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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 86 - 86
22 Nov 2024
Lentini A Djoko J Putineanu D Tribak K Coyette M Yombi J Cornu O
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Aim. Bone infections often manifest with soft tissue complications such as severe scarring, fistulas, or ulcerations. Ideally, their management involves thorough debridement of infected bone and associated soft tissues, along with achieving stable bone structure, substantial tissue coverage, and long-term antibiotic therapy. The formation of a multidisciplinary team comprising orthopedic surgeons, plastic surgeons, and infectious disease specialists is essential in addressing the most complex cases. Method. We conducted a retrospective study during six years (2018-2023) at our university center. Focusing on the most challenging cases, we included patients with bone infections in the leg and/or foot requiring free flap reconstruction. Each patient underwent simultaneous bone debridement and reconstruction by the orthopedic team, alongside soft tissue debridement and free flap reconstruction by the plastic surgery team. Targeted antibiotic therapy for either 6 weeks (acute) or 12 weeks (chronic osteitis) was initiated based on intraoperative cultures. Additional procedures such as allografts, arthrodesis, or autografts were performed if necessary. We analyzed the rates of bone union, infection resolution, and limb preservation. Results. Forty-five patients were enrolled. Twenty-four patients (53.3%) had urgent indications (e.g., open infected fractures, osteitis, acute osteoarthritis, or wound dehiscence), while 21 (46.7%) underwent elective surgery (e.g., septic pseudarthrosis or chronic osteitis). Two patients underwent amputation due to flap failure (4.4%), and one patient was lost to follow-up. Follow-up of the remaining 42 patients averaged 28 months (range: 6–60 months). During this period, 35 patients (83.4%) experienced no recurrence of infection. Similarly, 35 patients (83.4%) achieved bone union. Overall, the rate of lower limb preservation was 93.3%. Conclusions. Managing bone infection coupled with soft tissue defects brings significant challenges. Although the majority of patients treated here belong to a complex framework based on the BACH classification, the outcomes achieved here appear to align with those of the simpler cases, thanks to optimal care with a dedicated septic ortho-plastic team. Our study demonstrates a notable success rate in treating infection, achieving bone consolidation, and preserving lower limb function


Bone & Joint Open
Vol. 5, Issue 8 | Pages 621 - 627
1 Aug 2024
Walter N Loew T Hinterberger T Alt V Rupp M

Aims

Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI.

Methods

A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint 360
Vol. 12, Issue 1 | Pages 36 - 39
1 Feb 2023

The February 2023 Trauma Roundup360 looks at: Masquelet versus bone transport in infected nonunion of tibia; Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multicentre randomized clinical trial; Is the T-shaped acetabular fracture really a “T”?; What causes cut-out of proximal femur nail anti-rotation device in intertrochanteric fractures?; Is the common femoral artery at risk with percutaneous fragility pelvis fixation?; Anterior pelvic ring pattern predicts displacement in lateral compression fractures; Differences in age-related characteristics among elderly patients with hip fractures.


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 11 - 16
1 Jan 2023
San-Julián M Gómez-Álvarez J Idoate MÁ Aquerreta JD Vázquez-García B Lamo-Espinosa JM

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 541 - 547
17 Aug 2022
Walter N Hierl K Brochhausen C Alt V Rupp M

Aims

This observational cross-sectional study aimed to answer the following questions: 1) how has nonunion incidence developed from 2009 to 2019 in a nationwide cohort; 2) what is the age and sex distribution of nonunions for distinct anatomical nonunion localizations; and 3) how high were the costs for surgical nonunion treatment in a level 1 trauma centre in Germany?

Methods

Data consisting of annual International Classification of Diseases (ICD)-10 diagnosis codes from German medical institutions from 2009 to 2019, provided by the Federal Statistical Office of Germany (Destatis), were analyzed. Nonunion incidence was calculated for anatomical localization, sex, and age groups. Incidence rate ratios (IRRs) were determined and compared with a two-sample z-test. Diagnosis-related group (DRG)-reimbursement and length of hospital stay were retrospectively retrieved for each anatomical localization, considering 210 patients.


