L15 - Bone pathology: osteomyelitis, metabolic disorders and bone tumours (Dr Francesca Maggiani) Flashcards
- Reviewing bone anatomy and histology - Describing the development of bone infection - Explaining the physiopathology of metabolic bone disease - Describing the different cancers as by the recent reviewed classification
What are the two main types of bone structure
🦴 Cortex (compact bone) – Hard outer shell with parallel osteons.
🕸 Cancellous (medullary) bone – Sponge-like trabecular bone.
What is the function of the cortex (compact bone)?
💪 Provides strength, supports weight, and resists lateral trauma.
What is the function of cancellous (trabecular) bone?
🩸 Hosts hematopoietic marrow, which produces blood cells and contains fat.
What are the two main categories of bone pathology?
🦠 Diseases (e.g., infections, trauma, metastasis)
🎗 Tumors (Primary bone tumors are rare; metastases are more common)
Why are metastistic bone tumours more common than primary bone tumours?
🎯 Bones are a common site for cancer cells to spread and the skeleton is a large and complex structure with a rich blood supply.
What are the two main types of bone shapes?
📏 Tubular bones (long bones like arms and legs, small tubular bones in hands and feet)
📐 Flat bones (e.g., pelvis, scapula)
How does bone growth occur from infancy to adulthood?
🌱 Bone is constantly deposited and resorbed, allowing it to grow and adapt until full skeletal maturity (around 18-20 years old).
How does bone growth occur from infancy to adulthood?
🌱 Bone growth from infancy to adulthood involves cartilage formation, ossification (cartilage hardening into bone), and remodeling, with growth plates at the ends of long bones facilitating length increase, which ceases in early adulthood.
What role does bone play in mineral homeostasis?
⚖️ Acts as a calcium & phosphate reservoir, releasing minerals when needed.
How does immobilisation (e.g. after a fracture) affect bone structure?
🛌 underutilised bone weakens, leading to changes not only at the fracture site but in the entire limb
How is bone susceptible to infections?
🩸 Highly vascularized – Bloodborne infections can reach the bone easily.
Wat are the three main ways infection reaches the bone?
🚑 Hematogenous spread (via bloodstream)
🦠 Contiguous spread (from soft tissue or joints)
🔪 Direct implantation (trauma, surgery)
How can orthopedic surgery lead to bone infections?
🏥 Prostheses can be contaminated during surgery, leading to postoperative infections.
Why are diabetic patients at higher risk of bone infections?
🍬 Poor circulation leads to chronic ulcers that may extend into the bone.
⚡ Neuropathy reduces pain sensation, delaying ulcer detection.
What is a common outcome of chronic diabetic ulcers affecting the bone?
⚠️ Amputation – Often toes or foot due to chronic infected ulcers.
What bones are most commonly affected by infection in children?
👶 Long bones – Typically single-site, but can be multifocal in 5-20% of cases.
What bones are most commonly affected by infection in adults?
🏋️ Spine – Lumbar (lower back region) > thoracic > cervical vertebrae.
How does haematogenous spread cause bone infections?
🦠 Pathogens enter the bloodstream and infect the bone, either as the first site or secondary to another infection.
What are potential entry points for pathogens in haematogenous spread?
🦷 Oral cavity
🍽 Gastrointestinal tract
🩹 Skin (minor trauma)
Why are haemodialysis patients at increased risk for bone infections?
💉 Contaminated needles can introduce bacteria into the bloodstream, leading to osteomyelitis.
Is haematogenous osteomyelitis usually single or multifocal?
🎯 Usually single focus, but 5-20% can be multifocal.
Where do bone infections typically localise in children?
👶 Long bones – In babies (0-2 years), infections localize in the epiphysis & metaphysis due to sluggish blood flow.
Why is the metaphysis prone to infections in young children?
🏗️ The growth plate (cartilage) at either end of the metaphysics, lacks blood vessels, creating a separation in circulation where pathogens can get trapped in the middle.
