Bone

BONE BIOLOGY AND BONE MARKERS

Bone cells

This pathway regulates osteoclast formation and bone resorption.

Important regulators

• PTH: Increases RANKL signaling indirectly, promoting osteoclast-mediated bone resorption during sustained elevation.
• Estrogen: Helps restrain osteoclast activity; estrogen deficiency increases bone resorption.
• Denosumab: Monoclonal antibody against RANKL, reducing osteoclast formation and activity.

Remember: RANKL activates osteoclasts; OPG blocks RANKL.

Bone formation and resorption markers

FCPS tip: CTX is a commonly used bone resorption marker; ALP is associated with osteoblast activity but is not specific to bone unless bone-specific ALP is measured.

PARATHYROID HORMONE AND HYPERPARATHYROIDISM

Jaw and dental manifestations

A. Loss of lamina dura

• Reduced or absent lamina dura may occur.
• It is a classic but not universal finding.
• It is not specific to hyperparathyroidism.

B. Generalized osteopenia

• Reduced bone density.
• Trabeculae may appear sparse.
• Cortical bone may become thinner.

C. Ground-glass appearance

• May occur due to altered bone remodeling.
• Can overlap radiographically with other conditions, so clinical and biochemical correlation is essential.

D. Brown tumors

Brown tumors are focal, non-neoplastic lesions caused by excessive bone remodeling in hyperparathyroidism.

Brown tumor versus central giant cell granuloma

These lesions can look very similar histologically.

Exam pearl: If a giant-cell jaw lesion is identified, assess calcium, phosphate, PTH and ALP before labeling it a central giant cell granuloma.

INFLAMMATORY AND INFECTIVE BONE LESIONS

Osteomyelitis of the jaws

Osteomyelitis is inflammation and infection of bone and bone marrow, often associated with odontogenic infection, trauma or surgery.

A. Pathogenesis

• Infection reaches bone from an odontogenic source, trauma or surgical intervention.
• Inflammation increases tissue pressure and may impair local blood supply.
• Bone necrosis can occur, producing separated fragments of dead bone called sequestra.
• Reactive new bone may form around the affected area.

B. Important terminology

Types of osteomyelitis

Acute suppurative osteomyelitis

Clinical features may include:

• Severe pain and swelling.
• Fever and systemic illness.
• Tenderness and possible tooth mobility.
• Pus or drainage.
• Paresthesia in some cases.

Chronic suppurative osteomyelitis

• Persistent or recurrent pain.
• Draining sinus tracts.
• Sequestrum formation.
• Mixed radiolucent and radiopaque changes.
• Delayed healing.

Proliferative periostitis

• Commonly associated with a chronic odontogenic infection in younger patients.
• Periosteal new bone forms in successive layers.
• Produces the classic onion-skin appearance.

Radiographic features of osteomyelitis

Plain radiographs may lag behind clinical disease. CT is useful for cortical destruction and sequestra; MRI is useful for marrow and soft-tissue involvement.

Management

• Identify and control the source of infection.
• Obtain appropriate cultures when indicated.
• Use antibiotics based on clinical severity, likely organisms and culture results where available.
• Drain abscesses when present.
• Remove sequestra or debride necrotic bone when indicated.
• Treat the causative dental source, preserving or removing teeth according to restorability and infection control.
• Manage underlying systemic risk factors.

FCPS tip: Onion-skin periosteal reaction in a young patient with chronic odontogenic infection suggests proliferative periostitis (Garre osteomyelitis).

MEDICATION-RELATED OSTEONECROSIS OF THE JAW

MRONJ

Medication-related osteonecrosis of the jaw is a condition involving exposed bone, or bone that can be probed through an intraoral or extraoral fistula, in a patient exposed to relevant medications.

A. Drugs associated with MRONJ

Risk is particularly important with high-dose antiresorptive therapy used for cancer-related bone disease. Risk also depends on duration, comorbidities and local factors.

B. Diagnostic criteria

The classic criteria include:

1. Current or previous treatment with an antiresorptive medication, alone or in combination with certain other implicated drugs.
2. Exposed bone, or bone probeable through an intraoral or extraoral fistula, persisting for more than eight weeks.
3. No history of radiation therapy to the jaws and no metastatic disease to the jaws.

C. Risk factors

• Extraction or other dentoalveolar surgery.
• Periodontal or periapical infection.
• Poor oral hygiene.
• Prolonged or high-dose antiresorptive therapy.
• Cancer and associated therapies.
• Diabetes and smoking may contribute to overall risk.

D. Common sites

The mandible is affected more often than the maxilla.

Staging

F. Management principles

• Prevention through dental assessment and treatment of active disease before high-risk therapy when feasible.
• Oral hygiene and regular dental follow-up.
• Antimicrobial rinses and analgesia for appropriate cases.
• Antibiotics when infection is present.
• Surgical debridement or resection for selected cases according to stage and specialist assessment.

