1. PEER SUPPORT MSK Pharmacology -Virginia Lam

2. 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?!)

3. ◦ 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)

4. ◦ 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)

5. 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 ◦ Paget’s disease

6. When reviewing the blood, you also found that Mary’s 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)

7. 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 1αhydroyxlation of vitamin D ◦ Increase renal tubular reabsorption of calcium

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

9. ◦ What will you give to treat hypocalcaemia? ◦ IV 10% calcium gluconate ◦ Oral calcium replacement ◦ You also found out that Mary hasn’t 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 αhydroxycholecalciferol)

10. 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

11. ◦ 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

12. 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

13. ◦ 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

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

15. ◦ Treatment: ◦ Fluid ◦ Loop diuretic ◦ Bisphosphonates ◦ Oral phosphate