Week 9 - bone pain Flashcards
Describe the basic epidemiology of Paget’s disease. (LO1)
- Second most common metabolic bone disease.
- More common in males.
- Unusual in <40s.
Describe the pathophysiology of Paget’s disease. (LO1)
- Increased bone cell activity.
- Osteoclasts are larger in size, therefore, resorb more bone.
- This leads to osteoblasts laying down bone in a haphazard way resulting in poor bone architecture.
- As a result, we see expansion of poor quality bone.
- The marrow is replaced with fibrous tissue (which isn’t as strong) and blood vessels - leading to the bone sometimes feeling warm due to increased blood flow.
Which bones are usually affected by Paget’s disease? (LO1)
Normally only one bone is affected.
- Femur.
- Spine.
- Skull.
- Sternum.
- Pelvis.
- Any bone in the body can be affected.
List some neurological symptoms of Paget’s disease. (LO1)
- Obstructive hydrocephalus - fluid not circulating around the brain.
- Cranial nerve palsies - nerve going through the skull not working.
- Deafness - if the skull expands.
- Paraplegia or quadriplegia - if the spine is affected.
- Tinnitus.
List some investigations for Paget’s disease. (LO1)
- Plain radiographs.
- CT.
- MRI.
- PET CT.
- Isotope bone scans.
List some presentations of Paget’s disease. (LO1)
On examination, the affected bone will be:
- Warm - due to increased blood flow.
- Tender - due to periosteum being stretched.
- Deformed.
Briefly describe the genetic factor associated with Paget’s disease. (LO1)
- There is a small genetic link with a defect in the SQSTM1 gene.
- However, it is unknown what triggers this defect.
List the complications caused by expansion of the pelvis due to Paget’s disease. (LO1)
- Pain in the hip joint.
- Bone deformity.
- Bone pain.
- Increased risk of fracture.
- Sclerotic and lytic areas on x-rays.
- Osteoarthritis in neighbouring joints.
Rare:
- Cardiovascular symptoms.
- Metabolic symptoms.
- Neoplasia.
Describe the findings of an x-ray in Paget’s disease. (LO1)
- Bones expanded.
- Cortical thickening.
- Mixture of sclerotic and lytic areas.
Describe the management of Paget’s disease. (LO1)
- Zoledronate 5mg - reduce osteoclast function.
- Analgesia - to relieve symptoms.
- Vitamin D.
- Physiotherapy.
- Surgery - to repair fractures, replace joints or for spinal stenosis.
Describe the basic epidemiology of bone metastases. (LO2)
- 400,000 diagnoses of bony metastases are made in the US annually.
- The general incidence of advanced malignant tumours with bone metastasis is 30-75%.
- The presence of bone metastases indicates a poor prognosis.
List the most common cancers to metastasise to bones. (LO2)
Most common primary tumours for bone metastases are organs that naturally lie near bone:
- Prostate cancer - 65-75% of prostate cancer cases will involve metastasis to the bone.
- Breast cancer - 65-75%.
- Thyroid cancer - 60%.
- Lung cancer - 30-40%.
- Bladder cancer - 40%.
- Renal cell carcinoma - 20-25%.
- Melanoma - 14-45%.
List the three types of bone metastases. (LO2)
- Osteolytic.
- Osteoblastic.
- Mixed.
Describe osteolytic bone metastases. (LO2)
- Mediated by osteoclasts which break down the bone matrix.
Which cancers is osteolytic bone metastases more likely to be found in? (LO2)
- Multiple myeloma.
- Renal cell carcinoma.
- Melanoma.
- Breast cancer.
Describe osteoblastic bone metastases. (LO2)
- New bone is laid down by osteoblasts, forming sclerotic lesions.
- This is not always preceded by bone resorption.
Which cancers is osteoblastic bone metastases more likely to be found in? (LO2)
- Prostate cancer.
- Carcinoid.
- Small cell lung cancer.
Describe mixed bone metastases. (LO2)
- Both destruction and deposition of bone.
Which cancers is mixed (lytic+blastic) bone metastases more likely to be found in? (LO2)
- Breast cancer - 15-20% have a mixed type of bone metastasis.
- GI cancers.
- Squamous cancers.
List the three mechanisms of spread of bone metastases. (LO2)
- Epithelial-mesenchymal transition.
- Micro-environmental support.
- Vascular adhesion and extravasation.
All of these work together to allow the tumour to spread.
