Use of the Bioabsorbable Activa IM-Nail™ in Pediatric Diaphyseal Forearm Fractures: a Cohort Study of 30 Patients
Phase: NA
Conditions: Fracture Fixation, Intramedullary, Forearm Fracture, Fracture Healing, Child, Only, Implant Complication
Sponsor: Children's Fractures Interest Group, Denmark

Date: 05/24/2021 
NCT ID: Not yet assigned. 
 
Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
Version 3.5 – May 2021 – Protocol ID: H-21004012 
 
 
 
 
 
 
Study protocol 
 
Use of the bioabsorbable Activa IM-Nail™ in pediatric 
diaphyseal forearm fractures: a cohort study of 30 patients 
 
Morten Jon Andersen, Peter Søndergaard, Bo Sanderhoff Olsen and Jeppe Vejlgaard Rasmussen 
 
Herlev and Gentofte University Hospital, Copenhagen, Denmark 
 
 
 
 
 
 
 
 
 
The Danish Data Protection Agency ID: P-2020-1197 
The Danish National Committee On Health Research Ethics ID: H-21004012 

Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
Version 3.5 – May 2021 – Protocol ID: H-21004012 
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Abstract ...................................................................................................................................................................................................... 3 
Introduction ................................................................................................................................................................................................ 4 
Background ................................................................................................................................................................................................. 4 
Epidemiology .......................................................................................................................................................................................... 4 
Treatment options .................................................................................................................................................................................. 4 
Metal Elastic Stable Intramedullary Nailing (ESIN) ................................................................................................................................... 5 
Hardware removal .................................................................................................................................................................................. 5 
Bioabsorbable implants .......................................................................................................................................................................... 5 
Objectives ................................................................................................................................................................................................... 6 
Primary objective .................................................................................................................................................................................... 6 
Secondary objectives............................................................................................................................................................................... 6 
Hypothesis .............................................................................................................................................................................................. 6 
Methods and materials ............................................................................................................................................................................... 6 
Study design ........................................................................................................................................................................................... 6 
Selection and withdrawal of participants................................................................................................................................................. 7 
Surgical technique and post-operative regime ......................................................................................................................................... 9 
Risks, side effects and disadvantages ...................................................................................................................................................... 9 
Variables .............................................................................................................................................................................................. 10 
Outcomes ............................................................................................................................................................................................. 11 
The Radiographic Union Score ............................................................................................................................................................... 11 
Faces Pain Scale – Revised (FPS-R) ......................................................................................................................................................... 11 
Visual analogue scale............................................................................................................................................................................ 12 
Bias ...................................................................................................................................................................................................... 12 
Study size ............................................................................................................................................................................................. 13 
Statistics ............................................................................................................................................................................................... 13 
Discussion ................................................................................................................................................................................................. 13 
Ethics and security .................................................................................................................................................................................... 13 
Ethics ................................................................................................................................................................................................... 13 
Identification of the implant .................................................................................................................................................................. 14 
Hospital records .................................................................................................................................................................................... 14 
Data security ........................................................................................................................................................................................ 14 
Publication ................................................................................................................................................................................................ 15 
Perspective ............................................................................................................................................................................................... 15 
Disclosures and economy .......................................................................................................................................................................... 15 
Literature .................................................................................................................................................................................................. 16 

Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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Abstract 
Background 
Pediatric diaphyseal forearm fractures are common and one of the most frequent reasons for orthopedic 
care. Fractures in need of surgery are often treated with metal Elastic Stable Intramedullary Nails (ESIN). 
Nail removal after 6-12 months is generally advocated. Surgical hardware removal has few complications; 
however, it is a substantial burden on the child, the family and healthcare economy. Bioabsorbable 
Intramedullary Nails (BIN) have been developed for the same indications as metal ESIN. The use of 
bioabsorbable implants would deem hardware removal unnecessary and relieve the child of further surgery 
and reduce healthcare costs. 
Methods 
We aim to recruit all children in the catchment area of Herlev and Gentofte University Hospital 
(Copenhagen, Denmark) with acute unstable diaphyseal forearm fractures. Participants will be operated 
with BIN and followed consecutively for 2 years with interim analysis of data after 6 months. We will report 
radiological healing using the Radiographic Union Score (RUS) 3 months after surgery together with any 
adverse events during follow-up. 
Discussion 
This study will provide important preliminary data and asses the feasibility of using the bioabsorbable 
Activa IM-Nail™ in pediatric diaphyseal forearm fractures. This study is a pilot study for initiating an RCT 
comparing BIN to metal ESIN hypothesizing that BIN is not an inferior treatment. 
Keywords 
Pediatric fracture, bioabsorbable implant, diaphyseal forearm fracture, intramedullary nails, BIN, ESIN 
 
