Bone Canopies in Pediatric Renal Osteodystrophy.

Abstract

Pediatric renal osteodystrophy (ROD) is characterized by changes in bone turnover, mineralization, and volume that are brought about by alterations in bone resorption and formation. The resorptive and formative surfaces on the cancellous bone are separated from the marrow cavity by canopies consisting of a layer of flat osteoblastic cells. These canopies have been suggested to play a key role in the recruitment of osteoprogenitors during the process of bone remodeling. This study was performed to address the characteristics of the canopies above bone formation and resorption sites and their association with biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney disease (CKD) patients (stage 2-5) across the spectrum of ROD. Canopies in CKD patients often appeared as thickened multilayered canopies, similar to previous reports in patients with primary hyperparathyroidism. This finding contrasts with the thin appearance reported in healthy individuals with normal kidney function. Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa-B ligand (RANKL). The number of surfaces with visible canopy coverage was associated with plasma parathyroid hormone (PTH) levels, bone formation rate, and the extent of remodeling surfaces. Collectively, these data support the conclusion that canopies respond to the elevated PTH levels in CKD and that they possess the molecular machinery necessary to respond to PTH signaling.