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1. General Principles & Basic Science MCQs

Practice Set 743 of 789

This practice set contains high-yield board review questions covering key concepts in 1. General Principles & Basic Science. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 14841

Topic: Biology, Genetics & Bone Healing

A 14-year-old female presents with an impending pathologic fracture of the proximal femur with a characteristic "shepherd's crook" deformity. Radiographs show a "ground-glass" medullary appearance. Which of the following represents the genetic etiology of her condition?

. Somatic post-zygotic mutation in GNAS
. Germline mutation in FGFR3
. Germline mutation in COMP
. Autosomal recessive mutation in COL2A1
. Autosomal dominant mutation in RUNX2

Correct Answer & Explanation

. Somatic post-zygotic mutation in GNAS

Explanation

Fibrous dysplasia results from a somatic, post-zygotic activating mutation in the GNAS gene. This leads to increased intracellular cAMP, which impairs proper osteoblast differentiation and leads to the production of immature woven bone.

Question 14842

Topic: 1. General Principles & Basic Science

When evaluating a patient for synovial chondromatosis, the distinction between primary and secondary forms is critical. Which of the following radiographic features strongly favors a diagnosis of primary rather than secondary synovial chondromatosis?

. Highly variable size of intra-articular loose bodies
. Uniform size of the calcified loose bodies
. Presence of advanced joint space narrowing and osteophytes
. Absence of synovial hypertrophy on MRI
. Location exclusively in the popliteal cyst

Correct Answer & Explanation

. Uniform size of the calcified loose bodies

Explanation

Primary synovial chondromatosis typically presents with multiple intra-articular cartilaginous loose bodies of uniform size due to synchronized metaplasia. Secondary chondromatosis features loose bodies of highly variable sizes resulting from fragmented degenerative cartilage.

Question 14843

Topic: Biology, Genetics & Bone Healing

A 7-year-old child presents to the orthopedic clinic with extreme shoulder hypermobility, allowing the patient to touch the bilateral shoulders together anteriorly in the midline. The patient also has delayed closure of the cranial sutures. A mutation in which of the following genes is responsible?

. GNAS
. RUNX2
. SLC26A2
. EXT1
. NF1

Correct Answer & Explanation

. RUNX2

Explanation

Cleidocranial dysplasia is caused by a mutation in the RUNX2 (CBFA1) gene, a master transcription factor for osteoblast differentiation. Patients exhibit absent or hypoplastic clavicles, delayed cranial suture closure, and supernumerary teeth.

Question 14844

Topic: Biology, Genetics & Bone Healing

An infant presents with recurrent fractures, cranial nerve palsies, and pancytopenia. Radiographs show a "bone-within-bone" appearance and generalized osteosclerosis. The infantile malignant form of this disease is most commonly due to a defect in which of the following?

. Osteoclast ruffled border formation (TCIRG1)
. Type 1 collagen synthesis (COL1A1)
. Osteoblast differentiation (RUNX2)
. Chondrocyte proliferation (FGFR3)
. Cartilage oligomeric matrix protein (COMP)

Correct Answer & Explanation

. Osteoclast ruffled border formation (TCIRG1)

Explanation

Malignant infantile osteopetrosis is commonly caused by mutations in TCIRG1, leading to an absent or defective ruffled border in osteoclasts. This failure of bone resorption results in uniformly dense, brittle bones and obliterates the medullary cavity, causing pancytopenia.

Question 14845

Topic: Biology, Genetics & Bone Healing
A 6-year-old child with osteogenesis imperfecta (type III) is receiving intravenous pamidronate. What is the primary mechanism of action of this medication in treating her condition?
. Inhibiting osteoblast apoptosis
. Stimulating Wnt signaling pathways
. Inhibiting osteoclast-mediated bone resorption
. Increasing the synthesis of type 1 collagen
. Promoting gastrointestinal calcium absorption

Correct Answer & Explanation

. Inhibiting osteoclast-mediated bone resorption

Explanation

Bisphosphonates like pamidronate are a mainstay of medical therapy for osteogenesis imperfecta. They work by inducing osteoclast apoptosis and inhibiting osteoclast-mediated bone resorption, thus decreasing bone turnover and increasing cortical thickness.

