Abstract
ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.
Highlights
Bone injuries represent an important medical problem worldwide, producing significant healthcare and societal expenditure
There is a lack of multicentric, randomized clinical trials in the literature, capable of defining the value of current regenerative medicine strategies based on MSCs
Nonunions after long bone fractures are a challenging scenario to evaluate the efficacy of cell therapy or other competing technologies
Summary
Bone injuries represent an important medical problem worldwide, producing significant healthcare and societal expenditure. Since Weber and Cech (1976), quoted by Müller et al [6], atrophic nonunion is associated with poor vascularity and shows insufficient bone bridging to stabilize the fracture, insufficient bone biological activity in the fracture, and failure of previous treatments These require augmentation to procure bone healing, and the current standard treatment considered as the benchmark is autologous bone grafting, obtained from the same patient at a different surgical site and transplanted to the reconstruction site. The ORTHOUNION proposal focuses on testing the efficacy of expanded BM-hMSC in two different doses (100 and 200 × 106 cells), versus iliac crest bone autograft, the currently accepted standard therapy, to biologically augment surgical treatment of long bone nonunions
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