A 45-year-old asthmatic on inhaled salmeterol plus budesonide for 6 months has well-controlled symptoms but is found to have reduced bone mineral density at follow-up. The most likely contributing drug-related mechanism is:

• A Systemic absorption of inhaled budesonide reducing osteoblast activity and increasing osteoclast activity via GR-mediated transcriptional effects ✓
• B Salmeterol-induced calcium channel blockade in osteoblasts
• C Beta-2 agonist activity of salmeterol stimulating PTH release
• D Budesonide reducing vitamin D synthesis in the skin via unknown mechanism

Explanation

Inhaled corticosteroids (ICS), though primarily acting locally, undergo some systemic absorption — especially at high doses. Glucocorticoid receptor activation in osteoblasts suppresses transcription of RANKL and increases osteoprotegerin, but more importantly, glucocorticoids inhibit osteoblast differentiation and collagen synthesis (via AP-1/Runx2 suppression) while promoting osteoclast survival. Chronic systemic glucocorticoid exposure (even from ICS) reduces bone mineral density. This risk is dose-dependent and is an important reason to use the lowest effective ICS dose and add calcium/vitamin D supplementation in patients on long-term moderate-to-high dose ICS.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.