Question 14846

Topic: Biology, Genetics & Bone Healing

A patient with spondyloepiphyseal dysplasia (SED) congenita has widespread epiphyseal involvement and spinal abnormalities. The genetic defect responsible for this condition predominantly affects which of the following collagens?

. Type I collagen
. Type II collagen
. Type IV collagen
. Type IX collagen
. Type X collagen

Correct Answer & Explanation

. Type II collagen

Explanation

Spondyloepiphyseal dysplasia congenita is caused by mutations in the COL2A1 gene, affecting type II collagen. Type II collagen is primarily found in hyaline cartilage, including articular cartilage and the nucleus pulposus.

Question 14847

Topic: Biology, Genetics & Bone Healing

A 2-year-old presents with bowing of the lower extremities and delayed walking. Radiographs demonstrate metaphyseal flaring and lucency mimicking rickets. However, laboratory evaluation reveals normal serum calcium, normal phosphorus, and normal vitamin D levels, but notably low serum alkaline phosphatase. What is the most likely diagnosis?

. Metaphyseal chondrodysplasia, Schmid type
. X-linked hypophosphatemic rickets
. Osteogenesis imperfecta
. Hypophosphatasia
. Vitamin D dependent rickets type II

Correct Answer & Explanation

. Hypophosphatasia

Explanation

Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase. It presents with rickets-like skeletal changes but is uniquely characterized by a low serum alkaline phosphatase level.

Question 14848

Topic: Biology, Genetics & Bone Healing

A 12-year-old girl is evaluated for delayed dental eruption and abnormal shoulder mobility. Physical exam reveals she can bring her shoulders together anteriorly. Radiographs show absent clavicles and delayed ossification of the pubic symphysis. Which transcription factor is mutated in this patient?

. SOX9
. RUNX2 (CBFA1)
. COMP
. GLI3
. SHH

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant disorder caused by a mutation in the RUNX2 (CBFA1) gene, a master transcription factor for osteoblast differentiation. It is characterized by clavicular aplasia or hypoplasia and delayed dental eruption.

Question 14849

Topic: Biology, Genetics & Bone Healing

A 22-year-old female presents with severe back pain and neurological deficits. Imaging reveals a large, expansile, aneurysmal bone cyst in the sacrum that is deemed surgically unresectable. Which of the following medical therapies targets the RANKL pathway and is most appropriate for this lesion?

. Zoledronic acid
. Methotrexate
. Denosumab
. Imatinib
. Doxorubicin

Correct Answer & Explanation

. Denosumab

Explanation

Denosumab, a monoclonal antibody against RANKL, is highly effective in treating aggressive or surgically inaccessible aneurysmal bone cysts (ABCs) and giant cell tumors of bone. It inhibits osteoclast-like giant cells, leading to ossification of the cystic lesion.

Question 14850

Topic: Biology, Genetics & Bone Healing

A neonate presents with severe bowing of the tibias, respiratory distress due to tracheomalacia, and a 46,XY karyotype but female external genitalia. This condition is associated with a mutation in which of the following?

. COL2A1
. FGFR3
. SOX9
. SLC26A2
. EXT1

Correct Answer & Explanation

. SOX9

Explanation

Campomelic dysplasia is a rare, frequently lethal osteochondrodysplasia caused by mutations in the SOX9 gene. It is characterized by bowed long bones (especially the tibias), tracheomalacia, and sex reversal in approximately two-thirds of 46,XY individuals.

