Relation between hypomineralized periosteocytic lesions and bone mineralization in vitamin D-resistant rickets

Summary

Hypomineralized periosteocytic lesions (HPL) are peculiar bone features associated with osteomalacia in vitamin D-resistant rickets (VDRR). To determine whether HPL result from defective bone mineralization, tetracycline double-labeled cortical bone specimens from VDRR children were analyzed before (n=13) and after treatment with phosphate supplements combined with vitamin D₂ (Pi+D, n=20) or 1,25-dihydroxyvitamin D₃ (Pi+1,25) (n=22). On microradiographs of undecalcified sections, the percentage of osteocytes with HPL was determined separately in the old interstitial bone, the well calcified resting osteons, and in the less mineralized growing osteons. Using histomorphometric methods, dynamic parameters of cortical bone mineralization were assessed on the same samples. In untreated patients, HPL were more prominent in the less calcified bone areas, in accordance with the reported decrease with bone aging. In contrast to therapy with Pi+D, Pi+1,25 reduced HPL frequency in all cortical areas in correlation with improvement of dynamic parameters of bone mineralization. In addition, HPL frequency progressively decreased with the duration of treatment, further demonstrating that the lesion resulted in part from the defective cortical bone mineralization. However, HPL frequency was unrelated to the severity of osteomalacia in untreated children and the lesion persisted in more than 20% of young osteocytes despite complete correction of bone mineralization parameters. The data support the hypothesis that an abnormal osteocytic function, which may be part of the VDRR phenotype, is involved along with overall impaired bone mineralization in the etiology of the periosteocytic lesion.