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During the past few decades, significant advances have been made in the treatment of proximal humerus fractures. Nonetheless, their management remains controversial. T his article describes the key points for decision-making and the currents trends in the treatment of complex proximal humeral fractures. T he surgeon should define the fracture pattern and decide whether surgical intervention will benefit the patient. Furthermore, the preoperative plan needs to evaluate whether the viability of the humeral head can be preserved and proximal humeral anatomy can be restored. Osteosynthesis can be accomplished by various means, including open transosseous sutures, percutaneous fixation, conventional plating, intramedullary nailing, and locking plates. T he latter have gained considerable popularity over the last few years because they address the issue of poor bone stock in elderly patients. Furthermore, prosthetic replacement with either hemiarthroplasty or the more recently introduced reverse total shoulder arthroplasty offers an option in difficult cases that need surgical treatment and are unsuitable for open reduction-internal fixation. Nonetheless, the superiority of any technique has not yet been proven in the clinical setting. [ABSTRACT FROM AUTHOR]

Bone healing represents a physiological process of repair and restoration of function. Recent advances in a variety of medical disciplines have enabled scientists and clinicians to characterise this phenomenon at the molecular level. A number of molecular mediators and cells interact utilising different pathways. Despite the involvement of many local and systemic factors failure of the naturally occurring mechanisms can occur leading to either delayed union or non-union. This review article is focused on the recent understanding of the mechanisms governing the bone repair process. [ABSTRACT FROM AUTHOR]

Summary: The ideal management of complex proximal humeral fractures continues to be debatable. Evolution of proximal humeral fracture management, during the past decade, led to the implementation of many innovations in surgical treatment. Even though the pendulum of treatment seems to swing towards new trends such as locked plating, hemiarthroplasty remains a valid and reliable option that serves the patient''s needs well. Hemiarthroplasty is indicated for complex proximal humeral fractures in elderly patients with poor bone stock and when internal fixation is difficult or unreliable. Hemiarthroplasty provides a better result when it is performed early post-injury. Stem height, retroversion and tuberosity positioning are technical aspects of utmost importance. Additionally reverse total shoulder arthroplasty is an alternative new modality that can be used as a primary solution in selected patients with proximal humeral fracture treatment. Failed hemiarthroplasty and fracture sequelae can be successfully managed with reverse total shoulder arthroplasty. Individual decision-making and tailored treatment that takes into consideration the personality of the fracture and the patient''s characteristics should be used. [Copyright &y& Elsevier]

Summary: Patients’ perspectives in clinical research have become increasingly interesting and important. Much effort has recently been made to understand, evaluate and promote the patients’ active roles in and unique views on their involvement in clinical research, and how these may help resolve old and new problems in research planning, conduct and implementation. In this article issues regarding informed consent, differences between medical care and medical research, confidentiality, conflicts of interest and disclosure of study results are considered from the patients’ point of view. [Copyright &y& Elsevier]

Summary: PubMed and Ovid Medline were searched to investigate the role of intramedullary nailing in the treatment of diaphyseal humeral non-union. Of 474 abstracts, 9 retrieved articles fulfilled our inclusion criteria and described management in 166 cases of humeral shaft non-union using several types of intramedullary nails. Union ranged from 40 to 100%; part of the variation could be explained by the quality index of the selected articles. Exchange nailing alone was not effective. Exposure of the fracture site and use of bone grafting were key to successful treatment. The total incidence of severe complications, including radial nerve damage, was very low. Thus, intramedullary nailing in the treatment of humeral shaft non-unions can lead to successful outcomes when associated with autologous bone grafting. [Copyright &y& Elsevier]

Examines the position of the axillary nerve in relation to the upper border of the muscle. Vertical distances from the upper deltoid border to the nerve; Correlation between the deltoid ratio and the vertical distance; Role of deltoid dimensions in the estimation of the nerve position.

