422.3 🩺 內科專科考前版

422.3.0.1 📌 䞀頁重點

  • 22E:
    • Romosozumab (Evenity, FDA 2019; Taiwan healthcare 2023+) — anti-sclerostin; CV caveat (FRAME, ARCH)
    • Burosumab (anti-FGF-23) for X-linked hypophosphatemia + tumor-induced osteomalacia (TIO)
    • Zoledronic acid q12-24 mo considered acceptable interval after initial response
    • Denosumab discontinuation rebound: must bridge to bisphosphonate (typically zoledronic acid)
    • Dual-anabolic sequential: teriparatide → romosozumab → bisphosphonate
    • AACE 2024 osteoporosis guideline updates
  • Taiwan: 健保 alendronate, risedronate, ibandronate, zoledronic acid (條件); 健保 denosumab (條件); 健保 teriparatide (條件 — severe osteoporosis); romosozumab (條件 expanding); 健保 calcitriol; 健保 phosphate binder for CKD; burosumab 自費 倚 (rare); CTAOH/TES + Taiwan Osteoporosis Society 指匕

422.3.0.2 🌟 Pearls (15)

422.3.0.2.1 Pharmacology
  1. Romosozumab dual mechanism: anti-sclerostin → anabolic (Wnt) + anti-resorptive
  2. Romosozumab CV warning (FRAME, ARCH): contraindicated within 1 yr MI/stroke
  3. Bisphosphonate ONJ: jaw osteonecrosis; 0.001-0.01% in osteoporosis dose; 1-10% in oncology dose; pre-treatment dental clearance important
  4. Atypical femur fracture: subtrochanteric, transverse; rare; > 5 yr bisphosphonate; surveillance
  5. Bisphosphonate flu-like reaction: zoledronic acid 30%; pre-medicate paracetamol
  6. Denosumab + bisphosphonate sequential: do not stop denosumab without zoledronic acid bridge
  7. Teriparatide + abaloparatide: only 2 yr lifetime use (osteosarcoma risk in rats — controversial in humans)
  8. Strontium ranelate: withdrawn many countries (CV)
422.3.0.2.2 Vit D + Mineral
  1. 25-D < 12 ng/mL = severe deficiency → high replacement
  2. Calcitriol vs cholecalciferol: use calcitriol in CKD (skip kidney activation), hypoparathyroidism, granulomatous
  3. Granulomatous hypercalcemia: ectopic 1,25-D from macrophages; sarcoid, TB, lymphoma; treat with steroid + low-Ca + low-Vit D
  4. Burosumab anti-FGF-23: X-linked hypophosphatemic rickets (PHEX), TIO
422.3.0.2.3 CKD-MBD
  1. CKD-MBD spectrum: high-turnover (osteitis fibrosa cystica from severe HPT) vs adynamic (low PTH from over-suppression)
  2. Cinacalcet: positive allosteric modulator CaSR → ↓ PTH; for 2°/3° HPT in CKD or parathyroid CA
  3. Etelcalcetide: IV calcimimetic for dialysis patients; once-weekly with HD

422.3.0.3 📍 Taiwan + 健保

422.3.0.3.1 Drugs
  • 健保 calcium + cholecalciferol / calcitriol
  • 健保 alendronate (Fosamax, 70 mg PO weekly)
  • 健保 risedronate (Actonel)
  • 健保 ibandronate (Boniva)
  • 健保 zoledronic acid (Aclasta) IV q1y 條件 (severe / 䞍耐 PO)
  • 健保 denosumab (Prolia) Q6 mo 條件 (severe / 䞍耐 PO bisphosphonate)
  • 健保 teriparatide (Forteo) Q1d × 2 yr 條件 (severe + multiple fractures + 䞍 response other)
  • 健保 abaloparatide (Tymlos) — 自費 倚 / 條件
  • Romosozumab (Evenity) 健保 條件 (severe; 12 monthly)
  • 健保 raloxifene
  • 健保 calcitonin nasal (rarely used)
  • 健保 cinacalcet for severe 2° HPT in HD
  • 健保 phosphate binder (calcium-based, sevelamer, lanthanum)
  • Burosumab 自費 (rare; X-linked hypophosphatemia, TIO)
422.3.0.3.2 Workup
  • 健保 DXA L-spine + hip + femoral neck
  • 健保 vertebral fracture assessment (VFA)
  • 健保 25-OH Vit D, PTH, Ca, P, ALP
  • 健保 24h urine Ca + Cr
  • 健保 SPEP, tissue transglutaminase 條件
422.3.0.3.3 孞會 + 指匕
  • TES + Taiwan Osteoporosis Society + DAROC + Taiwan Renal Society
  • AACE 2024 Osteoporosis
  • ASBMR Position Statements
  • KDIGO CKD-MBD 2017 + updates