Bone & Joint 360
Vol. 11, Issue 2 | Pages 37 - 41
1 Apr 2022


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims. Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. Methods. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation. Results. All rats tolerated the treatment well and no obvious adverse effects were found. By comparison, the HSR signal (three hrs/day) treatment group achieved the best healing outcome, in that endochondral ossification and bone consolidation were enhanced. In addition, HSR signal treatment (one one hr/day) had similar effects to treatment using the classic signal (three three hrs/day), indicating that treatment duration could be significantly shortened with the HSR signal. Conclusion. HSR signal may significantly enhance bone formation and shorten daily treatment duration in DO, making it a potential candidate for a new clinical protocol for patients undergoing DO treatments. Cite this article: Bone Joint Res 2021;10(12):767–779


Bone & Joint Open
Vol. 2, Issue 10 | Pages 825 - 833
8 Oct 2021
Dailey HL Schwarzenberg P Webb, III EB Boran SAM Guerin S Harty JA

Aims

The study objective was to prospectively assess clinical outcomes for a pilot cohort of tibial shaft fractures treated with a new tibial nailing system that produces controlled axial interfragmentary micromotion. The hypothesis was that axial micromotion enhances fracture healing compared to static interlocking.

Methods

Patients were treated in a single level I trauma centre over a 2.5-year period. Group allocation was not randomized; both the micromotion nail and standard-of-care static locking nails (control group) were commercially available and selected at the discretion of the treating surgeons. Injury risk levels were quantified using the Nonunion Risk Determination (NURD) score. Radiological healing was assessed until 24 weeks or clinical union. Low-dose CT scans were acquired at 12 weeks and virtual mechanical testing was performed to objectively assess structural bone healing.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 321 - 327
3 May 2021
Walter N Rupp M Hierl K Pfeifer C Kerschbaum M Hinterberger T Alt V

Aims. We aimed to evaluate the long-term impact of fracture-related infection (FRI) on patients’ physical health and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of FRIs of long bones was assessed. Methods. A total of 37 patients treated between November 2009 and March 2019, with achieved eradication of infection and stable bone consolidation after long bone FRI, were included. Quality of life was evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an International Classification of Diseases of the World Health Organization (ICD)-10 based symptom rating (ISR) and compared to normative data. Results. With a mean follow-up of 4.19 years (SD 2.7) after the last surgery, the mean SF-36 score was 40.1 (SD 14.6) regarding the physical health component and 48.7 (SD 5.1) regarding the mental health component, compared to German normative values of 48.4 (SD 9.2) (p < 0.001) and 50.9 (SD 8.8) (p = 0.143). The mean EQ-5D index reached 0.76 (SD 0.27) with a mean EQ-5D visual analogue scale (VAS) rating of 65.7 (SD 22.7) compared to reference scores of 0.88 (p < 0.001) and 72.9 (p < 0.001). Mean scores of the ISR did not reveal significant psychological symptom burden, while an individual analysis showed moderate to severe impairments in 21.6% (n = 8) of the patients. Conclusion. Even a mean 4.2 years (SD 2.7) after surgically successful treatment of FRI of long bones, patients report significantly lower quality of life in comparison to normative data. Future clinical studies on FRIs should focus on patient-related outcome measures enabling best possible shared treatment decision-making. Prevention methods and interdisciplinary approaches should be implemented to improve the overall quality of life of FRI patients. Cite this article: Bone Joint Res 2021;10(5):321–327