This text provides a historical overview of the development of orthopaedics in Greece, focusing on the contributions of three influential doctors: Ioannis Chrysospathis, Theodoros Garofalidis, and Georgios Hartofilakidis. Chrysospathis played a key role in establishing orthopaedics as a medical specialty in Greece, while Garofalidis and Hartofilakidis made significant contributions to the field through their research, publications, and leadership positions. Their work helped shape the modern practice of orthopaedics in Greece. [Extracted from the article]

A letter to the editor is presented in response to the article "Is There a Safe Area for the Axillary Nerve in the Deltoid Muscle? A Cadaveric Study," by Ozgur Cetik and Murad Uslu in a previous issue.

Summary: Necrotising fasciitis is a rapidly progressive, life threatening soft tissue infection. In a significant proportion of patients, the extremities are involved as a result of trauma, needle puncture or extravasation of drugs, often leading to limb loss and devastating disability. In this systematic review of necrotising fasciitis of the upper and lower extremities, we report on the clinical characteristics, the predisposing factors, the associated diseases, the pathogenic bacteria, the surgical treatment and the final outcome in terms of limb loss and mortality. Data for a total of 451 patients were analysed for each parameter of interest. A percentage of 22.3% of the reviewed patients underwent amputation or disarticulation of a limb following failure of multiple debridements to control infection and the mortality rate was estimated as high as 21.9%. [Copyright &y& Elsevier]

Summary: Successful operative treatment of a humeral shaft non-union may be a challenge for the surgeon. Several treatment options have been reported over the years. A systematic review of the literature was performed. Twenty-three retrieved articles (level of evidence IV) fulfilled our inclusion criteria and dealt with aseptic diaphyseal humeral non-union managed by plating, intramedullary nailing and external fixation based on Ilizarov''s principles. Despite an obvious superiority of plating in the treatment of humeral shaft non-unions, there is no doubt that intramedullary nailing as well as external fixation devices have a role. An algorithm of management of the humeral shaft non-unions following a rational approach is suggested. [Copyright &y& Elsevier]

Summary: Few data are available in the literature regarding fat embolism in cases of bilateral femoral and pathological femoral fractures. The incidence of bilateral femoral fractures ranges from 2–9.5% of the total number of patients with femoral fractures, and they usually occur in high energy trauma and multitrauma patients. Although injury severity scores tend to underestimate the severity of these injuries, fat embolism seems to occur in increased frequency ranging from 4.8–7.5%. Intramedullary nailing, which is the preferred surgical treatment, triggers a systemic inflammatory response that poses an additional burden to pulmonary function. In addition, the femur is a common site of metastatic bone disease. The treatment of impending and actual pathological fractures is complicated by increased rates of lung damage due to various factors. Fat embolism during treatment—mainly with intramedullary nails—generally seems to range from 0–10%. [Copyright &y& Elsevier]

Abstract: Aim: In order to assess the effect of osteoporosis on healing time, the files of 165 patients with femoral shaft fractures that were treated in our institution with locked-reamed intramedullary nailing were retrospectively reviewed. Patients and methods: Patients with open fractures, pathological fractures, revision surgery, severe brain injuries and prolonged ITU stay were excluded. In all patients the Singh-index score for osteoporosis and the canal bone ratio (CBR) were assigned. Sixty-six patients fulfilled the inclusion criteria. Patients were divided into two groups; group A (29 patients) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (37 patients) of patients between 18 and 40 years old with no signs of osteoporosis. Results: In all group A patients Singh score ≤4 and CBR>0.50 were assigned, suggesting the presence of osteoporosis, whereas all group B patients were assigned with Singh score ≥5 and CBR<0.48. Fractures of group A healed in 19.38±5.9 weeks (12–30) and in group B 16.19±5.07 weeks (10–28), P =0.02. Conclusions: Fracture healing of nailed femoral diaphyseal fractures is significantly delayed in older osteoporotic patients. Further studies are required to clarify the exact impact of osteoporosis in the whole healing process. [Copyright &y& Elsevier]

