Greater Amounts Of Bone Research Articles

VEGF with AMD3100 endogenously mobilizes mesenchymal stem cells and improves fracture healing.

ABSTRACTA significant number of fractures develop non‐union. Mesenchymal stem cell (MSC) therapy may be beneficial, however, this requires cell acquisition, culture and delivery. Endogenous mobilization of stem cells offers a non‐invasive alternative. The hypothesis was administration of VEGF and the CXCR4 antagonist AMD3100 would increase the circulating pool of available MSCs and improve fracture healing. Ex‐breeder female wistar rats received VEGF followed by AMD3100, or sham PBS. Blood prepared for culture and colonies were counted. P3 cells were analyzed by flow cytometry, bi‐differentiation. The effect of mobilization on fracture healing was evaluated with 1.5 mm femoral osteotomy stabilized with an external fixator in 12–14 week old female Wistars. The mobilized group had significantly greater number of cfus/ml compared to controls, p = 0.029. The isolated cells expressed 1.8% CD34, 35% CD45, 61% CD29, 78% CD90, and differentiated into osteoblasts but not into adipocytes. The fracture gap in animals treated with VEGF and AMD3100 showed increased bone volume; 5.22 ± 1.7 µm3 and trabecular thickness 0.05 ± 0.01 µm compared with control animals (4.3 ± 3.1 µm3, 0.04 ± 0.01 µm, respectively). Radiographic scores quantifying fracture healing (RUST) showed that the animals in the mobilization group had a higher healing score compared to controls (9.6 vs. 7.7). Histologically, mobilization resulted in significantly lower group variability in bone formation (p = 0.032) and greater amounts of bone and less fibrous tissue than the control group. Clinical significance: This pre‐clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non‐union fractures. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:1294–1302, 2019.

Tissue Segregation Enhances Calvarial Osteogenesis in Adult Primates

Calvarial defects of adult mammals have a limited potential for regeneration. Osteogenesis may be impaired by the intrusion within the defect of nonosteogenic tissues during healing, which inhibits centripetal bone deposition from the margins of the defects. Using a primate model, we evaluated bone regeneration in calvarial defects treated with demineralized bone matrix versus defects treated according to the strategy of guided tissue regeneration. Sixty-four defects, 25 mm in diameter, were prepared in 16 adult male baboons (Papio ursinus). In each animal, 2 contralateral defects were covered with a template of porous polymer, 35 mm in diameter. Templates were positioned over the calvarial margins to prevent penetration of the pericranium and the temporalis muscle within the defects, thus maintaining tissue segregation during healing. The third defect was implanted with allogeneic demineralized bone matrix, as positive control. The fourth defect was left untreated and was used as negative control. Undecalcified bone sections (7 microns thick) were prepared from the harvested specimens 3 and 6 months after surgery. Although untreated defects showed limited osteogenesis after fusion of the pericranium with the dura, defects covered with the polymeric template often showed extensive bone deposition extending centripetally from the margins of the craniotomies. Histomorphometry demonstrated that defects treated with demineralized bone matrix and defects covered with the polymeric template had greater amounts of bone and osteoid when compared with untreated defects (p < 0.01). At 6 months, greater amounts of bone formed in demineralized bone matrix-treated defects when compared with defects covered with the polymeric template (p < 0.01). The results of this study show that calvarial membranous bones of adult primates retain the potential to regenerate when segregation between the different tissue components participating in the healing of the wound is maintained. In the same model, however, implantation of allogeneic demineralized bone matrix, used as a positive control provided the most effective treatment for the defects.

Heterotopic Bone After Hip Arthroplasty Defining the Patient at Risk

Periarticular heterotopic bone (HB) formation after hip arthroplasty can be prevented by indomethacin or radiation. It is therefore important to identify patients at risk. The authors analyzed 124 consecutive cases of primary total hip arthroplasty (THA) performed by the same trans-trochanteric operative approach in 124 patients. Heterotopic bone occurred more often in men (84%) than in women (67%), and greater amounts of bone were formed in men. On anteroposterior (AP) roentgenographs, the median area of projected HB in men was 24.7 cm2 and 0.69 cm2 in women. Heterotopic bone was less common in patients with polyarthritis compared with patients with osteoarthrosis. In women with osteoarthrosis, old age was associated with the occurrence of HB; women older than 65 years of age had 0.70 cm2 of HB on AP roentgenographs (mean), whereas those younger than 65 years had 0.18 cm2. Hypertrophic osteoarthrosis was more common in men, but associated with HB only in women. Women with hypertrophic osteoarthrosis developed the same amount of HB as men with osteoarthrosis. Men with osteoarthrosis or sequelae after fractures, older women with osteoarthrosis, and women with hypertrophic osteoarthrosis should be considered for prophylactic treatment against HB formation after a THA.