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Non-union in a neck of fifth metatarsal fracture: A case report

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Trauma Case Reports
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Case Report
Non-union in a neck of fth metatarsal fracture: A case report
David T. Bui
, Aaron J. Pym, David Lunz, JeS. Ling
Prince of Wales Hospital, Sydney 2031, Australia
Unlike more common 5th metatarsal fractures such as those aecting the base (Zone 1 avulsion-types, Zone 2 Jones-types, or Zone
3 Stress-types) [1] or shaft (spiral dancer's fracture, or stress-types) [2], neck of fth metatarsal fractures are extremely rare [3]. In
a forty-nine subject series on the incidence of 5th metatarsal fractures, only 2% (1/49) aected the metatarsal neck [4]. Distal fth
metatarsal fractures are generally treated non-operatively with good outcomes [2,5]. However, a case of non-union in a neck of 5th
metatarsal fracture is yet to be reported in the literature.
As such, there is a lack of guidance relating to the treatment of this rare type of injury. We present the case of a 27 year old woman
who sustained a neck of 5th metatarsal fracture leading to non-union, which was treated successfully with debridement, autologous
bone graft and recombinant human platelet derived growth factor (rhPDGF) and beta-tricalcium phosphate (BTP) granules, combined
with internal xation.
Literature review
A search of SCOPUS, Medline, and PubMed search engines using the keywords fth OR 5thAND metatarsal*AND fracture*
AND neckAND non-union* OR non-union*was performed on 27th of July 2017. Searches were not limited by dates. Any article
reporting a case or case series of 5th metatarsal neck fracture non-union including either the presentation, management or com-
plications were included for review. Studies were excluded if they were published in a language other than English, or duplicate
publication. 15 results were identied by search, with 9 unique studies, however amongst these no case of non-union in a fth
metatarsal neck fracture was identied in the accompanying abstract or full-text publication.
Case report
The patient gave explicit and written consent to the publication of the present report.
A 27 year old project ocer presented to the oce of the senior author 8 weeks after sustaining a transverse fracture to the neck
Accepted 22 November 2018
Corresponding author.
E-mail address: (D.T. Bui).
Trauma Case Reports 18 (2018) 37–41
Available online 27 November 2018
2352-6440/ © 2018 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
of the 5th metatarsal of her left foot. This occurred after an inversion injury of the hindfoot whilst dancing. The patient was a t and
healthy non-smoker with no previous history of injury to this foot. Her past medical history was signicant for post-traumatic stress
disorder, which was well controlled on a selective serotonin reuptake inhibitor (SSRI), and mild asthma managed with a standard
reliever and preventer.
Management of the fracture at that point had been non-weight-bearing in a sti-soled postoperative shoe and crutches for 1 week,
followed by full-weight-bearing thereafter. At this rst visit (8 weeks post injury) the patient reported considerable foot pain and had
diculty mobilising. On examination there was signicant tenderness to palpation directly over the fracture site. Radiographs
performed 2 weeks prior to this presentation demonstrated a clear fracture line with minimal evidence of healing (Fig. 1). She was
transferred into a fracture boot to better stabilise the fracture, however, on follow up 5 weeks after this appointment, now 13 weeks
post injury, she described persistent pain with clear evidence of non-union on plain radiographs and CT scan (Figs. 2, 3, 4). With clear
evidence of a symptomatic, established non-union, the patient was consented for surgery.
