Bone and Joint Pathology Flashcards
How is osteoporosis defined qualitatively and quantitatively?
- Qualitative: low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and increased fracture risk
- Quantitative: Bone mineral density 2.5 standard deviations below the young health adult mean value
Who gets osteoporosis? What are the main risk factors?
Affects 1:2 F and 1:5 males > 50 years in UK
The major risk factors for osteoporosis are age and post menopausal oestrogen deficiency (primarily affects trabecular bone, leading to compression fractures of vertebral bodies - loss of height)
Additional risk factors include low BMI, low vitamin D levels, endocrine diseases such as thyrotoxicosis, primary hyperparathyroidism and cushing’s, and GI abnormalities such as IBD and coeliac
Describe the pathogenesis of osteoporosis
Loss of bone density due to increased breakdown by osteoclasts and decreased bone formation by osteoblasts.
Describe the clinical presentation of osteoporosis
- Fracture is the only cause of symptoms in osteoporosis. There may be sudden onset of severe pain in the spine, radiating to the front suggesting a vertebral crush fracture
- Colles fractures typically follow a fall on an outstretched arm, whilst fractures of the proximal femur usually occur in older individuals falling on their side of their back
What is the investigation of choice in osteoporosis?
- DEXA Scan (dual energy x-ray absorptiometry) - measures mineral per surface area of bone, usually the lumbar spine and proximal femur. Patient’s value is expressed in relation to reference range: useful for tracking course of osteoporosis and determining risk
What non-pharmacological measures are taken to prevent osteoporosis?
- Calcium and Vitamin D should be taken to reduce non-vertebral fractures
- Lifestyle measures - weight bearing exercise for 30 minutes 3 times a week to increase BMD. Reduce smoking and alcoholism
- Fall prevention - physiotherapy and assessment of home safety
What pharmacological treatments may be used in Osteoporosis?
- Bisphosphonates - adhere to hydroxyapatite and inhibit osteoclasts, reducing bone resorption
- HRT - oestrogen increases bone mineralisation. However, concerns over breast and endometrial cancer, and increased risk of thrombosis
- Selective oestrogen receptor modulator (SERM) - selectively activates oestrogen receptors on bone, reducing side effects of HRT.
What is Paget’s Disease (ostetitis deformans), and who does it primarily affect
- Paget’s disease is a focal disorder of remodelling in which an initial event of excessive resorption is followed by a compensatory increase in new bone formation
- Usually asymptomatic, thus epidemiological studies are complicated
- Effects both men and women (2:3) over the age of 40
What are the clinical features of Paget’s disease? How many individuals with radiological signs of disease experience symptoms?
60-80% of those with Pagets are asymptomatic. For those with disease, it may present with:
- Bone pain, often in the spine or pelvis
- Joint pain when the involved bone is near to a joint, leading to osteoarthritis
- Deformities - a bowed tibia and skull changes
- Nerve / spinal cord compression
- Hypercalcaemia
- Rarely high output cardiac failure due to increased vascularisation of bone
What investigations are performed in Paget’s disease?
- Often discovered incidentally following an asymptomatic elevation of serum ALP.
- X-ray may show bone expansion, thickening of trabeculae and loss of distinction between cortex and trabeculae
- Calcium and phosphate usually normal
- Isotope bone scans show extent of skletal involvement
What is the treatment for Paget’s disease?
- Mainstay of treatment for Paget’s disease is Bisphosphonate, either intravenously or orally. This helps to maintain normal ALP
What is Rickets / Osteomalacia?
- Osteomalacia is defective mineralization of newly formed bone matrix or osteoid
- Rickets is a failure to mineralise new bone at growth plates
What is the aetiology of osteomalacia? What is the most common cause?
- Normal bone mineralization requires adequate levels of vitamin D, calcium, phosphate and adequate activity of ALP
- The most common cause of osteomalacia is hypophosphataemia due to hyperparathyroidism secondary to Vitamin D deficiency
Review the causes of rickets / osteomalacia
Deficient intake / absorption of vitamin D
- Inadequate sun exposure, low dietary intake
- Malabsorption - coeliac, Chron’s disease, primary biliar cirrhosis
Defective 1-alpha hydroxylation
- Chronic kidney disease
Primary renal phosphate wasting
- Renal tubular acidosis
- Fanconi syndrome
- Multiple myeloma
Inhibitors of mineralisation
- Metabolic acidosis
- Bisphosphonates, fluoride, aluminium
Describe the clinical presentation of osteomalacia
Often identified incidentally and may be asymptomatic. Symptomatic presentation includes:
- Bone pain and tenderness
- Muscle weakness
- Short stature
- Multiple bone deformities
- Fractures
What investigations are performed for suspected osteomalacia? What are the results?
- Serum ALP : elevated in over 90% of cases
- Low serum calcium, phosphate and vitamin D
- Elevated PTH may be present in response to hypocalcaemia
What is the treatment for Osteomalacia?
- Treatment of vitamin D deficiency:
- Vitamin D alone
- Vitamin D with calcium
- High dose vitamin D
- Adequate sunlight exposure
Are most bone tumors primary or secondary? Which primary tumors tend to metastasise to bone?
The majority of bone tumors are secondary metastases. They are frequently from the 5B’s
- Breast
- Bronchus (Lung)
- Kidney
- Prostate
- Thyroid
Osteosarcoma is the most common malignant of tumor of the bone (approx 150 cases p/a in the UK). In whom does it occur, and what is the aetiology?
- Occurs mainly in adolesents with a second peak in those over 60. Twice as common in males as females.
- For the majority of cases there is no recognizable aetiological cause. For others:
- It is often related to Paget’s disease in over 60s
- May occur in adolescents as a component of Li Fraumini syndrome (p53 abnormality)
- May occur in those with RB1 (retinoblastoma) abnormalities
Describe the pathology of osteosarcoma
- Most commonly in long bones, particularly around the knee (proximal tibia and distal femur) and proximal humerus. (close to the knee, away from the elbow)
- Macroscopically, arises in the metaphysis and shows areas of ahemorrhage and necrosis together with new bone formation in subperiosteal regions
- It shows aggressive local growth and rapid haematogenous systemic dissemination, with frequent pulmonary metastasis
Describe the symptoms and signs of osteosarcoma
Symptoms
- Bone pain and lump around the site of origin
- May be a history of preceeding trauma, though no causal relationship is known to exist
- Cough and haemoptysis may indicate metastasis. Other malignant features such as anorexia and weight loss are infrequent unless advanced
Signs
- Swelling and deformity of bone, area is hot and may be audible bruits.
- Often associated with fever
What investigations should be performed for suspected osteosarcoma, and what will the resuts be?
- ALP inappropriately raised
- Plain X-ray demonstrates local destruction of bone with area of new bone formation. In adults, coexisting Paget’s disease may be present.
What is a chondrosarcoma? Who is affected, and which sites are most likely affected?
- Cancer derived from transformed cartilage producing cells
- Largely a tumour of adulthood and old age (most > 50 years)
- Most commonly found at pelvis, though may also occur at femur, humerus and scapula
Chondrosarcomas often present with a long history, and are amienable to curettage or resection. In rare cases they may be dedifferentiated - much poorer prognosis
