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PRECICE Intramedullary Limb Lengthening System: A Review of Clinical Effectiveness

CADTH Rapid Response Report: Summary With Critical Appraisal

and .

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; .

Context and Policy Issues

Limb lengthening procedures have been of great interest to orthopedic surgeons since the early 20th century, when Italian surgeon Alessandro Codivilla published a paper detailing the use of Codivilla’s nail to accomplish lower limb lengthening.1-3 Over the course of the next century, a greater understanding of the physiology of the bone has led to major advances in the techniques and devices used for limb lengthening.1,4 There is currently a wide selection of limb lengthening techniques and appliances for orthopedic surgeons to utilize in their practice. These include unilateral external fixation, external ring fixation (e.g., Ilizarov technique), lengthening over nail, and intramedullary lengthening nails.1,4,5 Intramedullary lengthening nails can further be classified as either mechanically activated nails, motorized nails, or magnetically driven nails.3,6 These devices can be employed to correct both congenital and acquired problems, including femoral deficiencies, tibial aplasia, achondroplasia, rickets, Blount’s disease, osteogenesis imperfecta, Ollier’s disease, post-traumatic growth arrest, avascular necrosis, congenital femoral deficiency, and fibular hemimelia, among many others.4,7

The PRECICE system is one of the more recently developed intramedullary lengthening implants.3,8 It is a magnetically driven implantable limb lengthening intramedullary nail that can be adjusted using a remote control.3 Internal nails may offer a solution to some of the problems associated with external fixation devices, including soft tissue scarring, muscle tethering, and inflammation and infection caused by the wires and pins.1,5,6,9 In addition, internal devices may be more convenient due to their concealed nature and may provide patients with benefits to their pain and discomfort.1,3,5,8,9

The purpose of this report is to summarize and critically appraise the evidence available regarding the clinical effectiveness of the PRECICE intramedullary limb lengthening system for the correction of lower or upper limb deformities in adults and children. This report will be complementary to a previous CADTH report, published in 2017, entitled “Intramedullary Distraction Devices for Lower-Limb Lengthening: Clinical Effectiveness and Guidelines,”10 that identified literature on the clinical effectiveness of intramedullary distraction devices for patients requiring lower-limb lengthening.

Research Question

What is the clinical effectiveness for the use of the PRECICE intramedullary system for the correction of lower or upper limb deformities in adults and children?

Key Findings

Evidence from three non-randomized studies was identified regarding the clinical effectiveness for the use of the PRECICE intramedullary system for the correction of lower or upper limb deformities in adults and children. Overall, the evidence appeared to support the use of the PRECICE nail, which was generally favoured or considered equivalent to either limb reconstruction system external fixation or the intramedullary skeletal kinetic distractor system for the outcomes assessed. Limitations of the evidence, including variation in the length of follow-up, a study sample sizes, and a lack of randomization to treatment arms, made it difficult to draw definitive conclusions regarding the clinical effectiveness of the PRECICE nail.

Methods

Literature Search Methods

This report makes use of a literature search developed for a previous CADTH report.10 The original limited literature search was conducted in April 2017 on key resources including MEDLINE, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and guidelines. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 01, 2012 and April 11, 2017 year. Internet links were provided, where available. The original search was supplemented by a second limited literature search conducted in November 2017 on key resources PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases and a focused Internet search. No methodological filters were applied to limit retrieval by publication type. The second search was limited to English language documents published between February 1, 2017 and November 10, 2017

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.

Table 1. Selection Criteria.

Table 1

Selection Criteria.

Exclusion Criteria

Articles were excluded if they did not meet the selection criteria outlined in Table 1, they were duplicate publications, or were published prior to 2012. Uncontrolled, single-arm trials were also excluded.

Critical Appraisal of Individual Studies

The included non-randomized studies (NRS) were critically appraised using the Downs and Black checklist.11 Summary scores were not calculated for the included studies; rather, a review of the strengths and limitations of each included study were described narratively.

Summary of Evidence

Quantity of Research Available

A total of 616 citations were identified in the literature search. Following screening of titles and abstracts, 596 citations were excluded and 20 potentially relevant reports from the electronic search were retrieved for full-text review. Additionally, three potentially relevant publications were retrieved from the grey literature search. Of these 23 potentially relevant articles, 20 publications were excluded for various reasons, while three publications met the inclusion criteria and were included in this report. Appendix 1 describes the PRISMA flowchart of the study selection.

Additional references of potential interest are provided in Appendix 5.

Summary of Study Characteristics

Three NRS7,12,13 published were included in this report. Detailed characteristics of the individual studies included in this report are provided in Appendix 2.

Study Design

Three relevant NRS were identified.7,12,13 All three studies were retrospective reviews of patients who underwent limb lengthening with either the PRECICE intramedullary limb lengthening system or an alternative limb lengthening system.7,12,13

Year of Publication and Country of Origin

The NRS by Szymczuk et al.12 and Hammouda et al.7 were both conducted at the Sinai Hospital of Baltimore in the United States. These two studies were both published in 2017.7,12 The NRS by Laubscher et al.,13 which was published in 2016, included patients at the Royal National Orthopaedic Hospital in the United Kingdom.

Patient Population

The study by Szymczuk et al.12 included 62 patients diagnosed with congenital femoral deficiency, with or without fibular hemimelia, who underwent femoral lengthening. Patients were included if their surgery was between January 2006 and January 2015, and follow-up information was available for a minimum of one year after their surgery.12 The mean age of patients in years was 9.4 (± 3.8) and 15.4 (± 4.9) in the two treatment groups.12

Twenty-nine skeletally immature patients younger than 18 years of age (between ages 7-17 years old) were recruited for the Hammouda et al.7 study. This study included 17 males and 11 females, who underwent femoral lengthening with a reamed intramedullary lengthening nail inserted through the greater trochanter.7 Patients, who were not followed-up for a minimum of one year, were excluded.7

The study by Laubscher et al.13 recruited 22 skeletally mature patients, who underwent a total of 33 femoral lengthening procedures between September 2009 and October 2014. Patient age ranged between 15 and 57 years.13 The patients who underwent bilateral lengthening were treated as separate cases for the analysis.13 Lengthening was performed in 22 male femurs and 11 female femurs.13

Interventions and Comparators

Two studies 12,13 compared the PRECICE intramedullary nail with external fixation using the limb reconstruction system (LRS) for patients who underwent femoral lengthening.

