Emerging Options for Biologic Enhancement of Stress Fracture Healing in Athletes

Timothy L. Miller, MD; Christopher C. Kaeding, MD; Scott A. Rodeo, MD


J Am Acad Orthop Surg. 2020;28(1):1-9. 

In This Article

Concentrated Bone Marrow Aspirate

Concentrated bone marrow aspirate is a biologic treatment that uses an individual's own mesenchymal stromal cells to stimulate bone healing. The local application of bone marrow aspirate concentrate (BMAC) for the treatment of delayed healing is a promising alternative to autogenous bone grafting and may help to reduce donor site morbidity, although rigorous data on its efficacy are currently lacking.[8] Osteoblastic progenitor cells are available in the bone marrow aspirate of the iliac crest, proximal tibial metaphysis, and calcaneus (Figure 2), with the iliac crest providing the highest yield of osteoblastic progenitor cells.[9] A review of in vivo studies on the use of BMAC for the treatment of segmental bone defects in animal long bones indicated markedly increased torsional stiffness in BMAC-treated defects and earlier bone healing on histologic evaluation when BMAC was applied.[10]

Figure 2.

Image showing bone marrow (A) aspirated from the calcaneus with the use of a 30-mL syringe. Intraoperative AP fluoroscopy image (B) of the left fifth metatarsal as bone marrow aspirate concentrate is injected percutaneously into the intramedullary canal at the site of a proximal metaphyseal delayed union. C, Intraoperative photograph of concentrated bone marrow aspirate mixed with calcium chloride being injected into a proximal fifth metatarsal delayed union site.

Autologous BMAC injection has been shown to improve bone healing in distraction osteogenesis of the tibia.[11] Multiple authors have advocated its use in the management of fractures at high-risk sites because it can be applied in multiple ways. These include percutaneous injection to the surface of the bone, intramedullary injection with or without demineralized bone matrix, and after core decompression at metaphyseal sites. A systematic review by Imam et al[12] concluded that the most common BMAC applications for bone include enhancement of healing of fractures, nonunions, and bone defects. The same study, however, concluded that standardization of commercial processing of the material has yet to be optimized to assure consistency of the final product.[12] Murawski and Kennedy[13] demonstrated that percutaneous screw fixation of acute proximal fifth metatarsal fractures augmented with BMAC provided predictable healing results while permitting athletes a return to sport at their previous levels of competition at a mean of 5 weeks postsurgery with few complications. In addition, augmentation of femur fracture fixation with autologous BMAC has shown a trend toward decreased time to union.[14] It should be noted that although multiple studies using BMAC for sports-related fractures including stress fractures among elite athletes have shown shorter healing times than those previously reported without its use, no controlled comparative study has been published on this topic. Although there are some early data to support a role for BMAC in bone healing, it must be understood that the number of true stem cells by formal criteria is very low in currently available minimally manipulated formulations available in the United States.[15–17] It is critically important to distinguish minimally manipulated cell preparations from sorted, culture-expanded, laboratory-prepared cells. The current FDA regulations do not permit ex vivo cell sorting and subsequent culture to isolate and expand the quantity of stem cells. In fact, some have suggested that the term stem cell be abandoned in favor of connective tissue progenitors to make clear that current techniques used by clinicians in the United States contain very few stem cells. Connective tissue progenitors are defined as a heterogeneous population of tissue resident cells that can proliferate and generate progeny with the capacity to differentiate into one or more connective tissues. These cells are present in many tissues including adipose tissue and possess a limited capacity for tissue repair and osteogenic differentiation.[18] However, connective tissue progenitors do not possess the characteristics of self-renewal and the ability to reconstitute all of the parenchymal cells of a specific tissue, and thus should be distinguished from a pluripotent stem cell.