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Biology, Genetics & Bone Healing MCQs

Practice Set 33 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 641

Topic: Biology, Genetics & Bone Healing

Denosumab is increasingly utilized to downstage unresectable or metastatic giant cell tumors of bone (GCT). Which of the following accurately describes the primary cellular mechanism by which Denosumab exerts its therapeutic effect in this specific tumor?

. Inhibition of the RANK ligand (RANKL) expressed by the neoplastic spindle-shaped mononuclear cells
. Binding directly to the RANK receptors on the surface of the reactive multinucleated giant cells
. Direct induction of apoptosis in the multinucleated giant cells via the p53 pathway
. Direct inhibition of vascular endothelial growth factor (VEGF) leading to tumor necrosis
. Stimulation of osteoprotegerin (OPG) production by native osteoblasts

Correct Answer & Explanation

. Inhibition of the RANK ligand (RANKL) expressed by the neoplastic spindle-shaped mononuclear cells

Explanation

In Giant Cell Tumor of bone (GCT), the true neoplastic cells are the spindle-shaped mononuclear cells, which express high levels of RANKL. This RANKL recruits and activates reactive, normal osteoclast-like giant cells that cause bone destruction. Denosumab is a monoclonal antibody that binds to RANKL on the neoplastic mononuclear cells, preventing them from activating the giant cells.

Question 642

Topic: Biology, Genetics & Bone Healing

A 32-year-old female is diagnosed with a giant cell tumor of the distal femur. The lesion is eccentric, expansile, and lytic. Histology reveals multinucleated giant cells in a background of mononuclear stromal cells. If neoadjuvant targeted pharmacotherapy is utilized, what is its primary mechanism of action?

. Inhibition of VEGF receptors
. Activation of the p53 tumor suppressor gene
. Inhibition of RANKL
. Tyrosine kinase inhibition of c-KIT
. Cross-linking of DNA double strands

Correct Answer & Explanation

. Inhibition of RANKL

Explanation

Giant cell tumor of bone (GCT) consists of neoplastic mononuclear stromal cells that express RANKL. RANKL recruits and activates normal multinucleated osteoclast-like giant cells, causing extensive bone resorption. Denosumab, a monoclonal antibody against RANKL, inhibits this process and is an effective targeted therapy for GCT.

Question 643

Topic: Biology, Genetics & Bone Healing

A 32-year-old male presents with a purely lytic, expansile lesion extending into the subchondral bone of the distal femur. Biopsy reveals multinucleated giant cells intermixed with mononuclear stromal cells. Which targeted medical therapy directly inhibits the specific molecular pathway driving this pathology?

. Imatinib
. Denosumab
. Methotrexate
. Zoledronic acid
. Doxorubicin

Correct Answer & Explanation

. Denosumab

Explanation

Giant Cell Tumor of Bone (GCTB) is driven by neoplastic mononuclear stromal cells that overexpress RANKL, recruiting reactive osteoclast-like giant cells. Denosumab, a monoclonal antibody against RANKL, directly targets this pathway and is highly effective in treating GCTB.

Question 644

Topic: Biology, Genetics & Bone Healing
During the evaluation of a patient suspected of having a lumbar disk herniation, T1- and T2-weighted MRI scans reveal a hyperintense lobular, well-defined lesion in the L2 vertebral body. What is the most likely diagnosis?
. Metastatic focus
. Bony island
. Intravertebral disk herniation
. Osteoporosis
. Hemangioma

Correct Answer & Explanation

. Hemangioma

Explanation

The findings are characteristic of hemangioma. When the hemangioma is large enough, vertical striations may be visible on plain radiographs. Axial CT scans commonly reveal a speckled appearance. Metastatic lesions are typically hypointense on T1-weighted images because they replace the fatty marrow. Bony islands, like cortical bone, are dark on T1- and T2-weighted images. Intravertebral disk herniation would have characteristics similar to the disk and be in continuity with the disk. Osteoporosis is more diffuse.