One study7 evaluated the clinical outcomes of patients following femoral lengthening with either the PRECICE nail or the intramedullary skeletal kinetic distractor (ISKD).

Outcomes

Three studies 7,12,13 assessed femoral lengthening achieved and rate of complications or adverse events. Range of motion, or preservation of range of motion, was measured in two studies.12,13 One study12 evaluated distraction index and consolidation index. Another study13 evaluated rate of lengthening, modified healing index, time to full weight bearing, and several patient reported outcomes, including scar appearance satisfaction, mean visual analog score for pain, and ability to perform activities of daily living.

Summary of Critical Appraisal

The critical appraisal of the studies is summarized below and details are presented in Appendix 3.

Due to the non-randomized nature of these studies, all three included publications were susceptible to a number of biases that may have influenced the effectiveness of their results. For example, none of these studies considered potentially confounding characteristics when forming treatment groups or when analyzing the outcomes measured.7,12,13

There were differences in the time of follow-up and age of patients between treatment groups in all studies,7,12,13 which may have had an effect on the measurement of outcomes. The authors of one study12 noted that the PRECICE nail was used in patients older than 9 years of age, but the LRS system was used in children as young as 3 years old. This approach may have resulted in the LRS group being overrepresented by potentially higher risk patients. In all three NRS,7,12,13 the patients and outcome assessors were aware of their treatment interventions (unblinded). In two studies,7,12 the characteristics of patients that were excluded from the study due to insufficient follow-up data were not described. One study13 relied on patient interviews following the completion of their treatment for data on patient pain, ability to perform activities of daily life, and patient preference to repeat their procedure with the same lengthening system. Because of the time between treatment and patient interviews, this information would be susceptible to a recall bias. Several of the authors of one study7 disclosed financial ties to companies involved with limb lengthening devices, including Ellipse Technologies, the developer of the PRECICE system. In addition, the sample sizes ranged from 22 in the Laubscher et al.13 study to 62 in the Szymczuk et al.12 study.

Along with these limitations, several strengths were identified for the included literature. In the three NRS,7,12,13 the objective, inclusion and exclusion criteria, interventions of interest, and main outcomes were explicit and described with an appropriate amount of detail. Patient characteristics, including age, gender, patient history, and underlying etiology were also stated. Patients appeared to be recruited to both treatment groups throughout the same time period. Because these were retrospective reviews, patient populations, staff, and care settings are likely representative of those of interest, which should increase the generalizability of the results.

Summary of Findings

The overall findings of the included literature are summarized below. A detailed summary of the main findings are available in Appendix 4.

What is the clinical effectiveness for the use of the PRECICE intramedullary system for the correction of lower or upper limb deformities in adults and children?

Mean Lengthening Achieved

Three NRS7,12,13 assessed the outcome of mean lengthening achieved in patients undergoing limb lengthening with the PRECICE intramedullary system. Szymczuk et al.12 and Laubscher et al.13 reported higher mean femoral lengthening with LRS fixation compared to the PRECICE nail. However, these studies 12,13 also reported similar lengthening goal achievement rates for both treatment groups. Neither comparison in either study achieved statistical significance.12,13

One NRS7 observed a higher mean lengthening achieved in the PRECICE group compared to the ISKD group. Although lengthening goals were not explicitly stated, it appears as if all patients reached their target lengths.7

Range of Motion

Range of motion (i.e.,movement) was evaluated in two of the identified studies.12,13 Szymczuk et al.12 provided a series of values corresponding to range of motion patients were capable of throughout the lengthening process. These numbers are presented in Appendix 4. The authors noted that a significant decrease in the range of motion at the end of lengthening and at consolidation was observed in external fixation patients, despite similar values for preoperative flexion between groups.12

The study by Laubscher et al.13 assessed the preservation of knee range of movement following lengthening. The authors reported a higher rate of full preservation of range of motion in the PRECICE group than in the LRS group.13

Adverse Events

Adverse events were monitored and reported in all three identified NRS.7,12,13 The authors generally reported insignificant differences in rates of adverse events between the PRECICE and LRS groups. One exception was the number of pin site or superficial infections, which were observed to occur more frequently in patients who underwent LRS lengthening in two studies.12,13 The NRS7 comparing the PRECICE nail to the ISKD nail reported an increased complication rate in the ISKD group. This difference, however, did not reach statistical significance.

Patient-reported Outcomes

The NRS by Laubscher et al.13 evaluated patient-reported outcomes in the PRECICE and LRS groups, which were gathered by interview following the completion of their treatment. Patients in the PRECICE group were more satisfied with the cosmetic appearance of their scaring following lengthening, experienced less pain (as measured with the mean visual analogue score), and were more likely to be able to perform their activities of daily living throughout lengthening.13

Limitations

Although a number of limitations were identified in the critical appraisal of the studies, additional shortcomings exist. Overall, insufficient evidence, which provided answers to our research question, was available. No relevant health technology assessments, systematic reviews, meta-analyses, or randomized controlled trials were identified regarding the clinical effectiveness of the use of the PRECICE intramedullary system for the correction of lower or upper limb deformities in adults and children. All three studies included in this report were non-randomized, and, therefore, were susceptible to a number of biases to which these types of studies are prone. In addition to the number of publications identified (N=3), the sample sizes ranged from 2213 to 6212 patients.

The Laubscher et al.13 study focused on skeletally mature patients, resulting in a limited amount of data to draw upon when making treatment decisions for this group. Additionally, all three studies 7,12,13 considered patients undergoing femoral lengthening only, meaning that no evidence regarding the clinical effectiveness of the PRECICE nail for the lengthening of other bones or limbs was identified.

Finally, the studies were conducted in the United States 7,12 and the United Kingdom;13 hence generalizability to the Canadian setting is unclear.