FCPS tip: MRONJ is associated with antiresorptive medications, especially bisphosphonates and denosumab. A drug holiday is not automatic; decisions require coordination with the treating clinician because interruption may have significant consequences.

OSTEORADIONECROSIS

Osteoradionecrosis (ORN)

Osteoradionecrosis is necrosis of irradiated bone following radiation therapy, often involving the jaws.

Pathophysiology

Radiation can cause:

• Reduced vascularity.
• Cellular damage.
• Fibrosis and impaired tissue repair.
• Reduced capacity for healing after trauma or extraction.

Clinical features

• Persistent exposed bone in a previously irradiated region.
• Pain, infection or a non-healing extraction socket.
• Possible pathological fracture in advanced disease.

Prevention and management

• Dental assessment and elimination of active infection before radiotherapy when feasible.
• Avoid unnecessary trauma to irradiated bone.
• Use conservative local care and infection control when appropriate.
• Specialist management for persistent or extensive disease; surgery may be needed in advanced cases.

Exam distinction: MRONJ is associated with implicated medications; osteoradionecrosis is associated with prior radiation to the jaw.

FIBRO-OSSEOUS LESIONS

Fibro-osseous lesions are conditions in which normal bone is replaced by fibrous tissue containing mineralized material. Diagnosis depends on the combination of clinical features, radiographic appearance and histopathology.

Fibrous dysplasia

Fibrous dysplasia is a developmental bone disorder in which normal bone is replaced by fibrous tissue and irregular immature bone.

A. Pathogenesis

• Associated with activating mutations in the GNAS gene.
• Causes abnormal osteoblastic differentiation and bone formation.
• May affect one bone or multiple bones.
• Craniofacial bones are commonly involved.

B. Types

C. Clinical features

• Usually develops in childhood or adolescence.
• Painless, slowly enlarging bony swelling.
• Facial asymmetry may develop.
• Lesions may stabilize after skeletal maturity.

D. Radiographic features

E. Histology

• Fibrous connective tissue containing irregular immature woven bone.
• Trabeculae may have curved, irregular shapes.
• Classically described as Chinese-letter or alphabet-soup pattern.
• Osteoblastic rimming is typically absent.

F. Management

• Observation for stable, asymptomatic lesions.
• Surgery or contouring for functional impairment, significant deformity or other indications.
• Recurrence or regrowth may occur, particularly if treated before skeletal maturity.

FCPS tip: Ground-glass lesion with blending borders + Chinese-letter woven bone without prominent osteoblastic rimming = fibrous dysplasia.

Ossifying fibroma

Ossifying fibroma is a benign, well-demarcated fibro-osseous neoplasm that can expand the jaws.

Clinical features

• Commonly affects the mandibular premolar–molar region.
• Often presents in young to middle-aged adults.
• Causes slowly progressive, usually painless swelling.
• May displace teeth or cause facial asymmetry.

Radiographic features

• Well-circumscribed lesion.
• May be radiolucent, mixed or predominantly radiopaque, depending on mineralization.
• Often has a distinct boundary or corticated rim.
• Expansion may occur, sometimes with displacement of adjacent structures.

Histology

• Fibrous stroma containing varying amounts of mineralized material.
• Bone trabeculae and/or cementum-like deposits may be present.

Management

• Surgical enucleation or excision depending on the lesion.
• Recurrence is generally uncommon after complete removal of conventional lesions.
• Juvenile variants can behave more aggressively and recur more frequently.

Fibrous dysplasia versus ossifying fibroma

Memory trick: Fibrous dysplasia blends; ossifying fibroma separates.

Cemento-osseous dysplasia (COD)

COD is a benign fibro-osseous condition, usually occurring around the apices of vital teeth. It is important not to mistake it for an inflammatory periapical lesion.

Types

Radiographic evolution

Clinical points

• Often asymptomatic.
• More commonly detected in middle-aged adults, especially women.
• Teeth associated with periapical COD are usually vital.
• Biopsy is generally avoided in classic asymptomatic cases because unnecessary surgery may introduce infection.

COD versus periapical inflammatory disease

FCPS tip: Multiple periapical lesions around vital mandibular incisors that mature into radiopaque masses suggest periapical COD, not multiple radicular cysts.

GIANT CELL LESIONS

Central giant cell granuloma (CGCG)

CGCG is an intraosseous lesion containing multinucleated giant cells within a fibrovascular stroma.

Clinical features

• Commonly occurs in children and young adults.
• More frequent in females.
• Frequently affects the anterior mandible.
• May cross the midline.
• Can cause swelling, tooth displacement and cortical expansion.

Types

Radiographic features

• Well-defined or less-defined radiolucency.
• Unilocular or multilocular appearance.
• Expansion and tooth displacement may occur.
• Root resorption is more likely in aggressive lesions.