 

Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
Version 3.5 – May 2021 – Protocol ID: H-21004012 
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Introduction 
Pediatric diaphyseal forearm fractures are common and one of the most frequent reasons for orthopedic 
care [1]. The fractures are often treated by surgical stabilization with metal Elastic Stable Intramedullary 
Nails (ESIN) [2]. Nail removal after 6-12 months is generally advocated [3–5]. Surgical hardware removal has 
few complications; however, it is a substantial burden on the child, the family and healthcare economy [6]. 
Bioabsorbable Intramedullary Nails (BIN) have been developed for the same indications as metal ESIN. The 
use of bioabsorbable implants would deem hardware removal unnecessary and relieve the child of further 
surgery and reduce the healthcare costs [7]. 
Background 
Epidemiology 
Fractures constitute 10-25% of all pediatric injuries. During childhood almost 50% of boys and 30% of girls 
will sustain a fracture. The type, pattern and cause of fracture varies from one country to another [8]. 
Pediatric diaphyseal fractures of the radius and/or ulna are one of the most common reasons for 
orthopedic care in children [1]. With an incidence of 6.8 (8.3 for boys and 5.2 for girls)/10.000 this injury 
accounts for 3-6% of all pediatric fractures [8,9], occurring primarily between the age of 5 and 14 (median 
8.5) [10]. The last three decades have shown a dramatic increase in the incidence of these fractures; 
however, the precise cause is unknown [2,8]. Speculations point to inactivity, obesity and vitamin D 
deficiency as causes for lowered bone mineral density and increasing numbers of pediatric fractures [11]. 
Treatment options 
Due to the complex relationship between the radius and ulna the prognosis is dependent on fractures 
healing without excess shortening, rotation or angulation. Historically minimally displaced diaphyseal 
forearm fractures have been managed successfully with closed reduction and casting [12]. The last two 
decades has shown a significant increase in the percentage of operatively managed fractures [13]. Non-
operative treatment requires less than 10-15° of angulation and less than 5 mm of shortening at the DRUJ. 
Re-displacement in the cast is seen in about 10% of cases and requires re-reduction or surgical fixation [12]. 
 
As with any other fracture, demand for better outcome has developed during the last two decades. There 
are especially strict demands for movement of the elbow, forearm and wrist. A functional range of 
movement was in 1981 declared as flexion/extension of 30-130 degrees and forearm rotation of 50-50 
degrees [14], but the study did not include children. More recent studies have reported that contemporary 
tasks such as using a mobile phone, tablet or a computer keyboard requires additional degrees of 

Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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movement [15,16]. Functional demand together with parental and socioeconomic pressure is expanding 
the indication for surgical stabilization of pediatric forearm fractures. 
The most common methods for treating unstable pediatric forearm fractures are open 
reduction and internal fixation (ORIF) using plates and screws or intramedullary (IM) nailing [17]. ORIF with 
plates and screws yields good reduction and a stable osteosynthesis, but also requires large soft tissue 
dissection and often also hardware removal.  
There is not enough evidence to support one surgical method over another but with the 
introduction of the minimally invasive ESIN, the proportion of this method has increased significantly 
[2,13,17,18] making this the preferred operative technique. 
Metal Elastic Stable Intramedullary Nailing (ESIN) 
The method of ESIN was introduced in the 1970s using Kirschner wires. In the 1990s ESIN specific implants 
became widely available. ESIN has since shown to produce excellent results with few complications [4,19]. 
Advantages include closed fracture reduction, minimal soft tissue dissection, early motion, sustained 
reduction and easy hardware removal. Complications are rare but do exist in the form of soft tissue 
irritation, superficial radial nerve injury, extensor pollicis longus tendon rupture, delayed union, malunion, 
refractures and infection [3,20,21]. 
Several metallic alloys have been used to produce ESIN implants. The most widely used is 
titanium (Ti6Al14V) which has suitable elastic properties [4]. The Titanium Elastic Nail System (DePuy 
Synthes, Raynham, Massachusetts, USA) is commonly used and has been used in our institution for several 
years. 
Hardware removal 
Removal of metal implants including ESIN after fracture surgery in children is currently the practice in 
Denmark and is sanctioned by the Danish Health Authority. Implant removal is done because of potential 
interference with the child’s growing skeleton, late tissue reactions, difficulty in late removal and concerns 
about stress shielding due to metal stiffness [22].  
Bioabsorbable implants 
It is important to retain a common and unified nomenclature within this research field. Liu et al. [23] 
suggest that foreign implants or other kinds of biomaterials eventually absorbed by the body be labeled as 
“absorbable” or with the prefix “bio”. The term “absorbable” focuses on the host’s metabolism of degraded 
products of the implanted material. Within this study protocol and the final manuscript, we will adhere to 
the label “bioabsorbable implants”. 

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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Bioabsorbable implants have been known since the 1970s and over the years many different 
materials have been investigated. The use of bioabsorbable implants is increasing and has proved a safe 
and feasible method of stabilizing fractures in the growing skeleton [24–26]. By using bioabsorbable 
implants the need for implant removal is overcome and risks of late tissue reactions, stress shielding and 
infections are lowered [27]. 
Implants made from oriented poly L-lactide-co-glycolide (PLGA) copolymers are strong 
enough to support fractured bones. The monomers of PLGA are L-lactic acid and glycolic acid, which are 
part of the normal metabolic chemistry of human cells. PLGA implants undergo a controlled degradation 
through hydrolysis forming lactic acid and glycolic acid which are absorbed by the cells and metabolized 
into carbon dioxide and water. The implant retains strength and size for at least eight weeks and over the 
course of approximately two years the implant will be completely absorbed [28]. Medical grade PLGA 
implants manufactured by Bioretec Ltd. (Hermiankatu 22, Tampere, Finland) are sterilized with gamma 
radiation. Gamma radiation also reduces molecular weight of oriented PLGA implants. The reliability and 
safety of the Activa IM-Nail™ has been described in the manufacturer’s premarket trials and one RCT [7], 
the implant is FDA and CE approved for the same purpose as in the present study.  
Objectives 
Primary objective 
The primary objective of this study is to evaluate the amount of radiological healing three months after 
surgery with the Activa IM-Nail™ for pediatric diaphyseal forearm fractures. 
Secondary objectives 
The secondary objectives are to report the functional outcome, calculate refracture rate and any other 
complications up to two years following surgery and to describe MRI findings two years after insertion of 
Activa IM-Nail™. 
Hypothesis 
We hypothesize that radiological healing is established three months after surgery with the Activa IM-
Nail™. 
Methods and materials 
Study design 
We use a cohort study design [29] conformed to the STROBE Statement [30]. We aim to recruit all children 
with diaphyseal forearm fractures (cohort) operated with BIN (exposure) and report radiological healing 

Study protocol - Use of the bioabsorbable Activa IM-Nail™ 
 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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(outcome). This study design is relevant in reporting radiological healing and calculating absolute risk of 
adverse events based on the exposure in our cohort. 
Selection and withdrawal of participants 
Setting 
The study will be performed in the Capital Region of Denmark, Europe. Patients in Herlev and Gentofte 
University Hospital’s catchment area (population 700.000 of which 80.000 are children age 3-15) are 
eligible for recruitment.  
Participants 
This study investigates the treatment of pediatric forearm fractures; therefore, this study cannot be 
conducted in consenting adults. Forearm fractures occur in all age groups and thus it is not possible to 
select only older children for inclusion. This study is believed to have great positive implications for the 
participants and successive patients with the same condition. 
Participants eligible for recruitment are patients from 2 years of age until physeal closure with an acute 
traumatic diaphyseal forearm fracture of the radius, ulna or both. Fractures need to be complete (not 
unicortical or green stick) and displaced more than 50% of bone width or angulated more than 10° in any 
plane or irreducible or unstable after reduction. 
 