Conclusions and Implications for Decision or Policy Making

Three relevant publications, comprised of three NRS, were identified. The PRECICE nail was generally favoured or considered equivalent to either LRS external fixation or the ISKD system for the outcomes assessed.7,12,13 Regarding the mean lengthening achieved, two studies12,13 observed a higher value in the LRS group than in the PRECICE group. One study7 found the mean lengthening achieved to be higher in the PRECICE group compared to the ISKD group. However, these differences did not achieve statistical significance, and the femur lengthening goal was achieved in a large majority of patients, regardless of their treatment group.7,12,13 Two studies 12,13 that monitored range of motion reported better movement in the PRECICE groups, although this difference was not always statistically significant. One observation made in these studies12,13 is that the PRECICE nail was less prone to pin site of superficial infections than LRS external fixation.

Although the results indicate favourable outcomes for patients undergoing lengthening with the PRECICE nail, decision-makers must take into consideration the limitations of these studies that were identified in this report. In addition, the authors of one study12 advised that the PRECICE nail is not as practical in children with congenital femoral deficiency under the age of 9, whereas the monolateral external fixator can be used in children as young as 3 years of age. This suggests that patient characteristics must be considered when deciding on the appropriate treatment for the target population.

References

1.
Birch JG. A brief history of limb lengthening. J Pediatr Orthop. 2017 Sep;37 Suppl 2:S1-S8. [PubMed: 28799987]
2.
Green SA. The evolution of remote-controlled intramedullary lengthening and compression nails. J Orthop Trauma [Internet]. 2017 Jun [cited 2017 Nov 15];31(Suppl 2):S2-S6. Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC5426692 [PMC free article: PMC5426692] [PubMed: 28486283]
3.
Calder PR, Laubscher M, Goodier WD. The role of the intramedullary implant in limb lengthening. Injury. 2017 Jun;48 Suppl 1:S52-S58. [PubMed: 28449859]
4.
Hasler CC, Krieg AH. Current concepts of leg lengthening. J Child Orthop [Internet]. 2012 Jun [cited 2017 Nov 15];6(2):89-104. Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC3364349 [PMC free article: PMC3364349] [PubMed: 23730339]
5.
Tiefenboeck TM, Zak L, Bukaty A, Wozasek GE. Pitfalls in automatic limb lengthening -first results with an intramedullary lengthening device. Orthop Traumatol Surg Res [Internet]. 2016 Nov [cited 2017 Nov 15];102(7):851-5. Available from: http://www​.sciencedirect​.com/science/article​/pii/S1877056816300883?via%3Dihub [PubMed: 27527249]
6.
Wiebking U, Liodakis E, Kenawey M, Krettek C. Limb lengthening using the PRECICE™ nail system: complications and results. Arch Trauma Res [Internet]. 2016 Dec [cited 2017 Nov 15];5(4):e36273. Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC5253187 [PMC free article: PMC5253187] [PubMed: 28144605]
7.
Hammouda AI, Jauregui JJ, Gesheff MG, Standard SC, Herzenberg JE. Trochanteric entry for femoral lengthening nails in children: is it safe? J Pediatr Orthop. 2017 Jun;37(4):258-64. [PubMed: 28481811]
8.
Schiedel FM, Vogt B, Tretow HL, Schuhknecht B, Gosheger G, Horter MJ, et al. How precise is the PRECICE compared to the ISKD in intramedullary limb lengthening? Reliability and safety in 26 procedures. Acta Orthop [Internet]. 2014 Jun [cited 2017 Nov 15];85(3):293-8. Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles/PMC4062798 [PMC free article: PMC4062798] [PubMed: 24758320]
9.
Popkov A, Foster P, Gubin A, Borzunov D, Popkov D. The use of flexible intramedullary nails in limb lengthening. Expert Rev Med Devices. 2017 Sep;14(9):741-53. [PubMed: 28817981]
10.
Young C, Farrah K, Frey N. Intramedullary distraction devices for lower-limb lengthening: clinical effectiveness and guidelines [Internet]. Ottawa (ON): CADTH; 2017 Apr 18 [cited 2017 Nov 15]. (CADTH rapid response report: reference list). Available from: https://www​.cadth.ca​/sites/default/files​/pdf/htis/2017/RA0904​%20Lower-Limb%20Lengthening%20Final.pdf
11.
Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health [Internet]. 1998 Jun;52(6):377-84. Available from: http://www​.ncbi.nlm.nih​.gov/pmc/articles​/PMC1756728/pdf/v052p00377.pdf [PMC free article: PMC1756728] [PubMed: 9764259]
12.
Szymczuk VL, Hammouda AI, Gesheff MG, Standard SC, Herzenberg JE. Lengthening with monolateral external fixation versus magnetically motorized intramedullary nail in congenital femoral deficiency. J Pediatr Orthop. 2017 Jul 28. [PubMed: 31503231]
13.
Laubscher M, Mitchell C, Timms A, Goodier D, Calder P. Outcomes following femoral lengthening: An initial comparison of the PRECICE intramedullary lengthening nail and the LRS external fixator monorail system. Bone Joint J. 2016 Oct;98-B(10):1382-8. [PubMed: 27694593]

Abbreviations

IM

intramedullary

ISKD

intramedullary skeletal kinetic distractor

LRS

limb reconstruction system

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

NR

not reported

NRS

non-randomized study

Appendix 1. Selection of Included Studies

Image app1f1

Appendix 2. Characteristics of Included Publications

First Author, Publication Year, CountryStudy DesignPatient CharacteristicsIntervention(s)Comparator(s)Clinical Outcomes, Length of Follow-up
Szymczuk et al., 201712

United States		NRS, retrospective reviewPatients diagnosed with congenital femoral deficiency, with or without fibular hemimelia that underwent femoral lengthening.

N = 62 (30 in PRECICE group and 32 in LRS external fixation group).

Age (mean): 15.4years in PRECICE group and 9.4 years in LRS monolateral external fixation group.