Histology

• Multinucleated giant cells in a fibrovascular stroma.
• Hemorrhage and hemosiderin may be present.
• Histology alone may not reliably distinguish CGCG from a brown tumor.

Management

• Curettage or surgical excision depending on extent and behavior.
• Selected cases may be managed with intralesional corticosteroids or other specialist-directed therapies.
• Evaluate calcium, phosphate, PTH and ALP to exclude hyperparathyroidism.

Cherubism

Cherubism is a rare inherited condition causing bilateral jaw enlargement, usually beginning in childhood.

Key features

• Often autosomal dominant.
• Associated with variants in SH3BP2 in many cases.
• Bilateral enlargement of the posterior mandible and sometimes maxilla.
• Painless, symmetrical swelling produces a characteristic cherubic facial appearance.
• May cause upward displacement of the eyes and dental eruption abnormalities.
• Often stabilizes and regresses after puberty, although residual deformity may remain.

Radiographic features

• Bilateral, multilocular radiolucencies.
• Expansion of the jaws.
• Tooth displacement and eruption disturbances may occur.

Management

• Observation during growth when appropriate.
• Surgery is reserved for severe functional, ocular, airway or cosmetic problems.

MCQ tip: Bilateral, symmetrical multilocular jaw lesions in a child + regression after puberty = cherubism.

BENIGN BONE TUMORS

Osteoma

Osteoma is a benign proliferation of mature compact or cancellous bone.

Types

Clinical features

• Slow-growing, painless bony mass.
• May be discovered incidentally.
• Can cause facial asymmetry or interfere with function depending on location.

Common sites

• Mandibular angle and body.
• Condylar region.
• Paranasal sinuses.
• Other craniofacial bones.

Gardner syndrome association

Multiple osteomas can be an early clue to Gardner syndrome, which is associated with familial adenomatous polyposis.

FCPS tip: Multiple jaw osteomas in a young patient should prompt consideration of Gardner syndrome and appropriate medical evaluation.

Osteoid osteoma

Osteoid osteoma is a benign bone-forming tumor classically associated with localized pain.

Features

• Usually small, commonly less than 1.5–2 cm.
• Pain is often worse at night.
• Pain classically improves with NSAIDs.
• A central nidus may be surrounded by reactive sclerosis.

Radiographic features

• Small radiolucent nidus.
• Surrounding reactive sclerosis.
• CT is particularly useful for identifying the nidus.

Exam tip: Night pain relieved by NSAIDs + small nidus with surrounding sclerosis = osteoid osteoma.

Osteoblastoma

Osteoblastoma is a benign bone-forming tumor that can resemble osteoid osteoma but is generally larger and less characteristically relieved by NSAIDs.

MALIGNANT BONE TUMORS

Osteosarcoma

Osteosarcoma is a malignant bone tumor characterized by malignant cells producing osteoid.

A. Epidemiology and clinical features

• Common primary malignant bone tumor in adolescents and young adults.
• Jaw osteosarcoma tends to occur at an older age than osteosarcoma of long bones.
• May present with painful or painless swelling.
• Tooth mobility, paresthesia and rapid enlargement may occur.
• Widening of the periodontal ligament space may be an early clue in jaw lesions.

B. Radiographic features

These findings are not always present and are not individually diagnostic.

C. Histology

The defining feature is malignant osteoid produced by tumor cells.

D. Laboratory findings

• ALP may be elevated but is neither sensitive nor specific enough to diagnose osteosarcoma.
• LDH may also be elevated in some cases.

E. Management

• Urgent referral to a specialist sarcoma team.
• Imaging and biopsy for diagnosis and staging.
• Wide surgical resection when feasible.
• Chemotherapy according to tumor site, subtype and protocol.

FCPS tip: Malignant osteoid + sunburst periosteal reaction = osteosarcoma.

Ewing sarcoma

Ewing sarcoma is a malignant small round-cell tumor of bone and soft tissue, most common in children and young adults.

Genetics

• Commonly associated with a EWSR1–FLI1 fusion, usually resulting from t(11;22).
• Molecular confirmation is important because several small round-cell tumors may resemble it histologically.

Clinical features

• Painful swelling.
• Fever may occur.
• May resemble osteomyelitis clinically.
• Jaw involvement can cause swelling, tooth mobility or paresthesia.

Radiographic features

• Permeative or moth-eaten bone destruction.
• Periosteal reaction may show an onion-skin pattern.
• Soft-tissue mass may be present.

Histology and immunohistochemistry

• Small round blue cells.
• CD99 is commonly positive but is not entirely specific.
• Molecular testing helps confirm the diagnosis.

Management

• Multiagent chemotherapy.
• Local control with surgery and/or radiotherapy depending on the site and response.