The patient was positioned in the lateral position and a direct lateral approach was made to the foot centred over the 5th
metatarsophalangeal joint. The non-union was identied and debrided back to bleeding cancellous surfaces. A 1 cm incision was
made over the lateral border of the calcaneum taking care to avoid the sural nerve and cancellous bone was harvested as autologous
bone graft. The autologous bone graft was then mixed with Augment © Wright Medical Group N.V. , which consists of platelet
derived growth factor (PDGF) and beta-tricalcium phosphate granules. A generous amount of this mixture was then packed into the
fracture site, followed by internal xation along the lateral border of the bone with a 1.5 mm Medartis hand module T plate with 3
screws in each fragment in compression mode (Fig. 5). The wound was then closed in layers and she was discharged in a fracture boot
non-weight-bearing for 6 weeks. At 6 weeks post-operatively, there were clinical and radiological signs of healing, and she was
transitioned to partial weight-bearing in the boot, starting with 25% of her weight in week 7, increasing her weight-bearing by 25%
per week till she was fully weight-bearing by 10 weeks. At 4 months post-operatively, there was radiographic evidence of complete
union on radiographs (Fig. 6), and there was no tenderness over the fracture site, however, she reported more global symptoms
consistent with Chronic Regional Pain Syndrome (CRPS) and required a multi-modal treatment plan including input from a chronic
pain clinic. At 12-months post-operatively, her CRPS had improved and she had returned to full activity including exercise.
Fractures of the base and shaft of the 5th metatarsal are common, however, isolated fractures of the neck of the 5th metatarsal are
extremely rare. [3]. Furthermore, a non-union of this rare fracture has not been reported in the literature.
Fig. 1. Radiograph 6 weeks post-injury.
D.T. Bui et al. Trauma Case Reports 18 (2018) 37–41
Non-union is dened as the cessation of the reparative processes of healing without bone union, diagnosed on the basis of both
radiographic and clinical ndings. In particular, there is an emphasis on a failure of progression of healing on serial radiographs
[6,7]. A number of risk factors have been implicated which can be divided into patient factors (age, gender, medical comorbidities
e.g. anaemia, diabetes), environmental factors (smoking, medications e.g. steroids) and injury factors (high or low energy trauma,
vascular supply of fracture, presence of infection) [8,9]. In this case report, the patient was of good health with no patient,
Fig. 2. Radiograph non-union 13 weeks post-injury.
Fig. 3. CT Axial non-union 13 weeks post-injury.
Fig. 4. CT sagittal non-union 13 weeks post-injury.
D.T. Bui et al. Trauma Case Reports 18 (2018) 37–41
environmental or injury risk factors for non-union. However, treatment factors such as a failure to adequately immobilise a fracture,
can also lead to non-union. In this particular case, the patient had been weightbearing from 1 week after the time of injury, an
approach that has been advocated in the literature for distal shaft and neck fractures [1]. This early weightbearing protocol is
appropriate for most base and shaft fractures of the 5th metatarsal, but may not provide adequate immobilisation for fractures of the
neck of the 5th metatarsal, which is an area subject to dierent stresses. It is possible that an initial period of immobilistaion and
nonweightbearing in either a cast or fracture boot may have resulted in fracture union, obviating the need for surgery.
Treatment options for established non-union can be either non-operative or operative. The evidence supporting many non-op-
erative modalities is relatively weak in non-long bones and foot and ankle surgery, such as in electrical stimulation [10], ultrasound
[11] and extracorporal shockwave therapy [12].
Operative management of non-union can involve the use of biological enhancements and mechanical processes. The gold
standardin biological techniques is autologous bone graft, however there are many other options including allograft implantation,
Fig. 5. Preliminary intraoperative xation.
Fig. 6. Radiograph 4 months post-operative demonstrating complete healing.
D.T. Bui et al. Trauma Case Reports 18 (2018) 37–41
bone graft substitutes, use of growth factors including bone morphogenic proteins (BMP) and platelet derived growth factor (PDGF),
osteoconductive scaolds and osteoprogenitor stemcells. These can be combined with mechanical methods such as debridement,
distraction and xation strategies [13].
In the case we have presented, we have used Augment mixed with calcaneal autograft, combined with rigid internal xation and a
period of non-weight-bearing in the post-operative period, to address the issues of biology and mechanical stability or lack thereof.
