Prophylactic treatment of skeletal metastases, tumor-induced osteolysis, and hypercalcemia in rats with the bisphosphonate Cl2MBP.
BACKGROUND
The purpose of this study was to investigate the influence of a prophylactic bone protective treatment with the bisphosphonate dichloromethane/diphosphonic acid (Cl2MBP) in an experimental model of osteolysis with intraosseous implantation of the Walker carcinosarcoma 256 B.


METHODS
The biphosphonate was given as a high-dose, short-term treatment (30 mg/5 days sc) followed by a treatment-free interval (1-7 weeks) or as a low-dose, long-term prophylactic treatment (2.5 or 5.0 mg/day/3 weeks sc). Osteolysis was measured with a radiographic and histologic grading system.


RESULTS
The high-dose short-term prophylactic treatment was shown clearly to inhibit tumor osteolysis. The osteoprotective effect decreases with increasing length of the treatment-free interval. A similar positive result could be achieved following the low-dose long-term prophylactic treatment. Dosage could not be shown to influence the inhibition of tumor osteolysis in the long-term bone protective treatment. A possible direct influence of the treatment on tumor growth could be ruled out. The prophylactic treatment does not inhibit body weight increase. Animals treated prophylactically showed less weight loss than the controls after tumor implantation.


CONCLUSIONS
These results show that a prophylactic treatment with Cl2MBPs protects the skeleton effectively against tumor osteolysis.
Institute of Pathology, Heidelberg University, Federal Republic of Germany.
B
B
Krempien
C
C
Manegold
D000818:Animals; D001859:Bone Neoplasms / Q000517:prevention & control* / Q000556:secondary; D002279:Carcinoma 256, Walker / Q000517:prevention & control* / Q000556:secondary; D004002:Clodronic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D006934:Hypercalcemia / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D010014:Osteolysis / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects
D004164:Diphosphonates; D004002:Clodronic Acid