Bone Tumors and Their Characteristics
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Questions and Answers

What is the preferred site for a chondroma (enchondroma)?

  • Metaphyseal portion of tubular bones of hands and feet (correct)
  • Proximal femur
  • Epiphysis of long bones
  • Diaphysis of long bones

    • What is the most common benign tumor found in bone?

  • Osteochondroma (correct)
  • Chondroma
  • Fibrous dysplasia
  • Osteosarcoma

    • What is the relationship between cartilage and bone in endochondral bone formation?

  • Cartilage is replaced by bone.
  • Cartilage and bone develop independently of each other.
  • Cartilage is converted directly into bone.
  • Cartilage is absorbed by osteoclasts, and bone is laid down on the cartilaginous framework. (correct)

    • Which of the following is NOT a characteristic of osteochondromas?

    <p>They are typically found in the diaphysis of long bones.</p> Signup and view all the answers

    What is the primary cause of Multiple Hereditary Exostosis Syndrome?

    <p>Genetic mutation</p> Signup and view all the answers

    What is the most common location for osteochondromas to arise?

    <p>Knee</p> Signup and view all the answers

    Which of the following describes the morphology of an osteochondroma?

    <p>A sessile or mushroom-shaped lesion, 1-10 cm in size</p> Signup and view all the answers

    What is the clinical significance of osteochondromas?

    <p>They can cause pain and deformity, and may rarely transform into a chondrosarcoma.</p> Signup and view all the answers

    An osteoma is most likely to cause clinical issues due to which of the following?

    <p>Obstruction of sinuses or compression of the brain</p> Signup and view all the answers

    What is the primary differentiating factor in size between an osteoid osteoma and an osteoblastoma?

    <p>Osteoid osteomas are typically less than 2cm, while osteoblastomas are greater than 2cm</p> Signup and view all the answers

    A patient presents with dull, achy pain that worsens at night, and is relieved by aspirin. This is most indicative of which condition?

    <p>Osteoid osteoma</p> Signup and view all the answers

    Which of the following is the most common location for an osteoid osteoma?

    <p>Femur or tibia</p> Signup and view all the answers

    What is a key histological feature of both osteoid osteomas and osteoblastomas?

    <p>Interconnecting trabeculae of woven bone lined by osteoblasts</p> Signup and view all the answers

    What is the typical treatment for an osteoblastoma?

    <p>Curettage</p> Signup and view all the answers

    Which of the following is the most common primary malignant bone tumor?

    <p>Osteosarcoma</p> Signup and view all the answers

    What is the typical location of an osteosarcoma?

    <p>Metaphyseal region of long bones</p> Signup and view all the answers

    Which embryonic germ layer gives rise to the mesenchyme, the precursor to bone and cartilage?

    <p>Mesoderm</p> Signup and view all the answers

    What is a characteristic feature of Maffucci syndrome?

    <p>Accompanied by hemangiomas</p> Signup and view all the answers

    What type of tumor is characterized by its origin from mesenchymal tissue?

    <p>Sarcoma</p> Signup and view all the answers

    Which statement about chondrosarcoma is correct?

    <p>High-grade chondrosarcomas can show pleomorphism and frequent mitoses.</p> Signup and view all the answers

    Compared to malignant bone tumors, benign bone tumors typically present in which age group?

    <p>Younger individuals</p> Signup and view all the answers

    At what age is enchondromatosis, as seen in Ollier disease, most commonly identified?

    <p>40 years</p> Signup and view all the answers

    What type of cartilage is primarily associated with conventional chondrosarcoma?

    <p>Hyaline and myxoid cartilage</p> Signup and view all the answers

    Which of the following characteristics is most commonly associated with woven bone?

    <p>Collagen arranged in an irregular feltwork pattern</p> Signup and view all the answers

    What is a key feature of bone-forming tumors?

    <p>Production of bone by neoplastic cells</p> Signup and view all the answers

    What radiographic feature is characteristic of low-grade chondrosarcomas?

    <p>Endosteal scalloping with flocculent densities</p> Signup and view all the answers

    Where do osteomas typically arise?

    <p>From the subperiosteal surface</p> Signup and view all the answers

    What is a common symptom that is associated with osteomas?

    <p>Generally Asymptomatic</p> Signup and view all the answers

    What is a characteristic feature of Osteomas?

