Extent of alkaline phosphatase cytochemistry vs. extent of tetracycline fluorescence in the evaluation of histodynamic variables of bone formation

Alkaline phosphatase (ALP) activity is a new histomorphometric index of the extent of osteoblastic surfaces involved in mineralization. To assess its validity in the evaluation of bone formation, we carried out a comparative study between histomorphometric values obtained on the basis of the extent of tetracycline labeling and of the length of ALP-positive endosteal surfaces. The following variables were compared (indicated by ALP when based on the extent of ALP positivity): trabecular mineralizing surface (MS/BS vs. ALP.SBS); osteoid mineralizing surface (MS/OS vs. ALPS/OS); bone formation rate (BFR/BS vs. ALP.BFR/BS); and adjusted appositional rate (Aj.AR vs. ALP.Aj.AR). Bone biopsies from 39 patients with chronic renal failure and different types of renal osteodystrophy were considered (48 ± 12 years of age; 19 men and 20 women). Patients were double labeled with tetracycline and biopsies were embedded in glycol-methacrylate at +4°C. Patients showed various types of renal osteodystrophy and were assigned to different groups of pathologies. Although it differed in incidence according to the different groups, ALP activity was found in typical plump osteoblasts bordering osteoid seams and in flat cells, either in contact with osteoid or along the quiescent surfaces of bone in continuity with it. Tetracycline codistributed with all these features to variable extents, according to groups. In all patients, however, ALPS/BS and ALPS/OS respectively exceeded MS/BS and MS/OS. In consequence of this, ALP.BFR/BS and ALP.Aj.AR were greater than BFR/BS and Aj.AR, respectively. For each of the variable considered, differences among groups of patients with different types of renal osteodystrophy were highly significant. Good correlations were found between the variables measured with the two methods. Correlations of ALP.BFR/BS and ALP.Aj.AR with serum indices of bone metabolism (calcium, phosphate, osteocalcin, ALP, and C-terminal PTH) were comparable with those of BFR/BS and Aj.AR, respectively. On the basis of the results obtained in our population study, the length of bone surfaces covered by ALP-positive osteoblastic cells greatly overestimates the extent of mineralizing surface as assessed by tetracycline labeling and cannot be assumed to be a reliable indicator of the true extent of the mineralizing surface. Histodynamic variables evaluated by considering bone surfaces positive to ALP to be mineralizing surfaces do not give more accurate information on bone metabolism compared with those derived by taking into account the extent of tetracycline labeling.