Cortical bone remodeling in autosomal dominant osteopetrosis: a study of two different phenotypes

Previous analyses of cancellous bone remodeling in autosomal dominant osteopetrosis (ADO) have suggested a diminished osteoclastic resorption at the endocortical surface. Consequently, cortical width increases with age in both ADO type I and II. By means of histomorphometric methods, the remodeling cycle of the Haversian surface in the iliac crest has recently been reconstructed in normal individuals. The aim of the present investigation was to study cortical bone remodeling in ADO type I and II. Transcortical iliac crest bone biopsies obtained from 21 ADO patients were studied. Of these, 14 had ADO type I and seven had ADO type II. Twenty of the patients had received intravital double labeling with tetracycline before the biopsies were obtained. The static histomorphometric parameters for cortical bone mass and structure were compared with a control group of 21 sex- and age-matched individuals. Regarding the dynamic histomorphometric parameters for reconstruction of the cortical bone remodeling cycle, the ADO type I material was compared with control material from 14 sex- and age-matched individuals, whereas the ADO type II material was compared with control material from six sex-matched but younger individuals. Significant increases were seen in absolute as well as fractional cortical widths in both ADO types. Furthermore, an age-related increase was observed in both absolute and fractional cortical widths in ADO type I, whereas ADO type II was nonsignificant with regard to age. The fractional cancellous width was reduced in both type I and type II. However, only in ADO type I did the fractional cancellous width significantly correlate inversely with age. In the control group, neither cortical dimensions nor cancellous width correlated significantly with age. No significant differences were observed between patients and the control group in osteon dimensions; fractional resorptive, formative, or quiescent sites; resorptive or formative remodeling rates; remodeling periods; or activation frequency. An age-related increase in cortical porosity was seen in the group of normal individuals, but not in the two patient groups. The fractional remodeling space was increased in the ADO type II group. In conclusion, cortical dimensions are increased in both ADO type I and II and positively correlated to age in type I. However, cortical remodeling at the Haversian surface is essentially normal in both ADO type I and II. This could be explained by a defective endocortical bone resorption, as no periosteal accretion was observed, and because cancellous bone remodeling previously has been described to be normal.