Rheumatology - Osteoporosis Flashcards

Question

Calcium intake 1) Example of food with high Ca 2) Calcium supplements - Examples - S/E

Answer 1

Cheese, Sardine, Almond, Yogurt, Tofu Ca supplements (Calcium carbonate, Calcium citrate) - Taken with food, gastric acidity promote calcium absorption - S/E: Dyspepsia and constipation (increase fluid and fiber intake to mitigate)

Answer 2

Requirement: target 25 hydroxyvitamin D level at 30ng/mL - Mean Vit. D requirement: 1000IU/day - 2000IU /day for obese, limited sun exposure, malabsorption Sources: - Synthesis of cholecalciferol (Vit. D3) in the skin under UV light 10-15 minutes sunlight exposure every day over face, hands, arms - Food/ supplements

Answer 3

Examples: - Brisk walking, jogging, stair climbing, Tai Chi, Dancing Benefits: - Retard bone loss - Increase muscle mass and strength - Improve balance, reduce fall risk - Improve QoL

Answer 4

□ Antiresorptives: oestrogen (HRT), SERM, bisphosphonate, RANKL inhibitor □ Anabolic agent: teriparatide/ Abloparatide (PTH), romosozumab (anti-sclerostin Ab)

Answer 5

1st line: oral bisphosphonate (+ raloxifene or HRT if under 65 without hip fracture) → Raloxifene: generally less effective, more for lower risk pt who prefer to ↓CA breast risk → HRT: NO longer indicated for osteoporosis ALONE, can be used if vasomotor symptoms Add-on therapy: → IV bisphosphonate: if refractory to GI S/E of oral form → Denosumab: refractory to bisphosphonate, poor compliance or CKD → Anabolic agent: severe osteoporosis, fractures or unresponsive to other Tx

Answer 6

- Indication: Young woman with Early menopause, concurrent decrease menopausal symptoms, reduce cholesterol - MoA: ↓bone resorption, ↓urinary Ca excretion, ↓stromal cell cytokine production → ↓osteoclastogenesis - S/E: ↑risk of CA endometrium → must add progestogen if uterus intact ↑risk of CA breast and CA cervix Venothrombolic disease

Answer 7

Selective estrogen receptor modulators (SERMs), eg. raloxifene Indication: Young post-menopausal women with low risk of hip fracture MoA: Estrogen-agonist effect in bone: Decrease bone resorption Estrogen-antagonist effect on breast and endometrium: ↓ER+ breast cancer, no risk of endometrial CA Effect: ↓vertebral fracture risk by 50% but not non-vertebral fracture S/E: Venous thromboembolism Hot flushes Leg cramps ** Discontinue if prolong immobilization**

Answer 8

Examples: Etidronate, alendronate, risedronate, Zoledronate (IV) MoA: Anti-resorptive Pyrophosphate derivative → binds to bone surface and absorbed by Osteoclasts → competitive inhibitor of PPi-requiring farnesyl pyrophosphate synthase (FPPS) reaction → inhibition of mevalonate pathway (i.e. steroidogenesis pathway) → specific inhibition of bone resorption + induce apoptosis of osteoclasts Effect: ↓fracture risk by 50% in both vertebral and non-vertebral fractures (incl. hip) Precautions: - Poor intestinal absorption, take 30min before meal - C/O Poor renal function (eGFR<30) - Avoid Ca or Vit D supplements >1h before bisphosphate (affect absorption) S/E → Upper GI disturbance (~5%), eg. oesophagitis → Flu-like illness (fever, malaise, generalized myalgia) esp at 1st exposure → Oversuppression of bone turnover due to persistent action → Require drug holidays if undergo dental work (remind pt to ensure good dental hygiene) → Atypical femoral fracture due to excessive bone formation → Osteonecrosis of jaw due to limited bone healing following trauma (eg. dental work)

Answer 9

RANKL Ab, eg. denosumab MoA: human mAb vs RANKL → interferes with RANKL → ↓osteoclast differentiation and activation Effect: ↓vertebral fracture by 50%, ↓non-vertebral fracture by 30% S/E: rash, atypical femoral fracture (very rare), hypocalcemia, osteonecrosis of jaw (very rare), sudden vertebral collapse if abrupt withdrawal **Can use for poor renal function, unlike bisphosphonate**

Answer 10

PTH, eg. teriparatide (SC low-dose PTH analogue). Abaloparatide Biphasic action of PTH on bone: → Low dose, intermittent → anabolic action eg. daily IMI can ↑BMD and ↓vertebral fracture risk by 70% → High dose, continuous → catabolic action with resorption of cortical > trabecular bone Effect: ↓vertebral fracture by 70%, ↓non-vertebral fracture by 30% S/E: Mild leg cramps Injection site pain and bruising Hypercalcaemia C/O - Long-term use (osteosarcoma risk) - History of skeletal malignancies/ metastases - History of radiation to bone

Answer 11

MoA: inhibit osteoclast activity (as same as intrinsic ligand) Effect: ↑BMD by 2-3%, ↓vertebral fracture risk by 30% but not non-vertebral fracture Short-term use for post-osteoporotic fracture pain relief

Answer 12

Fracture at subtrochanteric region/ diaphysis of femur Radiological features: - Predominant transverse fracture line - Periosteal callus formation - Minimal comminution Risk factors: - Long-term bisphosphonate (>7 years, rare) - Denosumab use (rare)

Answer 13

Definition: Area of exposed bone in maxillofacial region Does not heal within 8 weeks after identification In patient receiving or exposed to bisphosphonate With no history of radiation therapy to craniofacial region ``` RF: Age >65 Periodonititis Bisphosphonate use > 2 years Smoking DM Invasive bone procedures (e.g. tooth extraction) ```

Answer 14

Romosozumab MoA: Humanized monoclonal Ab against Sclerostin 1. Sclerostin cannot bind to LRP-5 and LRP-6 receptors and cannot inhibit downstream Wnt pathway > Uninhibited activation of Wnt signaling pathway and bone formation 2. Decrease RANKL expression 3. Uninhibit osteoblast differentiation and mineralization S/E: Injection site reaction Hypocalcaemia ONJ, AFF C/O: - Cardiovascular risk - Recent MI/ Stroke

Answer 15

Non-operative: - Manipulation and cast application for 4-6 weeks - Conservative wait for symptom improvement in 6 weeks Operative: - Vertebral body augmentation procedures - Open surgery if significant neurological deficit/ kyphotic deformity/ pain