Question 14851

Topic: 1. General Principles & Basic Science

A 14-year-old boy with severe anemia and recurrent fractures presents with jaw swelling. Radiographs show a dense, 'bone-within-bone' appearance of the skeleton and osteomyelitis of the mandible. The primary cellular defect in this condition is characterized by:

. Defective type I collagen synthesis
. Failure of osteoclasts to form a ruffled border
. Excessive osteoblast proliferation and matrix production
. Impaired provisional calcification of the physis
. Activating mutation of the G-protein signaling pathway

Correct Answer & Explanation

. Failure of osteoclasts to form a ruffled border

Explanation

The condition is osteopetrosis, characterized by dense, brittle bones and complications like bone marrow failure and mandibular osteomyelitis. It is caused by osteoclast dysfunction, most commonly a failure to form a ruffled border or a defect in carbonic anhydrase II, preventing normal bone resorption.

Question 14852

Topic: Biology, Genetics & Bone Healing

A 9-year-old girl is able to bring her shoulders together anteriorly in the midline. She has delayed eruption of her secondary teeth. Radiographs demonstrate absent clavicles and a widened symphysis pubis. Which transcription factor is mutated in this disorder?

. SOX9
. RUNX2 (CBFA1)
. IHH
. Wnt
. BMP-4

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

This is Cleidocranial Dysplasia, an autosomal dominant condition characterized by hypoplastic or absent clavicles, delayed fontanelle closure, and dental anomalies. It is caused by a mutation in the RUNX2 (also known as CBFA1) gene, an essential transcription factor for osteoblast differentiation.

Question 14853

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy with recurrent fragility fractures, blue sclerae, and dentinogenesis imperfecta is treated with cyclic intravenous pamidronate. What is the expected and characteristic radiographic finding on long bone X-rays following multiple cycles of this therapy?

. Progressive anterolateral bowing of the diaphysis
. Dense, parallel transverse metaphyseal bands
. A generalized 'bone-within-bone' appearance
. Obliteration of the medullary canal
. Progressive radiolucency of the secondary ossification centers

Correct Answer & Explanation

. Dense, parallel transverse metaphyseal bands

Explanation

Bisphosphonates, such as pamidronate, inhibit osteoclast-mediated bone resorption. In growing children, cyclic administration produces dense transverse bands in the metaphyses (often called 'Zebra lines') corresponding to the periods of treatment.

Question 14854

Topic: Biology, Genetics & Bone Healing

A 68-year-old male presents with generalized fatigue, worsening back pain, and a recent humeral shaft fracture after a minor fall. Radiographs demonstrate multiple punched-out lytic lesions.

Which of the following factors is primarily responsible for the suppression of osteoblastic activity in this patient's disease process?

. Macrophage colony-stimulating factor (M-CSF)
. Dickkopf-1 (DKK-1)
. Vascular endothelial growth factor (VEGF)
. Fibroblast growth factor receptor 3 (FGFR3)
. Transforming growth factor-beta (TGF-beta)

Correct Answer & Explanation

. Dickkopf-1 (DKK-1)

Explanation

This patient has multiple myeloma, characterized by punched-out lytic lesions. Myeloma cells secrete DKK-1, which inhibits the Wnt signaling pathway, thereby suppressing osteoblast differentiation and activity.

Question 14855

Topic: Biology, Genetics & Bone Healing

Which of the following describes the earliest biochemical change occurring in the articular cartilage during the pathogenesis of osteoarthritis?

. Decreased water content and increased proteoglycan concentration
. Increased water content and decreased proteoglycan concentration
. Increased collagen type II concentration and decreased water content
. Decreased collagen type II concentration and increased proteoglycan concentration
. Increased chondrocyte apoptosis with decreased water content

Correct Answer & Explanation

. Increased water content and decreased proteoglycan concentration

Explanation

The earliest biochemical change in osteoarthritis is an increase in the water content of the articular cartilage. This is accompanied by a decrease in proteoglycan concentration and an alteration in the collagen network.

Question 14856

Topic: Biology, Genetics & Bone Healing

A 35-year-old male undergoes curettage and cementation of a giant cell tumor of the distal femur. Six months later, he develops a massive recurrence that is deemed unresectable. Medical therapy with denosumab is initiated. What is the mechanism of action of this medication?

