Acute Bone Loss Research Articles

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study—Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury

Accelerated sub-lesional bone loss is common in the first 2–3 years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An ‘acute interventional cohort’ (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4 mg zoledronic acid (ZOL) at baseline. A ‘chronic non-interventional cohort’ (n = 9) with TSCI (duration 1–5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4 years). At baseline, the ‘acute’ cohort had higher serum CTx, P1NP and sclerostin concentrations, while the ‘chronic’ cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48 months. Left distal femoral and proximal tibial BMD declined by mean ~ 6–13% at 12 months and ~ 20–23% at 48 months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial

IntroductionPersons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that...

Progress in Prevention and Treatment of Acute Bone Loss in Orthopedics

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient’s bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians’ understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.

Identification of gravity-responsive proteins in the femur of spaceflight mice using a quantitative proteomic approach

Although the microgravity (μ-g) environment that astronauts encounter during spaceflight can cause severe acute bone loss, the molecular mechanism of this bone loss remains unclear. To investigate the gravity-response proteins involved in bone metabolism, it is important to comprehensively determine which proteins exhibit differential abundance associated with mechanical stimuli. However, comprehensive proteomic analysis using small bone samples is difficult because protein extraction in mineralized bone tissue is inefficient. Here, we established a high-sensitivity analysis system for mouse bone proteins using data-independent acquisition mass spectrometry. This system successfully detected 40 proteins in the femoral diaphysis showing differential abundance between mice raised in a μ-g environment, where the bone mass was reduced by gravity unloading, and mice raised in an artificial 1-gravity environment on the International Space Station. Additionally, 22 proteins, including noncollagenous bone matrix proteins, showed similar abundance between the two groups in the mandible, where bone mass was unaltered due to mastication stimuli, suggesting that these proteins are responsive to mechanical stimuli. One of these proteins, SPARCL1, is suggested to promote osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand. We expect these findings to lead to new insights into the mechanisms of bone metabolism induced by mechanical stimuli. SignificanceWe aimed to investigate the gravity-response proteins involved in bone metabolism. To this end, we established a comprehensive analysis system for mouse bone proteins using data-independent acquisition mass spectrometry, which is particularly useful in comprehensively analyzing the bone proteome using small sample volumes. In addition, a comprehensive proteomic analysis of the femoral diaphysis and mandible, which exhibit different degrees of bone loss in mice raised on the International Space Station, identified proteins that respond to mechanical stimuli. SPARCL1, a mechanical stimulus-responsive protein, was consequently suggested to be involved in osteoclast differentiation associated with bone remodeling. Our findings represent an important step toward elucidating the molecular mechanism of bone metabolism induced by mechanical stimuli.

Surgical repair of large segmental bone loss with the induced membrane technique: patient reported outcomes are comparable to nonunions without bone loss.

To compare the outcomes of patients with segmental bone loss who underwent repair with the induced membrane technique (IMT) with a matched cohort of nonunion fractures without bone loss. Retrospective analysis on prospectively collected data. Academic medical center. Two cohorts of patients, those with upper and lower extremity diaphyseal large segmental bone loss and those with ununited fractures, were enrolled prospectively between 2013 and 2020. Sixteen patients who underwent repair of 17 extremities with segmental diaphyseal or meta-diaphyseal bone defects treated with the induced membrane technique were identified, and matched with 17 patients who were treated for 17 fracture nonunions treated without an induced membrane. Sixteen of the bone defects treated with the induced membrane technique were due to acute bone loss, and the other was a chronic aseptic nonunion. Healing rate, time to union, functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA) and pain assessed by the Visual Analog Scale (VAS). The initial average defect size for patients treated with the induced membrane technique was 8.85cm. Mean follow-up times were similar with 17.06 ± 10.13months for patients treated with the IMT, and 20.35 ± 16.68. months for patients treated without the technique. Complete union was achieved in 15/17 (88.2%) of segmental bone loss cases treated with the IMT and 17/17 (100%) of cases repaired without the technique at the latest follow up visit. The average time to union for patients treated with the induced membrane technique was 13.0 ± 8.4months and 9.64 ± 4.7months for the matched cohort. There were no significant differences in reported outcomes measured by the SMFA or VAS. Patients treated with the induced membrane technique required more revision surgeries than those not treated with an induced membrane. Outcomes following treatment of acute bone loss from the diaphysis of long bones with the induced membrane technique produces clinical and radiographic outcomes similar to those of long bone fracture nonunions without bone loss that go on to heal. III.

Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice

Background: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. Study Design: Controlled laboratory study. Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors’ hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. Clinical Relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.

Induced Membrane Technique is Effective for the Management of Acute Traumatic Bone Loss in Both Diaphyseal and Metaphyseal Lower Extremity Fractures.

To compare outcomes of Masquelet's induced membrane technique (IMT) in metaphyseal and diaphyseal fractures with acute bone loss. Retrospective cohort study Setting: Four Level 1 Academic Trauma CentersPatients/Participants: Patients acutely treated with IMT for traumatic lower extremity bone loss at four Level 1 trauma centers between 2010-2020. Operative treatment with placement of cement spacer within three weeks of initial injury followed by staged removal and bone grafting to the defect. Fracture union, infection, revision grafting, time to union, and amputation. 120 fractures met inclusion criteria, including 43 diaphyseal fractures (DIM) and 77 metaphyseal fractures (MIM). Demographic characteristics were not significantly different, except for age (DIM 34 years vs MIM 43 years, p< 0.001). Union after treatment with IMT was 89.2% overall. After controlling for age, this was not significantly different between DIM (41/43, 95.3%) and MIM (66/77, 85.7%) (p =0.13), nor was the rate of infection between groups. There was no difference in any secondary outcomes. The overall union rate in the current series of acute lower extremity fractures treated with induced membrane technique was 89%. There was no difference in successful union between patients with diaphyseal bone loss or metaphyseal bone loss treated with IMT. Similarly, there was no difference in patients with tibial or femoral bone loss treated with induced membrane. Defect size after debridement may be more prognostic for secondary operations rather than the limb segment involved or the degree of soft tissue injury. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Biological aspects to enhance fracture healing.

The ability to enhance fracture healing is paramount in modern orthopaedic trauma, particularly in the management of challenging cases including peri-prosthetic fractures, non-union and acute bone loss. Materials utilised in enhancing fracture healing should ideally be osteogenic, osteoinductive, osteoconductive, and facilitate vascular in-growth. Autologous bone graft remains the gold standard, providing all of these qualities. Limitations to this technique include low graft volume and donor site morbidity, with alternative techniques including the use of allograft or xenograft. Artificial scaffolds can provide an osteoconductive construct, however fail to provide an osteoinductive stimulus, and frequently have poor mechanical properties. Recombinant bone morphogenetic proteins can provide an osteoinductive stimulus; however, their licencing is limited and larger studies are required to clarify their role. For recalcitricant non-unions or high-risk cases, the use of composite graft combining the above techniques provides the highest chances of successfully achieving bony union.

BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism

Bromodomain-containing protein 9 (BRD9), a component of non-canonical BAF chromatin remodeling complex, has been identified as a critical therapeutic target in hematological diseases. Despite the hematopoietic origin of osteoclasts, the role of BRD9 in osteoclastogenesis and bone diseases remains unresolved. Here, we show Brd9 deficiency in myeloid lineage enhances osteoclast lineage commitment and bone resorption through downregulating interferon-beta (IFN-β) signaling with released constraint on osteoclastogenesis. Notably, we show that BRD9 interacts with transcription factor FOXP1 activating Stat1 transcription and IFN-β signaling thereafter. Besides, function specificity of BRD9 distinguished from BRD4 during osteoclastogenesis has been evaluated. Leveraging advantages of pharmacological modulation of BRD9 and flexible injectable silk fibroin hydrogel, we design a local deliver system for effectively mitigating zoledronate related osteonecrosis of the jaw and alleviating acute bone loss in lipopolysaccharide-induced localized aggressive periodontitis. Overall, these results demonstrate the function of BRD9 in osteoclastogenesis and its therapeutic potential for bone diseases.