    <p>Are typically slow-growing tumors made of woven and lamellar bone</p> Signup and view all the answers

    Which of the following genetic abnormalities is most commonly associated with osteosarcoma?

    <p>Multiple acquired genetic abnormalities, none specific</p> Signup and view all the answers

    A patient presents with a painful, progressively enlarging mass. Radiographic imaging reveals a 'Codman's triangle'. Which of the following tumors should be suspected?

    <p>Osteosarcoma</p> Signup and view all the answers

    Which of the following is the most common site of origin for osteosarcoma?

    <p>Metaphysis of long bones</p> Signup and view all the answers

    Which of the following best describes the typical microscopic features of an osteosarcoma?

    <p>Pleomorphic osteoblasts with large hyperchromatic nuclei and mitoses</p> Signup and view all the answers

    Which of the following is a common pattern of metastasis for osteosarcoma?

    <p>Hematogenous spread to the lung, brain, and bone</p> Signup and view all the answers

    What histological pattern is typically observed in the bone formation of osteosarcomas?

    <p>Lace-like architecture or broad sheets</p> Signup and view all the answers

    In terms of overall survival, what is the approximate 5 year survival rate for patients with osteosarcoma without known metastases?

    <p>60-70%</p> Signup and view all the answers

    What is the relationship between osteosarcoma and other cartilage-forming tumors?

    <p>Osteosarcoma is the most common malignant cartilage-forming tumor</p> Signup and view all the answers

    What is the main characteristic that differentiates a fibrous cortical defect from a non-ossifying fibroma?

    <p>Fibrous cortical defects usually resolve without treatment.</p> Signup and view all the answers

    Which grade of chondrosarcoma has the highest 5-year survival rate?

    <p>Grade 1</p> Signup and view all the answers

    Which type of fibrous dysplasia involves the presence of endocrine abnormalities?

    <p>Polyostotic fibrous dysplasia</p> Signup and view all the answers

    What is the typical treatment approach for chondrosarcoma?

    <p>Wide surgical excision</p> Signup and view all the answers

    What is a common feature of fibrous cortical defects?

    <p>They often occur in the long bones.</p> Signup and view all the answers

    Which grade of chondrosarcoma is associated with metastases to the lungs and skeleton?

    <p>Grade 3</p> Signup and view all the answers

    What histological pattern is characteristic of a fibrous cortical defect?

    <p>Proliferation of fibroblasts in a 'storiform' pattern</p> Signup and view all the answers

    In what age group do fibrous cortical defects commonly present?

    <p>Children aged over 2 years</p> Signup and view all the answers

    Study Notes

    Neoplasms of Bone and Cartilage

    • Neoplasms of bone and cartilage are discussed in a medical presentation.
    • Benign tumors are more prevalent than malignant tumors.
    • Approximately 2,400 new malignant bone diseases are diagnosed annually.
    • Roughly 1,300 deaths are caused by bone malignancies annually.
    • Tumors' presentation varies from asymptomatic to large, painful, and deforming.
    • Primary and secondary tumor origins are distinguished for diagnostic purposes.
      • Primary tumors develop in otherwise normal bone.
      • Secondary tumors develop on a background of prior bone pathologies, like Paget's disease, osteomyelitis, or inflammatory related conditions.

    Tumor Nomenclature

    • Embryonic development involves three germ layers.
      • Ectoderm forms skin, hair, glands and sensory organs, and neural components.
      • Endoderm forms epithelia, liver, and urinary bladder.
      • Mesoderm gives rise to mesenchyme (embryonic connective tissue) which develops into fibroblasts, chondroblasts, and osteoblasts.
    • Malignant tumors originating from epithelial tissue are called carcinomas.
    • Malignant tumors arising from mesenchymal cells are classified as sarcomas.
    • Bone and cartilage tumors emerge from mesenchyme, therefore they are sarcomas.

    Bone Tumors

    • Benign bone tumors are more prevalent than malignant ones.
    • Benign tumours are frequently diagnosed earlier in life than malignant ones.
    • Specific bone tumors are linked to particular age groups and bones, aiding diagnosis.

    Bone-Forming Tumors

    • Bone-forming tumors involve production of bone by neoplastic cells, usually forming woven bone and variably patterned.
    • Lamellar bone has regularly arranged collagen sheets, typically formed during slower growth periods and adult remodeling.
    • Woven bone displays irregular collagen patterns, often appearing in periods of rapid growth, such as during fetal development, fracture repair or in diseased conditions.