We exclude patients 
• 
with fractures that are well managed conservatively (undisplaced or minimally displaced) 
• 
with previous ipsilateral forearm fracture 
• 
with fractures unsuited for intramedullary nailing (e.g. multifragmentary, metaphyseal or 
epiphyseal) 
• 
with fractures with ipsilateral wrist or elbow involvement (e.g. Monteggia or Galeazzi variants) 
• 
unable to participate in follow-up 
• 
with existing bone pathology (e.g. tumor, osteogenesis imperfecta, degenerative disease) 
• 
in whom internal fixation is otherwise contraindicated (e.g. active or potential infection)  
 
Recruitment 
Recruitment starts May 25th, 2021 and is estimated to take 12 months. Patients may be seen primarily in 
our Emergency Department (ED) or referred by local clinics or another hospital. Patients with displaced 
forearm fractures are reviewed daily by the department’s trauma surgeons. Any patients eligible for 
recruitment are referred to the PI for evaluation. Eligible patients are contacted by the PI and invited to a 

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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scheduled visit as soon as possible. The parents are informed of the possibility of bringing an assessor. 
Parents, and when applicable the child, are informed face-to-face about the project. Parents are given both 
oral and written information. Patients are recruited at Herlev and Gentofte University Hospital by the 
principal investigator (PI). 
Informed consent 
Children are not able to give informed consent to participate in a study. Therefore, all legal guardians are 
asked to consent on behalf of the child. Oral and written information about the study, together with 
general information about participating in a research project from the Danish National Committee on 
Health Research Ethics is given face-to-face by the PI prior to asking for consent. Information is given in an 
undisturbed environment at the pediatric ward. The PI is the head of pediatric orthopedic trauma and is 
very skilled in communication with both parents and injured children. 
Unstable or displaced diaphyseal forearm fractures usually do not require emergent 
treatment, but we strive to treat fractures as soon as possible. In planning, both surgeons and operating 
personnel need time to prepare for the specific procedure. Therefore, we ask that consent is given the day 
before surgery at the latest. Parents will in most cases have at least 24 hours to consider enrollment 
however, there might be factors (e.g. open fracture or neurovascular compromise) that dictate more 
emergent treatment requiring consent with less consideration time. 
If participation is declined the patient will receive standard treatment with TEN, and 
standard rehabilitation and follow-up after 2 and 6 weeks and 6 months. TEN will be removed 
approximately 6 months after insertion during a scheduled outpatient operation under general anesthesia. 
Follow-up 
Outpatient visits are scheduled at 2 and 6 weeks, 3 and 6 months and 1 and 2 years following surgery. 
All participants live in the catchment area of our hospital with short transportation time. Information about 
the time and place for the follow-up examination is sent via the electronic health record (EHR) and 
physically by mail to the current address registered in the Civil Registration System. Parents are usually very 
keen to take their children for follow-up appointments making the risk of missing an appointment low. Any 
participants who miss an appointment will be contacted by phone to reschedule. 
Withdrawal 
If a participant chooses to discontinue the follow-up examinations for any reason, the date and reason for 
drop-out is recorded and the latest examination will be carried forward in the analysis. In case of 
reoperation, the patients continue with their follow-up examinations and they are included in the 2-year 
analysis. In case of drop-out before the first follow-up visit the participant will be excluded from the 

