Bone Growth During Daily Or Intermittent Calcitriol Treatment During Renal Failure with Advanced Secondary Hyperparathyroidism

Abstract and Introduction

Abstract

Calcitriol is a standard therapy for secondary hyperparathyroidism in chronic renal failure. We evaluated whether the effect of daily or intermittent calcitriol administration is more efficient in enhancing bone growth in renal failure with advanced secondary hyperparathyroidism in weanling 5/6 nephrectomized rats loaded with phosphorus to induce severe secondary hyperparathyroidism. The animals were treated daily or three times weekly with calcitriol for 4 weeks but the total weekly dose of calcitriol was the same. Although calcitriol increased the serum calcium, it did not lower parathyroid hormone (PTH) or improve tibia and body length. Animals with renal failure and advanced secondary hyperparathyroidism had decreased PTH/PTHrP, which was accompanied by an increase in the cyclin kinase inhibitor p57^Kip2. Calcitriol treatment upregulated the PTH/PTHrP receptor but also increased inhibitors of cell proliferation such as p21^Waf1/Cip1, IGFBP3, and FGFR3. Calcitriol also enhanced markers of chondrocyte differentiation, such as IGF1, Vitamin D receptor, FGF23, and bone morphogenetic protein-7. Receptor activator of nuclear factor-κβ ligand levels improved with calcitriol treatment but without changes in osteoprotegerin suggesting an enhancement of osteo/chondroclastogenesis and mineralization. Overall, both daily and intermittent calcitriol had similar effects on endochondral bone growth in phosphorus-loaded rats with renal failure.

Introduction

Calcitriol is a standard treatment for secondary hyperparathyroidism and renal bone disease. Whether daily calcitriol administration is more effective than intermittent therapy in improving growth in children with chronic renal failure and advanced secondary hyperparathyroidism remains to be defined. In pediatric patients with Stage 3–4 chronic renal failure with mild elevations of parathyroid hormone (PTH), daily calcitriol was equally effective as intermittent therapy in the reduction of PTH and enhancement of growth.^[1,2] A greater improvement of osteitis fibrosa was demonstrated during intermittent calcitriol therapy in children maintained on peritoneal dialysis with refractory secondary hyperparathyroidism, although 30% of the patients developed low turnover bone.^[3] Conversely, Mehls et al. reported that only daily calcitriol and not intermittent administration enhanced growth in rats with renal failure after 2 weeks of treatment.^[4] The divergence of growth findings in these studies suggests that daily and intermittent calcitriol may have different effects on endochondral bone growth. In the growth plate, calcitriol has dose-dependent inhibitory effects on chondrocyte proliferation and matrix synthesis.^[5,6] The aim of the current study is to assess the effects of daily or intermittent calcitriol on chondrocyte proliferation and differentiation in young rats with renal failure and advanced secondary hyperparathyroidism.

Kidney Int. 2007;72(5):582-591. © 2007  Nature Publishing Group

Cite this: Bone Growth During Daily Or Intermittent Calcitriol Treatment During Renal Failure with Advanced Secondary Hyperparathyroidism - Medscape - Sep 01, 2007.