Long-term use of proton pump inhibitors (PPIs) can lead to decreased calcium absorption due to reduced gastric acidity, which is essential for calcium solubility and absorption in the intestine. This chronic hypochlorhydria may result in impaired bone mineralization, increasing the risk of osteoporotic fractures, particularly in the hip, wrist, and spine. Patients on prolonged PPI therapy should be monitored for bone health and advised on calcium and vitamin D intake to mitigate fracture risk.

Reference: Harrison's Principles of Internal Medicine, Jameson et al., 20th Edition.