The suitability of barium titanate (BaTiO3) ceramic for direct substitution of hard tissues was evaluated using both electrically stimulated (piezoelectric) and inactive (nonpolarized) test implants. Textured cylindrical specimens, half of them made piezoelectric by polarization in a high electric field, were implanted into the cortex of the midshaft region of the femora of dogs for various periods of time. Interfacial healing and bio-compatibility of the implant material were studied using mechanical, microradiographical, and histological techniques. Our results indicate that barium titanate ceramic shows a very high degree of biocompatibility as evidenced by the absence of inflammatory or foreign body reactions at the implant-tissue interface. Furthermore, the material and its surface porosity allowed a high degree of bone ingrowth as evidenced by microradiography and a high degree of interfacial tensile strength. No difference was found between the piezoelectric and the electrically neutral implant-tissue interfaces. Possible reasons for this are discussed. The excellent mechanical properties of barium titanate, its superior biocompatibility, and the ability of bone to form a strong mechanical interfacial bond with it, makes this material a new candidate for further tests for hard tissue replacement.

Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency). To further investigate whether the increased iron level plays a causal role in the onset of bone loss, we treated OVX rats with an orally active and bone targeted chelator that prevented iron accumulation in their skeletal tissues. The results showed that this treatment mitigated the loss of bone mass and the deterioration of bone micro-architecture. We also found that one possible mechanism of the protective action of iron chelation was to significantly reduce bone resorption. Thus, these findings provide a novel target and a potentially useful therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis and perhaps other age-related diseases.

The main purpose of this presentation is to describe those events occurring after the administration of various dose levels of corticosteroid (i.e., cortisol) which are relevant to the decay of osseous tissues (i.e., reduction in bone volume). Contradictory reports have attributed the osteoporotic action of cortisol to its anti-anabolic effect (reduced bone formation), catabolic effect (increased bone resorption) or a combination of anti-anabolic and catabolic effects. Thus, one of the objectives of this review is to clarify how cortisol reduces bone volume.Since a dichotomy between dose and time exists i n the effects of cortisol, the dose responses of osseous tissues to cortisol will be described.The description of corticosteroid action upon bone comes from the work of numerous investigators in our laboratory. We apologize that we have intentionally omitted most of the work of past investigators in order to avoid confusion. We acknowledge our debt for their contributions, but we found that our concepts can be presented more clearly by relating our discussion only to cortisol, because the actions of synthetic corticosteroids vary so widely (Berliner et al., '70). A marked re-orientation of our thinking in regard to corticosteroid action upon bone occurred during our studies on the influences of graded doses of cortisol upon the metabolism of strontium-85 in rats (Kenner, '70) and the cellular kinetic and cell population dynamics of bone cells (Roberts, '69). In these experiments we discovered that the effect of cortisol on bone is dose-and time-dependent -low doses of cortisol stimulate bone resorption and high doses of cortisol inhibit bone resorption.The findings of Roberts and Kenner stimulated us to repeat the rat studies of Follis ('51) and Sissons ('55) using a wider range of dose levels of cortisol. We found histologically that low doses of cortisol (1 and 5 mg/kg/day for 5 days) reduced the quantity of tibial metaphyseal bone and high doses (20 and 75 mg/kg/day) depressed bone resorption in intact rats. Furthermore, in hypophysectomized rats 50% of the tibial metaphyseal bone is resorbed in seven postoperative days, but we noted that high doses (20 and 75 mg/kg/day) depressed this bone resorption.A re-examination of our rabbit bone cell population counting data also showed that low doses of cortisol (0.05, 0.1, 0.5, and 1.0 mg of cortisol/kg/day for 30 days) reduced bone volume by increasing the number of osteoclasts and decreasing the number of osteoblasts in the tibial metaphysis.In a long-term experiment designed to study the influences of graded doses of cortisol upon the capacity to remove strontium-85, which had been in the bone of rats for two weeks, we noted that 0.6, 0.2, and 0.06 mg of cortisol/kg/day increased the rate of removal of radioactivity, while 2.0 mg or more of cortisol/kg/day decreased the rate of removal of strontium-85. Since the 85Sr is predominately a bone volume seeker, we interpreted these findings to mean that low doses of cortisol stimulate bone resorption, and doses greate...

A piezoelectric ceramic has been investigated as a direct substitute for hard tissues. Barium titanate (BaTiOz) power was slipcast and fired at 1430 degrees C for 2 hr, then made piezoelectric by polarizing. After 16 and 86 days of implantation in the cortex of the femoral midshafts, the femora with test specimens were sectioned into about 4-cm lengths. Their voltage outputs were measured under cyclic load at 1 Hz. The present results show that the voltage gradient at the implant surface is 0.15 mV/mm for the 16-day implantation with a 445-N (100-lbs.) load. This in turn can give rise to about 0.01 microA current flow in the adjacent area of the 16-day implant. The 86-day implant showed an order of magnitude higher voltage output compared to the 16-day implant with the same magnitude of loads. This is probably due to the "load-transfer" efficiency through the implants, since the voltage output is directly proportional to the actual load transferred to the implant. The more bone implant interface matures, the better the load transfer occurs through the implant, resulting in higher voltage output.

-The effect of the crushing and additive dose procedures used in EPR dosimeuy of enamel was studied on the signals with g-factors of 2.0045 and gl = 2.0018, g, = 1.9975. Eight~tions,~g~g fi size from <75 micrometers to 2 mm, were prepared from one tooth. Two cases wem investigated: crushing of a non-irradiated sample and of a sample previously irradiated (6 Gy tinm Wo gamma ray source). In the non-imadiated study, the intensity of the native signal at 2.0045 inaeased by circa 1.75 times as the grain size &cmased from maximum to minimum. A small decrease in radiation sensitivity (< 8%) was also observed with decreasing grain size. In the irradiated samples, crushing resulted in slight variations of reconstructed doses from expecmd values, but the worst possible case (grain sizes c 75 pm) showed that additional errors were less than 10%.The radiation sensitivity of enamel measumd immediately atter exposure is underestimated. It increases by about 15% in the fmt month. Based on the decomposition of the observed specq a new interpretation of transient signals is proposed which explains the above phenomena. Recommendations about how to use this interpretation in retrospective EPR dosimetry are given.