The kidney and bisphosphonates

Bisphosphonates are eliminated from the human body by the kidney. Renal clearance is both by glomerular filtration and proximal tubular secretion. Bisphosphonates given rapidly in high doses in animal models have induced a variety of adverse renal effects, from glomerular sclerosis to acute tubular necrosis. Nevertheless in the doses that are registered for the management of postmenopausal osteoporosis (PMO), oral bisphosphonates have never been shown to adversely affect the kidney, even (in post-hoc analysis of clinical trial data) down to estimated glomerular filtration rates of 15 ml/min. In addition fracture risk reduction has also been observed in these populations with stage 4 chronic kidney disease (CKD) with age-related reductions in glomerular filtration rate (GFR). Intravenous zoledronic acid is safe when the infusion rate is no faster than 15 min though there have been short-term (days 9-11 post-infusion) increases in serum creatinine concentrations in a small sub-set of patients from the postmenopausal registration trials. For these reasons intravenous zoledronic acid should be avoided in patients with GFR levels < 35 ml/min; and the patients should be well hydrated and have avoided the concomitant use of any agent that may impair renal function. Intravenous ibandronate has not to date been reported to induce acute changes in serum creatinine concentrations in the PMO clinical trial data, but the lack of head-to-head comparative data between ibandronate and zoledronic acid precludes knowing if one intravenous bisphosphonate is safer than the other. In patients with GFR levels < 30-35 ml/min, the correct diagnosis of osteoporosis becomes more complex since other forms of renal bone disease, which require different management strategies than osteoporosis, need to be excluded before the assumption can be made that fractures and/or low bone mass are due to osteoporosis. In addition, in patients who may have pre-existing adynamic renal bone disease, there is a lack of evidence of any beneficial effect or harm by reducing bone turnover by any pharmacological agent, including bisphosphonates on bone strength or vascular calcification. Bisphosphonates are safe and effective for the management of osteoporosis when used in the right dose and in the right patient population for the right duration.This article is part of a Special Issue entitled Bisphosphonates.

Research Highlights►The prevalence of osteoporosis and chronic kidney disease (CKD) both increase as age increases. ►Reduced renal function may be accompanied by a group of metabolic bone diseases, chronic kidney disease-mineral and bone disorder (CKD-MBD) as well as osteoporosis. ►Both CKD-MBD as well as osteoporosis may be associated with low trauma fractures and/or low bone mineral density. ►Stage 1-3 CKD (GFR < 90-30 ml/min) can be managed as osteoporosis with usual formulations of bisphosphonates, assuming there are no biochemical tests suggesting CKD-MBD. ►Stage 4-5 CKD (GFR < 30 ml/min or < 15 ml/min) may be considered for off-label use of bisphosphonates for a limited period of time (2-3 years) only if they have fractured and have a secure diagnosis of osteoporosis.