The impact of switching once-weekly teriparatide to denosumab in osteoporosis patients.

BACKGROUND: It has been reported that switching from daily (d) teriparatide (TPTD) to denosumab (DMAb) is effective for severe osteoporosis patients. However, there have been no reports about switching from weekly (w) TPTD to DMAb in patients with osteoporosis. Once-weekly 56.5-µg TPTD treatment increases bone mineral density (BMD) and reduces fracture events. The objective of the current retrospective study was to elucidate the impact of switching w-TPTD to DMAb in patients with osteoporosis. METHODS: In this study, 40 patients were treated with w-TPTD for 18 months and then switched to DMAb for 18 months. The sample included 2 men and 38 women with a mean age of 74.5 (60-85) years. Twenty-five subjects had primary osteoporosis, and 15 had secondary osteoporosis. The mean number of osteoporotic vertebral fractures was 4.1. Serum bone turnover markers and BMD were evaluated every 6 months. RESULTS: Bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase 5b (TRACP5b), markers of bone formation and resorption respectively, were not significantly different in w-TPTD subjects at 18 months compared with those at baseline (p > 0.05), but BAP and TRACP5b in subjects treated with DMAb were significantly lower at 36 months compared with those at baseline (p < 0.05). BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH) increased by 12.3%, 2.5%, and 2.2% by 36 months with DMAb treatment, significantly higher than at baseline (p < 0.05). Changes in BMD of FN and TH in primary osteoporosis patients were significantly higher than in secondary osteoporosis patients at 18 months (w-TPTD) and 36 months (DMAb, p < 0.05). CONCLUSION: BMD significantly increased in osteoporosis patients switched from w-TPTD to DMAb. However, the impact of switching from w-TPTD to DMAb in secondary osteoporosis patients was not as great as in primary osteoporosis patients at the view points of changes in BMD of FN and TH.

Repeated freeze-thaw cycles reduce the survival rate of osteocytes in bone-tendon constructs without affecting the mechanical properties of tendons.

Frozen bone-patellar tendon bone allografts are useful in anterior cruciate ligament reconstruction as the freezing procedure kills tissue cells, thereby reducing immunogenicity of the grafts. However, a small portion of cells in human femoral heads treated by standard bone-bank freezing procedures survive, thus limiting the effectiveness of allografts. Here, we characterized the survival rates and mechanisms of cells isolated from rat bones and tendons that were subjected to freeze-thaw treatments, and evaluated the influence of these treatments on the mechanical properties of tendons. After a single freeze-thaw cycle, most cells isolated from frozen bone appeared morphologically as osteocytes and expressed both osteoblast- and osteocyte-related genes. Transmission electron microscopic observation of frozen cells using freeze-substitution revealed that a small number of osteocytes maintained large nuclei with intact double membranes, indicating that these osteocytes in bone matrix were resistant to ice crystal formation. We found that tendon cells were completely killed by a single freeze-thaw cycle, whereas bone cells exhibited a relatively high survival rate, although survival was significantly reduced after three freeze-thaw cycles. In patella tendons, the ultimate stress, Young's modulus, and strain at failure showed no significant differences between untreated tendons and those subjected to five freeze-thaw cycles. In conclusion, we identified that cells surviving after freeze-thaw treatment of rat bones were predominantly osteocytes. We propose that repeated freeze-thaw cycles could be applied for processing bone-tendon constructs prior to grafting as the treatment did not affect the mechanical property of tendons and drastically reduced surviving osteocytes, thereby potentially decreasing allograft immunogenecity.

Quality assessment for processed and sterilized bone using Raman spectroscopy.

To eliminate the potential for infection, many tissue banks routinely process and terminally sterilize allografts prior to transplantation. A number of techniques, including the use of scanning electron microscopy, bone graft models, and mechanical property tests, are used to evaluate the properties of allograft bone. However, as these methods are time consuming and often destroy the bone sample, the quality assessment of allograft bones are not routinely performed after processing and sterilization procedures. Raman spectroscopy is a non-destructive, rapid analysis technique that requires only small sample volumes and has recently been used to evaluate the mineral content, mineral crystallinity, acid phosphate and carbonate contents, and collagen maturity in human and animal bones. Here, to establish a quality assessment method of allograft bones using Raman spectroscopy, the effect of several common sterilization and preservation procedures on rat femoral bones were investigated. We found that freeze-thawing had no detectable effects on the composition of bone minerals or matrix, although heat treatment and gamma irradiation resulted in altered Raman spectra. Our findings suggest Raman spectroscopy may facilitate the quality control of allograft bone after processing and sterilization procedures.

Distribution of bone marrow-derived cells in the fracture callus during plate fixation in a green fluorescent protein-chimeric mouse model.

To clarify the distribution of bone-marrow-derived cells in fractures treated by plate fixation, fracture models were created using the green fluorescent protein (GFP) chimeric mouse. We observed 2 types of fracture healing processes with different types of callus formation and cellular events by using Mouse Fix™, a device allowing plate fixation on the mouse femur, and differences in the distribution of bone-marrow-derived cells between the 2 types. The GFP chimeric mice were created by bone marrow transplantation. Fractures were created on the left femurs of mice and stabilized with either rigid (Group R) or flexible (Group F) plates to prepare undecalcified fresh-frozen sections. In Group F, a large external callus and a large intramedullary callus were formed mostly by endochondral ossification. The cells that made up the intramedullary callus and callus in the fracture gap were GFP positive, but most cells of the external callus were not. In Group R, bone union was achieved mostly without external callus formation, bone apposition occurred directly in the gap, and a small intramedullary callus was formed. As observed in Group F, this group had GFP-positive cells in the callus within the fracture gap and in the intramedullary calluses. The results of this study provided direct evidence of the distribution of bone-marrow-derived cells in the callus of fractures treated by plate fixation under different stability conditions.