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Biology, Genetics & Bone Healing MCQs

Practice Set 49 of 212

This practice set contains high-yield board review questions covering key concepts in Biology, Genetics & Bone Healing. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 961

Topic: Biology, Genetics & Bone Healing

A 28-year-old man sustains a closed midshaft tibia fracture and is treated with reamed intramedullary nailing. Which of the following biological processes best characterizes the primary mode of bone healing expected in this scenario?

. Primary bone healing via direct osteonal remodeling without callus formation
. Intramembranous ossification stemming exclusively from the periosteum
. Secondary bone healing characterized by endochondral ossification and callus formation
. Creeping substitution via osteoclastic cutting cones followed closely by osteoblasts
. Appositional bone growth originating strictly from the endosteum

Correct Answer & Explanation

. Secondary bone healing characterized by endochondral ossification and callus formation

Explanation

Intramedullary nailing provides relative stability to a fracture site. This mechanical environment promotes micro-motion at the fracture gap, which stimulates secondary bone healing. Secondary bone healing progresses through an inflammatory phase, soft callus formation, hard callus formation (via endochondral ossification), and remodeling. Primary bone healing (osteonal remodeling without a callus) only occurs under conditions of absolute stability, such as rigid compression plating.

Question 962

Topic: Biology, Genetics & Bone Healing
A transverse midshaft femur fracture is treated with a rigid locked intramedullary nail, resulting in a small gap with very low interfragmentary strain (< 2%). According to Perren's strain theory, what type of tissue will predominantly form in the fracture gap during the healing process?
. Granulation tissue
. Fibrocartilage
. Woven bone
. Lamellar bone
. Hyaline cartilage

Correct Answer & Explanation

. Lamellar bone

Explanation

Perren's strain theory dictates the type of tissue that can form in a fracture gap based on the strain the tissue can tolerate without failing. Bone requires very low strain to form. A rigid construct that limits interfragmentary strain to < 2% allows for primary (direct) bone healing, resulting predominantly in lamellar bone formation through cutting cones, without a significant cartilaginous intermediate. If strain is slightly higher (2-10%), endochondral ossification (woven bone/callus) occurs. Higher strains lead to fibrocartilage (10-30%) or granulation tissue (>30%).

Question 963

Topic: Biology, Genetics & Bone Healing

A 35-year-old man undergoes open reduction and internal fixation of a diaphyseal radius fracture with a compression plate and lag screw. During the healing process of a fracture treated with this type of absolute stability, which mechanism of bone healing predominates?

. Endochondral ossification
. Intramembranous ossification
. Primary bone healing via Haversian remodeling
. Chondroid bone formation
. Appositional bone growth

Correct Answer & Explanation

. Primary bone healing via Haversian remodeling

Explanation

Rigid internal fixation with absolute stability (e.g., lag screw and compression plate) minimizes interfragmentary strain and promotes primary (direct) bone healing. This occurs via direct Haversian remodeling, where osteoclast 'cutting cones' cross the fracture line followed by osteoblasts laying down new lamellar bone, without the formation of a cartilaginous callus (endochondral ossification), which is typically seen in secondary bone healing with relative stability.

Question 964

Topic: Biology, Genetics & Bone Healing
Which of the following cytokines is most responsible for the differentiation of macrophages into osteoclasts during bone remodeling and fracture healing?
. Transforming growth factor-beta (TGF-β)
. Bone morphogenetic protein-2 (BMP-2)
. Receptor activator of nuclear factor kappa-B ligand (RANKL)
. Interleukin-10 (IL-10)
. Osteoprotegerin (OPG)

Correct Answer & Explanation

. Receptor activator of nuclear factor kappa-B ligand (RANKL)

Explanation

RANKL is a key cytokine expressed by osteoblasts and osteocytes that binds to the RANK receptor on osteoclast precursors (which are of the monocyte/macrophage lineage). This interaction stimulates their differentiation, activation, and survival into mature bone-resorbing osteoclasts. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL, inhibiting this process. BMP-2 and TGF-β are primarily involved in osteoblast differentiation and bone formation.

Question 965

Topic: Biology, Genetics & Bone Healing

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is utilized in various spine and trauma applications to promote osteoinduction and bone healing. What is the primary intracellular signaling pathway directly activated upon BMP-2 binding to its cell surface receptor?

