Serum osteocalcin in Paget's disease of bone: basal concentrations and response to bisphosphonate treatment.

Serum osteocalcin concentrations were measured in 42 patients with Paget's disease of bone and elevated serum alkaline phosphatase (AP) levels. High serum osteocalcin levels were found in only 22 patients. Serum osteocalcin was significantly correlated with urinary hydroxyproline excretion (r = 0.747; P less than 0.001) and, to a lesser extent, with serum AP levels (r = 0.483; P less than 0.01). In 23 patients who were followed during treatment with iv (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate (APD) for 10 days, a dissociation among these 3 biochemical parameters was found. Urinary hydroxyproline excretion fell significantly (P less than 0.001), serum AP levels decreased, but not significantly, and serum osteocalcin concentrations increased progressively (P less than 0.001). This increase was greater when initial levels were lower than expected for the activity of the disease. The rise in serum osteocalcin correlated significantly with the concomitant increase in serum 1,25-dihydroxyvitamin D concentrations. Three months after initiation of treatment, all 3 parameters, urinary OHP excretion, serum AP, and serum osteocalcin levels, were near or within the normal range. These results indicate that serum osteocalcin is not a clinically useful parameter for assessment of the activity of Paget's disease. Its basal concentrations lag behind those expected from the activity of the disease, suggesting defective osteocalcin production. It appears that the functions of osteocalcin and AP as well as their initial expression by the osteoblasts are different and that this difference may be important for the quality of bone formed in Paget's disease. APD can modulate the release of osteocalcin, possibly through stimulation of 1,25-dihydroxyvitamin D production, although other factors may be involved.

Case-control analysis of allogeneic bone marrow transplantation versus maintenance chemotherapy for relapsed ALL in children.

In a retrospective study, the results of maintenance chemotherapy and allogeneic bone marrow transplantation (BMT) for children who reached a second complete remission (CR2) of their acute lymphoblastic leukemia (ALL) were compared. Case-control analysis was performed comparing 25 allogeneic transplant patients (cases) with 97 patients treated with maintenance chemotherapy (controls), who were matched for site of relapse, duration of CR1 and leukemia-free interval from onset of CR2. Until the first relapse, the children were treated according to standard protocols. The majority of patients suffered from a bone marrow relapse, mostly occurring more than 24 months after the onset of CR1. Remission reinduction treatment was heterogeneous. Patients treated with allogeneic BMT received high-dose chemotherapy and total body irradiation prior to BMT. Maintenance chemotherapy in controls was given for approximately 2 years. Following BMT, relapse rate was lower but the treatment-related mortality was higher compared with maintenance chemotherapy, resulting in leukemia-free survival rates at 4 years of 44% and 24%, respectively (not significant, NS). Case-control analysis of leukemia-free survival showed a hazard ratio of 0.756 in favor of BMT compared with chemotherapy (NS). If bone marrow relapses and central nervous system relapses were analyzed separately, a tendency to better leukemia-free survival was present after BMT compared with maintenance chemotherapy for patients with a relapse in the central nervous system, but for an isolated bone marrow relapse, no differences in leukemia-free survival were seen between the two groups of patients.

Circulating 1,25-dihydroxycholecalciferol after intravenous injections of 1 alpha-hydroxycholecalciferol in patients on regular haemodialysis.

The formation of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) after single intravenous injections of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) was examined in four patients with chronic renal failure on regular haemodialysis. Following 1-3 micrograms 1 alpha-OHD3, administered at weekly intervals, 1,25-(OH)2D3 appeared in the circulation within 1 h, and peak concentrations were reached between 2 h and 5 h. By 8 h serum 1,25-(OH)2D3 concentrations had started declining and by 44 h they had returned to baseline after 1 microgram 1 alpha-OHD3, but they were still above basal after 2 and 3 micrograms by an average of 30 pmol/l. One week after injections, concentrations were back to basal in all patients studied. The serum 1,25-(OH)2D3 dose response to injected 1 alpha-OHD3 was linear, indicating ample capacity of the liver 25-hydroxylase to further hydroxylate 1 alpha-OHD3. However, examination of the individual responses revealed lower increments in serum 1,25-(OH)2D3 concentrations in the patients with the highest basal serum 25-hydroxyvitamin D concentrations. Intravenous 1 alpha-OHD3 may be useful in the further study of the interactions between 1,25-(OH)2D3, calcium and PTH in chronic renal failure, as well as of the hepatic metabolism of vitamin D.