RESUMO
Much interest has been focused on the role of the immune system in bone remodeling. Here, we compare the production of Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (PBMC) in elderly Paget's patients, elderly osteoporotic patients and in normal elderly subjects. We studied Paget's patients (71.00 +/- 3.74 years), 7 osteoporotic patients (71.86 +/- 3.23 years), age and sex matched, and 5 elderly healthy control subjects (74.20 +/- 4.10 years) An ELISA test was used to quantify IL-1 beta and IL-6 in the supernatant culture of PBMC stimulated by phytohemagglutinin (PHA). IL-1 beta and IL-6 production from Paget's patients (IL-1 beta, 651.43 +/- 95.92 pg/ml; IL-6, 1402.85 +/- 148.11 pg/ml) was not statistically different from the production observed in the osteoporotic patients (IL-1 beta, 552.57 +/- 79.04 pg/ml; IL-6, 1458.85 +/- 118.35 pg/ml) and in the healthy elderly group (IL-1 beta, 717.60 +/- 131.34 pg/ml; IL-6, 1502.40 +/- 211.90 pg/ml). Although IL-1 and IL-6 can be involved in the bone remodeling process, we did not find any difference when we compared their production by PBMC in elderly normal, elderly osteoporotic and elderly Paget's patients.
Assuntos
Interleucina-1/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Osteíte Deformante/metabolismo , Osteoporose/metabolismo , Idoso , Doenças Ósseas Metabólicas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/citologia , MasculinoRESUMO
A random block study, with 50, 100, 200 and 400 mg of 3-dimethylamino-1-hydroxypropylidene-1, 1-bisphosphonate or dimethyl APD and 300, 600 and 900 mg of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate or pamidronate (APD), in daily oral doses, showed that all doses were active when assessed in patients with Paget's bone disease. Dimethyl APD administration was followed by an increase in 1.25 (HO)2D levels, an effect that must be confirmed. Neither severe side effects nor significant laboratory abnormalities were detected despite some decrease in white blood cell count seen with the higher dose of APD. Gastrointestinal tolerance of dimethyl APD was acceptable but further investigation is required.
Assuntos
Osso e Ossos/metabolismo , Difosfonatos/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Idoso , Fosfatase Alcalina/sangue , Temperatura Corporal/efeitos dos fármacos , Cálcio/sangue , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Ergocalciferóis/sangue , Humanos , Hidroxiprolina/sangue , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/metabolismo , Pamidronato , Comprimidos com Revestimento EntéricoRESUMO
We studied the effect of the intravenous administration of the bisphosphonate APD in 9 patients with Paget's bone disease. The medication was given in a daily dose of 25 mg for 7 days in 0.9% saline infusion over 2 hours. At the end of treatment a significant fall of serum calcium and phosphate was observed. The urinary excretion of calcium decreased markedly and the serum levels of the mid-molecule PTH fragment increased from (mean +/- SE) 85 +/- 11 to 122 +/- 16 pg/ml (p less than 0.05). A marked and rapid decline in the hydroxyprolinuria was observed from 297 +/- 61 mg/24 h to 194 +/- 51 mg/24 h (p less than 0.01); meanwhile the serum alkaline phosphatase decreased from 102 +/- 22 to 84 +/- 21 KAU (p less than 0.05). The effect of ADP on suppression of hydroxyprolinuria varied markedly from +1 to -81% and was negatively related to the basal hydroxyprolinuria (r = -0.90; p less than 0.001). The duration of the bone turnover suppression was short. A relapse greater than 30% in hydroxyprolinuria was observed in 6 of 8 patients 2 to 3 months after APD withdrawal. The short-term intravenous administration of ADP is a useful means to rapidly suppress the activity of Paget's bone disease. However, further studies should determine the optimum dose, the length of treatment, and the need to associate oral therapy to induce a prolonged remission.