The effect of bisphosphonate and intermittent human parathyroid hormone 1-34 treatments on cortical bone allografts in rabbits.

AIM: This study compares the effect of bisphosphonate and intermittent PTH administration on haversian remodeling in cortical bone allografts in rabbits. MATERIALS AND METHODS: An intercalary heat-treated cortical bone allograft was applied to a segment skeletal defect in the left femur of Japanese white rabbits. The rabbits were randomly assigned to one of three groups: the vehicle control group (CNT); the bisphosphonate group (B group); and the intermittent PTH treatment group (P group). Periodic radiographic evaluation was performed and peripheral quantitative computerized tomography (pQCT) was used to evaluate the total bone area (Area), bone mineral density (BMD), and bone mineral content (BMC). The allografts also underwent histological examination. RESULTS: The P group was radiographically superior in the latter stage, compared with the other groups. pQCT analysis of the allografts showed that the B group had a significantly higher Area and BMC. These parameters in the latter stage were significantly lower in the P group than in the other groups. The allograft of the B group was histologically mostly necrotic bone, whereas allograft of the P group showed abundant newly formed bone. CONCLUSION: In rabbits, bisphosphonate prevents resorption, but suppresses remodeling and incorporation; by contrast, PTH increases resorption and accelerates allograft remodeling and incorporation. Based on our preliminary data, we suggest that further research on the manner of administration of bisphosphonate and PTH - which have contrasting effects - can be beneficial in maintaining bone strength and in regulating remodeling and allograft incorporation.

Characterization of human multicentric osteosarcoma using newly established cells derived from multicentric osteosarcoma.

PURPOSE: Human multicentric osteosarcoma (HMOS) is a rare, aggressive variant of osteosarcoma, and its etiology is not clear. We used newly established HMOS cells, which were derived from primary (HMOS-A) and secondary (HMOS-P) lesions, respectively, to perform a basic study analyzing the cellular biology and gene expression of HMOS. METHODS: We performed a cell growth assay, an invasion assay, DNA microarray analysis, quantitative real-time RT-PCR (Qrt-PCR), and a telomerase assay and compared the results between HMOS-A, HMOS-P, and human osteosarcoma (HOS) cell lines (MNNG-HOS and Saos-2). RESULTS: The cell biological analysis revealed that HMOS-A and HMOS-P had similar characteristics to Saos-2, and the invasion assay showed that they had similar characteristics to MNNG-HOS. The DNA microarray study showed that the gene expression profiles of HMOS-A and HMOS-P were similar to that of MNNG-HOS, but the overexpression of MMP-2, MMP-9, and MT1-MMP was observed in HMOS-A and HMOS-P, which was correlated with the invasiveness of the extracellular matrix, and collagen type-4 (COL-4) and VEGF were also detected. HMOS-A and HMOS-P showed low telomerase activity similar to Saos-2, which are known to be telomerase negative, but a similar telomere length and telomerase protein to MNNG-HOS. CONCLUSIONS: HMOS-A and HMOS-P demonstrated strong invasive ability, and their gene expression profiles correlated with the invasiveness of the extracellular matrix. Their telomerase activity was low, but they did not shown the typical features of alternative lengthening of telomeres (ALT). HMOS-A and HMOS-P are useful models for further study of various biological aspects and therapeutic manipulation of HMOS.