Question 645

Topic: Biology, Genetics & Bone Healing

A 60-year-old Asian male presents with progressive hand clumsiness and gait disturbances. Radiographs and MRI demonstrate a continuous band of ossification along the posterior aspect of the cervical vertebral bodies, causing severe spinal canal stenosis. Which of the following molecular factors is most significantly implicated in the pathogenesis of this condition?

. Fibroblast growth factor receptor 3 (FGFR3) mutation
. Deficiency of tissue-nonspecific alkaline phosphatase (TNAP)
. Overexpression of Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-beta (TGF-beta)
. Mutations in the COL1A1 gene
. Elevated levels of circulating parathyroid hormone (PTH)

Correct Answer & Explanation

. Overexpression of Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-beta (TGF-beta)

Explanation

Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Research has shown that overexpression of osteogenic factors, particularly Bone Morphogenetic Proteins (BMP-2) and TGF-beta, plays a crucial role in the hyperostotic process of the posterior longitudinal ligament. It is highly prevalent in East Asian populations, and while genetics (like ENPP1 variants) play a role, BMP/TGF-beta signaling is a central downstream mechanism of the ossification process.

Question 646

Topic: Biology, Genetics & Bone Healing

The biomechanical properties of articular cartilage are dependent on its extracellular matrix. Which of the following components is primarily responsible for generating the tissue's compressive stiffness through osmotic swelling pressure?

. Type I collagen
. Type II collagen
. Aggrecan
. Elastin
. Fibronectin

Correct Answer & Explanation

. Aggrecan

Explanation

Aggrecan is the most abundant proteoglycan in articular cartilage. Its highly negatively charged glycosaminoglycan (GAG) side chains attract water, creating a strong osmotic swelling pressure. This swelling is resisted by the tensile strength of the Type II collagen network, providing articular cartilage with its characteristic compressive stiffness.

Question 647

Topic: Biology, Genetics & Bone Healing

When a full-thickness articular cartilage defect extends through the tidemark into the subchondral bone, marrow-derived mesenchymal stem cells fill the defect. The resulting repair tissue is biomechanically inferior to native hyaline cartilage. Which type of collagen predominates in this repair tissue?

. Type I collagen
. Type II collagen
. Type IX collagen
. Type X collagen
. Type XI collagen

Correct Answer & Explanation

. Type I collagen

Explanation

Defects that penetrate the subchondral bone heal via the formation of fibrocartilage. Unlike native articular hyaline cartilage, which is predominantly composed of Type II collagen, fibrocartilage is primarily composed of Type I collagen. Type I collagen lacks the complex structural organization needed to resist the compressive and shear forces of the joint, leading to earlier degradation.

Question 648

Topic: Biology, Genetics & Bone Healing
In the structural composition of native adult hyaline articular cartilage, which minor collagen primarily functions to cross-link fibrillar elements and regulate the diameter of the collagen fibrils?
. Type I collagen
. Type II collagen
. Type IX collagen
. Type X collagen
. Type I and III collagen

Correct Answer & Explanation

. Type IX collagen

Explanation

While Type II collagen constitutes 90-95% of the collagen in articular cartilage and provides the primary structural framework, Type IX (along with Type XI) is a minor collagen that plays a crucial role in covalently cross-linking the Type II fibrils, thereby regulating their diameter and stabilizing the matrix. Type X collagen is exclusively found in the calcified zone.

Question 649

Topic: Biology, Genetics & Bone Healing

Lubricin (PRG4) is a critical glycoprotein for boundary lubrication in synovial joints. Which cells are primarily responsible for synthesizing and secreting lubricin in healthy articular cartilage?

. Superficial zone chondrocytes
. Middle zone chondrocytes
. Deep zone chondrocytes
. Subchondral osteoblasts
. Fibroblasts in the joint capsule

Correct Answer & Explanation

. Superficial zone chondrocytes

Explanation

Lubricin (proteoglycan 4 or PRG4) is synthesized primarily by superficial zone chondrocytes and synoviocytes. It localizes to the articular surface where it provides crucial boundary lubrication, significantly reducing friction and wear during joint movement.

