Читать книгу Fractures in the Horse - Группа авторов - Страница 159

Osteobiologics is an emerging field of study in all species [62]. Various blood products, cellular treatments and growth factors are included in this group. Each have shown some positive effect on bone healing when dissecting the reams of literature around their use.

The two main blood products used in horses that have potential for use in fracture management are interleukin‐1 receptor antagonist protein (IRAP) and platelet‐rich plasma (PRP). IRAP is usually used as an intra‐articular medication, and for fractures involving the joint in which articular cartilage damage is present, there is a logic to use. The author is unaware of intralesional IRAP use in fractures.

PRP has been suggested as a product that could be applied at fracture sites [63]. Analysis of data does not provide convincing proof of efficacy, but various experimental and clinical studies suggest that it has promise, especially in light of the critical role of the clotting cascade in fracture healing. PRP is defined as a blood derivative where the platelet concentration is above baseline levels. It is meant to provide high concentrations of growth factors that are presumed to be anabolic to healing of any tissue. Several studies have shown positive effects including evidence for antimicrobial activity of platelet lysate [64]. In a meta‐analysis of PRP use, 91% of studies showed positive effects; histologic assessment of positive outcome reduced this to 84%, and radiological and biomechanical analyses dropped the positive benefit to 75 and 73%, respectively. Potential use of PRP in bone defects therefore continues to be debated [63].

Cellular product such as mesenchymal stem cells have been advocated to enhance fracture healing. Mesenchymal stem cells can be acquired from many tissues, but for fracture management they are generally obtained from bone marrow. In horses, bone‐marrow‐derived stem cells have been used in multiple tissues, but beneficial effects in fractures have not been proven. In experimental studies in other species, positive effects have been seen using bone marrow injections alone [65]. Bone marrow aspirate has been clinically evaluated and found to have positive effects [66], and bone marrow grafting has been shown to be successful for treating non‐unions in human patients [67]. Autologous, culture‐expanded mesenchymal stem cells have been reported in clinical studies or case reports in people. Most of these have been combined with scaffolds to create a cell–scaffold composite which in itself has been challenging. Healing of large cortical bone defects have been reported, but use in clinical cases has not yet been defined. Bone marrow aspirate, bone marrow aspirate concentrate and culture‐expanded mesenchymal stem cells have been used for non‐unions, osteotomies, distraction osteogenesis, spinal fusion and fractures; although the outcomes appear positive, more work is needed [68].

In the horse, there is experimental evidence supporting use of stem cells in bone healing. Stem cells loaded onto a tricalcium phosphate (TCP) implant with BMP improved healing in a third metacarpal bone defect model [69]. Others have shown no improvement in healing with osteoprogenitor cells in fibrin glue [70]. A review of the field has provided basic discussion around the theoretical use of stem cells to augment fracture healing, but critical experimental and clinical work around the best cell type, application method and matrix carrier is needed before recommendations can be made [71].

Growth factors have been used in human, and in some cases of equine, fracture repair. BMP has been most highly studied to date. BMP2 is known to stimulate progenitor cells to differentiate into osteoblasts, and BMP7 is known to stimulate angiogenesis. There is good clinical information in humans, although ectopic bone formation and high price are negative factors to its use [72]. In an experimental equine model, no significant increase in healing from BMP2/7 gene therapy application was seen [73]. FGF has also been shown to stimulate progenitor cell differentiation and angiogenesis. VEGF is initially released from the haematoma and promotes development of endothelial cells and vascular invasion and may be secreted by chondrocytes within callus to stimulate angiogenesis and new bone formation. Parathyroid hormone (PTH) has been shown to produce increased bone mass, bone strength and reduced bone loss, especially in cases of osteoporosis. Although PTH can stimulate fracture healing, it does not appear to act as a differentiation factor and may not be effective if the early stages of fracture healing are not optimized. Exogenous PTH has been found to be safe in horses [74]. PTH has also been implanted within a fibrin matrix into an equine subchondral bone cyst with a positive effect [75].

Overall, the use of exogenous growth factors appears logical, but a cost versus potential benefit debate is necessary before deciding on use.