Pharmacology of Bisphosphonates in Patients with Chronic Kidney Disease

Bisphosphonates are medications which bind strongly to mineral. They are ingested by osteoclasts and inhibit an enzyme necessary for bone resorption. The gastrointestinal absorption is poor and the only method of excretion is renal. Therefore, in patients with CKD the body accumulates a higher percentage of a dose of bisphosphonate. These medications remain attached to bone mineral for many years. Although the primary action is to inhibit bone resorption, secondarily bone formation is also inhibited, and in patients with CKD bisphosphonate use often leads to adynamic bone. In some experimental models in animals, the bisphosphonates can inhibit vascular calcification but this effect has not been seen in humans. Intravenous bisphosphonates may cause renal damage but oral doses do not reduce creatinine clearance. In stage 3 CKD, in patients who still have normal PTH, calcium, and alkaline phosphatase, randomized trials show similar benefits as in patients without CKD. Data from stage 4 and 5 CKD are very limited and no clear benefit has been shown.