Abstract: Aims and objectives: To measure long-term functional outcome and health-related quality of life following tibial fracture in association with the full spectrum of soft tissue injury. Methods: One hundred and thirty patients with different types of tibial injury were selected from our trauma database. This included 33 patients with compartment syndrome (no underlying fracture), 30 with closed diaphyseal tibial fractures, 45 with grade IIIB/IIIC open fractures and 22 requiring below knee amputation. Mean time to final follow-up was 37.4 months. The EQ-5D (EuroQol) questionnaire was used to assess these patients at this point. Patients had been treated according to standard unit protocols. Open fractures were jointly managed under the care of local plastic and orthopaedic surgeons using a policy of obtaining early soft tissue cover. Results: Patients with reconstructed IIIB fractures reported problems with pain and carrying out their normal activities more frequently than amputees whilst still reporting problems with mobility just as frequently. Anxiety and depression were more common in the patients with open fractures and amputees as were problems with self-care, though the latter were unusual overall. Stepwise logistic regression revealed that tibial injury type was significantly predictive of all measured outcomes except self-care (p <0.0001). Age, ISS, sex and time to follow-up were not significant predictors of response. Conclusions: These results show that patients with these injuries still report long-term problems with their health-related quality of life, though to varying degrees. This information is useful when determining the treatment options for these patients and it is important that it is shared with the patient prior to surgery where possible. [Copyright &y& Elsevier]

Reamed intramedullary nailing (RIN) is a surgical method of choice for treatment of diaphyseal fractures. This procedure affects the biological environment of bone tissue locally and systemically. This study investigated the influence of RIN on mesenchymal stem cells (MSCs) in patients with long bone fractures. The axis of C-X-C motif chemokine receptor 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) was selected since it is considered as major pathway for MSC homing and migration. Iliac crest bone marrow (IC-BM) samples and blood samples were collected at two different time points. One sample was collected before the RIN (BN) and the other immediately after RIN (AN). BM-MSCs were cultured and RT-qPCR was performed for CXCR4 mRNA levels and ELISA for the SDF-1 sera levels. The experimental study revealed that there was a correlation between the increase of SDF-1 levels in peripheral blood and a decrease in the levels of CXCR4 in MSCs in the IC-BM following RIN. The levels of SDF-1 showed a significant increase in the sera of patients after RIN. In conclusion, the present study is the first providing evidence of the effects of RIN on MSC population via the CXCR4/SDF-1 axis. The levels of serum SDF-1 factor were elevated after RIN while increased levels of SDF-1 in peripheral blood were inversely correlated with the mRNA levels of CXCR4 on BM-MSCs after RIN. Therefore, this study contributes to enlighten the systematic effects of RIN on the population of MSCs at a cellular level. [ABSTRACT FROM AUTHOR]

Objectives: To determine mortality predictors following fall related fractures in older patients. Materials and methods: Patients aged = 70 years hospitalized for fall related fractures were prospectively evaluated. Mortality was the main outcome. Age, functional-cognitive function, medications, comorbidities, fall history, fear of falls were also assessed. Outcomes: A total of 100 patients were enrolled. Ninety-one out of 100 (91%) suffered a hip fracture; 92 (92%) had surgery. The one-year post-discharge mortality was 20%. Univariate analysis revealed that older age, increased Charlson comorbidity index, low abbreviated mental test on admission, low modified Barthel index (MBI), fear of falls and delirium were significantly correlated with one-year post discharge mortality (p=.03, p=.003, p=.04, p=.005, p=.004, p=.015, respectively). Conclusion: Age, fear of falls and Charlson comorbidity index are predictors of one-year mortality after hospitalization for fracture. It is of utmost importance to identify older patients suffering from fracture at risk of dying that may benefit from patient-centered care. [ABSTRACT FROM AUTHOR]

Studies the endogenic factors for the occurrence of cervical hip fractures. Treatment of hemiarthroplasty with internal fixation; Condition of the fractured hip and of the ipsilateral knee; Mobility of the patient before the fracture.