Gender: 24 male patients, 38 female patients.		PRECICE magnetically motorized intramedullarynail.LRS external fixation.Range of motion, femoral lengthening achieved, distraction index, consolidation index, and rates of adverse events and complications. Final follow-up differed between groups, with 1.86 years (± 0.67) and 4.47 years (±2.73) being the mean time of final follow-up for the PRECICE and the LRS external fixation groups, respectively.
Hammouda et al., 20177

United States		NRS, retrospective reviewSkeletally immature patients who had a reamed intramedullary lengthening nail inserted through the greater trochanter.

N = 28 (31 femurs, 13 in PRECICE groupand 18 in ISKD group)

Age: 7 to 17 years (mean of 11.6 in PRECICE group and 14 in ISKD group).

Gender: 17 male patients, 11 female patients.		Femoral lengthening with the PRECICE nail.Femoral lengthening with the ISKD.Mean femoral lengthening achieved and complication rate. Follow-up time varied between groups, with a mean value of 1.9 years and 4.6 years for the PRECICE and ISKD groups, respectively.
Laubscher et al., 201613

United Kingdom		NRS, retrospective reviewSkeletally mature patients that underwent femoral lengthening procedures.

N = 22 (33 femurs, 20 in PRECICE group and 13 in LRS fixator system group)

Age: 15 to 57 years (mean of 25 in PRECICE group and 21 in LRS fixator group).

Gender: 22 male femurs, 11 female femurs.		PRECICE intramedullary lengthening nail.LRS fixator system.Mean femoral lengthening, rate of lengthening, modified healing index, preservation of range of motion, time to full weight bearing, and complication rate. In addition, patient reported outcomes including scar appearance satisfaction, mean visual analog score for pain, and ability to perform activities of daily living were assessed. Follow-up time varied between groups, with a mean value of 14.7 months and 28.8 months for the PRECICE and LRS fixator groups, respectively.

ISKD = intramedullary skeletal kinetic distractor; LRS = limb reconstruction system; NRS = non-randomized study

Appendix 3. Critical Appraisal of Included Publications

StrengthsLimitations
Szymczuk et al. 201712
  • The objective of the study was stated and explained in detail
  • Interventions of interest (PRECICE and LRS external fixation) were described
  • Main outcomes measured were clearly described in the Methods section. Procedure for measuring those outcomes were also described in detail
  • Patient characteristics, including age, gender, and patient history, were described
  • Inclusion and exclusion criteria were explicitly described
  • Actual probability values (P-values) were reported
  • Study participants and care setting appear to be representative of the population and care setting of interest
  • Patients appeared to be recruited to different interventions throughout the same time period
  • Appropriate statistical analysis (t-test) given the low sample size
  • Adverse events resulting from intervention were described in detail
  • Patients were not randomized to intervention groups; therefore, results may be susceptible to a number of biases
  • There is no mention of potential confounders or how they may have varied between groups
  • Time of follow-up and patient age was not consistent between treatment groups
  • The PRECICE nail was not used in children less than 9 years of age, resulting in an uneven distribution of these potentially higher risk patients into the LRS group
  • Unclear if there were any withdrawals or patients lost to follow-up
  • Patients and those measuring outcomes were not blinded to the intervention received
  • Although the difference in length of follow-up were described, there appears to be no adjustment for this discrepancy
  • Sample size calculations were not undertaken
Hammouda et al. 20177
  • The hypothesis, objective, and main outcomes of the study were described
  • Patient characteristics, including age, gender, and etiology were described for each treatment group
  • Information on the interventions of interest was given in detail, including description of the operative technique
  • Main findings are summarized clearly and are presented in both text and tabular forms
  • Adverse events appearto be well-documented
  • P-values are reported for the main outcomes
  • Due to the nature of the study (retrospective review), the patient population, staff, and care setting are likely representative of those of interest
  • Patients in both intervention groups appear to be recruited from the same population and throughout the same time period
  • Sample size (N = 31 femurs in 28 patients)
  • Patients were not randomized to intervention groups; therefore, results may be susceptible to a number of biases
  • There is no mention of principal confounders and how their distribution into treatment groups may have impacted the outcomes
  • The characteristics of patients that were not included in the study (due to in sufficient follow-up data) were not presented
  • Patients and those measuring outcomes were not blinded to the intervention received
  • Mean time of follow-up heavily varied between treatment groups (1.9 years in PRECICE group and 4.6 years in ISKD group) and the authors did not adjust for this in their data analysis
  • Study authors declared financial ties to companies with interest in limb lengthening systems
  • Sample size calculations were not undertaken
Laubscher et al. 201613
  • The aim and main outcomes of the study were described
  • The age, gender, and indication of patients in each treatment group were summarized
  • The interventions of interest, including the surgical techniques used to apply the lengthening devices were described in detail
  • Inclusion and exclusion criteria are provided
  • Main study findings were presented, including text and tabular summaries
  • Actual P-values are reported
  • No patients were lost to follow-up
  • Adverse events appear to be well-documented
  • Due to the nature of the study (retrospective review), the patient population, staff, and care setting are likely representative of those of interest
  • Main outcome measures appear to be accurate
  • Appropriate statistical analysis (t-test) given the low sample size
  • A statement suggesting there were no financial ties between study authors and commercial parties related to the subject of the article was provided
  • Sample size (N = 33 femurs in 22 patients)
  • Patients were not randomized to intervention groups; therefore, results may be susceptible to a number of biases
  • The distribution of potential confounders into each treatment group were not described
  • Confounders were not addressed when comparing group outcomes
  • Patients and outcome assessors were not blinded to the intervention received
  • Mean time of follow-up varied between treatment groups (14.7 months in PRECICE group and 28.8 months in LRS group) and the authors did not adjust for this in their data analysis
  • Patient-reported outcomes were measured by patient interview following the completion of their treatment (susceptible to recall bias)
  • Sample size calculations were not undertaken

ISKD = intramedullary skeletal kinetic distractor; LRS = limb reconstruction system

Appendix 4. Main Study Findings and Author’s Conclusions

Main Study FindingsAuthor’s Conclusions
Szymczuk et al. 201712
Retrospective comparison of patients diagnosed with congenital femoral deficiency (with or without fibular hemimelia) who underwent fem oral lengthening with either the PRECICE magnetically motorized intramedullary nail (N = 30) or with LRS external fixation (N = 32).

