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Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

ABSTRACT: Proximal humerus fractures are common in an aging population. The standard operative treatment is open reduction internal fixation (ORIF) using an angular stable plate. However, this procedure has complications such as a relatively high rate of secondary dislocation, humeral head necrosis or nonunion caused by delayed bony consolidation. Autologous bone marrow mononuclear cells (BMC) combined with a β-TCP scaffold could support bone healing and is considered clinically safe. This multicentric, randomized, open phase IIa clinical trial (Clinical Trials. Gov Identifier: NCT02803177, Eudra CT No: 2015-001820-51) evaluated whether autologous BMC with β-TCP in addition to ORIF reduces the incidence of secondary dislocations in patients with proximal humerus fracture. Ninty-four patients equally divided between verum group (BMC+β-TCP) and control group (ß-TCP only) were targeted and calculated. At the time of planned interim evaluation, ie, enrolment of 56 patients, no statistical difference in secondary dislocations or complications was demonstrated in either group after an observation period of 12 weeks. Radiographic bone healing and DASH score to determine shoulder function were comparable between both groups. Bone marrow harvest and BMC transplantation did not result in any severe adverse events. Therefore, the study was terminated after the interim analysis, as no other result could be expected. From the study results, it can be concluded that the application of autologous BMC is well tolerated, and bone healing can be achieved. Augmentation of bone defects with β-TCP could be shown to be feasible and might be considered in other clinical situations.

SUBMITTER: Seebach C

PROVIDER: S-EPMC10785220 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

Seebach Caroline C Nau Christoph C Henrich Dirk D Verboket Rene R Bellen Marlene M Frischknecht Nadine N Moeck Vivien V Eichler Kathrin K Horlohé Kay Hajo Schmidt KHS Hoffmann Reinhard R Bonig Halvard H Seifried Erhard E Frank Johannes J Marzi Ingo I

Stem cells translational medicine 20240101 1

Proximal humerus fractures are common in an aging population. The standard operative treatment is open reduction internal fixation (ORIF) using an angular stable plate. However, this procedure has complications such as a relatively high rate of secondary dislocation, humeral head necrosis or nonunion caused by delayed bony consolidation. Autologous bone marrow mononuclear cells (BMC) combined with a β-TCP scaffold could support bone healing and is considered clinically safe. This multicentric, r ...[more]

PMID: 37995325

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Project description:BackgroundLocal implantation of ex vivo concentrated, washed and filtrated human bone marrow-derived mononuclear cells (BMC) seeded onto β-tricalciumphosphate (TCP) significantly enhanced bone healing in a preclinical segmental defect model. Based on these results, we evaluated in a first clinical phase-I trial safety and feasibility of augmentation with preoperatively isolated autologous BMC seeded onto β-TCP in combination with angle stable plate fixation for the therapy of proximal humeral fractures as a potential alternative to autologous bone graft from the iliac crest.Methods10 patients were enrolled to assess whether cell therapy with 1.3 × 106 autologous BMC/ml/ml β-TCP, collected on the day preceding the definitive surgery, is safe and feasible when seeded onto β-TCP in patients with a proximal humeral fracture. 5 follow-up visits for clinical and radiological controls up to 12 weeks were performed.Resultsβ-tricalciumphosphate fortification with BMC was feasible and safe; specifically, neither morbidity at the harvest site nor at the surgical wound site were observed. Neither local nor systemic inflammation was noted. All fractures healed within the observation time without secondary dislocation. Three adverse events were reported: one case each of abdominal wall shingles, tendon loosening and initial screw perforation, none of which presumed related to the IND.ConclusionsCell therapy with autologous BMC for bone regeneration appeared to be safe and feasible with no drug-related adverse reactions being described to date. The impression of efficacy was given, although the study was not powered nor controlled to detect such. A clinical trial phase-II will be forthcoming in order to formally test the clinical benefit of BMC-laden β-TCP for PHF patients. Trial registration The study was registered in the European Clinical Trial Register as EudraCT No. 2012-004037-17. Date of registration 30th of August 2012. Informed consent was signed from all patients enrolled.

