothelin-1

908. (3294) Q2-4140:

A patientâs upper extremity radiographs are shown in Slide 1 and Slide 2. The most likely diagnosis is:

1) Enchondromatosis

3) Multiple hereditary exostoses

2) Eosinophilic granuloma

5) Spondyloepiphyseal dysplasia

4) Fibrous dysplasia

This patient has multiple hereditary exostoses. Note the multiple sessile osteochondromas on the humerus and ulna. A

characteristic bowing deformity of the forearm and pseudo-Madelung deformity of the wrist are also present.

Multiple hereditary exostoses is autosomal dominant. The putative tumor suppressive gene mutation is EXT1, EXT2. The risk of low-grade chondrosarcoma occurring is approximately 10%.

In most patients, the forearm deformity does not cause a major problem and can be treated nonoperatively. Correct Answe Multiple hereditary exostoses

909. (3295) Q2-4141:

slide 1                             slide 2

A patientâs upper extremity radiographs are shown in Slide 1 and Slide 2. What is the most likely inheritance pattern of this condition:

1) X-linked recessive

3) Autosomal recessive

2) X-linked dominant

5) Sporadic

4) Autosomal dominant

This patient has multiple hereditary exostoses. Note the multiple sessile osteochondromas on the humerus and ulna. A

characteristic bowing deformity of the forearm and pseudo-Madelung deformity of the wrist are also present.

Multiple hereditary exostoses is autosomal dominant. The putative tumor suppressive gene mutation is EXT1, EXT2. The risk of low-grade chondrosarcoma occurring is approximately 10%.

In most patients, the forearm deformity does not cause a major problem and can be treated nonoperatively. Correct Answe Autosomal dominant

910. (3296) Q2-4142:

slide 1                             slide 2

A patientâs upper extremity radiographs are shown in Slide 1 and Slide 2. Which of the following tumor suppressor genes is most likely involved:

1) Retinoblastoma (RB)

3) P16INK4A

2) p53

5) EXT1

4) NF1

This patient has multiple hereditary exostoses. Note the multiple sessile osteochondromas on the humerus and ulna. A

characteristic bowing deformity of the forearm and pseudo-Madelung deformity of the wrist are also present.

Multiple hereditary exostoses is autosomal dominant. The putative tumor suppressive gene mutation is EXT1, EXT2. The risk of low-grade chondrosarcoma occurring is approximately 10%.

In most patients, the forearm deformity does not cause a major problem and can be treated nonoperatively. Correct Answe EXT1

911. (3297) Q2-4143:

slide 1                             slide 2

A patientâs upper extremity radiographs are shown in Slide 1 and Slide 2. The risk of malignancy in this condition is approximately:

1) No risk of malignancy

3) 25%

2) 5% to 10%

5) 100%

4) 50%

This patient has multiple hereditary exostoses. Note the multiple sessile osteochondromas on the humerus and ulna. A

characteristic bowing deformity of the forearm and pseudo-Madelung deformity of the wrist are also present.

Multiple hereditary exostoses is autosomal dominant. The putative tumor suppressive gene mutation is EXT1, EXT2. The risk of low-grade chondrosarcoma occurring is approximately 10%.

In most patients, the forearm deformity does not cause a major problem and can be treated nonoperatively. Correct Answe 5% to 10%

912. (3298) Q2-4144:

Which of the following is an indication for surgery in patients with rheumatoid arthritis of the spine:

1) Posterior atlantodental interval between 14 mm and 16 mm

3) C ervico-medullary angle between 135° and 175°

2) Atlantodental interval >5 mm

5) Posterior atlantodental interval of 13 mm with subaxial subluxation

4) Odontoid migration of 4 mm above McGregorâs line

The review article by Kim and Hilibrand summarized the current indications for decompression and fusion in patients with rheumatoid arthritis and cervical spine disease.

The indications are:

A. Progressive neurologic deficit

1. Myelopathy â wide-based spastic gait, clumsy hands, change in handwriting, difficulty with fine motor control

B. Severe neck pain with atlantoaxial subluxation, atlantoaxial impaction, or subaxial subluxation

C . Atlantoaxial subluxation with a posterior atlantodental interval of <14 mm D. Atlantoaxial impaction â odontoid migration >5 mm above McGregorâs line E. Subaxial subluxation with a sagittal canal diameter <14 mm

F. C ervicomedullary angle <135°

C orrect Answer: Posterior atlantodental interval of 13 mm with subaxial subluxation

913. (3299) Q2-4145:

Which of the following statements is true concerning rheumatoid arthritis:

1) Rheumatoid arthritis does not affect life expectancy.

3) Erosion of the odontoid rarely occurs.

2) Men are affected twice as much as women.

5) Rheumatoid arthritis affects approximately 1% of the U.S. population

4) The atlantodental interval is the best prognostic factor for neurologic injury.