Describe epithelial-mesenchymal transition as a mechanism of spread for bone metastases. (LO2)
- Where epithelial cells transition into a mesenchymal cell.
- Epithelial cells have tight junctions which fix them to neighbouring cells.
- When they transition to mesenchymal cells, they lose the junctions making them more mobile, i.e. they can migrate.
Describe micro-environmental support as a mechanism of spread for bone metastases. (LO2)
- The seed and soil hypothesis states that the “soil”, which is distant tissue, bone in this case, is fertile ground for growth of the “seed” which is the primary cancer.
Describe vascular adhesion and extravasation as a mechanism of spread for bone metastases. (LO2)
- Cancer cells can interact with the endothelium, causing extravasation.
Describe the presentation of bone metastases. (LO2)
- No specific presentation.
- Usually diagnosed on the staging scans/follow-ups for the primary cancer.
- Main symptom is non-specific pain.
- Neurological symptoms can also occur if the spine is involved.
- The severity of pain can be affected by:
- Is a nerve being compressed?
- Is the bone metastasis causing damage to a nearby structure?
- The location of the bone metastasis.
List the potential neurological symptoms from a bone metastases of the spine. (LO2)
- Motor weakness.
- Paralysis.
- Sensory dysfunction.
- Bowel and bladder dysfunction - incontinence.
- Ataxia.
Describe Cauda Equina syndrome. (LO2)
- Where the bone metastasis can compress part of the spinal cord called the cauda equina.
- This is an emergency requiring urgent surgery as if untreated, it can cause permanent paralysis or worse.
- Symptoms include: back pain, incontinence, saddle/perineal anaesthesia.
- Treatment is laminectomy or decompression/removal of whatever is compressing the cord.
Describe the investigations for bone metastases. (LO2)
- X-ray - first line - shows osteolytic lesions (black), osteoblastic lesions (white). Requires >50% trabecular injury before lesions appear on x-ray.
- CT - shows good detail of bone and soft tissue.
- MRI - best for spinal cord and axial skeleton.
- PET - shows metabolic activity by showing tissue uptake of a dye-tagged metabolite, e.g. glucose. Can show early metastatic multiple myeloma.
Describe the management of bone metastases. (LO2)
- Bisphosphonates - inhibits bone demineralisation.
- Denosumab - monoclonal antibody, RANK-L inhibitor.
- External radiotherapy - tumour may shrink or be less active. Effective for pain relief (few weeks after the procedure).
- Radionuclide therapy - more effective for osteoblastic metastasis.
- Ablation - tumours are detroyed using heat/cold or chemicals. Indicated for symptomatic tumours.
- Surgery - only if necessary, i.e. risk of fracture, spinal cord compression, hip + long bones are affected.
Describe the prognosis of bone metastases. (LO2)
- Presence of bone metastases is evidence of tumour spread so it is associated with a poor prognosis.
- The exact survival is tumour dependent (the type of primary cancer).
Define pathological fracture. (LO3)
Loss of continuity of the cortex of a bone that has been weaked by a pre-existing condition.
What are some underlying causes for pathological fractures? (LO3)
- Tumours.
- Paget’s disease.
- Metabolic bone disease.
- Rheumatoid arthritis.
- Infection.
What is the most common cause of pathological fractures? (LO3)
- Osteoporosis followed by tumours.
- If a tumour is the cause of a pathological fracture, the tumour may be benign or malignant.
- If malignant, it is highly likely to be metastatic as opposed to a primary bone sarcoma.
Which areas are most commonly affected by pathological fractures? (LO3)
- Vertebrae of the thoracic and lumbar regions.
- Proximal femur and distal radius.
Describe the investigations for pathological fractures. (LO3)
- X-ray.
- 25-hydroxyvitamin D concentrations.
- FBC.
- Tests for metabolic disorders.
- Biopsy.
- Urine examination.
- CRP.
- Alkaline phosphatase.
- Albumin adjusted calcium.
- DEXA scan.
List some presentations of pathological fractures. (LO3)
- New skeletal deformities.
- Painful bony areas, swelling or bruising.
- Behaviour changes.
- Changes in sleep pattern.
- Many pathological fractures are asymptomatic, however.
Describe the management of pathological fractures. (LO3)
- Surgical stabilisation of the fracture is common, however this supplements the treatment of the underlying pathology.
- In primary malignancy, treatment of the tumour is the priority and the prognosis is usually very poor.
- With metastatic tumours, treatment of the primary malignancy is key along with surgical stabilisation.