    Tumors of Bone

    • Specific types of bone tumors, like osteoma, osteoid osteoma, osteoblastoma and osteosarcoma are mentioned.

    Osteoma

    • A round to oval tumor arising from the subperiosteal surface of the facial bones or skull bones.
    • Generally solitary and commonly observed in middle-aged individuals.
    • Gardner syndrome, characterized by multiple osteomas in young individuals(ages 10-15), frequently associated with multiple gastrointestinal (GI) adenomas.

    Osteoma: Morphology

    • Osteomas are slow-growing tumors composed of woven and lamellar bone, showcasing a cortical pattern with Haversian-like systems.
    • They may grow outwards or inwards.
    • There is little clinical significance except for the potential to obstruct sinuses or compress brain tissue.
    • Radiographic images are cited as visual aid

    Osteoid Osteoma and Osteoblastoma

    • These tumors have similar histologic features but differ in terms of size, site, and symptoms.
    • They are benign bone-producing tumors.

    Osteoid Osteoma

    • Has a smaller size (<2 cm).
    • Typically observed in younger patients (under 25 years old).
    • Often located in the appendicular skeleton or the posterior spinous processes.
    • The femur and tibia are frequently affected.
    • Pain is a common symptom, often worsening at night and alleviated by aspirin.

    Osteoblastoma

    • Larger in size (>2 cm).
    • Often in the spine and
    • pain is characterized as a dull, achy pain, not responsive to aspirin.
    • The associated bone is less reactive

    Osteosarcoma

    • A malignant mesenchymal tumor in which cancerous cells produce bone matrix.
    • the most frequent primary bone malignancy (20%) excluding multiple myeloma and lymphoma (marrow origin).
    • Patients of any age group can be affected, but there are bimodal peaks in frequency.
      • The majority of cases ({75%}) occur in younger individuals (under 20).
      • A less frequent peak is observed in older adults, often associated with chronic conditions.
    • The male-to-female ratio is approximately 1.6:1.
    • Often found in the metaphyseal areas of long bones in the extremities.
    • Any bone can be affected, especially long bones in the extremities in older individuals (older than 25 years of age)) where these are often located.

    Osteosarcoma: Pathogenesis

    • Approximately 70% of osteosarcomas show some acquired genetic abnormality; no specific abnormality is constantly present.
    • Genetic mutations in the retinoblastoma gene (RB) and the p53 gene are frequently found.
    • Osteosarcomas are more common to appear in growth-spur periods such as adolescence.

    Osteosarcoma: Clinical

    • Presents as a painful, progressively enlarging mass, sometimes with pathological fracture.
    • X-rays reveal a large lytic and blastic mass that may extend beyond the cortex accompanied by a raised periosteal reaction (Codman’s triangle)
    • These tumors aggressively invade surrounding tissue.
    • Metastases are common to lung, brain, and bone.
    • 5-year survival rates range from 60-70% without known metastasis to 20% with known metastasis.

    Osteosarcoma: Morphology

    • Subtypes are based on origin site, differentiation degree (histologic grade), primary versus secondary origin and individual histologic features.
    • The most common form is found in the long bone metaphysis, solitary and osteoblastic, intramedullary, and poorly differentiated.

    Osteosarcoma: Morphology (cont.)

    • Grossly, these tumors appear large, bulky, and gritty, potentially exhibiting areas of hemorrhage and degeneration.
    • They invade adjacent soft tissue and often extend into the medullary canal and/or join space.
    • Microscopically, the tumor displays pleomorphic osteoblasts with large, hyperchromatic nuclei and marked mitotic activity.
    • Bone formation may exhibit a lace-like or sheet-like architecture.
    • Features such as vascular invasion and necrosis are often present.

    Cartilage-Forming Tumors

    • These are the most common primary bone tumors (benign and malignant).
    • Osteosarcoma is the most frequent malignant type.
    • The tumors are characterized by the formation of hyaline or myxoid cartilage.
    • Specific types of cartilagenous tumors (osteochondroma, chondroma, chondrosarcoma) are mentioned.

    Cartilaginous Tumors

    • Osteochondroma, chondroma (enchondroma), and chondrosarcoma are listed as different types.