Rheumatoid arthritis is common and affects 0.5% to 1.5% of the U.S. population. Important points to remember include:

Women are affected twice as commonly as men. Rheumatoid arthritis reduces life expectancy.

Blockade of tumor necrosis alpha can be very effective.

The posterior atlantodental interval is more important than the anterior atlantodental interval.

A prospective study from Finland showed that over a 20-year period, patients with seropositive rheumatoid arthritis had the following risk of cervical spine disease:

Atlantoaxial subluxation â 23% Atlantoaxial impaction â 26% Subaxial subluxation â 19%

C orrect Answer: Rheumatoid arthritis affects approximately 1% of the U.S. population

914. (3300) Q2-4146:

Which of the following is a risk factor for progressive atlantoaxial subluxation in patients with rheumatoid arthritis of the cervical spine:

1) Male sex

3) HLA-b27 antigen

2) HLA-dr4 antigen

5) Seronegativity

4) Steroid use

In a review article, Kim and Hilibrand list the following as risk factors for progression of atlantoaxial subluxation in rheumatoid arthritis:

Male sex

Rheumatoid factor positivity Presence of subcutaneous nodules Rapid loss of carpal height

In contrast to the above, HLA-dr4 and HLA-b27 antigens are not significant risk factors. The use of steroids does not appear to be a significant risk factor.

C orrect Answer: Male sex

915. (3301) Q2-4147:

Which of the following posterior atlantodental intervals is associated with a very poor neurologic recovery following decompression and fusion:

1) <10 mm

3) 11 mm to 13 mm

2) 10 mm to 12 mm

5) 16 mm

4) 14 mm

In a review article, Kim and Hilibrand cite the reports of Boden which showed that, when the posterior atlantodental interval was

<10 mm, patients did not experience any neurologic recovery following surgery. In regard to preoperative posterior atlantodental interval, one should remember:

<10 mm No recovery

>10 mm Recovery of at least one Ranawat grade

>14 mm C omplete recovery

C orrect Answer: <10 mm

916. (3434) Q2-4355:

Osteochondroses of the tarsal navicular or the capitellum in a child is most likely the result of:

1) Genetic disorder

3) Benign neoplasm

2) Developmental disorder

5) Vascular insufficiency

4) Repetitive stress

The osteochondroses represent disordered growth and function of enchondral ossification under load or stress in a growing child. The causative stress is usually from overuse (eg, pitching). The disordered ossification is often accompanied by deformation of the cartilage and its adjacent interface with bone. In areas where the cartilage is under tension, the term apophysitis is also used.C orrect Answer: Repetitive stress

917. (3445) Q2-4372:

All of the following occur with focal nerve compression except:

1) Focal demyelination

3) C onduction block across the site

2) Nerve conduction velocity slowing

5) Small amplitude-short duration motor unit potentials

4) Fibrillation potentials and positive sharp waves

With focal nerve compression, focal demyelination is present. The axon remains intact but, with myelin loss, slowing of conduction occurs and a conduction block is possible.

C ommon findings with focal nerve compression include:

Focal demyelination

Nerve conduction velocity slowing C onduction block across the site Fibrillation potentials

Positive sharp waves

High amplitude-long duration motor unit potentials (chronic denervation)

In contrast, small amplitude-short duration motor unit potentials are found in myopathy. Correct Answe Small amplitude-short duration motor unit potentials

918. (3446) Q2-4373:

Which of the following is typically found on electrodiagnostic testing with denervation of skeletal muscle:

1) C omplex repetitive discharges

3) Myokymic potentials

2) Myotonic discharges

5) Myotonic discharges and myokymic potentials

4) Positive sharp waves and fibrillations

With electrodiagnostic testing, a clinician may find several characteristic features in different disorders: Denervation

Fibrillation

Positive sharp waves

Fasciculations

Neurogenic lesions

Fasciculations

Myokymic potentials

Myopathies

C omplex repetitive discharges

Myotonic discharges

C orrect Answer: Positive sharp waves and fibrillations

919. (3447) Q2-4374:

Which of the following factors is crucial for the differentiation of mesenchymal cells to osteoblasts:

1) Type X collagen

3) C BAF1/RUNX2

2) Type II collagen

5) Receptor activator of nuclear factor-kB ligand (RANKL)

4) Low level of beta-catenin

C BAF1/RUNX2 is a transcription factor that is essential for differentiation of mesenchymal cells to osteoblasts. This transcription factor is expressed during intramembranous bone formation and during hypertrophic phase of enchondral growth.

C leidiocranial dysplasia is caused by a failure to mineralize the cartilage anlagen. This genetic disorder is caused by a loss of function in C BAF1/RUNX2.