Where do bone infections most commonly occur in adults?
🦴 Spine – Thoracic > lumbar > cervical vertebrae, due to rich blood supply.
Why are IV drug users at higher risk for osteomyelitis?
💉 Contaminated needles introduce bacteria, leading to bloodstream infections that often affect the spine.
Which pre-existing conditions increase the risk of osteomyelitis
🩸 Hemoglobinopathies like sickle cell disease & beta thalassemia increase susceptibility to bone infections.
How can osteomyelitis be linked to skin ulcer development?
🩹 Infection gradually erodes through soft tissue, periosteum, cortex, and into the medulla (cancellous of the bone).
What do we see in a bone biopsy from an infection site?
🔬 Bone trabeculae being resorbed by osteoclasts, appearing like bite marks due to osteoclast activation.
What triggers osteoclast activation in bone infections
🦠 Inflammatory cytokines (e.g., interleukins) released by neutrophils and other immune cells.
What are osteoclasts
🏗️ Osteoclasts are the cells that degrade bone to initiate normal bone remodelling and mediate bone loss in pathologic conditions e.g. old or damaged bone tissue ( by increasing their resorptive activity)
What immune cells are predominantly found in an infected bone site?
🛡️ Neutrophils (polymorphs), along with other inflammatory cells and fibrinoid material.
How does bone infection lead to abscess formation
💥 Increased inflammatory cells & necrotic debris accumulate, forming an abscess that persists in the bone.
Why is bone infection different from soft tissue infection?
🏗️ Bone is a closed structure, so swelling increases intraosseous pressure, compressing blood vessels and reducing circulation.
How does increased intraosseous pressure worsen bone infection?
⚠️ Compressed blood vessels reduce circulation, preventing debris clearance and allowing the infection to spread.
How can bone infections spread within the bone
🔄 Via Haversian canals, allowing infection to move up or down the medulla and erode the cortex over time.
What happens when infection breaks through the cortex
💥 The periosteum lifts, forming a subperiosteal abscess, which can drain out or spread to soft tissue/joints.
How can infections spread to the bone from surrounding tissue
🦠 Contiguous spread – infection can originate from soft tissue, joints, or adjacent bone (e.g., skin ulcers).
What is the main consequence of cortical bone erosion in infection?
⚠️ Loss of structural integrity, making the bone fragile and at risk of fracture.
What is a common example of contigous spread of infection
🦷 Periodontal disease, where gum infections can spread deep into the jawbone.
How do decubitus (bedsore/pressure) ulcers lead to bone infections?
😷 Chronic ulcers in immobile patients (e.g., diabetic foot, pelvic bones, heels) can spread down to the bone.
What are common sites for decubitus-related osteomyelitis in immobile patients
🦠 Actinomyces and fungal (mycotic) infections, especially in the jawbone.
What medication is linked to bone necrosis (especially in the jaw)?
💊 Bisphosphonates, used to treat osteoporosis, can cause osteonecrosis of the jaw, sometimes linked to actinomyces infection.
Why are bisphonates used for osteoporosis?
🦴 They reduce bone resorption, helping prevent fractures and bone pain in elderly patients.
Why do women experience osteoporisis earlier than men
♀️ Women have lower initial bone density, and menopause accelerates bone loss due to decreased estrogen.
What is the major concern with direct incoculation infections in hospitals?
🏥 Surgical procedures, fractures, and orthopedic implants can introduce pathogens directly into the bone.
How do orthopedic implants and prosthetic joints increase infection risk?
🔩 they create a surface for bacterial colonisation and can become unstable over time, increasing infection risk
What is a prothesis revision and why does it carry infection risk?
🔄A prosthesis revision is the surgical replacement of a joint implant (e.g., hip, knee) due to loosening, wear, or failure which can introduce bacteria, making infection more likely.