Background: In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton's jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. Methods: MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. Results: Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. Conclusions: Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications. [ABSTRACT FROM AUTHOR]

The article focuses on the bone marrow mesenchymal stem/stromal cells (BM-MSCs) in the disease progression of B-cell lymphoma. It discusses the anti-apoptotic and chemotactic effect of malignant bone marrow (BM) and healthy donor (HD) derived BM-MSC, determination of MSC's incidence related bone marrow mononuclear cell (BMMC) fraction with the help of colony forming unit-fibroblast (CFU-F) assay.

For the evaluation of the functionality and mobility of the spine, several methods have been developed. The purpose of this study was to estimate the test-retest reliability of the Spinal Mouse, a new, non-invasive, computer-assisted wireless telemetry device for the assessment of the curvatures, the mobility and the functionality of the spine. Materials and methods: the test-retest reliability was evaluated in 50 adults with back or low back pain. Twenty four parameters were studied in the sagittal and frontal plane. For the characterization of the precision, the intraclass correlation coefficient and the standard error of measurement were used. Results: in the sagittal plane, 22 of the 24 parameters showed high and good reliability, while only two fair and poor. In the frontal plane, 17 parameters showed high and good reliability, five fair and two poor. Discussion: the Spinal Mouse showed excellent test-retest reliability in the sagittal plane, while a slightly inferior performance in the frontal plane, for the evaluation of curvatures, deformation and mobility of the spine. [ABSTRACT FROM AUTHOR]

Background: The primary purpose of this study was to investigate the sympathetic innervation of the long head of the biceps brachii tendon LHB via immunohistochemical staining for protein S-100 and neuropeptide Y (NPY) in patients with complex proximal humerus fractures, in individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC), and in cadaveric samples with no previously reported shoulder pathology. Methods: We investigated the presence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon (LHB) in patients with complex proximal humerus fractures and individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC). The correlation of morphological features with immunohistochemical evidence of neural element presence was also investigated. Forty-one LHB tendon specimens were examined. Seventeen were harvested from patients who underwent hemiarthroplasty for proximal humerus fractures, 14 were from individuals with biceps tendinosis in the context of a large RC tear, and ten were from cadaveric controls with no previous shoulder pathology. Histologic examination was performed using hematoxylin and eosin. Immunohistochemistry was used to detect the expression of the protein S-100, neuropeptide Y, and α1-adrenergic receptors, as well as to characterize the potential neural differentiation of tendon cells. Results: A strong correlation between the expression of NPY/S-100, α1-adrenergic/S-100, and α1-adrenergic/NPY was found. The LHB tendon has sympathetic innervation and α1-adrenergic receptors in acute and chronic pathological conditions. Conclusion: Our results provide useful guidance on the management of tendinosis and the handling of the LHB in hemiarthroplasties for fractures. [ABSTRACT FROM AUTHOR]

Abstract: The ulnar coronoid process plays a central role in elbow stability due to its unique anatomic characteristics. A fracture of the coronoid, although uncommon, represents a serious injury that can adversely affect functional outcome if not treated appropriately. Several surgical interventions addressing different fracture patterns are being increasingly recognised as effective treatment options even for smaller fragments. A review of the literature was performed in order to evaluate different treatment strategies applied to clearly defined fracture configurations. 14 articles reporting data for the management of 236 coronoid fractures met our inclusion criteria and were subjected to critical analysis. The data suggest that recognition of specific coronoid fracture patterns, use of appropriate classification systems and application of staged surgical protocols can stabilise the elbow effectively and lead to favourable outcomes. [Copyright &y& Elsevier]

