No abstract

The potential effects of a calcium channel blocker (nifedipine) on epiphyseal growth plate and bone remodeling have been investigated in growing rabbits. The treated group received 6 mg/kg/day nifedipine twice daily by gavage for 10 weeks. An untreated group was used as control; with this dose, neither toxic effects nor decrease in the body weight have been observed. No modifications of blood phosphocalcic parameters have been found. In the treated group there is a significant lower cancellous bone volume, lower osteogenesis, shorter labeled perimeters, and lower mineral apposition rate than in the control group. Epiphyseal growth plate thickness is lower than in the untreated animals and considerable morphological changes are observed in the growth zone compared with the control group. A decrease in the growth of humerus length was found. In conclusion, nifedipine affects bone physiology, especially with consequences on bone growth. These effects appear to be quantitatively important, and there is the possibility of bone side effects on therapeutic use in humans, especially in young subjects.

No abstract

We performed experimental studies to confirm the hypothesis that cellular damages occurring around implanted biphasic bioceramics could be related to a micro-particles release because of an insufficient sintering. First, an in vitro cytotoxicity study was performed on four biphasic ceramic (BCP) samples. Without treatment of the extraction medium, a cytotoxicity was observed, although after centrifugation this cytotoxicity disappeared in all samples. Second, micro-particles of hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) and 40% beta-TCP/60%HA mixture were used for a cell inhibition study. A decrease of cell viability was observed with the increase in particles concentration. At 10000 particles per cell, the viability and proliferation were completely inhibited. Third, HA, beta-TCP and BCP ceramic granules were implanted in rabbit femoral cavities for 12 weeks. No degradation of HA granules was observed. The degradation was higher for beta-TCP (40%) than for BCP (5%). On the other hand, new bone formation was significantly higher for beta-TCP (21%) and HA (18%) than for BCP (12%). More micro-particles were formed around BCP granules than around beta-TCP, and phagocytised by macrophages. The release of ceramic micro-particles could be related to the sintering process. BCP ceramic have to be sintered at only 1160 degrees C. Consequently, HA micro-particles of BCP ceramic are incompletely sintered and easily released after immersion or implantation. The microparticles could be at the origin of local inflammation and cell damage and could perhaps modify osteogenesis. Attention must be paid to this problem especially with BCP ceramics because of the sintering difficulties of this bioceramic.

Hydroxyapatite (HA) porous ceramics are increasingly used in biomedical applications. Their physical characteristics, such as porous volume, require perfect control of the pore shape, as well as the number and the size of their interconnections. The aim of our study was to evaluate a new HA ceramic using polymethylmethacrylate microbeads (PMMA) as the porous agent. Four interconnection sizes (30, 60, 100 and 130 microm) with a 175-260 microm pore size and three pore sizes (175-260, 260-350 and 350-435 microm) for a 130 microm interconnection size were tested. Various HA implants were appraised by microscopic evaluation in a 4.6 x 10 mm rabbit femur cancellous bone defect 12 weeks after implantation. The best osteoconduction result was obtained in the center of the ceramic by means of a 130 microm interconnection size and a 175-260 microm mean pore size. Bone formation obtained within the pores was double that obtained in our previous study where naphtalen microbeads were used as the porous agents.