Project description:BackgroundProximal humerus fracture is the third most common fracture type after hip and distal radius fracture in elderly patients. A comprehensive study by Palvanen et al. demonstrated an increase in the annual fracture rate of 13.7% per year over the past 33 years. Should this trend continue, the fracture rate would triple over the next three decades. The increasing incidence of low-energy fractures raises questions about the optimal treatment in terms of functional outcome, pain, and rehabilitation time, as well as the economical impact. Despite the high incidence and costs of proximal humerus fractures, there is currently no valid scientific evidence for the best treatment method. Several publications, including a Cochrane review outline the need for high-quality, well-designed randomized controlled trials.Methods/designThe study is a prospective, randomized, national multi-center trial. The hypothesis of the trial is that surgical treatment of displaced proximal humerus fractures achieves better functional outcome, pain relief, and patient satisfaction compared to conservative treatment. The trial is designed to compare conservative and surgical treatment of proximal humerus fractures in patients 60 years and older. The trial includes two strata. Stratum I compares surgical treatment with locking plates to conservative treatment for two-part fractures. Stratum II compares multi-fragmented fractures, including three- and four-part fractures. The aim of Stratum II is to compare conservative treatment, surgical treatment with the Philos locking plate, and hemiarthroplasty with an Epoca prosthesis. The primary outcome measure will be the Disabilities of the Arm, Shoulder and Hand (DASH) score and the secondary outcome measures will be the EuroQol-5D (EQ-5D) value, OSS, Constant-Murley Score, VAS, and 15D.Recruiting time will be 3 years. The results will be analyzed after the 2-year follow-up period.DiscussionThis publication presents a prospective, randomized, national multi-center trial. It gives details of patient flow, randomization, aftercare and also ways of analysis of the material and ways to present and publish the results.Trial registrationClinicalTrials.gov identifier: NCT01246167.

Project description:BACKGROUND:Treating proximal humerus fractures can be challenging because of large metaphyseal defects that conceal anatomical landmarks. In such cases, medial cortical support with, for example, calcar screws, is mandatory. Nevertheless, varus dislocations and implant failures in patients with impaired bone quality persist. Thus, the need for effective treatment of these patients exists. Hybrid double plate osteosynthesis was introduced as an alternative, yielding similar results as calcar screws. However, a biomechanical comparison of the stability of these two techniques is pending. METHODS:Cadaveric humeral specimens were treated with plate osteosynthesis and calcar screws (group 1, n = 9) or hybrid double plate osteosynthesis (group 2, n = 9) using a proximal humerus fracture model with a two-part fracture. Displacement, stiffness, failure mode, and ultimate load were examined biomechanically in a cyclic compressive-loading scenario. RESULTS:Although the hybrid double plate osteosynthesis (group 2) tended to confer higher stiffnesses than the medial support screws at higher cycles (group 1), this trend was below the level of significance. The displacement revealed non-significantly lower values for group 1 as compared with group 2 for cycles 50 and 2000, but at 5000 cycles, group 2 offered non-significantly lower displacement values than group 1. The ultimate load tended to be non-significantly higher in the hybrid double plate osteosynthesis group (group 2: 1342±369 N, group 1: 855±408 N). Both groups yielded similar failure rates, with the majority of failures in group 2 being gap closures (n = 8), whereas those in group 1 being plate dislocations (n = 4). CONCLUSIONS:The use of an additive plate osteosynthesis in the region of the bicipital groove may be a potential alternative to the previously-established method of using calcar screws. The biomechanical data obtained in this study suggests that hybrid double plate osteosynthesis is as rigid and robust as calcar screws.

Dataset Information

Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

Publications

Cell-Based Therapy by Autologous Bone Marrow-Derived Mononuclear Cells for Bone Augmentation of Plate-Stabilized Proximal Humeral Fractures: A Multicentric, Randomized, Open Phase IIa study.

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