Summary: The characterization of the molecular mediators regulating the fracture healing response over the past decade has vastly expanded our knowledge in this area at the molecular level. It is clear today that the physiological mechanisms governing the biology of bone repair and turnover are complex and far from being well understood. Several of the molecules implicated in the healing process have become available for use in the clinical setting thanks to advances made in recombinant technology. Current evidence of their effect in accelerating fracture healing in both experimental and clinical studies is promising. However, despite these findings, several factors require further investigation, including the ideal timing to administer these molecules, which is the most effective dose, and the factors affecting the lack of consistency in the experimental designs and animal models that have been used. In addition, the available evidence lacks phase III, level I studies. Until such studies become available, the results should be interpreted with caution. [Copyright &y& Elsevier]

Abstract: Objectives: This study aims to assess whether elderly patients (>65 years) with open tibial shaft fractures (OFs) have increased mortality rates than those with closed fractures (CFs). Patients and methods: Patients admitted during 2003–2005 with open/closed diaphyseal (AO 42) fractures of the tibia were eligible to participate. Exclusion criteria: Pathological and peri-prosthetic fractures. Results: A total of 54 patients (38 females) met the inclusion criteria. Twenty-six patients had sustained CF and 28 OF (Gustilo grade I (11), grade II (five), grade IIIa (two) and grade IIIb (10)). The OF group was statistically significantly different with higher injury severity score, secondary procedures and length of hospital stay (p <0.05). A higher rate of admission/length of stay to intensive care unit and complication rate was noted in the OF group. Mortality rate between the two groups was comparable (CF=2/26, OF=3/28). Conclusions: Elderly patients with OFs of the tibial shaft have similar mortality rate to those with CFs. [Copyright &y& Elsevier]

Abstract: We have studied the histologic and immunohistochemical changes of the long head of the biceps brachii tendon (LHB) in low-energy complex proximal humerus fractures. Our objective was to detect histological features, which may be correlated to pain generation. Biopsy samples were obtained during hemiarthroplasty procedures from 11 patients who suffered a complex proximal humerus fracture. The control group consisted of 10 samples harvested from human cadavers with no history of premortem shoulder problems and no gross shoulder pathology. Histologic investigation included quantitative measurement of tendon degeneration, cellularity, neoangiogenesis, inflammation and metaplasia, as well as immunohistochemical detection of cells with neural differentiation within the tendon tissue proper with S-100 protein and neuropeptide Y (N-Y). The found lesions were significantly more in the group of tendons from fractures compared to the control group (p <0.001). These lesions were also statistically correlated to each other, indicating a possible neural differentiation of tendon stromal cells. The LHB is a potential source of pain and the routine use of tenotomy/tenodesis of this tendon in hemiarthroplasty procedures for fracture may be reinforced by the results of this study. [Copyright &y& Elsevier]

The successful treatment of nonunions represents a major challenge for orthopaedic surgeons. Lately, ongoing advances made in the field of molecular medicine and molecular biology have increased our understanding of the pathways and involvement of mediators surrounding the bone healing process. As a result, the surgeon's armamentarium has been increased in terms of options for intervention. This article aims to provide an overview of minimally invasive techniques applicable in the treatment of nonunions of fractures. [ABSTRACT FROM AUTHOR]

Unlabelled: Although acute management of pelvic fractures and their long-term functional outcome have been widely documented, important information regarding malunion and nonunion of these fractures is sparse. Despite their relative rarity, malunions and nonunions cause disabling symptoms and have major socioeconomic implications. We analyzed the factors predisposing a pelvic injury to develop malunion/nonunion, the clinical presentation of these complications, and the efficacy of the reported operative protocols in 437 malunions/nonunions of 25 clinical studies. Treatment of these demanding complications appeared effective in the majority of the cases: overall union rates averaged 86.1%, pain relief as much as 93%, patient satisfaction 79%, and return to a preinjury level of activities 50%. Nevertheless, the patient should be informed about the incidence of perioperative complications, including neurologic injury (5.3%), symptomatic vein thrombosis (5.0%), pulmonary embolism (1.9%), and deep wound infection (1.6%). For a successful outcome, a thorough preoperative plan and methodical operative intervention are essential. In establishing effective evidence-based future clinical practice, the introduction of multicenter networks of pelvic trauma management appears a necessity.Level Of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Summary: The microenvironment theory has become very popular for providing mechanisms which explain the development of often lethal posttraumatic complications such as systemic inflammatory response syndrome (SIRS), adult respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). With the recent advances in molecular biology and the ever-expanding understanding of trauma pathophysiology, immunomonitoring in trauma patients attempts to characterise and quantify novel molecules in order to predict patients at risk. This review article assesses the existing evidence on the biomarkers of endothelial injury and their potential utility as quantification parameters of endothelial dysfunction in trauma patients. [Copyright &y& Elsevier]