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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analysis. The author will record any protocol violations. Participants are only removed from the study if 
they decline participation. 
Surgical technique and post-operative regime 
The preoperative investigations are the same as for operations with a conventional metal implant. They 
consist of clinical history, physical examination and radiographs in anterior-posterior (AP) and medial-
lateral (ML) plane. All operations will take place at our hospital and will be carried out by one of five 
experienced orthopedic trauma surgeons. The surgical procedure is almost identical with that of metal ESIN 
except the exchange to a bioabsorbable implant after dilation of the medullary canal. 
The Activa IM-Nail™ is implanted according to the manufacturer’s surgical technique. Operations are 
performed under general anesthesia together with a peripheral nerve block (PNB) [31]. Prophylactic 
antibiotics are given in the form of cloxacillin with dose according to the patient’s weight. In the case of 
allergy towards cloxacillin, cefuroxime will be used as an alternative. Patients are in the supine position 
with the injured arm on a radiolucent arm table. One incision is made over the radial aspect of the distal 
radius taking care not to harm the dorsal branch of the superficial radial nerve. Another incision is made 
over the radial aspect of the proximal ulna. The customized instrumentation for the Activa IM-Nail™ is 
used. The cortical bone is opened using an awl and an appropriate size dilator is used. The dilator is 
replaced with the appropriate size bioabsorbable nail under image intensification to the desired depth and 
the implant is cut flush with the cortical surface. Wounds are closed using absorbable sutures and dressed. 
The injured arm is put in an above elbow posterior splint. Post-operative radiographs are taken. The patient 
is discharged when the effect of the PNB has worn of and the child is well, either on the same day or day 
after surgery. No formalized physiotherapy or rehabilitation is given beside oral and written information on 
exercises. 
Risks, side effects and disadvantages 
Based on previous studies using the Activa IM-Nail™ [7] we predict that the risk of side effects is 
comparable or less than those seen with metal ESIN. 
Infection 
Any surgery caries the risk of infection, however previous studies have shown close to no infection risk 
[3,32] with the ESIN procedure. 
Nerve complications 
Studies have shown a 5% risk of nerve injury [32], however all cases had spontaneous recovery of nerve 
function. 

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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Extra visits to the outpatient clinic 
We follow all patients with six visits to the outpatient clinic. This is three more than with standard 
treatment and might be viewed as a disadvantage. 
Radiation 
Three extra radiographs are obtained during outpatient visits. A radiograph of an extremity leads to a 
radiation dose of less than 0.001 mSv and compares to 3 hours of background radiation. Three extra 
radiographs is far below the threshold of 0.1 mSv. 
MRI 
Two years after surgery an MRI is performed. We follow a special MRI-protocol without the need for 
sedation or anesthesia. 
Variables 
At recruitment baseline data will be collected:  
• 
Demographic data (age, gender, handedness, height and weight) 
• 
Injury data (date and time, left or right arm, location, activity, mechanism, open or closed fracture, 
diagnosis code, indication for surgery) 
• 
Historical data (metabolic disease, medication, other systemic illness) 
 
After surgery, operative data is collected (date and time of surgery, operative time, closed or open 
reduction, any complications). 
During follow-up in the outpatient clinic data will be collected on: 
• 
Pain (Faces Pain Scale - Revised) or VAS according to child’s age 
• 
Use of pain medication 
• 
Wound appearance (visible signs of infection) 
• 
Neurovascular status 
• 
Bilateral elbow and forearm range of motion (ROM) measured in degrees by goniometer 
• 
Forearm radiographs in AP and ML planes (Radiographic Union Score) 
 
2 years following surgery MRI findings (absorption of the nail, activity at fracture site, soft-tissue reactions) 
will be collected.  

