Visual Reference  ·  Chapter 28 Module 3
Adverse Effects, Osteoporosis Management, and Drug Interactions
Metabolic complications · GIO prevention framework · infectious risk · drug interactions · steroid-sparing agents
Metabolic Adverse Effects
Glucose
Hyperglycemia
  • Hepatic: upregulates PEPCK and G6Pase → increased gluconeogenesis
  • Peripheral: reduces GLUT4 translocation → insulin resistance
  • Pattern: predominantly postprandial; HbA1c underestimates early
  • Monitor: glucose 2 h after largest meal
Lipids
Dyslipidemia
  • Elevated LDL cholesterol, triglycerides (VLDL), total cholesterol
  • Mechanism: hepatic lipogenic enzyme upregulation + increased FFA flux from adipose tissue
  • Monitor lipids every 3 months if >7.5 mg/day prednisone equivalent
Muscle
Steroid Myopathy
  • Proximal limb weakness; CK normal or mildly elevated
  • Mechanism: MuRF1/MAFbx upregulation → myosin degradation
  • vs. inflammatory myositis: CK markedly elevated, needs more steroids
  • Fluorinated agents (dexamethasone, triamcinolone) highest risk
Glucocorticoid-Induced Osteoporosis Prevention Framework
Mechanism
Dual Attack on Bone Remodeling
  • Formation side: Suppresses Wnt/beta-catenin signaling → impairs osteoblast differentiation; induces osteoblast/osteocyte apoptosis
  • Resorption side: Increases RANKL expression, decreases osteoprotegerin → RANKL dominance drives osteoclast activation
  • Calcium: Reduces intestinal absorption + increases renal excretion → secondary hyperparathyroidism further activates osteoclasts
  • FRAX adjustment: Increase major fracture probability ~15% and hip fracture probability ~20% for prednisone >7.5 mg/day for >3 months (bone quality not captured by DXA)
AgentFracture Risk TargetKey Points Calcium + Vitamin D All patients ≥3 months Universal foundation; Ca 1000–1200 mg/day + vitamin D 600–800 IU/day; check 25-OH vitamin D at baseline Bisphosphonates (alendronate, risedronate, zoledronic acid) Medium/high risk (FRAX >10–20%) First-line; 50–70% vertebral fracture reduction; oral agents contraindicated if GFR <30–35; IV zoledronic acid annual alternative Denosumab Medium/high risk; bisphosphonate intolerance or GFR <30 Anti-RANKL antibody; rebound bone loss if doses missed — transition to bisphosphonate before stopping Teriparatide Very high risk (FRAX >20%; multiple vertebral fractures) Bone anabolic; superior to alendronate for vertebral fractures in GIO; 24-month limit; follow with antiresorptive agent
Key Drug Interactions
CYP3A4 Inducers
Reduced Glucocorticoid Levels
  • Rifampin: reduces prednisolone exposure 45–75%; causes acute transplant rejection
  • Phenytoin, carbamazepine, phenobarbital, efavirenz
  • Action: increase glucocorticoid dose; watch for toxicity when inducer stopped
CYP3A4 Inhibitors
Elevated Glucocorticoid Levels
  • Ritonavir + fluticasone inhaled corticosteroids: ~350-fold fluticasone increase → iatrogenic Cushing syndrome; use beclomethasone instead
  • Ketoconazole, itraconazole, clarithromycin: reduce glucocorticoid dose
Infection Prophylaxis Thresholds
PCP prophylaxis (trimethoprim-sulfamethoxazole 1 DS tablet 3x/week): prednisone equivalent >20 mg/day for >4 weeks (monotherapy) OR >10 mg/day for >4 weeks (combined with other immunosuppressants).   Live vaccines contraindicated if prednisone >20 mg/day for >2 weeks.   Recombinant zoster vaccine (Shingrix) recommended age ≥50 before therapy or at lowest dose interval.   TB screening (IGRA) required before long-term therapy in high-risk patients; treat latent TB with isoniazid before starting glucocorticoids.