    Endochondral Bone

    • Formation of endochondral bone occurs through a cartilage model.
    • Chondrocytes produce cartilage which is replaced by osteoclasts (bone-resorbing cells).
    • Osteoblasts lay down bone on the replaced cartilaginous framework.
    • The cartilage is not converted into bone.
    • Primary trabecular bone is formed.
    • Bone deposition occurs on metaphyseal surfaces.

    Osteochondroma

    • A benign cartilage-capped tumor attached to the underlying skeleton by a bony stalk.
    • The most common type of benign tumor in bone.
    • Typically observed in an 85% of cases as a solitary tumor, with late adolescence or early adulthood being a typical presentation.
    • The tumor originates from metaphyseal portions near growth plates in endochondral bones especially in knees and can be found in rib, pelvis and scapula.
    • Multiple Hereditary Exostosis Syndromes (MHE) are associated with increased risk of malignant transformation to a chondrosarcoma.

    Osteochondroma: Morphology

    • These lesions are typically sessile or mushroom-shaped, ranging in size from 1-10 cm.
    • Benign hyaline cartilage caps the tumor and is encased within a perichondrium.
    • The cartilage reveals a disordered or disorganized growth pattern consistent with growth plate.
    • Enchondral ossification is present in the cartilage.
    • The tumor's cortex merges with the surrounding bone cortex.

    Osteochondroma: Clinical

    • Typically slow-growing masses, often discovered incidentally during X-rays or physical examinations.
    • Individuals with hereditary exostosis syndrome may present with skeletal deformities influenced by their condition.
    • They generally stabilize when the growth plates close.
    • M alignment to solitary tumours is rare, but elevated in individuals possessing multiple herediatary exostosis syndrome

    Chondroma (Enchondroma)

    • A benign tumor composed of hyaline cartilage that is located inside the medullary cavity of the bone.
    • Often found in the tubular bones of hands and feet.
    • Enchondromatosis represents a condition characterized by the presence of multiple chondromas in different areas of the skeleton.
    • Ollier disease and Maffucci syndrome are identified as types of enchondromatosis.

    Chondroma (Enchondroma): Morphology

    • Lesions are usually less than 3 cm in size, translucent, and blue-gray in appearance.
    • They're typically found within the medullary cavity.
    • Benign hyaline cartilage sheets characterize the microscopic appearance.
    • Enchondral ossification is occasionally observed at the periphery of the lesion.
    • Central calcification may or may not be present.

    Chondroma (Enchondroma): Clinical

    • Typically asymptomatic.
    • Skeletal deformities may be observed in hereditary syndromes.
    • Radiographs reveal a radiolucent lesion with a rim of radiopaque bone ("O" sign).
    • Treatment often involves curettage or watchful waiting.
    • Malignant transformation to a chondrosarcoma is uncommon in isolated chondromas, but proportionally raised in occurrence in hereditary syndromes.

    Chondrosarcoma

    • This is a group of cartilage-producing tumors with a spectrum of clinical and pathologic features.
    • Classified according to site and histology, with 90% of tumors having a central location and conventional histology.
    • More common occurrence in individuals of advanced ages (>40 years) and the overall M:F ratio of 2:1.
    • Rare form of chondrosarcoma arises from multiple enchondroma.

    Chondrosarcoma: Morphology

    • Conventional chondrosarcomas consist of malignant hyaline and myxoid cartilage.
    • These form large, bulky tumors with gray-white translucent nodules.
    • Tumors having a myxoid component tend to display a more gelatinous consistency.

    Chondrosarcoma: Grading

    • Tumors are categorized into grades 1, 2, and 3 based on their cellularity, pleomorphism, mitotic activity within the tissue; grade 1 is low, grade 3 is high.
    • Low grade tumors display minimal cellularity, are bland-appearing, and have only a few mitoses. Occasionally endochondral ossification is present.
    • High grade tumors exhibit marked hypercellularity, pleomorphism, and many pathological mitoses.

    Chondrosarcoma: Clinical

    • Usually develops within the central skeleton, such as the pelvis, shoulders, and ribs.
    • Distal extremities are less frequently affected.
    • It causes a progressively enlarging, painful mass.
    • Radiographs reveal cartilage nodules with endosteal scalloping.

