Utilization of bone histomorphometry in renal osteodystrophy: demonstration of a new approach using data from a prospective study of lanthanum carbonate

Abstract

The aim of this study was to develop a novel approach to the analysis of bone histomorphometric data and outcomes presentation that would simplify the characterization of renal osteodystrophy and facilitate clinical decision-making. Data were derived from a randomized trial of dialysis patients treated for one year with a dose of lanthanum carbonate or calcium carbonate (up to 3750 mg/day and 9000 mg/day, respectively). Histomorphometric analyses of baseline and end-of-study bicortical transiliac bone biopsies were performed. Activation frequency, bone formation rate/bone surface, osteoclast surface/ bone surface, osteoblast surface/bone surface, mineralization lag time, and osteoid thickness were determined to provide a measure of overall bone cell activity (bone formation, bone resorption, bone turnover) and risk of developing osteopenia (bone balance). A novel approach of qualitatively grouping these numerical data as "improved", "unchanged", or "worsened" based on deviation from normal was used to facilitate interpretation of clinical relevance. Using our method, lanthanum carbonate was shown to improve histomorphometric parameters measured. These improvements were superior to those produced by calcium carbonate. These data add valuable clinical relevance to the previously published qualitative data from the same cohort [D'Haese et al. 2003]. Lanthanum carbonate moderated extreme forms of renal osteodystrophy, whereas calcium carbonate treatment increased the incidence of adynamic and predominant hyperparathyroid bone disease. This study provides an approach to the prospective evaluation of bone disease progression with therapy, and its application supports the safety and greater efficacy of one-year lanthanum carbonate versus calcium carbonate therapy as a means to normalize bone turnover in dialysis patients.