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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Outcomes 
The primary objective is quantified using the Radiographic Union Scale (RUS) [33] based on degree of callus 
formation and visibility of fracture line on AP and ML plain radiographs. We define established healing as a 
RUS of > 9. 
Secondary objectives are described as absolute risk of refracture, time to established healing (weeks), pain 
(Faces Pain Scale – Revised (FPS-R) or visual analogue scale (VAS)), elbow and forearm range of motion (in 
degrees), visible signs of infection, neurovascular complications and any reoperation. MRI findings 
(absorption of the nail, activity at fracture site, soft-tissue reactions) after 2 years are described. 
The Radiographic Union Score 
Fracture healing based on plain radiographs has largely been a subjective evaluation by the orthopedic 
surgeon. Whelan et al. developed the Radiographic Union Score (RUS) in order to quantify healing in tibial 
fractures [33]. RUS is a score derived from assessing AP and lateral radiographs. Each cortex (anterior, 
posterior, medial and lateral) is assigned a score of 1 to 3. A cortex with a visible fracture line and no callus 
is given a score of 1, a cortex with callus but a visible fracture line is scored as 2 and a cortex with bridging 
callus and no visible fracture line is scored as 3 (Table 1). Scores are added to give a minimum score of 4 
(not healed) and a maximum of 12 (healed). 
Table 1 – The Radiographic Union Score 
Score per cortex 
Callus 
Fracture line 
1 
Absent 
Visible 
2 
Present 
Visible 
3 
Present 
Not visible 
Table 1 - The individual cortical scores (anterior, posterior, medial, and lateral) are added to provide a RUS of 4 (definitely not 
healed) to 12 (definitely healed). 
RUS has since been shown to be a reliable and repeatable outcome measure to assess fracture healing, not 
only in the tibia [34–36]. RUS has also been shown to correlate well with physical properties of healing and 
a RUS of > 9 to be equal to established bone healing [37]. We find that the use of RUS is warranted in 
quantifying healing in our population. The surgeon who sees the patient in the outpatient clinic will 
calculate RUS. 
Faces Pain Scale – Revised (FPS-R) 
To measure the outcome of pain in children below 8 years of age we use the Faces Pain Scale – Revised 
(FPS-R) [38]. It is a self-report measure of pain intensity developed for children. It was adapted from the 
Faces Pain Scale [39] to make it possible to score the sensation of pain on the widely accepted 0-to-10 

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 in pediatric diaphyseal forearm fractures: a cohort study of 30 patients 
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metric. The scale shows a close linear relationship with visual analog pain scales (VAS) across the age range 
of 4-16 years. It is easy to administer and requires no equipment except for the photocopied faces (Figure 
1). The child is asked to point to the face that shows how much pain the child is in at that moment. Faces 
are scored 0-10 so 0 equals no pain and 10 equals very much pain. 
 
Figure 1 – Faces of the FPS-R. The child is instructed to point to the faces that shows how much pain the child is in at that moment. 
Faces are scored 0, 2, 4, 6, 8 or 10 from left to right. 
 
Visual analogue scale 
To quantify pain in children age 8 and above we will use a visual analogue scale (VAS) (Figure 2). VAS has 
been extensively investigated in quantifying pain in older children [40,41]. The child is asked to put a mark 
on the line corresponding to the child’s pain at that moment. A mark to the far left equals no pain and a 
mark to the far right equals worst possible pain. The line is 10 cm long and the child’s mark is measured 
from left to right in cm with one decimal e.g. 3.4 cm equaling a VAS of 3.4. If the child cannot cooperate to 
using VAS, FPS-R is used instead. 
 
Figure 2 - Visual analogue scale (VAS) for quantifying pain in children age 8 and above. 
 
Bias 
We strive to minimize bias in our study. Displaced forearm fractures do not go unnoticed. A strict protocol 
for referrals for treatment are in place in Denmark. All eligible patients referred to Herlev and Gentofte 
University Hospital will be asked to participate in the study. We speculate that by enrolling 30 participants 
the cohort will be representative of the background population. We speculate that these efforts will limit 