What is osteomalacia? (LO4)
- Osteomalacia is a disorder that arises as a result of vitamin D deficiency and means that our bones are unable to mineralise properly.
- The result is bones that are weak and soft and at greater risk of fractures than normal.
Describe the basic epidemiology of osteomalacia. (LO4)
- Osteomalacia affects adults as it only occurs in mature skeletal bones.
- Osteomalacia is a result of vitamin D deficiency and so those most at risk are those with a deficiency.
- This deficiency may have occurs for a number reasons such as:
1. Lack of sunshine.
2. Low vitamin D diet.
3. As a result of a medical condition that causes intestinal malabsorption.
4. A liver and kidney disease that prevents regulatory enzymes from working.
List the risk factors for developing osteomalacia. (LO4)
- Darker skin.
- Older in age.
- Infirm (inpatient at hospital).
- GI disorders.
- Chronic liver disease or renal failure.
- Those on anticonvulsant medications.
- Those on strict diets, e.g. lacto vegetarians.
- People who use excessive high factor sunblock.
- Rare hereditary disorders.
Describe the role of vitamin D in bone mineralisation. (LO4)
- Bone mineralisation is when calcium and phosphate are deposited into the osteoid framework by osteoblasts.
- In order to do this, vitamin D needs to be able to regulate the levels of calcium and phosphate in the blood.
- Vitamin D from our food and UV exposure is converted to 25-(OH)-vitamin D by the enzyme 25-hydroxylase.
- It then travels to the kidneys where an enzyme 1-α-hydroxylase converts 25-(OH)-vitamin D to 1,25-(OH)-vitamin D (calcitriol).
- Calcitriol is responsible for reabsorption of calcium in the kidneys to prevent it being excreted in the urine and phosphate absorption in the gut as well as preventing parathyroid hormone synthesis and secretion which resorbs calcium and some phosphate from the bone into the blood stream.
Describe the pathophysiology of osteomalacia. (LO4)
- Vitamin D is needed in order for osteoblasts to deposit calcium and phosphate into the osteoid framework of bone. This is known as bone mineralisation.
- Vitamin D, alongside parathyroid hormone, regulates calcium and phosphate in the blood.
- Vitamin D from food and UV is hydroxylated in the liver before being converted to its active form in the kidneys.
- Calcitriol regulates reabsorption of calcium and phosphate.
- When there is a lack of vitamin D, calcium and phosphate cannot be regulated correctly.
- Osteoblasts do not then have enough calcium and phosphate to deposit into the organic matrix.
Describe the presentation of osteomalacia. (LO4)
- Can exist with no symptoms.
- Chronic, non-specific widespread musculoskeletal pain.
- Aching.
- Weakness in hip or proximal leg.
- Increase in fractures, especially the vertebrae.
- Skeletal deformity (rickets).
- Waddling gait.
- Rare - hypocalcaemia seizures.
List the investigations for osteomalacia. (LO4)
- FBC.
- Serum calcium.
- Alkaline phosphatase.
- Liver function tests.
- Urea and electrolytes.
- X-rays.
Describe the management of osteomalacia. (LO4)
- Education of how to prevent osteomalacia is important, e.g. how to get sufficient vitamin D in your diet.
- Especially important to educate the at-risk groups.
- Lifestyle factors, e.g. improving diet and adding supplements if needed.
- Aiming to get at least 15 minutes of sun exposure to hands, forearms and face 3x a week. (Longer exposure for people with darker skin as it takes longer to absorb the same amount of vitamin D).
Describe the prognosis of osteomalacia. (LO4)
- Normally pretty good.
- Unlike osteoporosis, it can be cured by replacing vitamin D through oral supplements.
List the most common causes of osteomyelitis. (LO5)
- Post-trauma osteomyelitis - adults.
- Post-surgery osteomyelitis - adults.
- Acute haematogenous osteomyelitis - children.
- Direct osteomyelitis - from nearby joint infection.
1 and 2 are types of ‘exogenous’ osteomyelitis, whereby infection is spread through inoculation. 3 is caused by blood-borne bacteria and is known as ‘haematogenous’ spread.
List the most causative organisms of osteomyelitis. (LO5)
- S. aureus.
- Streptococcus.
- Enterobacter spp.
- H. influenzae.
- P. aeruginosa - especially in intravenous drug users.
- Salmonella spp - especially in patients with sickle cell disease.
Describe the basic epidemiology of osteomyelitis. (LO5)
- Reported incidence of peripheral bone infection: 2% per year in developed countries.
- More likely in men than women.
