A Pizzoferrato — Page 9

PubMedDate not supplied

Effects of orally administered bisphosphonates on bone loss in a disuse osteopenia model involving the rat.

OBJECTIVE: This study was carried out to evaluate the effectiveness of two newly synthesized bisphosphonates (BPs) [Alendronate (4-amino-1-hydroxybutylidene-1, 1-bisphosphonic acid (AHBuBP)) and Neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonic acid (AHHexBP)], administered orally, in reducing experimentally induced bone loss. METHODS: Unilateral sciatic nerve section was performed on the Sprague-Dawley rat to induce osteopenia in one of the hind limbs. Histomorphometric measurements of the tibial trabecular bone and femur ash content determinations were effected to assess the degree of osteopenia. For comparison Chlodronate (dichloromethylene-1-bisphosphonic acid (Cl2MBP) was employed as the reference drug. CONCLUSIONS: The results of this investigation show that both BPs were significantly active in reducing the osteopenic process in the involved limb and were more active than Chlodronate.

Administration, Oral↗

PubMedDate not supplied

[A prospective study on nephrotoxicity induced by continuous infusion of high-dose ifosfamide (15/m2)].

BACKGROUND: A good response rate to high-dose ifosfamide (HDIFO) has been reported in metastatic osteosarcoma and soft tissue tumors. As standard dose of IFO (< 12 g/m2) can give several renal complications and patients previously treated with nephrotoxic drugs are at high risk of nephrotoxicity, a prospective study to evaluate the pattern of nephrotoxicity induced by HDIFO was carried out. METHODS: Twelve patients (11 metastatic osteosarcoma, 1 synovial sarcoma; mean age 17, R 14-34) were treated with 4 courses of HDIFO/ MESNA (15 g/m2, IV 5 day continuous infusion with bicarbonate and K supplements). All but two were previously treated with cisplatin and methotrexate. Several parameters of renal function were measured before treatment, after each HDIFO course and two months after chemotherapy completion. RESULTS: Significant changes in the urinary excretion of beta 1-microglobulin, beta 2-microglobulin, Alanine Aminopeptidase, N-Acetil-beta, D-glucosaminidase and a significant reduction in phosphate tubular absorbtion according to the cumulative dose of IFO infused, were observed. Phosphaturia and hypophosphatemia occurred in all the patients studied. In 5 patients, CrCl fell below 70 ml/min with normal serum creatinine level after 45 g/m2 IFO. Plasma bicarbonate concentration less than 20 mmol/l was observed in 5 of 48 HDIFO courses. Glycosuria was detected in 4 patients. Two months after chemotherapy completion, mild glycosuria and slightly reduced CrCl persisted in two patients, whereas the other parameters of renal function studied were similar to the baseline values. An acute, usually reversible subclinical nephrotoxicity involving glomerule and renal tubule was demonstrated in all the patients treated with HDIFO. A persisting subclinical renal impairment was shown with mild glycosuria (2/12 patients) and slightly reduced CrCl (2/12 patients).

Adolescent↗