Why is infection a concern in prosthesis revisions?
⚠️ Infections can weaken bone, cause implant failure, and may require removal of the prosthesis before placing a new one.
Why is a frozen section biopsy used before prosthesis revision
🧪 To check for infection before implanting a new prosthesis—if infection is present, antibiotic treatment is needed first.
What is a frozen section biopsy>
a rapid pathological procedure where a tissue sample is quickly frozen, sliced, and examined under a microscope during surgery, allowing for immediate diagnosis and guiding surgical decision
How are post-surgical infections classified based on time of onset?
⏳ Acute (<3 months), chronic (>3 months), or unlikely surgical (>24 months, likely hematogenous spread).
How can a bone infection spread from an external source?
🦠 Osteoclasts erode the cortex, allowing the infection to move from soft tissue into the bone.
Why is installing a prosthesis in an infected bone problematic?
🚫 It traps the infection, worsening the spread, rather than allowing proper healing. Therefore infected tissue must be treated before placing a new prosthesis, or the infection can spread and worsen!
what does the 5% - 40% statistic refer to in prosthesis revision
🏥 5-40% of prosthesis revisions are associated with infections. Infection can complicate surgery, requiring further revisions or removal of the prosthesis.
What is the key difference between rickets and osteomalacia?
👶 Rickets occurs in children (developing skeleton).
🧑🦳 Osteomalacia occurs in adults (mature skeleton).
Both result from poor bone mineralization due to vitamin D or calcium deficiency.
Where does rickets occur
typically in the growing skeleton
What i the major manifestation of rickets
Rickets major manifestation is mechanical weakness in the long bones of the lower limbs which bend and become deformed under the influence of body weight
What causes osteomalacia and rickets
❌ Vitamin D or calcium deficiency leads to poor bone mineralization, resulting in weak and deformed bones.
what is the process of Vitamin D activation
🌞 Vitamin D activation begins in the skin when exposed to UVB sunlight. The inactive form (7-dehydrocholesterol) is converted to cholecalciferol (Vitamin D3), which is then processed by the liver into calcidiol (25-hydroxyvitamin D) and finally by the kidneys into the active form calcitriol (1,25-dihydroxyvitamin D)
What happens if you dont get enough sunlight?
🚫 Without adequate sunlight, vitamin D remains inactive, reducing calcium absorption, leading to hypocalcemia, impaired bone mineralization, and increased risk of osteomalacia (adults) or rickets (children).
What historical era saw a high prevalence of rickets
🎩 Victorian Age – Poor nutrition & limited sun exposure in industrialized cities led to widespread rickets.
How do liver & kidney diseases contribute to osteomalacia?
🏥 Vitamin D activation occurs in the liver & kidney.
Dysfunction in either organ can impair calcium absorption, weakening bones.
Why is gastrointestinal health important for bone strength?
🍽️ The intestines absorb calcium; GI disorders can impair calcium uptake, leading to bone weakness.
What are the intrinsic causes of Vitamin D disturbance?
💡 Inadequate production → ⛅️ Low UVB exposure, 🌞 Excessive sunscreen use, 🏾 Darker skin pigmentation
🥛 Dietary deficiency → Low intake of vitamin D-rich foods (e.g., oily fish, fortified dairy)
🦠 Malabsorption → Gut disorders like Celiac disease, Crohn’s disease 🏥
🔄 Metabolic dysfunction → Liver or kidney diseases affecting Vitamin D activation 🏥
How can kidney disease cause osteomalacia
🚰 Chronic Kidney Disease (CKD) → 🛑 Impaired activation of Vitamin D
🌀 Renal Tubular Disorders → 🔄 Phosphate loss, disrupting bone mineralization
What are the genetic causes of osteomalacia and rickets?