Question 650

Topic: Biology, Genetics & Bone Healing

A partial-thickness articular cartilage laceration that does not penetrate the tidemark into the subchondral bone is observed incidentally during arthroscopy. Which of the following best describes the expected physiological healing response of this specific lesion?

. Robust regeneration via hyaline cartilage synthesis
. Complete filling with fibrocartilage via subchondral bleeding
. Little to no healing response due to lack of vascular access
. Extensive woven bone formation within the defect
. Rapid chondrocyte proliferation from the deep zone

Correct Answer & Explanation

. Little to no healing response due to lack of vascular access

Explanation

Partial-thickness cartilage injuries do not violate the subchondral bone and therefore do not access the marrow elements necessary for a hematoma or stem cell response. Consequently, they elicit little to no healing response due to the avascular nature of articular cartilage.

Question 651

Topic: Biology, Genetics & Bone Healing

A 34-year-old man underwent open reduction and internal fixation of a closed both bones forearm fracture 11 months ago. The radiographs shown in Figures 32a and 32b reveal a 3-mm gap and loose screws. What is the best treatment option?

. Vascularized fibular graft
. Locked intramedullary rodding
. Tricortical iliac crest grafting and compression plating
. Cancellous autograft and plating
. BMP-7

Correct Answer & Explanation

. Cancellous autograft and plating

Explanation

In an atrophic nonunion with a good soft-tissue envelope, adequate plating with cancellous bone graft can be used to span defects of up to 6 cm. Cortical graft from the fibula or iliac crest is not necessary. BMP-7 is a bone graft substitute and should not be used alone in this patient because the hardware is loose.

Question 652

Topic: Biology, Genetics & Bone Healing

A 45-year-old man has had left thigh pain for the past 4 months. An AP radiograph, bone scan, MRI scans, and biopsy specimens are shown in Figures 6a through 6f. What is the most appropriate treatment?

. Physical therapy
. Medical management
. Radiation therapy
. Prophylactic internal fixation
. Wide resection

Correct Answer & Explanation

. Medical management

Explanation

The radiograph demonstrates thickened trabeculae and thickened cortices in the left proximal femur compared to the right, and the bone scan shows increased uptake in this area. The MRI scans show thickened trabeculae with normal marrow signal. These findings are diagnostic of Paget's disease. Medical treatment, including bisphosphonates and calcitonin, is indicated for painful bone lesions. Hadjipavlou AG, Gaitanis IN, Kontakis GM: Paget's disease of the bone and its management. J Bone Joint Surg Br 2002;84:160-169.

Question 653

Topic: Biology, Genetics & Bone Healing

A 15-year-old boy with epilepsy who is treated with phenytoin sustains a vertebral compression fracture during a breakthrough seizure. Radiographs of the spine reveal generalized osteopenia. What is the most likely cause of the osteopenia?

. Induced osteoporosis
. Acquired osteomalacia
. Calcitonin effect
. Hyperparathyroidism
. Disuse osteoporosis

Correct Answer & Explanation

. Acquired osteomalacia

Explanation

As a side effect of treatment, phenytoin induces osteomalacia, or rickets, in growing children, through interference with metabolism of vitamin D. Oral supplementation of vitamin D can minimize this effect in patients who are undergoing prolonged treatment with phenytoin.

Question 654

Topic: Biology, Genetics & Bone Healing

A 62-year-old woman with a bone mass density (BMD) T-score of -2.0 sustained a subcapital fracture of her hip. She is an avid tennis player, and history reveals no previous fractures. What is the most appropriate follow-up care?

