Effects of irradiation on cortical bone and their time-related changes. A biomechanical and histomorphological study.

The effects of high-dose irradiation on the biomechanical and morphological properties of cortical bone and their time-related changes were studied in male Sprague-Dawley rats. A single fraction of 3500 rads was applied to the middle part of the right thigh. Age and sex-matched control rats that did not receive radiation were used for comparison. Two weeks after irradiation, the animals had lost weight and disappearance of bone cells, shrunken osteocytes, and significantly decreased bone-turnover activities were noted. The bone marrow showed reduced hematopoietic elements and sinusoids with increased fat. No change in the torsional strength and geometric properties of bone was noted at this time. Six to ten weeks after irradiation, histopathological abnormalities of the bone persisted, and there was an accelerated resorption process. However, significant increases in the strength and cortical area of bone appeared only in the non-irradiated, contralateral femur. On the irradiated side, decreased cortical area and increased porosity of bone were found at fourteen to eighteen weeks when compared with the control rats. Other histomorphological properties, such as bone porosity, osteocyte count, and periosteal new-bone formation, appeared to recover eighteen weeks after irradiation, as they became similar to the values for the age-matched normal control rats.

Effect of diphosphonate on the prevention of X-radiation-induced inhibition of bone formation in rats.

A histologic and histometric study of the effect of EHDP (ethane-1-hydroxy-1,1-diphosphonate) on the alveolar wound healing of irradiated animals is presented. This drug was selected based on its osteosclerotic effect when applied at low doses. The three left mandibular molars of 80 male Wistar rats were extracted. The rats were grouped into 4 sets of 20 rats each. Group I received no further treatment; Group II received daily intraperitoneal injections of EHDP (7.5 mg/Kg of body weight during 10 days); Group III: 15 Gy of X-radiation were applied to the head; and Group IV were irradiated and injected with EHDP as were animals of Groups III and II. Half of the animals were killed after 14 days and the other half 30 days post-extraction. Sections were made at the level of the mesial socket of the first molar in a bucco-lingual orientation, on which histometric determinations of bone activity were made. The results showed the attenuation of the inhibitory effect of radiation on bone formation when the animals were treated with EHDP.

Whole-body irradiation inhibits the escape phenomenon of osteoclasts in bones of calcitonin-treated rats.

The escape phenomenon is characteristic of osteoclastic bone resorption in organ cultures, and calcitonin only transiently inhibits parathyroid hormone (PTH)-stimulated resorption. The present study demonstrated that the transient inhibition of osteoclastic bone resorption, a phenomenon reminiscent of escape, occurs in the bones of calcitonin (ECT)-treated rats and that whole-body irradiation inhibits this escape. Rats were treated with daily subcutaneous injections of ECT for 72 h. At 24 h ECT decreased the incidence of osteoclast profiles with ruffled borders both in the growth plate-metaphysis junction (GPMJ) and the metaphyseal trabecular bone region (MT). However, by 72 h the incidence in the MT had been restored to the level of the control. The trabecular bone volume in the ECT-treated bone did not differ significantly from the control value. Whole-body irradiation (600 rad) before the first injections of ECT prevented the re-activation of the ruffled border formation and increased the trabecular bone volume at 72 h. Irradiation diminished the number of osteoclasts in the ECT-treated bones to the level of the control. ECT-treated bones contained a greatly increased number of macrophage-like cells (MO). Irradiation prevented this ECT-induced increase in the number of MO. These results strongly suggest that the escape phenomenon in vivo involves the calcitonin-induced proliferation of cells in the mononuclear phagocyte system, with resultant increases in the number of osteoclasts and in the bone resorption activity of osteoclasts.

Osteoclast kinetics in osteopetrotic (ia) rats cured by spleen cell transfers from normal littermates.

Excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in young ia rats can be corrected by irradiation and transfer of spleen cells from normal littermates. Cell population analyses and 3H-thymidine (3H-TdR) autoradiographic methods were used to determine osteoclast population dynamics and kinetics of incorporation of nuclei following whole-body irradiation and spleen cell transfer in ia/ia rats and in untreated ia rats and their (ia/+) normal littermates. The numbers of osteoclasts per metaphyseal area were greater in ia rats than in (ia/+) normal littermates. Untreated ia rats had greater rates of incorporation of 3H-TdR-labeled nuclei into osteoclasts but were reduced to near normal values following irradiation and spleen cell transfer. Labeled osteoclast nuclei were first seen in the primary spongiosa of the femoral metaphysis and with increasing time appeared at greater distances from the epiphyseal growth plate as the bones grew In length. These sites of osteoclast neogenesis correspond to sites where restoration of bone resorption is initially seen following bone marrow and splenic transplants in the treatment of osteopetrosis.

Irradiation injury of bone tissue. A vital microscopic method.

A vital microscopic method using the titanium chamber for observation of bone irradiation injury in situ is described. The subsequent development of bone tissue resorption and replacement with a pathologic immature bone could be observed and recorded.

Effects of therapeutic radiation on microstructure of the human mandible.

Mandibular bone from eight patients who had received therapeutic radiation (6,000-7,200 rads) for intra-oral cancer was obtained at surgery (1 month to 9 years after radiation) and compared histologically with non-irradiated mandibular bone from five subjects. Measurements made on the internal remodeling process of cortical bone included the extent of internal surface and the fraction indicating resorption, and the proportions of osteones which were incomplete (less than 3/4 filled with matrix), complete, and plugged. Appreciable differences were observed in all parameters except plugged osteones. The findings suggested early cessation of osteogenesis, and somewhat later cessation of resopriton, without subsequent resumption of either process. The histologic appearance of the osteoblasts, osteoclasts, and osteones was in accord. Microfractures found in the irradiated bone were not seen to have healed. Radiation damage to the osteoprogenitor cells is postulated.

99Tcm-DP accumulation in rabbit skull bones after 60Co gamma irradiation.

Histology demonstrated new bone formation and bone destruction in rabbit mandibles irradiated with 20 Gy in a single exposure, but no abnormality following 10 Gy in a single exposure. Gamma camera examination of the 99Tcm-DP distribution could not demonstrate any abnormalities, and is concluded not to be effective in demonstrating early radiation injury to bone tissue. Radiation therapy is considered a negligible source of false positive findings in scintigraphy of the facial skeleton.