Bone disease in predialysis, hemodialysis, and CAPD patients: Evidence of a better bone response to PTH

Abstract

The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy

“…It is well accepted that elevations in PTH are primarily responsible for the high bone turnover in the majority of individuals with late-stage CKD, and PTH measurements are used to predict HTO renal osteodystrophy. (58,(60)(61)(62)(63)(64) Although we cannot exclude the possibility that assay sensitivity may have limited our ability to detect the earliest rise in PTH, several recent clinical observations support our preclinical result because PTH levels do not uniformly predict bone turnover when diagnosed via a bone biopsy. (65)(66)(67) These findings raise the possibility that PTH may not be the sole determinant of elevated bone turnover.…”

Indicações de paratireoidectomia no hiperparatireoidismo secundário à insuficiência renal crônica

“…Outros fatores, como a alteração do metabolismo da vitamina D, hiperfosfatemia, acidose (54) e redução na expressão do receptor do PTH (55) contribuem para a dessensibilização do esqueleto à ação do hormônio. Assim, níveis de PTH 2 a 4 vezes o limite superior do valor de referência são considerados adequados em pacientes com IRC moderada a grave (56,57). Em pacientes em hemodiálise, a histologia óssea tende a estar pouco alterada quando os valores do PTH estão 2 a 3 vezes elevados (56)(57)(58).…”

The meaning of aluminium exposure on human health and aluminium-related diseases

“…Aluminium delivered by transferrin to osteoblasts, thanks to the high expression of transferrin receptors on their surface, exerts an antiproliferative effect on osteoblasts, followed by a low bone turnover and osteomalacia (63) . ABD has been reported in patients who underwent chronic parenteral nutrition with high aluminium contaminations (64) and in dialysed patients (65) . Aluminium-transferrin complexes are also taken up by parathyroid cells, resulting in reduced parathyroid hormone secretion and hypoparathyroidism, which plays a relevant role in the development of ABD (66) .…”