Background: Although the tendon of the long head of the biceps is a well-known source of shoulder pain, the pathophysiological basis of this pain has yet to be explained. The aim of this study was to detect and characterize any nervous element of the tendon and to determine a possible explanation for pain originating from this structure. Methods: The nature of the neuronal innervation of the tendon of the long head of the biceps was studied immunohistochemically, in four tendons from different human cadavers, with use of neurofilament antibody 2H3, neurofilament-like antibody 3A10, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase. Results: A large neuronal network, asymmetrically distributed along the length of the tendon with a higher degree of innervation at the tendon origin, was identified by the neurofilament and neurofilament-like antibodies 2H3 and 3A10. This innervation was found to be positive for calcitonin gene-related peptide and substance P, suggesting the presence of thinly myelinated or unmyelinated sensory neurons. It was also positive for tyrosine hydroxylase, suggesting a post-ganglionic sympathetic origin. Conclusions and Clinical Relevance: These findings demonstrate that the tendon of the long head of the biceps is innervated by a network of sensory sympathetic fibers, which may play a role in the pathogenesis of shoulder pain. [ABSTRACT FROM AUTHOR]

Abstract: Bone grafting is not routinely required in primary arthrodesis in the absence of infection, avascular necrosis, bone defect or previous non-union; when any of the above factors is present, autograft is the gold-standard method. However, donor site morbidity and the quantitative and qualitative limitations of autograft have led to the development of alternatives. This study documents the use of the bone morphogenetic protein BMP-7 in a total of 19 joint fusions (ankle, subtalar, talonavicular, pubic and sacroiliac). Healing rates of 90% and satisfactory subjective functional outcome in 70% of cases were recorded over a minimum follow-up of 15 months. These data should provide a sound foundation for future clinical trials evaluating the application of BMP-7 in the fusion of joints. [Copyright &y& Elsevier]

Summary: The effective treatment of the often debilitating, longlasting and large-asset-consuming complication of fracture non-unions has been in the centre of scientific interest the last decades. The use of alternative bone substitutes to the gold standard of autologous graft includes the osteoinductive molecules named bone morphogenetic proteins (BMPs). A multicenter registry and database (bmpusergroup.co.uk) focused on the application of BMP-7/OP-1 was created in December 2005. We present the preliminary results, using the prospective case-series of aseptic tibial non-unions as an example. Sixty-eight patients fulfilled the inclusion criteria for this observational study, with a minimum follow-up of 12 months. The median duration of tibial non-union prior to BMP-7 application was 23 months (range 9–317 mo). Patients had undergone a median of 2 (range 0–11) revision procedures prior to the administration of BMP-7. In 41% the application of BMP-7 was combined with revision of the fixation at the non-union site. Non-union healing was verified in 61 (89.7%) in a median period of 6.5 months (range 3–15 mo). No adverse events or complications were associated with BMP-7 application. The safety and efficacy of BMP-7 was verified in our case series, and was comparable to the existing evidence. The establishment of multicenter networks and the systematic and long-term follow- up of these patients are expected to provide further information and significantly improve our understanding of this promising osteoinductive bone substitute. [Copyright &y& Elsevier]