Phenotype of cleidocranial dysplasia includes: Short stature

Hypoplasia/aplasia of the clavicles

Delayed ossification and closure of cranial sutures

Defects in tooth eruption and extra teeth

C orrect Answer: C BAF1/RUNX2

920. (3448) Q2-4375:

Which of the following disorders occurs with a loss of function mutation (heterozygous) in C BAF1/RUNX2:

1) Achondroplasia

3) C leidocranial dysplasia

2) Osteopetrosis

5) Tertiary hyperparathyroidism

4) Primary osteoporosis

C leidocranial dysplasia is caused by a failure to mineralize the cartilage anlagen. This genetic disorder is caused by a loss of function in C BAF1/RUNX2.

Phenotype of cleidocranial dysplasia includes: Short stature

Hypoplasia/aplasia of the clavicles

Delayed ossification and closure of cranial sutures

Defects in tooth eruption and extra teeth

C orrect Answer: C leidocranial dysplasia

921. (3449) Q2-4376:

A patient sustains a humeral fracture that results in radial nerve palsy. At which of the following time points would an electrodiagnostic study be performed to check the integrity of the radial nerve:

1) Immediately following the injury

3) 14 days following the injury

2) 7 days following the injury

5) 6 to 8 weeks following the injury

4) 21 days following the injury

At 6 to 8 weeks following the injury, a clinician should perform an electrodiagnostic study to detect reinnervation. A needle electromyogram will show small amplitude polyphasic motor unit potentials.

The following is the typical of sequence of electrodiagnostic findings: Severance of the nerve

Positive sharp waves and fibrillation potentials at 2 weeks

Incomplete nerve injury

Small amplitude motor unit potentials at 6 to 8 weeks

C orrect Answer: 6 to 8 weeks following the injury

922. (3453) Q2-4381:

Which of the following factors plays a major role in inducing cells to form osteoblasts with resultant intramembranous bone formation:

1) Stable beta-catenin

3) Receptor activator of nuclear factor-kB ligand (RANKL)

2) SOX9

5) Type II collagen

4) Osteoprotegerin (OPG)

Bone forms from either intramembranous bone formation or enchondral bone formation.

Intramembranous bone formation occurs in the skull, maxilla, mandible, clavicle, and subperiosteal surface of long bones. This is

a complex process and is controlled by a signaling pathway called canonical Wnt and sonic hedgehog signaling. Beta-catenin is not degraded, and it enters the cell nucleus to induce genes for bone formation. The two most important transcription factors are C BFA1/RUNX2 and osterix (OSX). Stable beta-catenin drives the process toward intramembranous bone formation.

Angiogenesis is also important and vascular endothelial factor alpha (VEGF-A) plays an important role in bone formation. Correct Answe Stable beta-catenin

923. (3454) Q2-4382:

Which of the following statements is true concerning intraoperative acetabular fractures following uncemented total hip arthroplasty:

1) The incidence is highest with an elliptical modular cup design.

3) The incidence is highest with an elliptical monoblock design.

2) The incidence is highest with a true elliptical modular cup design.

5) Plate fixation in addition to augmentation of the cup with screws is often necessary.

4) The location of the fracture is most likely to be anterosuperior.

Intraoperative acetabular fractures with uncemented cups are rare. This Mayo C linic study showed a fracture rate of 3.5% with an elliptical monoblock cup. The rate with the monoblock cup was significantly higher than the elliptical modular and hemispherical modular designs (both <0.5%). The fractures were usually found posterior superior (12/21), direct posterior (posterior wall) (6/21), and much less commonly anterosuperior or medial. If the cup was unstable after the fracture, then it was removed, and another cup with screw fixation was used. All fractures healed uneventfully with no adverse sequelae. The authors recommend under-reaming ≤2 mm regardless of cup design.C orrect Answer: The incidence is highest with an elliptical monoblock design.

924. (3456) Q2-4384:

Which of the following is associated with achondroplasia:

1) Heterozygous loss of function mutation, C BF1/RUNX2

3) Parathyroid hormone-related protein (PTHrP) â loss of function mutation

2) C ollagen type X mutation

5) PTHrP activating mutation

4) Activating mutation of fibroblast growth factor receptor-3 (FGFR-3)

In achondroplasia, an activating mutation of the FGFR-3 is present.

During enchondral growth, the proliferation of the chondrocytes is controlled by fibroblast growth factor (FGF). FGF interacts with a cell surface tyrosine kinase receptor, FGFR-3. An activating mutation causes increased signaling for limitation of cartilage proliferation in the growth plate, resulting in short limbs.