Acute bone loss following SARS-CoV-2 infection in mice.

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has infected more than 650 million people worldwide. Approximately 23% of these patients developed lasting "long-haul" COVID symptoms, including fatigue, joint pain, and systemic hyperinflammation. However, the direct clinical impact of SARS-CoV-2 infection on the skeletal system including bone and joint health has not been determined. Utilizing a humanized mouse model of COVID-19, this study provides the first direct evidence that SARS-CoV-2 infection leads to acute bone loss, increased osteoclast number, and thinner growth plates. This bone loss could decrease whole-bone mechanical strength and increase the risk of fragility fractures, particularly in older patients, while thinner growth plates may create growth disturbances in younger patients. Evaluating skeletal health in patients that have recovered from COVID-19 will be crucial to identify at-risk populations and develop effective countermeasures.

The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling.

The ubiquitin‒proteasome system (UPS) plays a key role in maintaining protein homeostasis and bone remodelling. However, the role of deubiquitinating enzymes (DUBs) in bone resorption is still not well defined. Here, we identified the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) as a negative regulator of osteoclastogenesis by using the GEO database, proteomic analysis, and RNAi. Osteoclast-specific UCHL1 conditional knockout mice exhibited a severe osteoporosis phenotype in an ovariectomized model. Mechanistically, UCHL1 deubiquitinated and stabilized the transcriptional coactivator with PDZ-binding motif (TAZ) at the K46 residue, thereby inhibiting osteoclastogenesis. The TAZ protein underwent K48-linked polyubiquitination, which was degraded by UCHL1. As a substrate of UCHL1, TAZ regulates NFATC1 through a nontranscriptional coactivator function by competing with calcineurin A (CNA) for binding to NFATC1, which inhibits NFATC1 dephosphorylation and nuclear transport to impede osteoclastogenesis. Moreover, overexpression of UCHL1 locally alleviated acute and chronic bone loss. These findings suggest that activating UCHL1 may serve as a novel therapeutic approach targeting bone loss in various bone pathological states.

Is immediate internal fixation safe in induced membrane technique?

This study aimed to evaluate the treatment outcomes of patients treated with induced membrane technique (IMT) for the reconstruction of bone defects and to identify factors associated with the success and failure of the modified technique. Between January 2016 and April 2021, a total of 23 adult patients (20 males, 3 females; median age: 39.9 years; range, 20 to 69 years) who underwent bone reconstruction using the IMT for established pseudoarthrosis and acute bone loss were retrospectively analyzed. Fracture type, the size and location of bone defect, the nature of the index injury, the type of fixation, the interval between stages of the operation, and any diagnosis of infection or other complications of the patients were assessed. The median bone union was achieved in 6.6 (range, 4 to 11) months. The median index of reconstruction was 19 (range, 10 to 30%). The main complications were recurrent infection in two cases and nonunion in one case. Massive graft resorption occurred in two cases. Immediate internal fixation is a reliable and effective method in the treatment of complex bone defects. A large volume of autograft is required for the reconstruction of long defects, which presents as a limiting factor, particularly in patients undergoing previous surgical interventions.

Induced membrane technique for acute bone loss and nonunion management of the tibia.

Objectives:To report our experience and clinical results of using the Masquelet technique for the treatment of tibial nonunions and acute traumatic tibial bone defects.Design:Retrospective study of prospectively collected data (Level IV).Setting:Level I trauma center in the UK.Patients/Participants:Consecutive patients with tibial nonunions and open fractures associated with bone loss.Intervention: Two-stage Masquelet Procedure for the tibia.Main Outcome Measurements:Clinical and imaging assessment at 6 weeks, 3,6,9,12 months, or until pain-free mobilization and union.Results:There were 17 eligible patients, with a mean size of bone defect of 6 cm (range, 4–8 cm) and an 88.2% union rate at a mean of 8 months (range 5–18 months). Mean range of motion was 95 degrees of knee flexion (range 80°–130°). All patients but 2 returned to their previous occupation.Conclusions:The Masquelet technique is simple, effective, and has a high rate of success for the management of a variety of situations including acute bone loss or infected nonunions and is associated with a low incidence of complications.