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selection bias. Efforts described in the follow-up section reduce the risk of loss to follow-up. Overall, we 
find a low risk of bias in our study for the chosen study design and size. 
Study size 
The surgical procedure for the Activa IM-Nail™ resembles that of TEN very much and performing surgeons 
are all experienced traumatologists. All surgeons will be thoroughly introduced to the procedure, the 
instruments and the implants, thereby minimizing learning curve phenomenon. We predict that 30 
participants will be sufficient in establishing the basis for planning a randomized trial. 
Statistics 
Data will be analyzed using SPSS (SPSS, Chicago, IL, USA). Descriptive statistics will be used to present the 
patient-related data, number of dropouts, radiological outcome and number of complications (categorical 
variables). Age and functional outcome (continuous variables) are expected to be expressed as medians 
with interquartile ranges. Changes in functional outcome between measurements are expected to be 
analyzed using Friedman test for related non-parametric data. A p-value of <0.05 is regarded as being 
significant. 
Discussion 
Operative treatment with metal ESIN is the preferred technique for stabilizing pediatric forearm fractures. 
Removal of the metal nails is generally advocated in many countries including Denmark. By using BIN, a 
second operation to remove the nails is avoided. 
The hypothesis is that satisfactory fracture healing is accomplished 3 months after operation with BIN. The 
only previous study on BIN used forearm rotation and not fracture healing as primary outcome [7]. The 
authors describe that all 15 fractures operated with BIN had healed after 2 years. 
The cost of one Activa IM-Nail™ ($400) is approximately 4 times higher compared with a traditional TEN 
($100). However the cost of implant removal is approximately $1900 [7,42] and the extra implant costs are 
readily balanced out. 
Ethics and security 
Ethics 
The implant is CE approved for the same indications as the use in this study. Permission from the Danish 
Data Protection Agency is obtained before the inclusion is initiated. The trial will be conducted in 
accordance with the Declaration of Helsinki of 1996 and principles of good clinical practice. 

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As with any treatment in the Danish healthcare system all patients are insured and covered by The Patient 
Compensation Association (Patienterstatningen). 
To quantify any unknown side effects or complications an interim analysis of data will be performed 6 
months after recruitment of the last patient. An absolute refracture rate of more than 25% is not tolerated 
and will be a criterion for stopping the study. 
In comparison with the standard follow up of pediatric forearm fractures there are 3 additional visits to the 
out-patient clinic with radiographs of the forearm in AP and ML view. Collectively, the effective dosage is 
0.003 mSv - far below 0.1 mSv and is considered insignificant. 
Identification of the implant 
The traceability of the device is identified by device name, catalogue number (REF) and batch number 
(LOT). 
Hospital records 
No access to the patient’s EHR regarding the study is made before informed consent to participate is given. 
In order to plan and conduct visits, admission and operation we ask that consent is given to access the 
patient’s EHR. We ask permission to retrieve patient-related data and to read entries regarding visits, 
admission and operation. We ask permission to access radiographs and MRIs.  
We ask that access the patient’s EHR is given until the conclusion of the project. 
Consent gives the person responsible for the trial and the relevant authorities direct access to obtain 
information in the patient's medical record for the purpose of carrying out the project as well as for control 
purposes. 
Data security 
The patient’s hospital records are stored securely in the hospital’s EHR (Epic Systems Corporation, Verona, 
Wisconsin, USA). 
The project’s Electronic Case Report Form (eCRF) is stored securely using Research Electronic Data Capture 
(RedCAP, Vanderbilt University, USA).  
Radiographs and MRIs are stored in the hospital’s Picture archiving and communication system (PACS). 
The project complies with the EU’s General Data Protection Regulation (GDPR) according to the Danish law 
on data protection Databeskyttelsesloven and Databeskyttelsesforordningen. 

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Publication 
The study will be reported to ClinicalTrials.gov before trial initiation.  
The results, both positive, negative and inconclusive, will be sent for submission in a peer reviewed 
international orthopedic journal, and the results will be presented at national and international scientific 
meetings. Reporting will adhere to the STROBE guidelines for cohort studies [30]. 
Perspective 
If proven safe and effective, the use of BIN would deem hardware removal unnecessary and relieve the 
child of further surgery and reduce the healthcare costs. 
This study is a pilot for a randomized controlled trial comparing the Activa IM-Nail™ (Bioretec Ltd., 
Hermiankatu 22, Tampere, Finland) to the Titanium Elastic Nail System (TEN) (Depuy Synthes, Raynham, 
Massachusetts, USA) which is currently used for pediatric forearm fractures in our hospital. This pilot study 
will diminish any learning curve, evaluate the clinical safety of the implant, and test the recruiting and 
follow-up of patients before embarking on the RCT. 
Disclosures and economy 
The initiative for this study has been taken solely by the authors. 
The authors and affiliated colleagues have not received any financial payments or other benefits from any 
commercial entity related to the subject of this study. The authors declare that they have no conflict of 
interest. 
Participants do not receive any economic benefits or gifts from the participation in this project. 

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