The important mutations that cause short stature include: Achondroplasia: Activating mutation of FGFR-3

Jansenâs metaphyseal chondrodysplasia: Activating mutation of PTHrP

Blomstrandâs chondrodysplasia: Loss of function mutation of PTHrP C leidocranial dysplasia: Heterozygous loss of function mutation, C BF1/RUNX2

Schmidâs type metaphyseal chondrodysplasia: Type X collagen mutation

C orrect Answer: Activating mutation of fibroblast growth factor receptor-3 (FGFR-3)

925. (3458) Q2-4389:

Which of the following is the best diagnostic test to establish the diagnosis of cubital tunnel syndrome:

1) Sensory nerve conduction velocity, finger to wrist

3) Mixed nerve conduction velocity, finger to wrist

2) Motor nerve conduction velocity across the elbow

5) Motor conduction, elbow to axilla

4) Motor conduction, Erbâs point to axilla

Motor nerve conduction velocity testing across the elbow is the best diagnostic test to establish the diagnosis of cubital tunnel syndrome.C orrect Answer: Motor nerve conduction velocity across the elbow

926. (3459) Q2-4391:

Which of the following are typically found following a complete laceration of a peripheral nerve after 3 weeks:

1) Fasciculation potentials

3) Myokymic potentials

2) Fibrillation potentials and positive sharp waves

5) C omplex repetitive discharges

4) Myotonic discharges

A complete laceration of a peripheral nerve is a denervation injury.

With electrodiagnostic testing, a clinician may find several characteristic features in different disorders: Denervation

Fibrillation

Positive sharp waves

Fasciculations

Neurogenic lesions

Fasciculations

Myokymic potentials

Myopathies

C omplex repetitive discharges

Myotonic discharges

C orrect Answer: Fibrillation potentials and positive sharp waves

927. (3461) Q2-4393:

When the cartilage anlagen is expressed during the process of enchondral ossification, which of the following types of collagen is produced:

1) Types I, III

3) Type X

2) Types II, IX, XI

5) Types I, III, X

4) Type I

During the time that the cartilage anlagen is formed, the chondrocytes (or mesenchymal cells) produce cartilage-specific collagen. The collagen expression is shifted from the bone collagens (types I, III) to the cartilage collagens (types II, IX, XI).

Important points:

Type I: Major bone collagen

Types II, IX, and XI: Major cartilage collagens

Type X: Major collagen of hypertrophying and mineralizing chondrocytes

C orrect Answer: Types II, IX, XI

928. (3462) Q2-4396:

Which of the following is associated with Jansenâs metaphyseal chondrodysplasia:

1) Heterozygous loss of function mutation, C BF1/RUNX2

3) Parathyroid hormone-related protein (PTHrP) â loss of function mutation

2) C ollagen type X mutation

5) PTHrP activating mutation

4) Activating mutation of fibroblast growth factor receptor-3 (FGFR-3)

Parathyroid hormone-related protein (PTHrP) has a specific inhibitory effect on chondrocyte differentiation (inability to hypertrophy). During enchondral growth, the chondrocytes hypertrophy and then mineralize to form bone.

Activating mutations of PTHrP cause a decrease in chondrocyte hypertrophy and result in short stature (Jansenâs metaphyseal chondrodysplasia). Blomstrandâs chondrodysplasia involves a loss of function mutation, resulting in accelerated chondrocyte hypertrophy and short stature.

Parathyroid hormone-related protein also affects Indian hedgehog signaling while Indian hedgehog induces PTHrP (self-regulating feedback loop). Indian hedgehog is a positive regulator of chondrocyte proliferation and osteoblastic differentiation in the perichondral ring.

C orrect Answer: PTHrP activating mutation

929. (3466) Q2-4403:

Which of the following statements is true concerning anterior cruciate ligament (AC L) tears in children with open physes:

1) The pattern of AC L failure is the same as adults.

3) The Lachmanâs test is seldom positive.

2) Associated meniscal tears are uncommon.

5) The pivot shift test is seldom positive.

4) The tear often occurs at the tibial insertion.

Although AC L injuries are less common in children than adults, this type of knee injury is becoming more common as children are involved in more athletic activities. Important points to remember include:

In children, the AC L collagen fibers extend from the ligament to epiphyseal cartilage. Many AC L injuries occur at the tibial insertion.

Tibial eminence avulsion fractures often accompany AC L injury. Associated meniscal injuries are common.

The physical examination findings are the same as in adults. Bicycle accidents are a common mechanism of injury.

C orrect Answer: The tear often occurs at the tibial insertion.

930. (3468) Q2-4405:

Which of the following is associated with Schmidâs type metaphyseal chondrodysplasia:

1) Type X collagen mutation

3) Activating mutation of fibroblast growth factor receptor-3 (FGFR-3)

2) Heterozygous loss of function mutation, C BF1/RUNX2

5) PTHrP loss of function mutation

4) Parathyroid hormone-related protein (PTHrP) activating mutation

Type X collagen mutations result in Schmidâs type metaphyseal chondrodysplasia.

C ollagen type X is uniquely expressed by hypertrophic chondrocytes. The extracellular matrix that is formed by the hypertrophic chondrocytes is easily degraded. There are high levels of expression of vascular endothelial growth factor A and marked ingrowth of blood vessels, osteoclasts, and osteoblasts. Hypertrophic chondrocytes are resorbed, and the matrix mineralizes. When defects in type X collagen exist, an interruption of normal longitudinal growth occurs.