Outcomes After Use of the Induced Membrane Technique for Fractures of the Upper Extremity

The purpose of this study was to review a series of cases in which the induced membrane technique was used for fractures with segmental bone loss in the upper extremity. We aimed to examine patient indications, outcomes based on union rates, and complications associated with this technique. An institutional review board-approved database at our institution was used to identify patients based on either diagnosis or procedure codes commonly used during the induced membrane treatment. The database was queried between 2003 and 2020 and included patients with segmental bone defects from acute trauma, nonunions, and infections. Demographic data, mechanism of injury, size and extent of the bone defect, treatment indication and methods along with intraoperative and postoperative complications were retrospectively reviewed. We identified 23 patients who met our inclusion criteria, including 15 patients with traumatic segmental bone loss and 8 patients with chronic nonunions and/or infections. Fourteen cases involving the bones of the forearm, 8 cases involving the metacarpals and 3 cases involving the phalanges were identified. Radiographic union was ultimately demonstrated in 21/23 patients (91.3%) with a median time to union of 20 weeks (range 13-29 weeks). A total of 10 patients required unplanned reoperation, with 4 nonunions requiring repeat plating and grafting procedures, and 1 patient ultimately underwent amputation for persistent infection. The induced membrane technique represents an effective treatment option for acute traumatic bone loss as well as chronic fracture nonunions. The technique has potential challenges, as 10 patients (43.5%) in our series required unplanned reoperations with 4 patients (17.4%) requiring a repeat intervention for persistent nonunion. IV.

Acute and severe trabecular bone loss in a rat model of critical illness myopathy.

Prolonged mechanical ventilation for critically ill patients with respiratory distress can result in severe muscle wasting with preferential loss of myosin. Systemic inflammation triggered by lung mechanical injury likely contributes to this myopathy, although the exact mechanisms are unknown. In this study, we hypothesized that muscle wasting following mechanical ventilation is accompanied by bone loss. The objective was to determine the rate, nature, and extent of bone loss in the femora of rats ventilated up to 10 days and to relate the bone changes to muscle deterioration. We have developed a rat model of ventilator-induced muscle wasting and established its feasibility and clinical validity. This model involves pharmacologic paralysis, parenteral nutrition, and continuous mechanical ventilation. We assessed the hindlimb muscle and bone of rats ventilated for 0, 2, 5, 8, and 10 days. Routine histology, microCT, and biomechanical evaluations were performed. Hindlimb muscles developed changes consistent with myopathy, whereas the femurs demonstrated a progressive decline in trabecular bone volume, mineral density, and microarchitecture beginning Day 8 of mechanical ventilation. Biomechanical testing showed a reduction in flexural strength and stiffness on Day 10. The bone changes correlated with the loss of muscle mass and myosin. These results demonstrate that mechanical ventilation leads to progressive trabecular bone loss parallel to muscle deterioration. The results of our study suggest that mechanically ventilated patients may be at risk of compromised bone integrity and muscle weakness, predisposing to post-ventilator falls and fractures, thereby warranting interventions to prevent progressive bone and muscle decline.

Management of Bone Failure in Fracture of the Distal Region of the Femur Using the Masquelet Technique with Fibula Graft Associated with Iliac-Crest Graft: Report of Two Cases.

Two cases of bone failure after fracture of the distal region of the femur treated with the Masquelet technique are presented. The first case involves acute bone loss, and the second, pseudarthrosis. The proper management of these lesions led to consolidation and a good functional result.

The Life and Works of Solomon Epstein, MD, FRCP (1940–2020)

The Life and Works of Solomon Epstein, MD, FRCP (1940–2020)

Management of acute bone loss following high grade open tibia fractures.