Hip & Knee Reconstruction Board Review 2007: High-Yield MCQs (Set 2) - Figure 22

. Antiresorptive bisphosphonate medication
. A repeat dual-energy x-ray absorptiometry scan (DEXA) and treatment if the T-score is less than -2.5
. A repeat DEXA scan and treatment if the T-score is greater than -1.5
. No treatment since the BMD is not in osteoporotic range
. (PTH) taraparatide hormone followed by surgery

Correct Answer & Explanation

. Antiresorptive bisphosphonate medication

Explanation

A DEXA scan is most appropriately used to establish a baseline score. Even if the bone mineral density is not within the osteoporotic range (T-score less than -2.5), a prior fragility fracture is a strong risk factor for a second fracture as a result of factors other than bone density, such as worsening vision or balance, confusion, or other predispositions to falls. The guidelines of the National Osteoporosis Foundation indicate that, following a fragility hip fracture, active anti-osteoporotic medication should be initiated, whether or not a DEXA scan is performed. A recent study showed that antiresorptive therapy following a hip fracture reduces not only the risk of a second fracture but also overall mortality.

Question 655

Topic: Biology, Genetics & Bone Healing

Figure 26 shows the MRI scan of a 60-year-old man who has had groin pain for the past 2 months. The patient reports pain with ambulation, and examination reveals an antalgic gait. He denies any history of steroid or alcohol abuse. Plain radiographs are normal. Management should include

Hip 2001 Practice Questions: Set 3 (Solved) - Figure 8

. core decompression.
. a vascularized fibula graft.
. intraosseous steroid injection.
. total hip replacement.
. protected weight bearing.

Correct Answer & Explanation

. protected weight bearing.

Explanation

The patient has transient osteoporosis of the hip. Transient osteoporosis is usually a self-limited condition that is most frequently seen in women in the third trimester of pregnancy and in men in the sixth decade of life. Transient osteoporosis is best treated with protected weight bearing.

Question 656

Topic: Biology, Genetics & Bone Healing

A healthy 52-year-old woman is seeking professional advice about management of osteoporosis. She has no risk factors for osteoporosis. What is the best recommendation for bone health for this patient?

Basic Science 2008 Practice Questions: Set 1 (Solved) - Figure 8

. Bone mineral density testing performed semiannually
. No treatment
. A healthy diet high in calcium
. 1,000 to 1,500 mg calcium supplement plus 400 to 800 IU vitamin D per day
. Estrogen therapy

Correct Answer & Explanation

. 1,000 to 1,500 mg calcium supplement plus 400 to 800 IU vitamin D per day

Explanation

Women older than age 50 years should receive daily supplementation with calcium and vitamin D to help preserve bone density. Bone mineral density testing is recommended for women age 65 years or older and postmenopausal women with at least one risk factor for osteoporotic fractures: prior fragility fracture, low estrogen levels, premature menopause, long-term secondary amenorrhea, glucocorticoid therapy, maternal history of hip fracture, or low body mass index. Hormone therapy is not approved for the treatment of osteoporosis. Gass M, Dawson-Hughes B: Preventing osteoporosis-related fractures: An overview. Am J Med 2006;119:S3-S11.

Question 657

Topic: Biology, Genetics & Bone Healing

During the evaluation of a patient suspected of having a lumbar disk herniation, T1- and T2-weighted MRI scans reveal a hyperintence lobular, well-defined lesion in the L2 vertebral body. What is the most likely diagnosis?

Spine Surgery 2000 Practice Questions: Set 1 (Solved) - Figure 24

. Metastatic focus
. Bony island
. Intravertebral disk herniation
. Osteoporosis
. Hemangioma

Correct Answer & Explanation

. Hemangioma

Explanation

The findings are characteristic of hemangioma. When the hemangioma is large enough, vertical striations may be visible on plain radiographs. Axial CT scans commonly reveal a speckled appearance. Metastatic lesions are typically hypointense on T1-weighted images because they replace the fatty marrow. Bony islands, like cortical bone, are dark on T1- and T2-weighted images. Intravertebral disk herniation would have characteristics similar to the disk and be in continuity with the disk. Osteoporosis is more diffuse. Ross JS, Masaryk TJ, Modic MT, Carter JR, Mapstone T, Dengel FH: Vertebral hemangiomas: MR imaging. Radiology 1987;165:165-169.