Comparison of PRECICE and LRS fixation with respect to range of motion (primary outcome)		“For [the LRS monolateral fixation] group, the lengthening goal was achieved in 28 (88%) of 32 patients; 2 patients had slow healing and 2 patients had premature consolidation. For [the PRECICE] group, the lengthening goal was achieved in 26 (87%) of 30 patients; 2 patients had sub luxation (1 knee and 1 hip) and 2 patients had delayed union.”(p5)

“The distraction index and [consolidation index] were similar in both groups where as the [range of motion] was better retained during the lengthening phase and at consolidation. The overall problem complication rate was significantly lower with the [intramedullary] lengthening nail. These findings in conjunction with patient and surgeon preference can help with decision making in regards to which lengthening technique to use. Further studies will be needed to continue to analyze the various techniques to help determine the best course of treatment for this unique patient population. Another important consideration is age of the patient. The PRECICE nail is not as practical in children with [congenital femoral deficiency] younger than 9 years, whereas the monolateral external fixator can be used as early as 3 years. In summary, we feel that the [intramedullary] lengthening nail represents a significant advance in technology for [congenital fern oral deficiency] lengthening. The increased potential for knee sub luxation must be guarded against by strict bracing protocols, and in cases of preoperative radiographic instability, prophylactic knee ligament reconstruction.” (p7)
Range of motionTreatmentgroupP-value
PRECICE (N =30)LRS fixation (N = 32)
ExtensionFlexionExtensionFlexion
Preoperative (degrees, ± SD)0.83 (± 3.1)127.7 (± 22.9)0.47 (± 2.18)123.3 (± 12.2)0.35
Postdistraction (degrees, ± SD)0.93 (± 3.3)96.3 (± 28.2)-0.6 (± 4.3)69.9 (± 30.2)0.0007
Postconsolidation (degrees, ± SD)-0.4 (± 2.1)121.5 (± 23.1)0.74 (± 4.9)81.3 (± 30.1)< 0.0001
Final follow-up (degrees, ± SD)-0.4 (± 2.0)119.6 (± 16.5)-0.7 (± 4.8)120.2 (± 19.9)0.90
Comparison of PRECICE and LRS fixation with respect to several treatment outcomes
OutcomeTreatment groupP-value
PRECICE (N = 30)LRS fixation (N = 32)
Femoral lengthening goal (cm, ± SD)4.97 (± 1.43)5.58 (± 1.82)0.15
Lengthening achieved (cm, ± SD)4.75 (± 1.40)5.55 (± 1.74)0.052
Distraction index (mm/d, ± SD)0.7 (± 0.18)0.7 (± 0.17)0.99
Consolidation index (d/cm, ± SD)34.77 (± 11.23)29.33 (± 12.68)0.08
Comparison of PRECICE and LRS fixation with respect to number of adverse events
Adverse event categoryTreatment groupP-value
PRECICE (N =30)LRS fixation (N = 32)
Total eventsAffected segmentsTotal eventsAffected segments
Problema [N (%)]8 (25.8)7 (23.3)32 (55.2)20 (62.5)< 0.001
Obstaclea [N (%)]19 (61.3)11 (36.7)20 (34.5)10 (31.3)0.66
Complicationa [N (%)]4 (12.9)4 (13.3)6 (10.3)5 (15.6)0.99
Total [N (%)]3118 (60.0)5826 (81.3)0.07
Hammouda et al. 20177
Retrospective comparison of patients who were younger than 18 years of age and underwent intramedullary femoral lengthening using the PRECICE (N =13) or the ISKD (N = 18) nail with at least one year of follow-up.“All of the patients achieved lengthening with a mean of 5.4 cm (range, 3 to 6.7 cm). ISKD group achieved the mean lengthening of 5.2 cm (range, 3.8 to 6.5 cm), whereas the PRECICE group achieved the mean of 5.6 cm (range, 3 to 6.7 cm) (Figs. 3, 4). No significant difference was observed between both groups in the lengthening achieved (P=0.35).”(p261)

“The complication rate of the ISKD cohort (39%) was greater than in the PRECICE cohort (23%); however, it did not achieve significance (P=0.45).”(p263)

“We conclude that using intramedullary lengthening nails inserted either through the tip or the lateral aspect of the [greater trochanter] in skeletally immature femurs can be safe. None of the patients in our cohort developed femoral head [avascular necrosis] or proximal valgus deformity. However, extrem e care shouldbe taken to a void injury of the blood supply when attempting to identify the entry point and during the reaming process. This part of the procedure should be performed by or at least very carefully supervised by the attending surgeon.” (p264)
OutcomeTreatmentgroupP-value
PRECICE (N = 13 segments)ISKD (N = 18 segments)
Mean lengthening achieved [cm (range)]5.6 (3-6.7)5.2 (3.8-6.5)0.35
Complication rate [N (%)]3 (23)7 (39)0.45
Laubscher et al. 201613
Retrospective comparison of skeletally mature patients who underwent femoral lengthening using the PRECICE nail (N = 20) or the LRS fixator (N = 13).“All cases in the Precice group achieved the desired length and 12 from 13 LRS cases. The mean modified [healing index] was found to be significantly shorter (31.3d/cm versus 47.1d/cm, p < 0.001) in the Precice group. This shorter [healing index] suggests that the regenerate formed more rapidly in the Precice group. The mean time to actual full weight bearing was also significantly shorter in the Precice group (3.6 months versus 4.8 months, p = 0.02).”(p1386)

