PARTNERS WITH
Ibandronate sodium, Boniva
Bisphosphonates
MECHANISM OF ACTION
Bisphosphonates diminish bone resorption through many different mechanisms including inhibition of osteoclasts activity. They are excreted by the kidney unmetabolized via glomerular filtration or stored in bones. Thus, a reduced glomerular filtration can lead to increased serum level.
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis), Water/electrolyte disturbances, Glomerular injury, Podocyte Injury
CLINICAL KIDNEY SYNDROME
AKI, Proteinuria/Albuminuria, Nephrotic syndrome
CARDIOVASCULAR ADVERSE EFFECTS
LYTE ABNORMALITIES
Hypocalcemia
RISK FACTORS
Patients are more prone to hypocalcemia if they have pre-existing hypovitaminosis D, hypoparathyroidism, secondary hyperparathyroidism, hypomagnesemia, are receiving concurrent treatment with aminoglycoside or interferon alpha, concurrent treatment with loop diuretics and/or have osteoblastic metastases.
MITIGATION STRATEGIES
To prevent hypocalcemia, calcium and vitamin D supplement should be started prior to treatment initiation and other electrolytes abnormalities should be corrected. Serum electrolytes and vitamin D level should be monitored according to guidelines. The treatment should be held in case of hypocalcemia.
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Discontinue offending drug
NOTES/COMMENTS
PHARMACOKINETICS
Molecular Weight
Volume of Distribution
Plasma Protein Binding
Metabolism
Bioavailability
Half-life elimination
Time to peak
Excretion
Dialyzable?
Unknown
REF:
Perazella MA, Markowitz GS. Bisphosphonate nephrotoxicity. Kidney Int. Dec 2008;74(11):1385-93. doi:10.1038/ki.2008.356
Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol. Jun 2006;17(6):897-907. doi:10.1093/annonc/mdj105
Miller PD, Jamal SA, Evenepoel P, Eastell R, Boonen S. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res. Oct 2013;28(10):2049-59. doi:10.1002/jbmr.2058
Dunstan CR, Felsenberg D, Seibel MJ. Therapy insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nat Clin Pract Oncol. Jan 2007;4(1):42-55. doi:10.1038/ncponc0688
Ott SM. Pharmacology of Bisphosphonates in Patients with Chronic Kidney Disease. Semin Dial. 2015 Jul-Aug 2015;28(4):363-9. doi:10.1111/sdi.12388
Domschke C, Schuetz F. Side effects of bone-targeted therapies in advanced breast cancer. Breast Care (Basel). Oct 2014;9(5):332-6. doi:10.1159/000368844
Jia N, Cormack FC, Xie B, Shiue Z, Najafian B, Gralow JR. Collapsing focal segmental glomerulosclerosis following long-term treatment with oral ibandronate: case report and review of literature. BMC Cancer. Jul 22 2015;15:535. doi:10.1186/s12885-015-1536-y
de Roij van Zuijdewijn C, van Dorp W, Florquin S, Roelofs J, Verburgh K. Bisphosphonate nephropathy: A case series and review of the literature. Br J Clin Pharmacol. 09 2021;87(9):3485-3491. doi:10.1111/bcp.14780
PATHOLOGY SLIDES:
ENTRY UPDATES:
Anna-Ève Turcotte
United States
Sep 25, 2022