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PEER SUPPORT MSK Pharmacology -Virginia Lam

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Case study Mary is 78 years old female. She came in to AED after a fall. She said the floor was wet, she slipped. Her right leg appeared shortened and externally rotated. What would you suspected? (1mark) RIGHT Fracture neck of fracture (inrta/extracapular?!)

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On her X ray, it showed decrease cortical thickness and generalised low bone density. You suspected osteoporosis. Who are at risk of having osteoporosis? (4) Old age Post menopausal loss Steroid treatment Vitamin D and calcium deficiency (easily correctable)

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How can you diagnosis for osteoporosis? (2) DEXA (Dual energy X ray absorptiometry) scan to look at bone density What is the diagnostic criteria? (1)

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What is the first line drug treatment? (1) Bisphosphonates (eg alendronic acid) What Is the mechanism of bisphosphonates? (2) Inhibit osteoclastic bone resorption by attaching to hydroxyapatitde binding sites on bony surface. Taken up by osteoclasts and interfere with its action What are the other indications of bisphosphonates? (2) Hypercalcaemia in malignancy Pagets disease

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When reviewing the blood, you also found that Marys calcium level is low Serum calcium: 2 mmol/L (ref 2.25-2.5) Adj. calcium: 2.1 mmol.L Why is it important to look at adjusted calcium? Serum calcium measured the ionised calcium level Adjusted calcium changes with albumin level Lower calcium level in patient with low level of binding protein (ie hypoalbuminaemia)

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What are the two hormones affect calcium homeostasis? Regulate by PTH from parathyroid gland and calcitonin from parafollicular cell from thyroid gland Action of PTH: Increase osteoclastic activity Increase intestinal absorption from the gut Increase 1hydroyxlation of vitamin D Increase renal tubular reabsorption of calcium

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The tricky vitamin D! increase PTH will increase 1hydroxylation of vitamin D More 1, 25(OH) 2 D 3 (calcitriol) will be made Thus increase bone resorption, intestinal calcium absorption and tubular reabsorption

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What will you give to treat hypocalcaemia? IV 10% calcium gluconate Oral calcium replacement You also found out that Mary hasnt been out in the sun for a while (like everybody else), and she is feeling tired and achy all the time. Her vitamin D is low. What can you give? Colecalciferol (Vitamin D3)/Calcium with colecalciferol Ergocalciferol (vitamin D2) Alfacalcidol (synthetic 1 hydroxycholecalciferol)

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3 months later, Mary visited your GP surgery to have her medication reviewed. She complained that she has a lot of abdominal discomfort after taking the bone pills that the doctor gave her in the hospital. You referred her to a consultant and they started her on denosumab. What is denosumab? monoclonal antibody for the tx of osteoporosis

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What is the mode of action? Receptor activator of nuclear factor kappa B ligand (RANKL) expressed by osteoblast, bind to RANK on the surface of pre- osteroclast and mature osteoclast. Activation of RANK by RANKL promotes the maturation of pre osteoclast Denosumab inhibits maturation of osteoclast by inhibiting RANKL. Without osteoclast, there will be no bone resorption and thus help with osteoporosis and bone degradation in bone metastasis

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Case 2 Albert is a 58 years old male. He visited your GP today, and complained of 6 month history of back pain & fatigue. What will you ask? SQUITAS Fatigue-anaemia/hypothyroid/diabetes.. Red flag System review

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After taking a history, you found out the pain has been long standing and not relieved by analgesia. Otherwise than that, there is nothing significant. You decide to take some blood. Serum calcium: 2.7 mmol/L (ref 2.25-2.5) Adj. calcium: 2.73 mmol.L What kind of sign and symptoms you are looking for? Symptoms: Muscle weakness, constipation, anorexia, nausea Signs: lytic bone, stones, confusion

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Possible causes of Hypercalcaemia: dehydration Hyperparathyroidism (adenoma) Malignancy Bone metastasis Multiple myeloma (plasma cell malignancy)

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Treatment: Fluid Loop diuretic Bisphosphonates Oral phosphate