. Wnt/beta-catenin
. MAPK/ERK
. Smad 1/5/8
. JAK/STAT
. NF-kappaB

Correct Answer & Explanation

. Smad 1/5/8

Explanation

Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily. When BMP-2 binds to its specific transmembrane serine/threonine kinase receptor, it phosphorylates the intracellular receptor-regulated Smads (R-Smads), specifically Smad 1, 5, and 8. These activated R-Smads then complex with the common-partner Smad (Co-Smad 4) to translocate into the nucleus and initiate transcription of osteogenic genes, including Runx2.

Question 966

Topic: Biology, Genetics & Bone Healing

A 30-year-old patient undergoes an antegrade reamed intramedullary nailing of a diaphyseal femur fracture utilizing dynamic locking holes. This mechanical construct permits controlled axial micromotion. This relative stability primarily promotes fracture healing through which of the following biological processes?

. Primary bone healing via cutting cones
. Intramembranous ossification exclusively
. Endochondral ossification
. Creeping substitution
. Direct osteoblastic apposition without an intermediate cartilage phase

Correct Answer & Explanation

. Endochondral ossification

Explanation

Constructs that provide relative stability (such as intramedullary nails, bridge plates, and external fixators) permit micromotion at the fracture site. This strain environment stimulates secondary bone healing, which occurs primarily via endochondral ossification. This process involves the formation of a hematoma, followed by a fibrocartilaginous soft callus, which is subsequently calcified into a hard woven bone callus and eventually remodeled. Primary bone healing (via Haversian remodeling/cutting cones) requires absolute stability and direct bone-to-bone contact.

Question 967

Topic: Biology, Genetics & Bone Healing

A 72-year-old woman presents with a 3-month history of vague, progressively worsening thigh pain. She denies any recent trauma but has been taking alendronate for the last 8 years. Radiographs reveal cortical thickening of the lateral femoral shaft with a transverse radiolucent line. What is the most appropriate next step in management?

. Discontinue alendronate and prescribe teriparatide exclusively without surgery
. Core decompression of the lateral cortex
. Prophylactic cephalomedullary nailing of the affected femur
. Open reduction and internal fixation with a dynamic compression plate
. Continue alendronate and recommend protected weight-bearing

Correct Answer & Explanation

. Prophylactic cephalomedullary nailing of the affected femur

Explanation

Atypical femur fractures (AFFs) are associated with prolonged bisphosphonate use. Patients presenting with prodromal pain and radiographic signs of an impending fracture, such as lateral cortical thickening and a transverse stress line (the "dreaded black line"), are at a high risk of progression to a complete fracture. The standard of care for an impending atypical femur fracture is prophylactic intramedullary nailing. Bisphosphonates should also be discontinued, and anabolic agents like teriparatide can be considered, but surgical stabilization is the primary orthopedic intervention.

Question 968

Topic: Biology, Genetics & Bone Healing

A 68-year-old woman treated with alendronate for 8 years presents with a 3-month history of an unprovoked dull ache in her right thigh. A radiograph of the femur reveals localized lateral cortical thickening and a transverse radiolucent line in the subtrochanteric region. What is the most appropriate next step in orthopaedic management?

. Discontinue alendronate and prescribe strict bed rest for 6 weeks
. Discontinue alendronate and switch immediately to denosumab
. Discontinue alendronate, initiate protected weight-bearing, and perform prophylactic intramedullary nailing
. Perform an open biopsy of the lesion to rule out metastatic disease
. Recommend extracorporeal shockwave therapy to the lateral thigh

Correct Answer & Explanation

. Discontinue alendronate, initiate protected weight-bearing, and perform prophylactic intramedullary nailing

Explanation

This patient has symptoms and classic radiographic signs (lateral cortical thickening, transverse radiolucent line, 'beaking') of an impending bisphosphonate-related atypical femur fracture. Because the lesion is symptomatic, she is at high risk for completion of the fracture. Prophylactic intramedullary nailing is indicated to prevent complete displacement and associated morbidity.