. Direct inhibition of osteoclast proton pumps
. Monoclonal antibody against RANKL, preventing osteoclast activation
. Inhibition of the Wnt/beta-catenin pathway
. Tyrosine kinase inhibitor targeting CSF-1R
. Selective estrogen receptor modulation

Correct Answer & Explanation

. Monoclonal antibody against RANKL, preventing osteoclast activation

Explanation

Denosumab is a fully human monoclonal antibody that binds to RANKL, preventing it from activating RANK on the surface of osteoclasts and their precursors. This effectively halts the bone destruction mediated by the reactive osteoclasts in giant cell tumors.

Question 14857

Topic: Biomechanics & Biomaterials

A 55-year-old male presents with severe acute monoarticular pain, erythema, and swelling in his first metatarsophalangeal joint. Joint aspiration reveals negatively birefringent, needle-shaped crystals under polarized light microscopy. Which of the following is the composition of these crystals?

. Calcium pyrophosphate dihydrate
. Basic calcium phosphate
. Monosodium urate
. Hydroxyapatite
. Cholesterol

Correct Answer & Explanation

. Monosodium urate

Explanation

The patient has an acute attack of gout. Gout is characterized by the deposition of monosodium urate crystals in the joint space, which appear as needle-shaped and negatively birefringent under polarized light microscopy.

Question 14858

Topic: Biology, Genetics & Bone Healing

A 10-month-old infant is evaluated for short stature, frontal bossing, and a waddling gait. Radiographs reveal widening of the physes, cupping of the metaphyses, and bowing of the long bones. Laboratory studies show normal calcium, low phosphorus, and elevated alkaline phosphatase. Which of the following describes the underlying histologic defect?

. Defect in type 1 collagen synthesis
. Failure of enchondral ossification due to FGFR3 mutation
. Failure of osteoid mineralization
. Defective osteoclast ruffled borders
. Hamartomatous proliferation of fibrous tissue

Correct Answer & Explanation

. Failure of osteoid mineralization

Explanation

The clinical and radiographic presentation is consistent with rickets. The fundamental histologic defect in rickets (and osteomalacia in adults) is the failure of osteoid mineralization, leading to widened, unmineralized growth plates.

Question 14859

Topic: 1. General Principles & Basic Science

A 60-year-old female complains of right knee pain, stiffness, and swelling. Aspiration yields cloudy, low-viscosity fluid. Polarized light microscopy reveals rhomboid-shaped, positively birefringent crystals. This finding is most frequently associated with which of the following metabolic conditions?

. Hyperparathyroidism and Hemochromatosis
. Chronic renal failure and Hyperuricemia
. Diabetes mellitus and Hypothyroidism
. Ochronosis (Alkaptonuria)
. Wilson's disease

Correct Answer & Explanation

. Hyperparathyroidism and Hemochromatosis

Explanation

The presence of positively birefringent, rhomboid-shaped crystals indicates calcium pyrophosphate dihydrate (CPPD) deposition disease (pseudogout). CPPD is strongly associated with hyperparathyroidism, hemochromatosis, hypothyroidism, and hypomagnesemia (the '4 Hs').

Question 14860

Topic: Biology, Genetics & Bone Healing

A 30-year-old female presents with distal femur pain. Imaging reveals an eccentric, lytic, epiphyseal-metaphyseal lesion extending to the subchondral bone. Biopsy confirms Giant Cell Tumor (GCT). If medical therapy is considered, what is the mechanism of action of Denosumab?

. Directly induces apoptosis of the neoplastic mononuclear cells
. Binds to RANKL, inhibiting the maturation and function of osteoclast-like giant cells
. Inhibits VEGF to restrict tumor angiogenesis
. Functions as an alkylating agent cross-linking tumor DNA
. Stimulates osteoblast-mediated bone apposition around the tumor

Correct Answer & Explanation

. Binds to RANKL, inhibiting the maturation and function of osteoclast-like giant cells

Explanation

Denosumab is a monoclonal antibody that binds to RANKL. In GCT, the neoplastic mononuclear cells express RANKL, which recruits reactive osteoclast-like giant cells; Denosumab halts this recruitment and subsequent bone destruction.

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