Introduction:Optimal treatment for acute post-traumatic bone loss in the tibia remains unclear. Distraction osteogenesis (DO) and induced membrane technique (IM) have been established as the mainstays of treatment. Aim of this article is to review the current evidence regarding the use of these two methods.Methods:A review of the MEDLINE database was performed with strict inclusion and exclusion criteria focusing on treatment of the acute bone loss after open tibia fractures with DO and IM. Bone union rate was taken as the primary outcome and infection rate as secondary outcome.Results:Four studies out of 78 on the use of the DO and three studies out of 18 on the use of the IM technique matched the inclusion criteria. Union rate in the DO group ranged between 92% and 100%, with infection rates between 0 and 4%. In the IM group, union was reached in 42% to 100% of cases, with septic complications occurring in 12% to 43%. Differences in union rate and infection rate reached statistical significance.Discussion:We found a considerable evidence gap regarding treatment of bone loss in high grade open tibia fractures. The limitations of our study prevented us from drawing clear causative conclusions on the results. Although our study points to higher union rates and lower infection rate with the use of the DO technique, the results remain preliminary and further high-level evidence is needed to establish the roles of DO and IM in treatment of acute bone loss in open tibia fractures. (www.actabiomedica.it)

Burn injury and restoration of muscle function.

Burn injury in children results in a systemic inflammatory reaction as well as a stress response. Consequences of these non-specific adaptive responses include resorptive bone loss and muscle catabolism. These adverse events can result in a post-burn fracture rate of approximately 15% and long-term muscle weakness that prolongs recovery. A randomized controlled trial of a single dose of the bisphosphonate pamidronate within the first ten days of burn injury resulted in the prevention of resorptive bone loss and continuous bone accrual. Examining the muscle protein kinetics in pediatric burn patients enrolled in that randomized controlled trial revealed that those who had been given the single dose bisphosphonate experienced preservation of muscle mass and strength. An in vitro study of mouse myoblasts incubated with serum from patients who participated in the randomized controlled study demonstrated that mouse myoblasts exposed to serum from patients given the single dose bisphosphonate exhibited greater myotube diameter than those from burned children given placebo. Moreover, the serum from bisphosphonate treated patients stimulated the protein anabolic pathways and suppressed protein catabolic pathways in these cells. Inasmuch as incubation of the myotubes with an antibody to transforming growth factor beta (TGFβ) rescued myotube size in the cultures with serum from patients who received the placebo to the same magnitude as cultures with serum from patients treated with single dose bisphosphonate, we postulate that post-burn bone resorption liberates muscle catabolic factors which cause muscle wasting. Future uses of bisphosphonates could include studies designed to prevent short-term acute bone resorption in conditions that may result in muscle wasting as well as in short-term interventions in chronic inflammatory conditions which may flare and cause acute bone and muscle loss.

Treatment of acute bone defects in severe lower limb Trauma

PurposeTo present our experience in the management of acute large bone defects treated with the use of vascularized fibular grafts supported by Ilizarov circular external frames. Patients and methodsDuring a period of 6 years (from 2007 to 2013) 8 patients with acute large bone defects (IVB according to Winquist modified classification) were treated at our institution with early bone reconstruction by means of microvascular fibular grafts. All patients were evaluated by the use of the following parameters: X-ray consolidation, discharge time, duration of treatment, malalignment of the lower limb and final leg length discrepancy, knee and ankle mobility (ROM), pain (VAS), number of eventual additive treatments (plastic surgery, etc.), walking independence (use of crutches), possibility to get back to work, subjective evaluation about the treatment and the result (SF-36, personal feelings about circular external fixator dressing) ResultsThe mean treatment time, often connected to the mean consolidation time, was 61 weeks and the mean number of operations was 7.6. Six of the eight patients got back to their previous daily activities and work, without any further issues. Discussionbased on our experience, Ilizarov and fibular vascular grafts are not alternatives, as often reported in literature. Their combined use, especially in lesions as those classified as Winquist IV B, can represent an effective tool in the surgeon's hands to solve the most difficult cases of acute bone loss caused by severe high-energy traumas.