Question 969

Topic: Biology, Genetics & Bone Healing

A 50-year-old woman is evaluated for a nonunion of a midshaft humerus fracture 6 months after injury. She was originally treated with a Sarmiento cast brace. Radiographs show atrophic bone ends with no callus formation. Laboratory markers for infection are negative. What is the most reliable surgical treatment?

. Open reduction and internal fixation with compression plating and autologous bone grafting
. Continuation of cast bracing with the addition of a bone stimulator
. Closed reamed intramedullary nailing without bone graft
. Application of a circular external fixator
. Placement of recombinant bone morphogenetic protein (BMP) without rigid fixation

Correct Answer & Explanation

. Open reduction and internal fixation with compression plating and autologous bone grafting

Explanation

Atrophic nonunions occur due to a lack of biology and require both mechanical stability and biological stimulation to heal. For an atrophic humeral shaft nonunion, the gold standard treatment is open reduction and internal fixation (typically using heavy compression plating) combined with autologous bone grafting (e.g., from the iliac crest) to provide the necessary osteoinductive and osteoconductive properties.

Question 970

Topic: Biology, Genetics & Bone Healing

A 65-year-old woman on long-term alendronate therapy presents with prodromal thigh pain followed by a low-energy transverse fracture of the femoral shaft. Radiographs show lateral cortical thickening at the fracture site. What is the primary pathophysiologic mechanism leading to this atypical fracture?

. Overactive osteoblast function leading to brittle bone
. Defective Type I collagen synthesis
. Suppression of targeted bone remodeling and accumulation of microdamage
. Increased osteoclastogenesis causing local osteolysis
. Primary hyperparathyroidism

Correct Answer & Explanation

. Suppression of targeted bone remodeling and accumulation of microdamage

Explanation

Long-term bisphosphonate use suppresses targeted osteoclastic bone remodeling. This impairs the normal repair of daily microdamage, leading to an accumulation of microcracks, increased bone brittleness, and eventually an atypical femur fracture.

Question 971

Topic: Biology, Genetics & Bone Healing

A 75-year-old woman with severe osteoporosis presents with acute back pain following a coughing fit. Radiographs show an acute L2 compression fracture with 20% height loss. She has intact neurology. What is the recommended first-line treatment?

. Kyphoplasty
. Vertebroplasty
. Posterior spinal fusion
. Analgesics, early mobilization, and medical management of osteoporosis
. Prolonged bed rest for 6 weeks

Correct Answer & Explanation

. Analgesics, early mobilization, and medical management of osteoporosis

Explanation

The initial management of an osteoporotic vertebral compression fracture without neurologic deficit is nonoperative, focusing on pain control, early mobilization to prevent deconditioning, and treating the underlying osteoporosis.

Question 972

Topic: Biology, Genetics & Bone Healing

According to Perren's strain theory, what is the maximum tissue strain allowable for primary (direct) bone healing to occur without the formation of a visible callus?

. Less than 2%
. Between 2% and 10%
. Between 10% and 15%
. Between 15% and 30%
. Up to 100%

Correct Answer & Explanation

. Less than 2%

Explanation

Primary bone healing requires absolute stability with an interfragmentary strain of less than 2%. Strains between 2% and 10% result in secondary bone healing characterized by callus formation.

Question 973

Topic: Biology, Genetics & Bone Healing

Bone Morphogenetic Proteins (BMPs) stimulate osteoblast differentiation and bone formation primarily by signaling through which of the following intracellular molecular pathways?

. Wnt/beta-catenin
. JAK/STAT
. Notch/Hes-1
. Smad 1/5/8
. RANK/RANKL

Correct Answer & Explanation

. Smad 1/5/8

Explanation

BMPs bind to serine/threonine kinase receptors on the cell surface, which subsequently phosphorylate and activate the intracellular Smad 1/5/8 pathway. This leads to the transcription of osteogenic genes like Runx2.

Question 974

Topic: Biology, Genetics & Bone Healing
During the secondary fracture healing process, the soft callus is gradually replaced by a hard callus. This transition is characterized by a shift in the predominant collagen type from:
. Type I to Type II
. Type II to Type I
. Type III to Type IV
. Type I to Type III
. Type X to Type II

Correct Answer & Explanation

. Type II to Type I

Explanation

The initial soft callus consists primarily of fibrocartilage, which is rich in Type II collagen. As endochondral ossification progresses, this cartilage is resorbed and replaced by woven bone (hard callus), which is predominantly composed of Type I collagen.