C orrect Answer: Type X collagen mutation

931. (3477) Q2-4416:

Which of the following is the most sensitive electrodiagnostic study to establish the diagnosis of carpal tunnel syndrome:

1) Nerve conduction across the finger to wrist segment

3) Motor conduction â wrist to elbow

2) Terminal latency

5) Sensory nerve conduction across the palm wrist segment

4) Mixed conduction â wrist to elbow

Sensory nerve conduction across the palm to wrist segment is the most sensitive electrodiagnostic finding in carpal tunnel syndrome.

The accuracy of electrodiagnostic testing is good: Sensitivity â 85% to 90%

Specificity â 95%

C orrect Answer: Sensory nerve conduction across the palm wrist segment

932. (3497) Q2-4441:

Which of the following is uniquely expressed by hypertrophying chondrocytes during longitudinal growth:

1) Stable beta-catenin

3) C BAF1/RUNX2

2) Type X collagen

5) Type II collagen

4) Parathyroid hormone-related protein (PTHrP)

C ollagen type X is uniquely expressed by hypertrophic chondrocytes. The extracellular matrix that is formed by the hypertrophic chondrocytes is easily degraded. There are high levels of expression of VEGFA and marked ingrowth of blood vessels, osteoclasts, and osteoblasts. The hypertrophic chondrocytes are resorbed, and the matrix mineralizes. When defects in type X collagen are present, then an interruption of normal longitudinal growth occurs.

Type X collagen mutations result in Schmidâs type metaphyseal chondrodysplasia. Correct Answe Type X collagen

933. (3499) Q2-4445:

Which of the following factors is critical for normal enchondral growth in regard to hypertrophying chondrocytes:

1) Stable beta-catenin

3) C BAF1/RUNX2

2) Parathyroid hormone-related protein (PTHrP)

5) Osterix

4) Type X collagen/vascular endothelial growth factor A (VEGFA)

C ollagen type X is uniquely expressed by hypertrophic chondrocytes. The extracellular matrix that is formed by the hypertrophic chondrocytes is easily degraded. There are high levels of expression of VEGFA and marked ingrowth of blood vessels, osteoclasts, and osteoblasts. The hypertrophic chondrocytes are resorbed, and the matrix mineralizes. When defects in type X collagen are present, then an interruption of normal longitudinal growth occurs.

Type X collagen mutations result in Schmidâs type metaphyseal chondrodysplasia. Correct Answe Type X collagen/vascular endothelial growth factor A (VEGFA)

934. (3513) Q2-4467:

Which of the following cells is primarily affected in patients with Gaucher disease:

1) Osteoblast

3) Osteocyte

2) Osteoclast

5) Macrophage

4) Platelet

Gaucher disease is caused by an accumulation of glucocerebrosides (glucosylceramide) in macrophages. The specific enzyme deficiency is glucocerebrosidase (acid beta-glucosidase, lysosomal enzyme). The disease inheritance pattern is autosomal recessive.

Erlenmeyer flask deformities of the metaphyses are a common bone remodeling condition present in patients with Gaucher disease.

C linical manifestations include pancytopenia, thrombocytopenia, and specific bone conditions such as osteonecrosis, bone crises, and fractures. Patients often have easy bruising and fatigability.

Patients with Gaucher disease are treated by replacement of the deficient enzyme. Correct Answe Macrophage

935. (3514) Q2-4468:

In patients with Gaucher disease, which of the following substances accumulates abnormally in macrophages:

1) Dermatan sulfate

3) Keratin sulfate

2) Heparan sulfate

5) Glucocerebrosides

4) C hondroitin sulfate

Gaucher disease is caused by an accumulation of glucocerebrosides (glucosylceramide) in macrophages. The specific enzyme deficiency is glucocerebrosidase (acid beta-glucosidase, lysosomal enzyme). The disease inheritance pattern is autosomal recessive.

Erlenmeyer flask deformities of the metaphyses are a common bone remodeling condition present in patients with Gaucher disease.

C linical manifestations include pancytopenia, thrombocytopenia, and specific bone conditions such as osteonecrosis, bone crises, and fractures. Patients often have easy bruising and fatigability.

Patients with Gaucher disease are treated by replacement of the deficient enzyme. The other answer choices refer to patients with mucopolysaccharidoses:

Syndrome                     Glycosaminoglycans

Hurler syndrome                Dermatan sulfate and heparan sulfate Hunter syndrome                Heparan and dermatan sulfate Sanfilippo syndrome           Heparan sulfate

Morquio syndrome              Keratin sulfate

Maroteaux-Lamy syndrome Dermatan sulfate

C orrect Answer: Glucocerebrosides

936. (3515) Q2-4469:

Which of the following enzyme deficiencies occurs in patients with Gaucher disease:

1) Alpha-L-iduronidase

3) Glucocerebrosidase

2) Beta-glucuronidase

5) Homogentisic acid oxidase

4) Acid phosphatase

Gaucher disease is caused by an accumulation of glucocerebrosides (glucosylceramide) in macrophages. The specific enzyme deficiency is glucocerebrosidase (acid beta-glucosidase, lysosomal enzyme). The disease inheritance pattern is autosomal recessive.