🧬 Familial Hypophosphatemia → 🚫 PHEX gene mutation → ⬇️ Phosphate reabsorption
🧬 Hypophosphatasia → 🚫 ALPL gene mutation → ❌ Alkaline phosphatase deficiency → Weak bones
How does osteomalacia affect the mature skeleton?
🦴 Inadequate mineralization at sites of active bone turnover
💥 Structural weakness → Formation of micro-fractures 📸
🔍 X-ray findings: Looser’s Zones (pseudofractures)
how do Looser’s zones appear on X rays
🔍On X-rays, Looser’s zones, also known as pseudofractures, appear as lucent lines (translucent bands) that traverse partway through a bone, usually perpendicular to the cortex, and are associated with osteomalacia and rickets
What histological features are seen in osteomalacia
The surface of bony trabeculae is covered by a thick layer of unmineralized osteoid, leading to bone fragility.
What is osteitis fibrosa cystica, and what causes it?
⚡ Osteitis fibrosa cystica (Von Recklinghausen’s disease of bone) is the result of excessive parathyroid hormone (PTH) stimulating bone resorption.
🦴 Overactive osteoclasts break down bone, leading to weakened, porous bones and potential cyst formation.
Why was osteitis fibrosa cystica misunderstood before 1927
❌ Before 1927, it was mistakenly believed to be a progressive malignant bone disorder.
🔬 It was later discovered to be due to excessive PTH secretion from parathyroid adenomas.
How is hyperparathyroidism diagnosed?
🩸 Raised plasma calcium is the key diagnostic marker.
📉 Uncontrolled PTH secretion continuously stimulates calcium release from bones, leading to structural weakness.
How is parathyroid hormone (PTH) normally regulated?
⚖️ PTH is regulated by blood calcium levels via a negative feedback loop:
🆙 Low calcium → ⬆️ PTH secretion to increase calcium levels
🆘 High calcium → ⬇️ PTH secretion to prevent excessive bone resorption
are parathyroid hormone (PTH) levels normally raised or decreased?
📈 Raised PTH (Hyperparathyroidism)
Primary hyperparathyroidism: Parathyroid adenoma → Excessive PTH
Secondary hyperparathyroidism: Chronic kidney disease, vitamin D deficiency → Compensatory PTH increase
Tertiary hyperparathyroidism: Prolonged secondary hyperparathyroidism → Autonomous PTH secretion
📉 Decreased PTH (Hypoparathyroidism)
Surgical removal of parathyroid glands (e.g., thyroidectomy)
Autoimmune destruction
Magnesium deficiency (Mg is essential for PTH secretion)
What are the X-ray findings in a giant cell tumour of bone
📸 Osteolytic mass (bone destruction), often expanding and thinning the cortex.
🦴 It appears as a radiolucent lesion, potentially mimicking aggressive bone pathology.
What histological features are seen in a giant cell tumor of bone?
🔬 Giant cell-rich lesion with multinucleated osteoclast-like cells.
🩸 Background of compressed blood vessels and mononuclear stromal cells.
How can hyperparathyroidism be mistaken for a bone tumour
❌ A giant cell tumor of bone and hyperparathyroidism-related lesions both contain giant cells and osteolysis.
🔍 Proper diagnosis requires checking PTH & calcium levels to rule out metabolic bone disease.
What histological features define a giant cell tumor of bone?
🔬 Multinucleated giant cells with a background of mononuclear stromal cells and compressed blood vessels.
Why was a 39-year-old woman misdiagnosed with a giant cell tumor?
❌ Her osteolytic lesion was initially interpreted as a primary bone tumor.
🩺 Later testing revealed elevated PTH and calcium levels, confirming hyperparathyroidism instead.
What is the treatment for a giant cell tumour of bone
🛠️ Curettage – Scraping out the tumor.
🦴 Bone cement – Stabilizes the affected area.
🚨 Severe cases may require joint replacement or bone resection.
How can osteomalacia and osteoporosis coexist in elderly patients?