Question 658

Topic: Biology, Genetics & Bone Healing

It has been shown that bisphosphonate-based supportive therapy (pamidronate or zoledronate) reduces skeletal events (onset or progression of osteolytic lesions) both in patients with multiple myeloma and in cancer patients with bone metastasis. The use of biphosphonate therapy has been associated with

Basic Science 2008 Practice Questions: Set 1 (Solved) - Figure 61

. increased medical complications of treatment.
. osteonecrosis of the jaw.
. improved long-term survival rates.
. anorexia.
. decreased quality of life measures.

Correct Answer & Explanation

. osteonecrosis of the jaw.

Explanation

The use of bisphosphonates has been recently associated with the development of osteonecrosis of the jaw. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor. Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density (ie, alendronate). The primary mechanism of action of these drugs is inhibition of osteoclastic activity, and it has been shown that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity, such as breast cancer and multiple myeloma, and have developed into a mainstay of treatment for individuals with these diseases. Although shown to reduce skeletal events, there has been no improvement in patient survival. Bamias A, Kastritis E, Bamia C, et al: Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors. J Clin Oncol 2005;23:8580-8587. Thakkar SG, Isada C, Smith J, et al: Jaw complications associated with bisphosphonate use in patients with plasma cell dyscrasias. Med Oncol 2006;23:51-56.

Question 659

Topic: Biology, Genetics & Bone Healing

Figure 11a shows the AP pelvis radiograph of a 25-year-old man who sustained a spinal cord injury 10 years ago. A bone scan and a CT scan are shown in Figures 11b and 11c. To prevent recurrence after resection, management should consist of

. radiation therapy.
. bisphosphonate therapy.
. antitubercular therapy.
. parathyroidectomy.
. a diet low in phosphate.

Correct Answer & Explanation

. radiation therapy.

Explanation

The studies reveal significant heterotopic ossification that appears to be mature. Following resection, the most reliable way to prevent recurrence is with low-dose external-beam radiation therapy. Bisphosphonate therapy can be considered; however, when terminated, heterotopic bone may reform. Heterotopic ossification is unrelated to the patient's endocrine status and is not associated with any metabolic abnormalities. Moore K, Goss K, Anglen J: Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fracture. J Bone Joint Surg Br 1998;80:259.

Question 660

Topic: Biology, Genetics & Bone Healing

A 72-year-old man has had persistent pain after undergoing a hemiarthroplasty 18 months ago. Radiographs are shown in Figures 50a and 50b. What is the most likely cause of his problem?

. Suboptimal cement technique
. Excessive activity level
. Oversized bipolar component
. Infection
. Osteoporosis

Correct Answer & Explanation

. Infection

Explanation

The radiographs demonstrate a rapid erosion of the bipolar component into the acetabulum. Although acetabular erosion is more common with unipolar hip arthroplasties, it can occur with bipolar components. Haidukewych and associates noted a very low erosion rate but none in the first 2 years. The second finding on the radiographs is the linear radiolucency progressing from the joint toward the end of the stem at the cement-bone interface suggesting chronic infection or diffuse loosening. The persistent pain since implantation also suggests chronic infection. High activity levels and osteoporosis do not lead to acetabular erosion in the first 2 years after hemiarthroplasty. While the cement technique is suboptimal, loosening and erosion should not be expected from this alone. An oversized bipolar head would extrude and not erode. Haidukewych GJ, Israel TA, Berry DJ: Long-term survivorship of cemented bipolar hemiarthroplasty for fracture of the femoral neck. Clin Orthop Relat Res 2002;403:118-126. Lestrange NR: Bipolar hemiarthroplasty for 496 hip fractures. Clin Orthop Relat Res 1990;251:7-19.

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