Erlenmeyer flask deformities of the metaphyses are a common bone remodeling condition present in patients with Gaucher disease.

C linical manifestations include pancytopenia, thrombocytopenia, and specific bone conditions such as osteonecrosis, bone crises, and fractures. Patients often have easy bruising and fatigability.

Patients with Gaucher disease are treated by replacement of the deficient enzyme. The other answer choices occur in different conditions:

Syndrome                   Enzyme

Hurler syndrome              Alpha-L-iduronidase Sly syndrome                  Beta-glucuronidase Alkaptonuria (ochronosis) Homogentisic acid oxidase

C orrect Answer: Glucocerebrosidase

937. (3516) Q2-4470:

Which of the following is the inheritance pattern of Gaucher disease:

1) Autosomal recessive

3) X-linked dominant

2) Autosomal dominant

5) Sporadic

4) X-linked recessive

Gaucher disease is caused by an accumulation of glucocerebrosides (glucosylceramide) in macrophages. The specific enzyme deficiency is glucocerebrosidase (acid beta-glucosidase, lysosomal enzyme). The disease inheritance pattern is autosomal recessive.

Erlenmeyer flask deformities of the metaphyses are a common bone remodeling condition present in patients with Gaucher disease.

C linical manifestations include pancytopenia, thrombocytopenia, and specific bone conditions such as osteonecrosis, bone crises, and fractures. Patients often have easy bruising and fatigability.

Patients with Gaucher disease are treated by replacement of the deficient enzyme. Correct Answe Autosomal recessive

938. (3517) Q2-4471:

Which of the following criteria are used to define osteoporosis:

1) Low bone mass, inadequate mineralization, normal micro architecture

3) Normal bone mass, normal mineralization, abnormal micro architecture

2) Low bone mass, normal mineralization, abnormal micro architecture

5) Low bone mass, normal mineralization, normal micro architecture

4) Normal bone mass, abnormal mineralization, abnormal micro architecture

The essential features of osteoporosis include: Low bone mass

Normal mineralization

Abnormal micro architecture

Osteoporosis is defined by the World Health Organization by comparing a patient's bone mineral density (BMD) to that of patients at the time of peak bone mass (T-score).

Normal bone mineral density is within 1 SD

Low bone mass (osteopenia) is between 1 SD and 2.5 SD below mean peak bone mass

Osteoporosis is more than 2.5 SD below mean peak bone mass

C orrect Answer: Low bone mass, normal mineralization, abnormal micro architecture

939. (3518) Q2-4472:

A 65-year-old woman has a bone mineral density test. Which of the following T-scores is diagnostic of osteoporosis:

1) T-score within 0.5 SD below the mean

3) T-score 1 SD to 2 SD below the mean

2) T-score within 1 SD below the mean

5) T-score more than 2.5 SD below the mean

4) T-score 1 SD to 2.5 SD below the mean

The essential features of osteoporosis include: Low bone mass

Normal mineralization

Abnormal micro architecture

Osteoporosis is defined by the World Health Organization by comparing a patient's bone mineral density (BMD) to that of patients at the time of peak bone mass (T-score).

Normal bone mineral density is within 1 SD

Low bone mass (osteopenia) is between 1.0 SD to 2.5 SD below individuals at peak bone mass

Osteoporosis is more than 2.5 SD below mean peak bone mass

C orrect Answer: T-score more than 2.5 SD below the mean

940. (3519) Q2-4473:

Which of the following genes have been implicated in the development of osteoporosis:

1) C BFA1, C OL2A1, and C OMP

3) C BFA1, FGFR3

2) C OL10A1, FGFR3

5) C OL9A2, C OMP, and FGFR3

4) C OL1A1, VDR, and LRP5

The essential features of osteoporosis include: Low bone mass

Normal mineralization

Abnormal micro architecture

The causes of osteoporosis are multifactorial; genetic predisposition may be important. The genes associated with the development of osteoporosis include:

C OL1A1 - C ollagen 1 alpha 1 (main bone collagen) VDR - Vitamin D receptor

LRP5 - Low density lipoprotein receptor related protein

The associations of several other genes include: C BFA1 - C leidocranial dysplasia

C OL2A1 - Achondrogenesis

C OMP - Multiple epiphyseal dysplasia

C OL10A1 - Schmid metaphyseal chondrodysplasia

FGFR3 - Achondroplasia

C OL9A2 - Multiple epiphyseal dysplasia

C orrect Answer: C OL1A1, VDR, and LRP5

941. (3520) Q2-4474:

