Can bisphosphonates play a role in the treatment of children with chronic kidney disease?

Abstract

In patients with chronic kidney disease (CKD) renal osteodystrophy, in the form of either low- or high-turnover bone disease, is quite common. While renal transplantation is expected to reverse renal osteodystrophy, long-term treatment with glucocorticoids before and/or after transplantation may lead to osteoporosis instead. Osteoporosis is defined as a skeletal disease with low bone mineral density, microarchitectural deterioration, and concomitant fragility. In adults, bisphosphonates are widely used to treat osteoporosis and other diseases associated with excessive bone resorption. In pediatric CKD patients the efficacy and safety of these drugs have not yet been addressed adequately and thus no evidence-based recommendations regarding the optimal type of bisphosphonate, dosage, or duration of therapy are available. Furthermore, while in adults the determination of areal bone mineral density is sufficient to diagnose osteoporosis, this is not the case in children. Instead, in pediatric patients, careful morphological assessment of bone structure and formation is required. Indeed, data from studies with uremic rats indicated that bisphosphonates, via a deceleration of bone turnover, have the potential not only to aggravate pre-existing adynamic bone disease, but also to impair longitudinal growth. Thus, the widespread use of bisphosphonates in children with CKD should be discouraged until the risks and benefits have been carefully elucidated in clinical trials.

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease

“…Altered kidney function has also been documented in select animal studies [13, 14]. In addition to documented nephrotoxicity, there is a theoretical concern that the drug will accumulate in the skeleton to levels above those that occur in individuals with normal kidney function [15–18]. This latter concern exists because of the absence of data describing skeletal accumulation of bisphosphonate in the setting of altered kidney function [19].…”

The Use of Bisphosphonates in Pediatrics

“…It frequently affects children with diffuse connective tissue diseases [21,22], inflammatory bowel diseases [23], chronic renal diseases [24,25], hematological malignancies [26,27,28,29], or solid tumors [30]. Systemic glucocorticoid treatment is associated with an initial increase in bone resorption and a subsequent reduction of bone formation, leading to decreased peak bone mass, microarchitectural deterioration and increased fracture risk [31,32,33,34].…”

Treatment of adynamic bone disease in a haemodialysis patient with teriparatide

“…This type of treatment alone is not associated with a controlled rise in PTH and can lead to non-reversible parathyroid gland hyperplasia [ 5 ]. Biphosphonates enhance osteoclast apoptosis and were contraindicated in this patient, since there were no osteoclasts or increased bone resorption on biopsy [ 6 , 7 ].…”