Augment (© Wright Medical Group N.V. ), is a completely synthetic, liquid injectable bone graft substitute composed of re-
combinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate (BTP) granules. RhPDGF-BB, also
known as becaplermin, is a potent recruiter of, and strong mitogenic factor for, cells crucial to musculoskeletal tissue repair, including
mesenchymal stem cells (MSCs), osteogenic cells and tenocytes [14]. It has been proven to be safe for human use and approved in
Australia and New Zealand, the United States, Canada and a number of other countries worldwide [15,16]. Additionally, rhPDGF-BB
has recently been found to represent a safe and ecacious treatment alternative to autologous bone graft in various foot and ankle
procedures including various ankle and hindfoot arthrodesis procedures [16].
In this case, we combined autologous bone graft from the calcaneum with Augment. The manufacturer of Augment neither
encourages nor discourages the addition of autograft bone to the preparation, however, this is routinely done at our institution as we
believe the patient's own bone is still the best scaold to promote bone healing, and the combination with Augment might oer the
optimal circumstances for osteogenesis, osteoinduction and osteoconduction. Given the success of healing in this case, the authors
propose the use of Augment as a potential adjunctive treatment for non-union of the 5th metatarsal neck, and this may be applicable
to non-unions elsewhere.
Ultimately, this case illustrates that early weightbearing, may lead to non-union in neck of 5th metatarsal fractures, in contrast to
most base and shaft fractures of the 5th metatarsal, where early weightbearing is entirely appropriate. As such, an initial period of
non-weightbearing in a cast or fracture boot may be best initial management for this rare fracture. If faced with the problem of non-
union in this fracture, we have shown that a combination of debridement, biologic enhancement with autologous bone graft mixed
with a commercial preparation of PDGF, and rigid stabilisation, can achieve successful union.
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[2] M.J. O'Malley, W.G. Hamilton, J. Munyak, Fractures of the distal shaft of the fth metatarsal. Dancer's fracture, Am. J. Sports Med. 24 (2) (1996) 240243.
[3] K.B. Landorf, Fifth metatarsal fractures are not all the same: proximal diaphyseal fractures are prone to delayed healing, Foot 8 (1) (1998) 3845.
[4] G. Arangio, The Jones fracture - transverse proximal diaphyseal fractures of the fth metatarsal: frequency by radiology, Foot 1 (4) (1992) 201204.
[5] Foot Pain in a Gymnast, Visual Diagnosis in Emergency and Critical Care Medicine, Second edition, (2011), p. 91.
[6] D.J. Hak, et al., Delayed union and nonunions: epidemiology, clinical issues, and nancial aspects, Injury 45 (Suppl. 2) (2014) S3S7.
[7] P. Megas, Classication of non-union, Injury 36 (Suppl. 4) (2005) S30S37.
[8] M. Panteli, et al., Biological and molecular prole of fracture non-union tissue: current insights, J. Cell. Mol. Med. 19 (4) (2015) 685713.
[9] C. Copuroglu, G.M. Calori, P.V. Giannoudis, Fracture non-union: who is at risk? Injury 44 (11) (2013) 13791382.
[10] B. Mollon, et al., Electrical stimulation for long-bone fracture-healing: a meta-analysis of randomized controlled trials, J. Bone Joint Surg. Am. 90 (11) (2008)
[11] J.W. Busse, et al., Low intensity pulsed ultrasonography for fractures: systematic review of randomised controlled trials, BMJ 338 (2009) b351.
[12] B. Petrisor, S. Lisson, S. Sprague, Extracorporeal shockwave therapy: a systematic review of its use in fracture management, Indian J. Orthop. 43 (2009).
[13] R. Dimitriou, et al., Bone regeneration current concepts and future directions, BMC Med. 9 (66) (2011).
[14] G.E. Friedlaender, et al., The role of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in orthopaedic bone repair and regeneration, Curr.
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[15] L.A. Solchaga, et al., Safety of recombinant human platelet-derived growth factor-BB in augment((R)) bone graft, J. Tissue Eng. 3 (1) (2012)
[16] C.W. DiGiovanni, et al., Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP): an alternative to autogenous
bone graft, J. Bone Joint Surg. 95 (13) (2013) 11841192.