Question 975

Topic: Biology, Genetics & Bone Healing

Denosumab is used to treat osteoporosis and giant cell tumors of bone by inhibiting osteoclast maturation and activity. Which naturally occurring molecule does Denosumab mimic in its mechanism of action?

. Osteocalcin
. Osteoprotegerin (OPG)
. Macrophage colony-stimulating factor (M-CSF)
. Transforming growth factor-beta (TGF-b)
. Sclerostin

Correct Answer & Explanation

. Osteoprotegerin (OPG)

Explanation

Denosumab is a targeted monoclonal antibody that binds to RANKL, preventing it from interacting with the RANK receptor on osteoclast precursors. This exactly mimics the action of Osteoprotegerin (OPG), an endogenous decoy receptor that regulates and inhibits osteoclastogenesis.

Question 976

Topic: Biology, Genetics & Bone Healing

What strain environment, as described by Perren's strain theory, is required to dictate secondary bone healing via endochondral ossification?

. Less than 2%
. Between 2% and 10%
. Between 10% and 15%
. Between 15% and 20%
. Greater than 20%

Correct Answer & Explanation

. Between 2% and 10%

Explanation

According to Perren's strain theory, secondary bone healing (callus formation) occurs in a strain environment between 2% and 10%. Strains less than 2% allow primary healing, while strains greater than 10% result in granulation tissue and nonunion.

Question 977

Topic: Biology, Genetics & Bone Healing

Which of the following molecules acts as a direct extracellular antagonist to the canonical Wnt signaling pathway, thereby inhibiting osteoblastogenesis and bone formation?

. Bone morphogenetic protein-2 (BMP-2)
. Osteoprotegerin (OPG)
. Sclerostin
. Receptor activator of nuclear factor kappa-B ligand (RANKL)
. Transforming growth factor-beta (TGF-beta)

Correct Answer & Explanation

. Sclerostin

Explanation

Sclerostin, produced primarily by osteocytes, binds to the LRP5/6 coreceptors on osteoblasts, directly inhibiting the canonical Wnt/beta-catenin pathway. This halts osteoblast differentiation and subsequent bone formation.

Question 978

Topic: Biology, Genetics & Bone Healing

A bone graft incorporates through a slow process where osteoclasts resorb the donor bone and osteoblasts lay down new viable bone. This process, known as creeping substitution, is most characteristic of which graft type?

. Autologous iliac crest cancellous bone
. Demineralized bone matrix (DBM)
. Structural cortical allograft
. Calcium phosphate cement
. Recombinant human BMP-2 on a collagen sponge

Correct Answer & Explanation

. Structural cortical allograft

Explanation

Structural cortical allografts heal via creeping substitution, an extremely slow process where host cutting cones progressively resorb and replace the necrotic donor bone. This often leaves the graft mechanically weak during the intermediate remodeling phase.

Question 979

Topic: Biology, Genetics & Bone Healing

Bone Morphogenetic Proteins (BMPs) induce osteoblastic differentiation from mesenchymal stem cells. Which intracellular signaling molecules are directly phosphorylated by BMP receptors to translocate to the nucleus?

. STAT3
. Beta-catenin
. Smad 1/5/8
. ERK 1/2
. NFATc1

Correct Answer & Explanation

. Smad 1/5/8

Explanation

Binding of BMPs to their serine/threonine kinase receptors leads to the direct phosphorylation of Smad 1, 5, and 8. These complex with Smad 4, translocate to the nucleus, and activate transcription factors such as Runx2.

Question 980

Topic: Biology, Genetics & Bone Healing

During distraction osteogenesis (Ilizarov technique), bone forms directly under tensional stress without a cartilaginous intermediate. This process is best characterized as:

. Primary bone healing
. Endochondral ossification
. Intramembranous ossification
. Creeping substitution
. Appositional gap healing

Correct Answer & Explanation

. Intramembranous ossification

Explanation

Distraction osteogenesis primarily relies on intramembranous ossification. Mesenchymal stem cells differentiate directly into osteoblasts under the influence of mechanical tension, entirely skipping the cartilaginous phase seen in endochondral healing.

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