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 89 - 89
1 Dec 2019
Freischmidt H Titze N Rothhaas C Gühring T Reiter G Grützner PA Helbig L
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Aim. Treatment of infected and non-infected non-unions remain a major challenge after orthopedic fracture-related surgery. In clinical practice, several revision surgeries are usually required, including a radical debridement and exchange of implants, to control or even eradicate the infection to finally achieve bone healing. However, a clear treatment algorithm in clinical practice may be difficult to follow due to the heterogeneous patient population. Thus, so controlled settings for research purposes is better achieved in standardized animal studies. So far, there exists no multi-stage animal model that can be realistically transferred to the clinical situation in humans. The importance of such a model is obvious in order to be able to investigate different therapy concepts for infected and non-infected non unions. Methods. In 20 female Sprague-Dawley rats, a critical size defect by a femur osteotomy with 5 mm width was done. The periosteum at the fracture zone was cauterized proximal and distal to the osteotomy to achieve an hypovascularized situation. After randomization, 10 animals were intramedullary infected with a multisensible Staph. aureus strain (10. 3. CFU). After 5 weeks, a second surgery was performed with removing the K-wire, debridement of the osteotomy-gap and re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Additional micro-CT analysis, histological, and histomorphometric analysis were done to evaluate bone consolidation or delayed union, respectively, by the score of Lane and Sandhu and to quantify callus formation and the mineralized area of the callus. Results. 5 weeks after the first surgery a non-union had formed in all septic and aseptic animals. According to the Lane and Sandhu score a significantly higher callus formation was found in the infected group. In all infected animals, the inoculated Staph. aureus strain was detected during the revision surgery. 8 weeks after the second surgery no bone healing could be detected in the µ-CT analysis in both groups and biomechanical testing showed a significant lower maximum torque in both groups as compared to the untreated contralateral femura. Conclusion. Here we show first results of a new two-stage pseudarthrosis animal model, which reflects a very realistic clinical situation of an infection-related non-union model. Based on this model, various therapeutic strategies in the treatment of infectious and non-infectious pseudarthrosis, such as the use of bone substitutes, can be evaluated in further studies


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1168 - 1176
1 Sep 2019
Calder PR McKay JE Timms AJ Roskrow T Fugazzotto S Edel P Goodier WD

Aims

The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients.

Patients and Methods

A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 178 - 188
1 Feb 2019
Chaudhary MM Lakhani PH

Aims

Double-level lengthening, bone transport, and bifocal compression-distraction are commonly undertaken using Ilizarov or other fixators. We performed double-level fixator-assisted nailing, mainly for the correction of deformity and lengthening in the same segment, using a straight intramedullary nail to reduce the time in a fixator.

Patients and Methods

A total of 23 patients underwent this surgery, involving 27 segments (23 femora and four tibiae), over a period of ten years. The most common indication was polio in ten segments and rickets in eight; 20 nails were inserted retrograde and seven antegrade. A total of 15 lengthenings were performed in 11 femora and four tibiae, and 12 double-level corrections of deformity without lengthening were performed in the femur. The mean follow-up was 4.9 years (1.1 to 11.4). Four patients with polio had tibial lengthening with arthrodesis of the ankle. We compared the length of time in a fixator and the external fixation index (EFI) with a control group of 27 patients (27 segments) who had double-level procedures with external fixation. The groups were matched for the gain in length, age, and level of difficulty score.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 80 - 80
1 Nov 2018
Li G
Full Access

Distraction histogenesis (DH) techniques have been widely accepted and practiced in orthopaedics, traumatology, and craniofacial surgery over the last two decades. Using DH methods, many previously untreatable conditions have been successfully managed with outstanding clinical outcomes. The biological mechanisms underlying DH have been studied and the tension-stress principles of tissue regeneration are attributed to upregulated gene expression, enhanced cell proliferation, angiogenesis and tissue remodelling and endogenous stem cell mobilization. The new methods of enhancing bone consolidation in DH are proposed and need further clinical studies. The novel applications of DH have now been extended for the treatment of vascular diseases, cranial defect (with neuronal disorders), hip and spinal deformity corrections and soft-tissue defects in addition to various bone defects and deformities. There are more surprises and novel mechanisms yet to be discovered for these novel applications of DH


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 117 - 117
1 Nov 2018
Tazawa R Minehara H Matsuura T Kawamura T Uchida K Inoue G Shoji S Sakaguchi N Takaso M
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Segmental bone transport (SBT) with an external fixator has become a standard method for treatment of large bone defect. However, a long time-application of devices can be very troublesome and complications such as nonunion is sometimes seen at docking site. Although there have been several studies on SBT with large animal models, they were unsuitable for conducting drug application to improve SBT. The purpose of this study was to establish a bone transport model in mice. Six-month-old C57BL/6J mice were divided randomly into bone transport group (group BT) and an immobile control group (group EF). In each group, a 2-mm bone defect was created in the right femur. Group BT was reconstructed by SBT with external fixator (MouseExFix segment transport, RISystem, Switzerland) and group EF was fixed simply with unilateral external fixator (MouseExFix simple). In group BT, a bone segment was transported by 0.2 mm per day. Radiological and histological studies were conducted at 3 and 8 weeks after the surgery. In group BT, radiological data showed regenerative new bone consolidation at 8 weeks after the surgery, whereas high rate of nonunion was observed at the docking site. Histological data showed intramembranous and endochondral ossification. Group EF showed no bone union. In this study, experimental group showed good regenerative new bone formation and was similar ossification pattern to previous large animal models. Thus, the utilization of this bone defect mice model allows to design future studies with standardized mechanical conditions for analyzing mechanisms of bone regeneration induced by SBT