D.T. Bui et al. Trauma Case Reports 18 (2018) 37–41
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Delayed bone healing and non-union occur in approximately 10% of long bone fractures. Despite intense investigations and progress in understanding the processes governing bone healing, the specific pathophysiological characteristics of the local microenvironment leading to non-union remain obscure. The clinical findings and radiographic features remain the two important landmarks of diagnosing non-unions and even when the diagnosis is established there is debate on the ideal timing and mode of intervention. In an attempt to understand better the pathophysiological processes involved in the development of fracture non-union, a number of studies have endeavoured to investigate the biological profile of tissue obtained from the non-union site and analyse any differences or similarities of tissue obtained from different types of non-unions. In the herein study, we present the existing evidence of the biological and molecular profile of fracture non-union tissue. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Full-text available
This article discusses nonclinical and clinical data regarding the safety of recombinant human platelet-derived growth factor-BB as a component of the Augment(®) Bone Graft (Augment). Augment is a bone graft substitute intended to be used as an alternative to autologous bone graft in the fusion of hindfoot and ankle joints. Nonclinical studies included assessment of the pharmacokinetic profile of intravenously administered recombinant human platelet-derived growth factor-BB in rat and dog, effects of intravenous administration of recombinant human platelet-derived growth factor-BB in a reproductive and development toxicity study in rats, and chronic toxicity and carcinogenicity of Augment in a 12-month implantation model. These studies showed that systemic exposure was brief and clearance was rapid. No signs of toxicity, carcinogenicity, or tumor promotion were observed even with doses far exceeding the maximum clinical dose. Results of clinical trials (605 participants) and commercial use of recombinant human platelet-derived growth factor-BB containing products indicate that these products are not associated with increased incidence of adverse events or cancer. The safety data presented provide evidence that recombinant human platelet-derived growth factor-BB is a safe therapeutic when used in combination products as a single administration during surgical procedures for bone repair and fusion. There is no evidence associating use of recombinant human platelet-derived growth factor-BB in Augment with chronic toxicity, carcinogenicity, or tumor promotion.
Full-text available
Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
Full-text available
Extracorporeal shockwave therapy is increasingly used as an adjuvant therapy in the management of nonunions, delayed unions and more recently fresh fractures. This is in an effort to increase union rates or obtain unions when fractures have proven recalcitrant to healing. In this report we have systematically reviewed the English language literature to attempt to determine the potential clinical efficacy of extracorporeal shockwave therapy in fracture management. Of 32 potentially eligible studies identified, 10 were included that assessed the extracorporeal shockwave therapy use for healing nonunions or delayed unions, and one trial was included that assessed its use for acute high-energy fractures. From the included, studies' overall union rates were in favor of extracorporeal shockwave therapy (72% union rate overall for nonunions or delayed unions, and a 46% relative risk reduction in nonunions when it is used for acute high-energy fractures). However, the methodologic quality of included studies was weak and any clinical inferences made from these data should be interpreted with caution. Further research in this area in the form of a large-scale randomized trial is necessary to better answer the question of the effectiveness of extracorporeal shockwave therapy on union rates for both nonunions and acute fractures.