FCPS tip: Young patient + small round blue cells + EWSR1–FLI1 fusion = Ewing sarcoma.

Chondrosarcoma

Chondrosarcoma is a malignant tumor that produces cartilage.

Clinical features

• More common in adults than in children.
• May affect the maxilla or mandible, including the anterior maxilla.
• Presents with slowly progressive swelling, pain or tooth displacement.

Radiographic features

• Destructive radiolucent lesion.
• Ring-and-arc or stippled calcification may occur.
• Cortical destruction and soft-tissue extension may be present.

Management

• Surgical resection is the main treatment.
• Conventional chondrosarcoma is relatively resistant to standard chemotherapy and radiotherapy; treatment depends on subtype and site.

Exam tip: Ring-and-arc calcification suggests a cartilaginous lesion such as chondrosarcoma.

Multiple myeloma

Multiple myeloma is a malignant proliferation of plasma cells in bone marrow.

Clinical features

• Usually affects older adults.
• Bone pain, fractures, anemia and renal impairment may occur.
• Jaw involvement can produce multiple radiolucent lesions.

Radiographic features

• Multiple well-defined punched-out radiolucencies.
• Loss of normal trabecular pattern.
• Mandibular lesions may be detected during dental imaging.

Laboratory findings

Management

• Hematology/oncology referral.
• Systemic treatment based on disease characteristics.
• Dental planning should account for bone fragility, infection risk and antiresorptive-associated jaw complications.

FCPS tip: Multiple punched-out lesions + monoclonal protein + anemia/renal impairment = multiple myeloma.

Metastatic tumors to the jaws

Metastatic malignancy should be considered when a jaw lesion is rapidly progressive or atypical, especially in an older adult with a cancer history.

Common primary sources

The relative frequency varies by population and sex. Common sources include:

• Breast.
• Lung.
• Kidney.
• Prostate.
• Thyroid.
• Colorectal malignancies.

Clinical features

• Pain and swelling.
• Tooth mobility.
• Paresthesia, including numb-chin syndrome.
• Non-healing extraction socket.
• Pathological fracture in advanced lesions.

Radiographic appearance

Exam tip: New numb-chin syndrome, particularly with a destructive mandibular lesion, warrants urgent evaluation for malignancy.

METABOLIC AND SYSTEMIC BONE DISEASE

Paget disease of bone (osteitis deformans)

Paget disease is a chronic disorder of bone remodeling involving excessive resorption followed by disorganized bone formation.

Pathogenesis

Classically, the disease progresses through overlapping phases:

1. Osteolytic phase: Increased osteoclast activity and bone resorption.
2. Mixed phase: Increased resorption and disorganized bone formation.
3. Sclerotic phase: Predominantly sclerotic, enlarged bone with abnormal architecture.

Clinical features

• Usually affects older adults.
• Skull and pelvis are common sites.
• Maxillary involvement may produce enlargement of the jaw.
• Teeth may become separated as the jaw enlarges.
• Dentures may become poorly fitting.
• Bone pain and deformity can occur.

Radiographic features

Laboratory findings

• ALP is often markedly elevated when disease activity is high.
• Calcium and phosphate are usually normal unless another disorder is present.

Histology

The classic finding is a mosaic pattern of lamellar bone, with irregular cement lines.

Complications

• Bone deformity and fractures.
• Hearing impairment with skull involvement.
• Rare malignant transformation, including osteosarcoma.

FCPS tip: Older patient + enlarged jaw + cotton-wool radiograph + elevated ALP with usually normal calcium = Paget disease.

Osteoporosis and osteopetrosis

These two conditions have opposite effects on bone density but can both affect the jaws.

Osteoporosis

• Reduced bone strength due to decreased bone mass and altered microarchitecture.
• Risk increases with age, menopause, corticosteroids and other factors.
• Dental management focuses on oral health, fracture risk and awareness of antiresorptive medications.

Osteopetrosis

• Dense but structurally abnormal bone due to defective osteoclast function.
• Severe forms may cause anemia and other cytopenias because of reduced marrow space.
• Dental complications include delayed eruption, infection and osteomyelitis.

MCQ tip: Osteoporosis = low bone mass; osteopetrosis = abnormally dense bone with impaired remodeling.

SIMPLE AND ANEURYSMAL BONE CYSTS

Simple bone cyst

A simple bone cyst, also called a traumatic bone cyst, is an intraosseous cavity without an epithelial lining.

Aneurysmal bone cyst (ABC)

An aneurysmal bone cyst is an expansile lesion containing blood-filled spaces.

Important: Aneurysmal bone cyst is a descriptive diagnosis that requires clinical and pathological assessment to exclude other lesions and underlying tumors.

MASTER FCPS COMPARISON TABLES

Fibro-osseous lesions

Giant-cell lesions

Malignant jaw lesions

Bone metabolism: laboratory comparison