“We conclude that we achieved significantly lower [healing index] and encountered fewer complications with a Precice nail femoral lengthening. Patients experienced better implant tolerance and were more satisfied with their treatment in the Precice group.”(p 1388)
OutcomeTreatmentgroupP-value
PRECICE (N = 20)LRS (N = 13)
Planned lengthening achieved [N (%)]20 (100)12 (92)NR
Mean lengthening [mm (range)]51.4 (25-68)59.7 (50-70)NR
Mean lengthening rate [mm/d (range)]0.93 (0.67-1.09)0.83 (0.55-1.13)NR
Preservation of knee range of movement [N (%)]20 (100)12 (92)NR
Mean healing index [d/cm (range)]31.3 (21.1-43.0)47.1 (34.4-67)<0.001
Mean time to full weight-bearing [months (range)]3.6 (2-7)4.8 (3-7)0.02
Comparison of PRECICE (N = 20) and LRS fixation (N = 13) with respect to patient-reported outcomes.
OutcomeTreatment groupP-value
PRECICE (N = 20)LRS (N = 13)
Mean scar ratinga (range)3.0 (1-5)7.5 (6-10)<0.001
Mean visual analogue scale for pain (range)During lengthening: 4.4 (1-7.5)
During consolidation: 2.2 (1-6)		During lengthening: 8.1 (5-10)
During consolidation: 5.3 (3-7)		<0.001
<0.001
Able to perform activities of daily life [N (%)]18 (90)5 (38)NR
Choose to have treatment again [N (%)]20 (100)9 (68)NR
a

The authors classified adverse events as problems, obstacles, or complications.

a

Mean scar rating was a patient-reported outcome on how patients perceived the cosmetic appearance of scars resulting from treatment, with 0 being the bestand 10 being the worst

ISKD = intramedullary skeletal kinetic distractor; LRS = limb reconstruction system

Appendix 5. Additional References of Potential Interest

Systematic Reviews and Meta-Analyses

Alternative Intervention

Xu WG. Comparison of intramedullary nail versus conventional Ilizarov method for lower limb lengthening: a systematic review and meta-analysis. Orthop Surg. 2017 May;9(2):159-66. PubMed: PM28589635

The objective of this systematic review and meta-analysis was to compare the lengthening and then nailing (LATN) technique to the conventional Ilizarov method for limb lengthening. A systemic search of potential relevant literature was performed in databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and the ISI Web of Knowledge, from their inception to 22 May 2015 using medical subject heading (MeSH) terms "Ilizarov," "bone lengthening," or "intramedullary nail." A total of 89 titles and abstracts were preliminarily reviewed, of which 4 studies eventually satisfied the eligibility criteria, consisting of one randomized controlled trial (RCT), two clinical controlled trials and one retrospective cohort study. A total of 354 limbs were included in the study, among which 183 were lengthened over an intramedullary nail, and 171 limbs were lengthened conventionally. The mean difference (MD) was -50.21 for the external fixation index between the two groups (95% CI, -51.83 to -48.59; P < 0.00001) with high heterogeneity (I2 = 99%); no significant difference in length was gained (MD = -0.30, 95% CI = -0.72 to 0.12; P = 0.16) with high heterogeneity (I2 = 80%); and there was high significant difference for the consolidation index (MD = -19.97; 95% CI, -21.59 to -18.35; P < 0.00001) with high heterogeneity (I2 = 100%). The overall rate of complications was relatively low, and differed significantly between the two groups. Through this meta-analysis, we find that LATN is superior to the conventional method in regards to the external fixation index and the consolidation index, which means that LATN is an effective technique that can decrease the time needed in external fixation.

Non-Randomized Studies

No Comparator

Hammouda AI, Jauregui JJ, Gesheff MG, Standard SC, Conway JD, Herzenberg JE. Treatment of post traumatic femoral discrepancy with PRECICE magnetic powered intramedullary lengthening nails. J Orthop Trauma. 2017 Feb 21;, 2017 Feb 21. PubMed: PM28379937

OBJECTIVE: Post traumatic limb length discrepancy (LLD) may present secondary to fracture shortening, malunion, or epiphyseal growth arrest. The purpose of this study was to evaluate the outcomes of lengthening post-traumatic femoral segments utilizing a recently available magnetic intramedullary (IM) lengthening system. DESIGN: Retrospective cohort study. SETTING: Urban Level II Trauma Center. Patients/Participants: This study was performed to review post-traumatic patients treated for femoral shortening at our institution between 2011 and 2015. We identified seventeen femurs lengthened (14 males and 3 females). The mean age was 30 years (range, 11 - 72 years). INTERVENTION: Magnetic IM lengthening system MAIN. OUTCOME MEASUREMENTS: Amount of lengthening achieved, consolidation index (CI), and complications encountered. RESULTS: The mean follow up was 2.2 years (range, 1 - 3.7 years). Sixteen patients achieved the planned lengthening, a mean of 3.8 cm (range, 2.3 - 6.0 cm). Regenerate consolidation occurred at a mean of 119 days (range, 57 - 209 days). The mean CI was 32 days/cm (range, 16 - 51 days/cm). Three patients (18 %) encountered complications. CONCLUSION: Intramedullary lengthening nails are an improvement over external fixators for treatment of post-traumatic femoral shortening. Within certain limits, their use can be extended to problems of LLD with angular/rotational deformity. LEVEL OF EVIDENCE: Therapeutic Level IV.

Kirane YM, Fragomen AT, Rozbruch SR. Precision of the PRECICE internal bone lengthening nail. Clin Orthop. 2014 Dec;472(12):3869-78. PubMed: PM24682741

BACKGROUND: Previous designs of internal bone lengthening devices have been fraught with imprecise distraction, resulting in nerve injuries, joint contractures, nonunions, and other complications. Recently, a magnet-operated PRECICE nail (Ellipse Technologies, Inc, Irvine, CA, USA) was approved by the FDA; however, its clinical efficacy is unknown. QUESTIONS/PURPOSES: We evaluated this nail in terms of (1) accuracy and precision of distraction, (2) effects on bone alignment, (3) effects on adjacent-joint ROM, and (4) frequency of implant-related and non-implant-related complications. METHODS: We reviewed medical and radiographic records of 24 patients who underwent femoral and/or tibial lengthening procedures using the PRECICE nail from August 2012 to July 2013 for conditions of varied etiology, the most common being congenital limb length discrepancy, posttraumatic growth arrest, and fracture malunion. This group represented 29% of patients (24 of 82) who underwent a limb lengthening procedure for a similar diagnosis during the review period. At each postoperative visit, the accuracy and precision of distraction, bone alignment, joint ROM, and any complications were recorded by the senior surgeon (SRR). Accuracy reflected how close the measured lengthening was to the prescribed distraction at each postoperative visit, while precision reflected how close the repeated measurements were to each other over the course of total lengthening period. No patients were lost to followup. Minimum followup from surgery was 3 weeks (mean, 14 weeks; range, 3-29 weeks). RESULTS: Mean total lengthening was 35 mm (range, 14-65 mm), with an accuracy of 96% and precision of 86%. All patients achieved target lengthening with minimal unintentional effects on bone alignment. The knee and ankle ROM were minimally affected. Of the complications requiring return to the operating room for an additional surgical procedure, there was one (4%) implant failure caused by a nonfunctional distraction mechanism and six (24%) non-implant-related complications, including premature consolidation in one patient (4%), delayed bone healing in two (8%), delayed equinus contracture in two (8%), and toe clawing in one (4%). CONCLUSIONS: We conclude that this internal lengthening nail is a valid option to achieve accurate and precise limb lengthening to treat a variety of conditions with limb shortening or length discrepancy. Randomized, larger-sample, long-term studies are required to further confirm clinical efficacy of these devices, monitor for any late failures and complications, and compare with other internal lengthening devices with different mechanisms of operation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Case Reports and Case Series