Background: Joint arthrodesis employing autogenous bone graft (autograft) remains a mainstay in the treatment of many foot and ankle problems. However, graft harvest can lead to perioperative morbidity and increased cost. We tested the hypothesis that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) homodimer combined with an osteoconductive matrix (beta-tricalcium phosphate [β-TCP]) would be a safe and effective alternative to autograft. Methods: A total of 434 patients were enrolled in thirty-seven clinical sites across North America in a prospective, randomized (2:1), controlled, non-inferiority clinical trial to compare the safety and efficacy of the combination rhPDGF-BB and β-TCP with those of autograft in patients requiring hindfoot or ankle arthrodesis. Radiographic, clinical, functional, and quality-of-life end points were assessed through fifty-two weeks postoperatively. Results: Two hundred and sixty patients (394 joints) underwent arthrodesis with use of rhPDGF-BB/β-TCP. One hundred and thirty-seven patients (203 joints) underwent arthrodesis with use of autograft. With regard to the primary end point, 159 patients (61.2% [262 joints (66.5%)]) in the rhPDGF-BB/β-TCP group and eighty-five patients (62.0% [127 joints (62.6%)]) in the autograft group were fused as determined by computed tomography at six months (p < 0.05). Clinically, 224 patients (86.2%) [348 joints (88.3%)]) in the rhPDGF-BB/β-TCP group were considered healed at fifty-two weeks, compared with 120 patients (87.6% [177 joints (87.2%)] in the autograft group (p = 0.008). Overall, fourteen of sixteen secondary end points at twenty-four weeks and fifteen of sixteen secondary end points at fifty-two weeks demonstrated statistical non-inferiority between the groups, and patients in the rhPDGF-BB/β-TCP group were found to have less pain and an improved safety profile. Conclusions: In patients requiring hindfoot or ankle arthrodesis, treatment with rhPDGF-BB/β-TCP resulted in comparable fusion rates, less pain, and fewer side effects as compared with treatment with autograft. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
1477 consecutive foot X-rays were reviewed over an 11-month period from the Lehigh Valley Hospital Center Emergency Services. 49 fifth metatarsal fractures were identified. Two transverse proximal diaphyseal fractures 3.0 cm distal from the fifth metatarsal tuberosity, the Jones fracture, were identified. The frequency of the Jones fracture in this group of fifth metatarsal fractures (n = 49) is 4%.
Recombinant human PDGF BB homodimer (rhPDGF-BB) is a potent recruiter of, and strong mitogenic factor for, cells crucial to musculoskeletal tissue repair, including mesenchymal stem cells (MSCs), osteogenic cells and tenocytes. rhPDGF-BB also up-regulates angiogenesis. These properties allow rhPDGF-BB to trigger the cascade of bone and adjoining soft tissue repair and regeneration. This mechanism of action has been established in numerous preclinical and clinical studies. Demonstration of the safety and efficacy of rhPDGF-BB in the healing of chronic foot ulcers in diabetic patients and regeneration of alveolar (jaw) bone lost due to chronic infection from periodontal disease has resulted in two FDA-approved products based on this molecule. A third product is in late stages of clinical development, with pilot and pivotal clinical studies of rhPDGF-BB mixed with an osteoconductive bone matrix (Augment® Bone Graft) in foot and ankle fusions demonstrating that this product is at least as effective as bone autograft, and has an improved safety profile. Additional combinations of rhPDGF-BB with tissue-specific matrices are also being studied clinically in additional musculoskeletal indications.
This paper is designed to be a guide to the classification and treatment of fifth metatarsal fractures. Types of fifth metatarsal fracture include: avulsion fracture of the tuberosity, proximal diaphyseal (Jones) fracture, proximal diaphyseal stress fracture, diaphyseal (shaft) fracture, and fractures of the neck and head. Diagnosis of these fractures can be made with a sound anatomical knowledge, identification of the mechanism of injury and previous symptoms, as well as appropriate X-ray examination. Confusion with diagnosis may occur due to the similarity of the proximal fractures on X-ray and the presence of normal variants around the base of the metatarsal. Treatment of fifth metatarsal fractures is usually conservative unless the fracture is a proximal diaphyseal fracture. Proximal diaphyseal fractures (Jones and stress) require long periods of nonweightbearing immobilization or internal fixation as they are prone to delayed union. Delayed union may occur due to the mechanics of the fifth metatarsal and the poor blood supply to the proximal diaphysis. To avoid unsatisfactory long-term results, clinicians must be aware of the different types of fifth metatarsal fracture, in particular the proximal diaphyseal fractures.