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 69 - 69
1 Apr 2018
VIDAL S CASTILLO I
Full Access

Background. Despite the known multifactorial nature of scaphoid wrist fracture non-union, a possible genetic predisposition for the development of this complication remains unknown. This pilot study aimed to address this issue by performing Single Nucleotide Polymorphisms (SNPs) analysis of specific genes known to regulate fracture healing. Materials and Methods. We reviewed 120 patients in a retrospective case-control study from the Hand Surgery Department of Asepeyo Hospital. The case group comprised 60 patients with confirmed scaphoid wrist non-union, diagnosed by Magnetic Resonance Imaging (MRI) and Computed Tomography (CT). The control group comprised 60 patients with scaphoid fracture and complete bone consolidation. Sampling was carried out with a puncture of a finger pad using a sterile, single-use lancet. SNPs were determined by real-time polymerase chain reaction (PCR) using specific, unique probes with the analysis of the melting temperature of hybrids. The X2 test compared genotypes between groups. Multivariate logistic regression analysed the significance of many covariates and the incidence of scaphoid wrist non-union. Results. We found significant differences in subjects who had a smoking habit (p=0.001), high blood pressure (p<0.001), and surgical treatment (p=0.002) in patients with scaphoid non-union. There were more Caucasians (p=0.04) and males (p=0.001) in the case group. Falls were the main mechanism of fracture. The CC genotype in GDF5 (rs143383) was more frequent in patients with scaphoid non-union compared to the controls (p=0.02). CT was prevalent in the controls (p=0.02). T allele in GDF5 was more frequent in patients without non-union (p=0.001). Conclusions. Individuals who were carriers of the CC genotype in GDF5 showed higher susceptibility to suffering scaphoid wrist non-union. Furthermore, being a carrier of CT and T allele suggests that this could be behave as a protection factor against non-union. This is the first clinical study to investigate the potential existence of genetic susceptibility to scaphoid wrist fracture non-union. Level of evidence. Level III, Cross Sectional Study, Epidemiology Study


Bone & Joint Research
Vol. 7, Issue 3 | Pages 232 - 243
1 Mar 2018
Winkler T Sass FA Duda GN Schmidt-Bleek K

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration.

Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 385 - 390
1 Jun 2017
Yang Y Lin S Wang B Gu W Li G

Objectives. Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods. We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results. Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion. The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 35 - 35
1 Apr 2017
Ciapetti G Fotia C Granchi D Rojewski M Rosset P Gómez-Barrena E Baldini N
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Background. Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. Within the REBORNE project, a multi-center orthopaedic clinical trial was focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union. Methods. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-ups (6, 12 and 24 weeks post-surgery). Results. A significant relationship with age was found only at Visit 6, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the starting value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with negative outcome. The BTM profile indicated remarkable bone formation activity after 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome. Conclusion. BTM related to bone cell function are useful to measure the efficacy of a regenerative approach based on expanded MSC. Level of evidence. Diagnostic Level IV. Work supported by the EC, Seventh Framework Programme (FP7), through the REBORNE Project, grant agreement no. 241879


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_2 | Pages 11 - 11
1 Jan 2017
Ciapetti G Granchi D Barrena EG Rojewski M Rosset P Layrolle P Donati D Spazzoli B Baldini N
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Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. The REBORNE project entailed a multi-center orthopaedic clinical trial focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial, to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union. Peripheral blood was collected from patients at fixed time-endpoints, that is at 6,12 and 24 weeks post-surgery for implantation of expanded autologus MSC and bone-like particles. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-up visits. A significant relationship with age was found only at 6 months, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the baseline value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with a negative outcome. The BTM profile apparently indicated a remarkable bone formation activity 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome. Blood markers related to bone cell function are useful to measure the efficacy of a expanded MSC-regenerative approach applied to long bone non-unions. Changes of the markers may provide a support to radiological assessment of bone healing