Which of the following dosages are correct in regard to the necessary daily calcium and vitamin D intake in patients between 19 and 50 years of age:

1) C alcium 1000 mg; vitamin D 400 IU

3) C alcium 1200 mg; vitamin D 200 IU

2) C alcium 1600 mg; vitamin D 400 IU

5) C alcium 2000 mg; vitamin D 1000 IU to 2000 IU

4) C alcium 1400 mg; vitamin D 400 IU

Appropriate amounts of calcium and vitamin D are crucial for good bone health. All therapeutic interventions for patients with osteoporosis require that calcium and vitamin D intake are adequate. The current recommendations for calcium and vitamin D are:

Ages 10-19 â C alcium 1000 mg; vitamin D 200 IU Ages 19-50 â C alcium 1200 mg; vitamin D 200 IU Ages 50-79 â C alcium 1400 mg; vitamin D 400 IU

Osteoporotic patient â C alcium 2000 mg; vitamin D 1000 IU to 2000 IU Correct Answe C alcium 1200 mg; vitamin D 200 IU

942. (3521) Q2-4475:

Which of the following are the correct daily intakes of calcium and vitamin D in a 60-year-old patient with no evidence of osteoporosis:

1) C alcium 1000 mg; vitamin D 400 IU

3) C alcium 1200 mg; vitamin D 200 IU

2) C alcium 1600 mg; vitamin D 400 IU

5) C alcium 2000 mg, vitamin D 1000 IU to 2000 IU

4) C alcium 1400 mg; vitamin D 400 IU

Appropriate amounts of calcium and vitamin D are crucial for good bone health. All therapeutic interventions for patients with osteoporosis require that calcium and vitamin D intake are adequate. The current recommendations for calcium and vitamin D are:

Ages 10-19â C alcium 1000 mg; vitamin D 200 IU Ages 19-50 â C alcium 1200 mg; vitamin D 200 IU Ages 50-79 â C alcium 1400 mg; vitamin D 400 IU

Osteoporotic patient â C alcium 2000 mg; vitamin D 1000 IU to 2000 IU Correct Answe C alcium 1400 mg; vitamin D 400 IU

943. (3522) Q2-4476:

Which of the following is the correct daily dietary intake of calcium and vitamin D in a patient older than 65 years of age with osteoporosis:

1) C alcium 1000 mg; vitamin D 400 IU

3) C alcium 1200 mg; vitamin D 200 IU

2) C alcium 1600 mg; vitamin D 400 IU

5) C alcium 2000 mg; vitamin D 1000 IU to 2000 IU

4) C alcium 1400 mg; vitamin D 400 IU

Appropriate amounts of calcium and vitamin D are crucial for good bone health. All therapeutic interventions for patients with osteoporosis require that calcium and vitamin D intake are adequate. The current recommendations for calcium and vitamin D are:

Ages 10-19 â C alcium 1000 mg; vitamin D 200 IU Ages 19-50 â C alcium 1200 mg; vitamin D 200 IU Ages 50-79 â C alcium 1400 mg; vitamin D 400 IU

Osteoporotic patient â C alcium 2000 mg; vitamin D 1000 IU to 2000 IU Correct Answe C alcium 2000 mg; vitamin D 1000 IU to 2000 IU

944. (3523) Q2-4477:

Which of the following therapies has an anabolic effect on bone (increases bone mass) in the treatment of women with postmenopausal osteoporosis:

1) Oral bisphosphonates

3) Subcutaneous parathyroid hormone (PTH)

2) Parenteral bisphosphonates

5) Oral vitamin D supplementation

4) Nasal calcitonin

Parathyroid hormone is the only FDA-approved anabolic method for the treatment of osteoporosis. Parathyroid hormone causes bone resorption and bone formation. The net effect is an increase in bone formation.

The indications for PTH therapy include:

High-risk patients for fracture (bone mineral density, T-score less than -3.0) Patients with refractory osteoporosis

Patients who cannot tolerate treatment with other methods

The contraindications to PTH therapy include:

Patients at risk for developing osteosarcoma

Pagetâs disease

Following irradiation of bone

C hildren with open physes

Patients with hyperparathyroidism

Patients with metastatic bone disease

C orrect Answer: Subcutaneous parathyroid hormone (PTH)

945. (3524) Q2-4478:

Which of the following therapies also has a significant analgesic effect in the treatment of women with postmenopausal osteoporosis:

1) Oral bisphosphonate

3) Subcutaneous parathyroid hormone

2) Parenteral bisphosphonate

5) Oral vitamin D supplementation

4) Nasal calcitonin

C alcitonin is produced by the C cells of the thyroid gland. Although the exact physiologic function of calcitonin is unknown, this hormone has a powerful inhibitory effect on the osteoclast.