Furmetz J, Kold S, Schuster N, Wolf F, Thaller PH. Lengthening of the humerus with intramedullary lengthening nails-preliminary report. Strategies Trauma Limb Reconstr [Internet]. 2017 Aug [cited 2017 Dec 7];12(2):99-106. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505882 PubMed: PM28439819

Distraction osteogenesis of the humerus with fully implantable lengthening is now possible since the diameter of the available nails was reduced to 10 mm and below. We report on the first intramedullary lengthening cases of the humerus with two different lengthening devices (FITBONE and PRECICE). Two different approaches and implantation techniques were used. We retrospectively reviewed clinical and radiographic data and pointed out results, pitfalls and complications of the procedure. Four adult patients with relevant length discrepancy of the humerus were treated with fully implantable systems in two centers between 2012 and 2015. Three patients were treated with FITBONE by an antegrade approach; one patient had lengthening with a PRECICE and a retrograde approach. Average nail lengthening was 55 mm (40-65 mm), and the average duration of lengthening was 70 days (52-95 days). The average distraction index was 0.72 mm/day (range 0.4-1.0 mm/day) or 12.5 days/cm (range 8.0-16.2 days/cm). The average consolidation index was 33.6 days/cm (range 25-45 days/cm). There was an implant failure (arrest) with the PRECICE. After consolidation and exchange with a technically improved implant, the course of treatment was uneventful. In patients with antegrade lengthening shoulder abduction decreased, and in the patient with the retrograde approach it improved but elbow extension decreased marginally. Reduced motion of the adjacent joints can be a major problem in intramedullary lengthening of the humerus. This first case series in the field of a rare indication suggests that lengthening of the humerus by fully implantable lengthening nails might be a valuable alternative to lengthening with external fixation. Main advantage of the PRECICE technology is the possible shortening in-between of lengthening.

Hammouda AI, Standard SC, Robert RS, Herzenberg JE. Humeral lengthening with the PRECICE magnetic lengthening nail. HSS J. 2017 Oct;13(3):217-23. PubMed: PM28983213

BACKGROUND: Different types of external fixators have been used for humeral lengthening with successful outcomes reported in literature. Motorized intramedullary (IM) lengthening nails have been developed as an alternative to external fixators for long bone lengthening in the lower extremity. QUESTIONS/PURPOSES: This case series reports on using the new technology of IM lengthening nails for humeral lengthening. We assessed the radiological healing and functional outcomes after using the PRECICE IM nail for humeral lengthening. METHODS: This multicenter retrospective study included a total of six humeri in five patients (mean age was 20 years) that underwent lengthening with the magnetic IM PRECICE nail in two centers in the USA. The etiology was humeral growth arrest post-bone cyst (two segments), post-septic growth arrest (two segments), and multiple hereditary exostosis (bilateral segments in one patient). The outcomes measured were the length achieved, distraction index (DI; the length achieved in mm divided by the duration of lengthening in days), consolidation index (CI; number of days from surgery until consolidation divided by the length of the regenerate in cm), complications encountered, and functional outcomes (shoulder and elbow range of motion, the upper extremity functional index (UEFI), and QuickDASH functional scores). RESULTS: The mean followup period was 1.8 years (0.9 to 2.4 years). All segments achieved the goal of lengthening; the mean was 5.1 cm (4.5 to 5.8 cm). Mean DI was 0.7 mm/day (0.5 to 0.8). Mean CI was 36 days/cm (25 to 45 days/cm). No complications were observed. At the last follow-up, all patients maintained their preoperative range of motion (ROM) except one patient had reduced shoulder ROM. QuickDASH score and upper extremity functional index showed postoperative improvement compared to the preoperative scores. CONCLUSION: IM lengthening nails can provide successful and safe humeral lengthening. Specifically, the PRECICE nail has accurate control over the lengthening process.

Kurtz AM, Rozbruch SR. Humerus lengthening with the PRECICE internal lengthening nail. J Pediatr Orthop. 2017 Jun;37(4):e296-e300. PubMed: PM28244924

BACKGROUND: Deformity and growth arrest of the humerus in children may result as sequelae of proximal humerus fractures and unicameral bone cysts, or as complications of their treatment. As approximately 80% of the growth of the humerus arises from the proximal physis, the resultant upper limb-length discrepancy can be substantial. Benefits to lengthening the shortened arm have been previously demonstrated with the use of external fixation devices. To our knowledge, no reports have been published on the use of intramedullary implants for this purpose. METHODS: A 15-year-old girl with humeral shortening secondary to proximal humeral growth disturbance following treatment for a unicameral bone cyst was treated with humeral osteoplasty and gradual lengthening with an off-label use of a fully implantable motorized intramedullary lengthening nail. A varus proximal humeral deformity and lateral starting point allowed for avoidance of the rotator cuff insertion. RESULTS: Humeral lengthening (5 cm) was achieved at 9 weeks, with bony union at 7 months, and hardware removal at 9(1/2) months. Shoulder and elbow motion was maintained during and after treatment. CONCLUSIONS: This is the first case report of humeral lengthening using a fully implantable motorized intramedullary lengthening nail. Although some technical limitations remain when compared with other methods, the procedure was well tolerated throughout the course of treatment. LEVEL OF EVIDENCE: Level IV-case report.