    Chondrosarcoma: Biologic Behavior

    • There is a clear link between grade and biologic behavior, particularly in conventional chondrosarcomas.
    • The most common, low-grade tumors are relatively indolent.
    • High grade is usually associated with poor prognosis.

    Fibrous and Fibro-osseous Tumors

    • These bone tumors and tumor-like lesions contain significant fibrous components.
    • Frequently encountered types of these tumors include: fibrous cortical defect, non-ossifying fibroma, fibrous dysplasia, and fibrosarcoma.

    Fibrous Cortical Defect

    • A common developmental defect rather than a true neoplasm, frequently observed in children aged 2 to 50%.
    • Most are located at the metaphysis of the distal femur and proximal tibia.
    • Half of these are bilateral or multiple.
    • Lesions size is usually less than 0.5 cm
    • They frequently resolve spontaneously.

    Fibrous Cortical Defect: Morphology

    • X-ray shows an elongated, demarcated radiolucency surrounded by sclerotic bone.
    • Gross appearance varies from gray to yellow-brown.
    • Histologically, the lesion displays a proliferation of fibroblasts which demonstrate a "storiform" or pinwheel pattern.

    Fibrous Cortical Defect/Non-ossifying Fibroma

    • Fibrous cortical defects larger than 5-6 cm are categorized as non-ossifying fibromas.
    • These typically present as an asymptomatic lesion or are detected incidentally in radiographic imaging.
    • These are generally slow-growing and have limited growth potential.
    • They eventually resolve spontaneously.
    • Larger lesions may show progressive enlargement or lead to pathological fractures.

    Fibrous Dysplasia

    • A benign bone tumor often mimicking developmental arrests, where normal bone components are present without having mature bone.
    • It arises during fetal development/growth.
    • The condition presents in 3 forms:
      • Monostotic - single bone involvement.
      • Polyostotic- multiple bone involvement.
      • Polyostotic with endocrine/Café-au-lait dysfunction - multiple bone involvement with skin pigmentation and associated endocrine abnormalities

    Fibrous Dysplasia: Monostotic

    • Most common type.
    • Occurs in puberty.
    • Typically affects femur, tibia, jaw, ribs, calvarium, and humerus.
    • Asymptomatic and often discovered incidentally.
    • May cause pain, fractures, or limb length discrepancies.
    • Typically doesn't transform into polyostotic fibrous dysplasia.

    Fibrous Dysplasia: Polyostotic

    • Less common.
    • Occurs in younger individuals (more common in early childhood).
    • Affects multiple bones.
    • Craniofacial involvement is significant, especially in cases characterized by extensive disease (100%).
    • May lead to significant skeletal deformities.

    Fibrous Dysplasia: Polyostotic with Cafe-au-lait spots & Endocrine dysfunction

    • Least common form.
    • Associated with endocrine abnormalities (sexual precocity, hyperthyroidism, pituitary adenoma, and adrenal hyperplasia).
    • Shows hyperpigmented, serpentine skin markings or "coast of Maine" lesions.
    • Skin manifestations are usually found on the same side of the body.

    Fibrous Dysplasia: Genetic

    • All fibrous dysplasia types share the same genetic mutation.
    • The clinical presentation is influenced by the gestational time of the mutation.
    • Early-onset cases tend to be more serious.
    • Mutation is a somatic gain-of-function in the GNAS gene.

    Fibrous Dysplasia: Clinical

    • Monostotic form: primarily presents with minimal symptoms. Surgery is considered for critical locations like the femoral neck.
    • Polyostotic form: often has progression. Transformation to sarcoma is rare. X-ray imaging typically shows a ground glass appearance with well-defined margins.

    Fibrous Dysplasia: Morphology

    • Tumors are often well circumscribed.
    • Intramedullary.
    • Vary in size.
    • Frequently appears tan-white, gritty textured, with curving trabeculae within woven bone.
    • These trabaculae resemble Chinese characters.

    Fibrosarcoma

    • A sarcoma with a fibroblastic phenotype.
    • Usually arises in older patients, but can occur at any age.
    • Males and Females are frequently affected equally.
    • Typically develops in individuals with prior benign bone conditions, bone infarcts or chronic bone conditions de novo / spontaneously .

    Fibrosarcoma: Morphology

    • Gross examination reveals large, hemorrhagic tumors that destroy bone and extend into soft tissues.
    • Histologically, malignant fibroblasts arranged in a herringbone pattern are seen.