The effects of calcitonin on the osteoclast include:

Flattening of the ruffled border

Withdrawal of the osteoclast from the bone surface

C alcitonin can be used as a treatment for osteoporosis. Salmon calcitonin is given intranasally. In addition to inhibiting bone resorption, there is a significant analgesic effect, especially in osteoporotic patients with vertebral fractures.

C orrect Answer: Nasal calcitonin

946. (3525) Q2-4479:

Which of the following complications may occur following bisphosphonate therapy:

1) Increase in hip fractures

3) Increase in falls

2) Increase in vertebral fractures

5) Impaired fracture healing

4) Osteonecrosis of the jaw

A rare, but significant, skeletal complication of bisphosphonate therapy is osteonecrosis of the jaw. Osteonecrosis of the jaw occurs more commonly in patients with metastatic bone disease who receive monthly treatments and tends to occur following major dental work. Patients should be queried about the condition of their teeth prior to starting bisphosphonate therapy.C orrect Answer: Osteonecrosis of the jaw

947. (3526) Q2-4480:

The mechanism of action of nitrogen-containing bisphosphonates is:

1) Toxic analogs of adenosine triphosphate (ATP)

3) Increased production of osteoprotegerin

2) Inhibition of protein prenylation

5) Decreased production of RANK receptor

4) Decreased production of receptor activator of nuclear factor-kB ligand (RANKL)

The mechanism of action of nitrogen-containing bisphosphonates is inhibition of protein prenylation. These agents cause programmed cell death of the osteoclast (apoptosis).

The nitrogen-containing bisphosphonates specifically inhibit farnesyl pyrophosphatase and prevent post-translational prenylation of guanosine triphosphate-binding proteins. Nitrogen-containing bisphosphonates disrupt the ruffled border and microtubules of the osteoclast.

The non-nitrogen containing bisphosphonates (etidronate, clodronate) produce toxic analogs of ATP. Correct Answe Inhibition of protein prenylation

948. (3527) Q2-4481:

Which of the following is the most common adverse effect of bisphosphonate therapy:

1) Osteonecrosis of the jaw

3) Fever and myalgia

2) Hypocalcemia

5) Diarrhea

4) Pruritic rash

The most common adverse effect of bisphosphonate therapy is fever and myalgia. When taken orally, bisphosphonates must be taken while fasting, with 8 oz of water, and the patient must remain upright for 30 minutes. Because these medications may cause esophageal irritation and possible erosion, they must be used carefully or not at all in patients with disorders of esophageal motility.

A rare, but significant, skeletal complication of bisphosphonate therapy is osteonecrosis of the jaw. Osteonecrosis of the jaw occurs more commonly in patients with metastatic bone disease who receive monthly treatments and tends to occur following major dental work. Patients should be queried about the condition of their teeth prior to starting bisphosphonate therapy.

C orrect Answer: Fever and myalgia

949. (3528) Q2-4482:

Parathyroid hormone (PTH) therapy is contraindicated in which of the following patients:

1) Patients with refractory postmenopausal osteoporosis

3) Patients with bone loss following anti-resorptive therapies

2) Patients at high risk for osteoporotic fractures

5) Men at high risk for osteoporotic fractures

4) Patients with Pagetâs disease

Parathyroid hormone is the only FDA-approved anabolic method for the treatment of osteoporosis. Parathyroid hormone causes bone resorption and bone formation. The net effect is an increase in bone formation.

The indications for PTH therapy include:

High-risk patients for fracture (bone mineral density, T-score less than -3.0) Patients with refractory osteoporosis

Patients who cannot tolerate treatment with other methods

The contraindications to PTH therapy include:

Patients at risk for developing osteosarcoma

Pagetâs disease

Following irradiation of bone

C hildren with open physes

Patients with hyperparathyroidism

Patients with metastatic bone disease

C orrect Answer: Patients with Pagetâs disease

950. (3529) Q2-4483:

Diphosphonates are contraindicated in patients with which of the following conditions:

1) Pagetâs disease

3) Hypocalcemia

2) Postmenopausal osteoporosis

5) Polyostotic fibrous dysplasia

4) Multiple myeloma

The mechanism of action of nitrogen-containing bisphosphonates is inhibition of protein prenylation. These agents cause programmed cell death of the osteoclast (apoptosis).

The nitrogen-containing bisphosphonates specifically inhibit farnesyl pyrophosphatase and prevent post-translational prenylation of guanosine triphosphate-binding proteins. Nitrogen-containing bisphosphonates disrupt the ruffled border and microtubules of the osteoclast.

Diphosphonates halt the osteoclast from resorbing bone and increasing the serum calcium level by resorbing bone and releasing the inorganic matrix. Diphosphonates are contraindicated in patients with hypocalcemia because they further lower the serum calcium level.

Diphosphonates are used in the treatment of:

Pagetâs disease Postmenopausal osteoporosis Multiple myeloma

Metastatic bone disease

Polyostotic fibrous dysplasia

C orrect Answer: Hypocalcemia