Bone Remodeling Rate and Remodeling Balance Are Not Co-Regulated in Adulthood: Implications for the Use of Activation Frequency as an Index of Remodeling Rate

Abstract

Use of activation frequency as a measure of remodeling rate assumes co-regulation of remodeling rate and remodeling balance. In iliac crest biopsy specimens from 57 healthy subjects 19-80 yr of age, no correlations were shown between these variables, an observation that challenges the use of activation frequency as an estimate of remodeling rate. The histomorphometric derivation of activation frequency assumes that the remodeling rate is dependent on the duration of the remodeling cycle and the amount of bone formed in individual remodeling units. This implies that remodeling balance and remodeling rate are co-regulated. We tested this assumption in normal human adult cancellous bone. Relationships between indices of bone formation at the basic multicellular unit (BMU) level (wall width and mineral apposition rate) and indices of remodeling rate (mineralizing perimeter and osteoid perimeter) were examined in iliac crest biopsies obtained from 57 healthy adults (24 men) 19-80 yr of age. Univariate analysis revealed a negative correlation between wall width and osteoid perimeter (r = -0.38; p = 0.0004), but there was no correlation between wall width and mineralizing perimeter or between mineral apposition rate and either mineralizing or osteoid perimeter. After adjustment for age and sex, the association between wall width and osteoid perimeter was no longer observed. Both wall width and mineral apposition rate correlated negatively with age (r = -0.75, p < 0.0001 and r = -0.27, p = 0.05, respectively). Our results indicate that remodeling balance and remodeling rate are not co-regulated in adult human bone. Activation frequency, as currently derived from histomorphometric variables, may therefore be unreliable as an indicator of remodeling rate.