    Fibrosarcoma: Clinical

    • Presents as a painful mass in the metaphysis of long bones or pelvis.
    • X-ray shows a large lytic mass extending into soft tissues.
    • Prognosis hinges on factors like tumor size, location, stage, and grade, particularly in higher-grade tumors difficult to surgically remove.

    Miscellaneous Tumors of Bone

    • Ewing sarcoma/PNET, giant cell tumor of bone, and aneurysmal bone cyst.

    Ewing Sarcoma/PNET

    • Two variants of the same tumor, often linked to 11;22 chromosomal translocations.
    • Undifferentiated and neural differentiation types are distinguished.
    • 6–10% of primary malignant bone tumors in children, second only to osteosarcoma.
    • Individuals often affected at an earlier age range, ages 10-15 years.
    • Males and females have similar frequency range

    Ewing Sarcoma/PNET: Morphology

    • These tumors arise in the medullary cavity and infiltrate the cortex, periosteum and surrounding soft tissue.
    • Typically have a soft, tan-white appearance with hemorrhage.
    • Histological examination reveals sheets of small, round blue cells with scant cytoplasm.
    • Homer-Wright rosettes, where cells form a circle around a central space, may be visible, suggestive of neural differentiation.

    Ewing Sarcoma/PNET: Clinical

    • Generally affects the diaphysis of long tubular bones or the flat bones of the pelvis.
    • Individuals usually present with a painful, tender mass.
    • Systemic symptoms like fever, an elevated erythrocyte sedimentation rate or elevated inflammatory markers suggest infection.
    • Anemia and leukocytosis may also be observed.
    • X-ray demonstrates a lytic lesion that extends into soft tissue, potentially showing a periosteal response characteristically manifested as "onion-skin" appearance.

    Giant Cell Tumor of Bone

    • A benign, but locally aggressive bone tumor.
    • Characterized by a mixture of mononuclear cells and multinucleated giant cells (osteoclast-type).
    • Typically affects adults aged 20-40 years.
    • Usually affects a solitary bone, commonly in the epiphysis or metaphysis of long bones, particularly in the knee.
    • Tumor erodes into the subchondral bone plate and destroys the overlying cortex.

    Giant Cell Tumor of Bone: Morphology

    • Gross appearance is large, red-brown, and may demonstrate cystic degeneration.
    • Typically characterized by uniform, oval, mononuclear cells (proliferating component).
    • Scattered multi-nucleated giant cells (osteoclast-type) are also apparent.
    • Reactive bone, necrosis, and hemorrhage are often present.

    Giant Cell Tumor of Bone: Clinical

    • Often unpredictable in behavior.
    • Conservative methods (curettage) may lead to a 60% recurrence rate potentially up to 4% of patients developing lung metastasis.
    • The treatment or surgical approach is usually dictated by the location of the lesion.

    Aneurysmal Bone Cyst

    • A benign tumor with multiloculated cystic spaces filled with blood.
    • Lesion often presents as a rapidly growing bone tumor.
    • Benign-behaving tumor.
    • Associated with 17p13 translocation and up-regulation of USP6 (deubiquitinating) enzyme.

    Aneurysmal Bone Cyst: Morphology

    • Grossly, the tumor exhibits multicystic spaces with gray septa ("thin walls").
    • The walls have plump uniform fibroblasts and mitotic figures.
    • Multinucleated osteoclast giant cells, and woven bone lined by osteoblasts are found within the septa.

    Metastatic Disease

    • The most common skeletal malignancies are metastasis. These occur late in the progression of a primary tumor.
    • These tumors may spread by direct extension, hematogenous/lymphatic, or intraspinal seeding.
    • Any type of primary cancer (e.g., prostate, breast, kidney, lung; in children, neuroblastoma, Wilms tumor) may metastasize to the skeleton.
    • X-rays may demonstrate a lytic, blastic, or mixed appearance.

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    Neoplasms of Bone and Cartilage Lecture Notes 2025 PDF

    Description

    Test your knowledge on various bone tumors such as chondromas, osteochondromas, and osteomas. This quiz covers clinical significance, morphology, and differentiating factors of these conditions. Understand the relationship between cartilage and bone in the context of endochondral bone formation.

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