Review Articles

Bernstein M. Practical aspects of posttrauma reconstruction with an intramedullary lengthening nail. J Orthop Trauma [Internet]. 2017 Jun [cited 2017 Dec 7];31 Suppl 2:S20-S24. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426691 PubMed: PM28486286

Limb equalization using the Ilizarov method has evolved and adapted the use of internal lengthening devices. One of the newest devices, termed "PRECICE," is a magnetically controlled telescoping nail. Complications such as pin site infection and skin irritation are eliminated. Despite trauma surgeons’ familiarity with intramedullary nailing, the Ilizarov method requires sound knowledge of deformity analysis and awareness of specific complications associated with distraction osteogenesis. This manuscript discusses some of the practical preoperative and intraoperative components of limb lengthening.

Fragomen AT, Rozbruch SR. Retrograde magnetic internal lengthening nail for acute femoral deformity correction and limb lengthening. Expert Rev Med Devices. 2017 Oct;14(10):811-20. PubMed: PM28893094

INTRODUCTION: The Precice magnetic internal lengthening intramedullary nail is being used with great success in femur lengthening and deformity correction with a retrograde approach. Areas Covered: Our personal history of limb lengthening and the Precice nail will be reviewed. Several technical aspects are discussed including design updates, pre operative planning, selection of nail length, the use of blocking screws and intra operative temporary external fixation, osteotomy practice, post operative management, and cost analysis. Expert Commentary: The phenomenal bone healing ability for the retrograde Precice nail after femoral osteotomy for lengthening, even after acute deformity correction, is recognized throughout the growing body of scientific publications on this topic. The few failures that have occurred appear to be attributable to excessive loading of the femur and implant during a vulnerable time of bone healing. Further studies with more uniform outcome criteria need to be conducted to better standardize user’s experiences. The higher one time cost of the implant is offset by the reduced number of surgeries needed when compared with the gold standard of lengthening-over-nail-technique, and we suspect that patients return to work sooner due to the ability to wear normal clothing and the reduction in pain throughout the entire lengthening process.

Fragomen AT, Rozbruch SR. Lengthening and deformity correction about the knee using a magnetic internal lengthening nail. SICOT J [Internet]. 2017 [cited Dec 7];3:25. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360097 PubMed: PM28322717

INTRODUCTION: The introduction of the internal lengthening nail (ILN) has changed the treatment of complex malalignment and shortening about the knee. Acute correction of the deformity and gradual lengthening through this osteotomy site has greatly simplified postoperative recovery. This manuscript is a review of the techniques that are currently being used in surgery. METHODS: The article is broken into two sections: distal femur osteotomy and tibia osteotomy. Each is addressed separately since they have different personalities. Also included are topics of particular interest that surface in ongoing conferences regarding the ILN. This work is a mix of expert opinion and best practice supported by peer reviewed publications on the topic. RESULTS: Most published series demonstrate excellent results with the ILN. Certain precautions are reiterated including avoiding mechanical failure, need for a percutaneous osteotomy, need for over-reaming, and the need for blocking screws. DISCUSSION: Current controversies will be brought to light and discussed. The reader should find this aspect particularly helpful in navigating this rapidly evolving field.

Sabharwal, S, et al. What’s new in limb lengthening and deformity correction. J Bone Joint Surg Am [Internet]. 2015 [cited 2017 Dec 7]; 97:137s-84. Available from: http://www.llrs.org/PDFs/Whats-New-2015.pdf

Hasler, CC, et al. Current concepts of leg lengthening. J Child Orthop [Internet]. 2012 Jun [cited 2017 Dec 7]; 6(2): 89-104. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364349/

Any lower limb discrepancy may be equalised by conservative means (insoles, prosthesis and orthosis). However, their long-term acceptance is low in regard to function, costs, expenditure and appearance. Timely epiphysiodesis is the best option in uniplanar deformities with adequate remaining growth and for patients whose predicted final body height is above the 50th percentile. However, many patients present late or with multi planar deformities, which warrant more sophisticated operative approaches. The history of surgical bone lengthening comprises 100 exciting years of struggling, development and ongoing learning. The initial strategy of acute or rapid incremental distraction had lasted almost half a century until Ilizarov recognised the benefits of biological periosteum-preserving osteotomies and incremental lengthening at slow rates (1 mm/day) at a 4 × 0.25-mm daily rhythm, well appreciated as callotasis. In parallel, ring and wire constructs made complex three-dimensional axial, translational and rotational bone moulding possible. Taylor Spatial Frames—built on hexapod strut-linked platform technology as known from flight simulators—took limb correction to a more reliable, more precise and aesthetical level, all the more that the whole process became web-based. It represents state-of-the-art methodology and technology for complex, multi-plane deformities. Due to the significant risk of secondary malalignment, indications for lengthening by unilateral fixation have shrunken to moderate amounts of length disparity and uni- to bi-planar deformities in patients with still open physes. Mechanical or motorised, minimally invasively placed nails prevent muscle fixation and, therefore, ease rehabilitation, increase patient comfort and potentially shorten the overall time of sick leave and refrain from sports activities. Hence, they offer a valuable alternative for low-grade complexity situations. It remains to be proved if the significantly higher implant costs are compensated by lower treatment costs. Overall, limb lengthening, particularly in combination with multi planar deformity correction, can still be an arduous endeavour. In any case, wise judgement of the patient’s deformity, medical and biological situation, psychosocial environment, selection of the appropriate method and hardware, as well as meticulous operating technique by an experienced surgeon are the cornerstones of successful outcomes.

About the Series

CADTH Rapid Response Report: Summary With Critical Appraisal
ISSN: 1922-8147

Version 1.0

Suggested citation:

PRECICE intramedullary limb lengthening system: a review of clinical effectiveness. Ottawa: CADTH. 2017 Dec. (CADTH rapid response report: summary with critical appraisal).

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