- More likely as age increases - diabetes, falls, etc.
What are the two categories of osteomyelitis? (LO5)
- Congenital.
- Acquired.
List the risk factors for acquired osteomyelitis. (LO5)
- Diabetes mellitus.
- Immunosuppression - due to long-term steroids/AIDS.
- Alcohol excess.
- Intravenous drug use.
- Penetrating injury.
- Recent surgery.
- Sickle cell anaemia.
- Rheumatoid arthritis.
- Chronic kidney disease/renal failure.
- Malnutrition.
Describe the risk factors for congenital osteomyelitis. (LO5)
- Sickle cell anaemia.
- Haemophilia.
- Rheumatoid arthritis.
Describe the general presentation of osteomyelitis. (LO5)
- Severe pain in the affected region.
- In patients with diabetic foot, pain may be absent due to peripheral neuropathy.
- Associated low-grade pyrexia.
- Pain is constant and worse at night.
- Can present with non-specific symptoms only.
- Possibly recent history of trauma.
- Site will be tender.
- Overlying swelling and erythema.
- If lower limb is affected, patient may not be able to weight bear.
What is acute-on-chronic osteomyelitis? (LO5)
- Adults most commonly present with this.
- An acute presentation may be the first presentation of chronic osteomyelitis.
- Previous infections may appear dormant for months or years before recurring.
Describe the presentation of acute osteomyelitis. (LO5)
- Local inflammation.
- Erythema.
- Tenderness.
- Swelling.
- Areas of point tenderness.
- Decreased range of motion above and below the affected area - this may be due to pain or indicate an associated septic arthritis.
- Torticollis and lower back pain may indicate axial osteomyelitis or lumbar discitis.
Describe the presentation of chronic osteomyelitis. (LO5)
- Typically low grade fever.
- Angular deformity or shortening of the limb - resulting from premature fusion of the physeal plate (particularly following childhood osteomyelitis).
- Acute or old healed sinuses.
- Fracture fixation.
- Evidence of previous operations, including scars and previous flap designs.
- Tenderness to percussion over the subcutaneous border of affected bones.
Describe the investigations for osteomyelitis. (LO5)
- Routine blood tests: FBC, CRP and ESR.
- Blood cultures - gram positive in around 60% of cases.
- Plain radiographs.
- MRI imaging - definitive diagnosis.
Why are plain radiographs not ideal for investigating osteomyelitis? (LO5)
- Performed often but they have a poor accuracy for osteomyelitis.
- Any visible signs tend to only be visible from ~7-10 days post-initial infection.
What are the potential findings from plain radiographs indicating osteomyelitis? (LO5)
- Osteopenia.
- Periosteal thickening.
- Endosteal scalloping.
- Focal cortical bone loss.
- Involucra.
- Sequestra.
What are the potential findings from MRIs indicating osteomyelitis? (LO5)
- Oedema.
- Cortical loss.
- Contrast enhancement of access rim.
Why is a bone biopsy done as part of investigations for osteomyelitis? (LO5)
- Gold standard diagnosis.
- Culture from bone biopsy at debridement (or curettage where there are associated ulcers).
- Has 90% sensitivity.
- Important to check for mycobacterium and fungal causes in relevant cases, such as immunosuppressed patients.
What is meant by involucra and why are these relevant? (LO5)
- Newly formed bone eveloping the sequestrum in infection of the bone.
- May start to appear in around day 7-10 post initial infection.
What is meant by sequestra and why are these relevant? (LO5)
- A fragment of necrosed bone that has been partially separated from the surrounding tissue.
- Can be seen on plain radiographs as early as 10 days post initial infection.
Describe the management of osteomyelitis. (LO5)
Depends on whether the patient is clinically well or deteriorating.
Clinically well:
- Analgesia.
- Splinting of limb.
- Long-term IV antibiotics >6 weeks, tailored to any cultures available, otherwise following local antimicrobial protocols.
- Usually this is all that’s needed.
Deteriorating: surgical intervention
- Abscess drainage.
- Dead bone (sequestrum) removed (curettage).
- Extensive infection may require removal of bone.
What should you be looking out for when examining a patient with osteomyelitis? (LO5)
Potential source of the infection.
- Pock marks.
- Sinuses from IV drug abuse.
- Cellulitic areas.
- Penetrating wounds.
- Stigmata of concurrent infection in another body system.
What is meant by curettage in relation to osteomyelitis management? (LO5)
Surgical scraping of the lining, to clean it of foreign matter (dead matter).