Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration

Abstract

P atients who have renal insufficiency develop secondary hyperparathyroidism (SHPT). High levels of parathyroid hormone (PTH) are associated with negative outcomes and play a key role in the development of chronic kidney disease-mineral and bone disorder (CKD-MBD). Excess PTH increases bone turnover, and as SHPT progresses, osteitis fibrosa develops. 1 However, due to bone resistance to PTH, a normal or moderately increased PTH concentration is not sufficient to maintain normal bone turnover. 2 Therefore, excessive suppression of PTH may exacerbate adynamic bone disease.

Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease

“…It has been described that cinacalcet increases bone mineral density when administered to patients on hemodialysis 37 . A very recent work revealed that this effect occurs independently of changes in PTH levels 38 .…”

Clinical evidence of direct bone effects of cinacalcet

“…Recent experimental data demonstrate direct bone actions of calcimimetics, independent of parathyroid hormone (PTH) suppression. 2 To confirm these data in humans, we performed a post hoc analysis on data collected in the frame of prospective, observational studies in patients referred for kidney transplantation. 3 Patients receiving cinacalcet (cases, n ¼ 65) were randomly matched 3:1 on PTH levels to patients free of cinacalcet (controls, n ¼ 166).…”

“…Previous studies have also reported that nonadherence was associated with both DSA and graft survival. 2,3 Then, it is unclear whether it is nonadherence that leads to the development of DSA and TCMR, which then resulted in worse transplant outcomes.…”

“…Kidney transplant recipients infected with coronavirus have a significant risk of graft loss and death. [1][2][3] However, the psychosocial impact of the COVID-19 pandemic on graft and patient outcomes in non-COVID kidney transplant recipients is unclear. The federal and local governments have enforced confinement orders to mitigate the spread of infection, but these restrictions have also limited health care access to "essential visits" only.…”

Direct bone effects of calcimimetics in chronic kidney disease?

“…In this issue of Kidney International, Díaz-Tocados et al 9 (2019) try to shed more light on the issue of a possible direct effect of calcimimetics on bone. They used a complex experimental study, which assessed the biochemical and bone histomorphometric changes produced by calcimimetics in rats that underwent parathyroidectomy receiving a constant PTH infusion.…”