🦴 Osteomalacia reduces bone mineralization, while osteoporosis reduces bone density.
What is a Brown tumour and how does it relate to hyperparathydroism
🦴 Brown Tumor is a giant cell lesion caused by excessive PTH in hyperparathyroidism.
What happens when PTH and calcium levels are both high?
🚨 Normally, high calcium should suppress PTH, but if PTH remains high despite high calcium levels this is a common sign for parathyroid adenoma
What is Paget’s Disease of the bone
🧩 it is a disease which leads to disorganised bone remodelling from excessive resorption and abnormal deposition.
how does PAget’s disease affect the bone?
🧱 it leads to a moseic pattern on histology with patchy, chaotic bone formation which is weak, structurally unsound bone
what are the symtoms for paget’s disease
🏥Bone pain, fractures, skull enlargement (📏 changing hat size!)
What are the key radiological and histological signs of paget’s disease
🦴 X-ray:
📏 Bone enlargement & cortical thickening
🕳️ Lytic lesions in some areas, sclerotic in others
🔬 Histology:
🧩 Mosaic bone pattern = Disorganized bone structure
❌ loss of lamellar organization → Weak bones prone to fracture
What viral infections are associated with Paget’s Disease of the bone?
🦠 Measles & Parvovirus have been linked to Paget’s disease where by chronic viral infection may disrupt normal bone remodeling
🔥 Fluctuating symptoms: Pain episodes that come & go
Why is Paget’s dosease clinically significant
🚨 because it increases the risk of osteosarcoma in the elderly ( osteosarcoma typically occurs in children and young adults but Paget’s disease is one of the few conditions linked to osteosarcoma in older adults)
What are primary bone tumours?
🦴 Tumors originating from bone-forming cells, NOT marrow or metastasis
✅ Benign tumors: Can cause pain & fractures but don’t spread
❌ Malignant tumors: Aggressive, can metastasize → Osteosarcoma
What are the common benign bone-forming tumors?
🦴 Benign bone tumors = Painful but non-metastatic
🔹 Osteoid osteoma: Small, painful tumor in young patients (1st–2nd decade)
🔹 Osteoblastoma: Larger than osteoid osteoma, also occurs in 1st–2nd decade
What are the different types of osteosarcomas & their age groups?
🎭 Osteosarcoma = Malignant bone tumor
🔥 High-grade intramedullary (accounting for 80% of cases –> most common) → Peak at age 15 (skeletal growth)
🏃 Periosteal (2%) → Early adulthood, peak in mid-20s
📅 Parosteal (5%) → Can occur throughout adult life
What is the radiological appearance of high-grade intramedullary osteosarcoma?
🦴 Mixed lytic & sclerotic lesion in the medullary cavity.
Cortical destruction → Tumor breaks through bone.
Periosteal elevation → Leads to subperiosteal new bone formation.
What happens when an osteosarcoma lifts the periosteum?
⚡ The periosteum reacts by forming new bone, visible as a white signal on X-ray which is called subperiosteal new bone formation
What radiological features suggest osteosarcoma?
📸 X-ray findings
Mixed bone destruction (lysis) & new bone formation.
“Sunburst” pattern → Tumor spicules radiating from the bone.
Codman’s triangle → Periosteum lifted by tumor growth.
How can you distinguish osteosarcoma histologically?
🔬 Sheets of malignant osteoblasts with irregular islands of tumor bone, disorganized, woven bone (not lamellar and atypical polygonal cells with mitotic activity
What is the role of the periosteum in osteosarcoma?
🦴 Periosteum is responsible for bone formation.
🦴 When lifted by tumor growth, it reacts by forming new bone.
🦴 Results in subperiosteal new bone formation seen on X-ray.
What is the most common site for osteosarcoma?
🎯 >90% occur in the metaphysis of long bones, especially:
Distal femur & proximal tibia (>50%)
Rare in ribs, spine, & hands/feet
What is the prognosis for osteosarcoma?
