Name 7 diseases likely to predispose to a fracture of the neck of the femur in a woman of 70yo?
- Paget's disease of bone
- Malignancies - osteosarcoma, B-cell lymphoma, multiple myeloma
- Renal osteodystrophy
- Stroke /TIA
In an 70yo women with pathological fracture, name 6 Ix.
- FBC - haematological malignancies
- Bone scans
- Bone biopsy
- Bone density e.g. dexa, U/S, quantitative CT
- Biochemistry - Ca, phosphate, Vit D, PTH
- Bone resorption markers - urinary hydroxyproline (for Paget's), urinary pyridine x-links of collagen
Name 7 groups of age-independent risks for osteoporosis.
- Glucocorticoids use
- Low BMI
- Medical disorders e.g. IBD, hyperparathyrodism, RA
- Premature menopause / hypogonadism
- Prolonged immobility
Describe 5 treatments for menopause.
- Bisphosphonates - mainstay of Tx
- SERM e.g. raloxifene
- HRT - not recommended in >51yo, used for premature menopause
- Calcitonin - if other Tx are exhausted
- New bone formation
- PTH (Forteo) - increases bone turnover but also bone formation
Name 3 histological finding of osteoporosis.
- Widely spaced and thinner trabeculae
- Haversian canals widening
- Mineral content of remaining bone normal
Name 4 groups of DDx (2 examples each) for 3/52 of leg pain & swelling in a 13yo.
- Trauma - soft tissue, fracture
- Infection - osteomyelitis, septic arthritis
- Inflammation - juvenile RA, seronegative arthropathy
- Tumour - osteosarcoma, Ewing's sarcoma, osteochondroma, aneurysmal bone cyst, osteoma
Name 5 Ix to perform on a boy with suspected osteosarcoma. What is the Ix for Dx?
- FBC - LFT, U/E, CRP, WCC, LDH
- X-ray - lytic + blastic, sunray appearance, Codman's triangle
- Joint aspiration
- Bone scan & Gallium scan
- MRI & CT
To Dx - bone biopsy
What is known about the pathogenesis of osteosarcoma?
- Develop at sites of greatest bone turnover e.g. Paget's
- Hereditary - mutation in Rb
- Non-hereditary - TP53 gene (tumour suppressor) is mutated and MDM2 (binds to TP53) is over expressed
A 65yo M came with corticospinal dysfunction, name 6 DDx.
- Spinal cord compression due to malignancy - prostate, lung, myeloma, NHL, ependyoma
- Disc prolapse
- Infection e.g. TB, epidural abscess
- Haematoma (warfarin)
- Stroke/TIA - unlikely if bilateral symptoms
Interpret: Nucleated RBC ++, metamyelocytes ++, Rouleux ++
- Leukoerythroblastic picture - immature RBC and WCC
- DDx - marrow infiltration or blood loss
- Rouleaux - RBC that form when there's high plasma protein concentration (raised ESR)
- DDx - inflammation, cancer, infections
What tests to order if marrow infiltration is suspected? (name 4)
- Skeletal survey e.g. MRI
- Urine and serum electrophoresis and immunofixation
- Bone marrow biopsy
- Bloods - FBC, film, ESR, UEC, LFT
What are Bence Jones proteins?
- These are monoclonal immunoglobulin light chains in the serum/urine
- Produced by neoplastic plasma cells, present in 2/3 of MM
- BJ + hypercalcemia can impair renal function enabling the protein to enter the urine.
Name 4 key signs of multiple myeloma.
- Calcium elevation
- Renal insufficiency
- Bone lesions (lytic)
Describe the pathogenesis of multiple myleoma.
- IL-6 may play a role in driving myeloma cell proliferation
- Osteoclast activating factors (OAF) is made by the myeloma cells [OAF activity is mediated by several cytokines e.g. IL-1, VEGF, TNF].
What leads to renal insufficiency in patients with multiple myeloma? (Name 6 ways)
- Bence Jones proteins damages tubules and interstitium
- Glomerular deposits of amyloid
- Recurrent infections
- NSAIDS use
What is MGUS?
- = Monoclonal gammopathy of undetermined significance
- A paraprotein is present in the blood (monoclonal band on electrophoresis) but
- with no other features of myeloma
- Occurs in 1% of 50yo +
What differentiates benign paraproteinaemia from a malignant one? (4 features)
- No bone marrow infiltration
- Low/constant paraprotein levels
- Absence of urine light chains
- Normal levels of other serum immunoglobulins