422.3.0.4 🎓 內專必懂 (15)

  1. Ca + P + Vit D + FGF-23 homeostasis
  2. Osteoblast/osteocyte/osteoclast biology
  3. RANK-L/OPG + sclerostin pathway
  4. Osteoporosis workup secondary causes
  5. DXA + TBS + VFA + FRAX
  6. Bisphosphonate types + holiday + ONJ + atypical fracture
  7. Denosumab + rebound prevention
  8. Teriparatide + abaloparatide anabolic timing
  9. Romosozumab + CV caveat (22E)
  10. Sequential anabolic → anti-resorptive
  11. Glucocorticoid-induced osteoporosis prophylaxis
  12. CKD-MBD spectrum + treatment (binders, calcitriol, cinacalcet)
  13. Paget’s + zoledronic acid
  14. Osteomalacia + rickets workup (Vit D, P, FGF-23)
  15. 22E new: romosozumab, burosumab, dual sequential anabolic, denosumab rebound recognition

422.3.0.5 ⚙ Osteoporosis Sequential Therapy (內專)

Step 1 — Severe osteoporosis (multiple fractures, T-score < -3, FRAX very high):
- Anabolic first preferred over anti-resorptive

Anabolic Options (sequential possible):
- Teriparatide 20 ÎŒg SC daily × 2 yr (lifetime)
- Abaloparatide 80 ÎŒg SC daily × 2 yr (lifetime)
- Romosozumab 210 mg SC monthly × 12 doses

Step 2 — Switch to anti-resorptive:
- Bisphosphonate (zoledronic acid IV q1y or alendronate weekly)
- OR denosumab Q6 mo

Step 3 — Long-term maintenance:
- Continue anti-resorptive
- Monitor BMD, CTX (CTX/P1NP if questioning adherence/effect)
- DXA q1-2 yr

Step 4 — Drug holiday:
- Bisphosphonate: 5 yr PO / 3 yr IV → reassess
- Denosumab: do NOT stop without zoledronic acid bridge

Important caveats:
- Anabolic-first paradigm: better BMD gain
- Romosozumab: avoid within 1 yr MI/stroke (FRAME, ARCH)
- Anti-resorptive after anabolic: maintains gains
- Sequential dual anabolic (teriparatide → romosozumab): emerging
- Combination simultaneous: not standard (cost + uncertain benefit)

422.3.0.6 ⚙ CKD-MBD Management (內專)

Pathophysiology:
1. CKD → P retention
2. ↑ FGF-23 (compensatory P excretion + 1,25-D inhibition)
3. ↓ 1,25-D
4. Hypocalcemia → 2° hyperparathyroidism
5. Eventually 3° hyperparathyroidism (autonomous)
6. Bone turnover abnormal: high (osteitis) or low (adynamic)
7. Vascular calcification + CV mortality

Stages of CKD + MBD:
- CKD 3a/b: monitor PTH, P, Ca, 25-D
- CKD 4: more frequent
- CKD 5/D (dialysis): aggressive

Treatment:
- Phosphate binder (with meals):
  - Calcium-based (carbonate, acetate): cheap but Ca load + vascular calcification
  - Sevelamer (non-Ca)
  - Lanthanum carbonate
  - Iron-based (sucroferric oxyhydroxide, ferric citrate)
- Active Vit D:
  - Calcitriol (oral or IV)
  - Paricalcitol (less hyperCa)
- Calcimimetic:
  - Cinacalcet (oral) for severe 2° HPT
  - Etelcalcetide (IV, dialysis-specific)
- 25-Vit D: cholecalciferol if 25-D low
- Surgery (parathyroidectomy) for refractory severe HPT or parathyroid CA

Targets (KDIGO 2017):
- PTH dialysis: 2-9x upper normal (~150-600 pg/mL)
- P near normal
- Ca within normal
- Avoid hypercalcemia
- Vit D 25-D > 30 ng/mL

422.3.0.7 ⚙ Glucocorticoid-Induced Osteoporosis Prophylaxis

Indication for prophylaxis:
- Prednisone > 5 mg/d × 3 mo (or equivalent)
- Lower threshold for elderly + already low BMD

Workup:
- DXA + VFA
- 25-D, Ca, P, PTH
- FRAX with glucocorticoid factor

Treatment:
- Lifestyle: Ca 1200 + Vit D 800-2000 + exercise + fall prevention
- Bisphosphonate 1st (alendronate, risedronate, zoledronic acid)
- Denosumab option
- Teriparatide for severe + high-dose long-term steroid
- Re-assess Q1-2 yr

Specific Risks:
- Glucocorticoid causes anti-osteoblast (apoptosis) + pro-osteoclast effects
- Trabecular bone (vertebra) > cortical
- Risk highest first 3-6 mo
- Persists after discontinuation; partial recovery possible

⚠ AI 草皿。