Localized osteosarcoma: ~60-70% 5-year survival with treatment.
Metastatic osteosarcoma: ~20-30% survival (most common spread is to the lungs).
What is the difference between benign and malignant bone tumors?
✅ Benign tumors
Do not metastasize, may cause local bone erosion.
Examples: Osteoid osteoma, osteoblastoma.
Treatment: Curettage, sometimes excision.
❌ Malignant tumors
Aggressive, can metastasize (commonly to lungs).
Examples: Osteosarcoma, chondrosarcoma.
Treatment: Chemotherapy, surgical resection.
What is an enchondroma?
A benign cartilage tumor that grows inside the medullary cavity of bone.
where are enchondromas most commonly found?
Small bones of the hands and feet
What are the common sites of osteochondroma?
Metaphysis of long bones, especially:
Distal femur
Proximal tibia
Proximal humerus
olliers disease vs mafucci sundrome
Ollier disease and Maffucci syndrome are both characterized by multiple enchondromas (benign cartilage tumors), but Maffucci syndrome is distinguished by the presence of hemangiomas (abnormal blood vessel growths) in addition to the enchondromas.
What is the radiological appearance of an enchondroma?
Well definied lytic lesions with “rings and arcs” calcifications due to cartilage mineralisation
What is an osteochondroma?
A benign bone tumor that forms as an exophytic growth with a cartilage cap.
What conditions are associated with multiple enchondromas/
✅ Ollier’s disease → Multiple enchondromas, risk of chondrosarcoma
✅ Maffucci syndrome → Enchondromas + hemangiomas, even higher risk of malignant transformation
How does an osteochondroma appear on X ray
Bony outgrowth that is continuous with the cortex and medullary cavity, covered by a cartilage cap.
What is the classic histological feature of chondroblastoma?
chicken wire calcification pattern and chondroblasts and giant cells
What is a chondromyxoid fibroma (CMF)
A rare benign tumour made of cartilage, myxoid and fibrous tissue
What is Multiple Hereditary Exostoses (MHE)?
genetic disorder causing multiple osteochondromas, associated with a 15% risk of transformation into chondrosarcoma
What is a chondroblastoma?
A benign epiphyseal cartilage tumor seen in children and adolescents.
Where do chondroblastomas most commonly occur?
Epiphysis of:
Proximal humerus
Distal femur
Proximal tibia
Where does chondromyxoid fibroma commonly occur
Tibia, pelvis, long bones
What is a chondrosarcoma?
A malignant cartilage-producing tumor that affects adults >40 years old.
What is the male-to-female ratio of chondrosarcoma?
2:1 (more common in men)
What are the common locations of chondrosarcoma?
Pelvis, femur, proximal humerus, ribs
What percentage of chondrosarcomas arise from osteochondromas?
15% of cases
What histological features are seen in chondrosarcoma?
✅ Chondrocytes with binucleation, atypia, increased cellularity
✅ Mitoses and necrosis in high-grade tumors
How is chondrosarcoma classified?
By site and histology:
Intramedullary or peripheral
Conventional (hyaline/myxoid), clear cell, dedifferentiated
How does chondrosarcoma appear on X-ray?
✅ Lytic lesion with “rings and arcs” calcifications
✅ Endosteal scalloping
How does chondrosarcoma differ from osteosarcoma?
✅ Osteosarcoma = Young patients (~20 years old), produces bone
✅ Chondrosarcoma = Older patients (>40 years old), produces cartilage
What conditions increase the risk of chondrosarcoma?
✅ Ollier’s disease
✅ Multiple hereditary exostoses (MHE)
What is dedifferentiated chondrosarcoma
A high grade variant where cartilage tumour trasnforms into undifferentiated sarcoma (e.g., spindle cell or osteosarcoma-like).
How does chondrosarcoma metastasise?
Hematogenous spread, primarily to the lungs.
