Title: Limb Lengthening for Achondroplasia
Date: 22 June 2007.
Context and policy issues:
Skeletal dysplasias are a group of over 200 genetic disorders that affect the size and shape of
the limbs, trunk and skull, typically resulting in short stature.1 Achondroplasia is the most
frequently encountered form of nonlethal skeletal dysplasia. It affects about 0.5 to 1.5 in 10 000
births, making it the most common cause of short-limbed dwarfism.1 In addition to short stature,
individuals with achondroplasia often develop pronounced forward curvature of the spine in the
lumbar region (lordosis) and spinal stenosis later in life, which may require surgery to correct.1
Other features of achondroplasia include neurological complications, craniofacial abnormalities,
sleep-disordered breathing, thoracolumbar kyphosis, angular deformities of the knee and leg,
otitis media, deafness, speech delay, weight gain and obesity.1,2 Functional, cosmetic and
psychological problems may also be encountered. 3
Lengthening of the arms and legs of individuals with achondroplasia can potentially result in
height gains of up to 30cm and may improve function.1,4 The Ilizarov technique is a method of
distraction osteogenesis developed in Russia in the 1950’s and introduced in North American in
the 1980’s.5 In addition to limb lengthening in achondroplasia, the Ilizarov technique is used to
correct limb length discrepancy, deformities, joint contractures, nonunion of fractures and
reconstruction following trauma, tumors, and infection.5 The procedure involves a partial cut of
the bone cortex followed by a short resting period. The bone is then slowly distracted at a rate of
about 1mm per day using a circular (Ilizarov) or uniplanar external device attached to the bone
by means of pins or wires.5,6 Slow progressive elongation allows new bone to regenerate across
the gap but prevents bone segments from rejoining.6 The external device remains in place about
1 to 2 months per centimeter of bone lengthened, allowing the newly formed bone to
consolidate.5,6 The Ilizarov technique has a number of advantages in that it allows new bone to
form without the use of bone grafting, does not require the ends of the bones to be internally
Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in
Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list
of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed.
HTIS responses should be considered along with other types of information and health care considerations. The information included in this
response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a
particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness
particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be
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fixated and allows for simultaneous correction of angular deformities.5 Complications are,
however, relatively common with the procedure, some of which include infection, pain, swelling
of the limb, neurovascular complications, contractures of the soft tissues, subluxation and
dislocation of adjacent joint, bone-related problems at the lengthened site and psychological
problems.5,7
Limb lengthening in achondroplasia is a contentious issue. A number of insurers in the United
States cover the Ilizarov technique to correct significant limb length discrepancies, bone defects
and deformities, but consider the technique cosmetic when used to correct short stature.8-10
The American Academy of Pediatrics’ Health Supervision for Children with Achondroplasia does
not specifically endorse or condemn limb lengthening, but states “Extended limb lengthening
using a variety of techniques has been used far more elsewhere than in North America. It can
result in substantial increases in ultimate height. However, it is arduous, not without risk, and
costly. Most families alternatively choose to modify the environment to accommodate the child
rather than the converse.”11
Similarly, the Little People of America’s Medical Advisory Board does not advocate or condemn
symmetric extended limb lengthening.12 In a position paper (Appendix), the Medical Advisory
Board states “There are no established medical indications for symmetric extended limb
lengthening (ELL). While it may have benefit in preventing certain orthopedic and neurological
complications in some skeletal dysplasias, the procedure is primarily being performed for
adaptive, cosmetic, and psychosocial reasons.”12 The Medical Advisory Board recommends that
individuals who are considering limb lengthening be old enough to participate in discussions of
its risks and benefits.12 Individuals who choose to undergo the procedure are cautioned to select
a multidisciplinary program with expertise in skeletal dysplasia that is equipped to follow patients
for 10 years or longer.12
Research question:
What is the clinical effectiveness of limb lengthening surgery for children with achondroplasia
compared to no treatment for quality of life, spinal stenosis, leg numbness, back pain and
posture?
Methods:
A limited literature search was conducted on key health technology assessment resources,
including PubMed, EMBASE, The Cochrane Library (Issue 2, 2007), University of York Centre
for Reviews and Dissemination (CRD) databases, ECRI’s HTAIS, EuroScan, international HTA
agencies, and a focused Internet search. Results include articles published between 2002 and
the present, and are limited to English language publications only.
Summary of findings:
Search Results
The literature search did not produce any health technology assessments, systematic reviews,
meta-analyses or controlled studies that evaluated limb lengthening relative to no treatment in
children with achondroplasia. Although surgical protocols may involve a series of lengthening
surgeries in all four limbs of individuals with achondroplasia,13 the literature search did not
locate any such reports. Two case series reports that described outcomes of lengthening the
lower limbs of individuals with achondroplasia using the Ilizarov technique were identified.14,15
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We did not specifically search for studies published prior to 2002, but several older case series
reports were identified.3,16-18 These studies did not, however, include the outcomes of interest.
They reported outcomes primarily dealing with the bone (i.e. percent lengthening, healing index,
and days with external fixator in place) and complications. As the Ilizarov technique originated
in Europe, there may be reports published in languages other than English that were not
identified by the search.
Case Series Reports
Vaidya et al. reported outcomes of 24 individuals with achondroplasia who underwent tibial
lengthening using the Ilizarov technique.14 Ilizarov device was used to externally fixate the
tibia.14 In total, 47 limbs were lengthened (bilateral tibial lengthening in 23 patients and unilateral
tibial lengthening in one patient). Deformities were gradually corrected as part of the operative
procedure and several patients also underwent femoral lengthening. The average patient age
was 12.9±7.5 years old and the average duration of follow-up was 2.4±1.0 years. Following
surgery, the average gain in tibial length was 6.8 ± 1.3 cm or 41.3% of the original length. In
76% of cases, the total amount of tibial lengthening exceeded 40%. The average time of
external fixation was 131 ± 29 days. The average healing index (the number of days required for
the complete healing of 1 cm of lengthened bone) was 26.1 ± 3.3 days per centimeter of
lengthening. Statistically significant improvements in measures of angular deformity of the tibia
were also observed. Overall, 46 complications were observed in 29 limbs, the most common of
which were pin tract infections and ankle equinus contractures. Complications necessitated 29
additional surgical procedures.
Vargas Barreto et al. reported the outcomes of 58 individuals who underwent 94 tibial
lengthening procedures using the Ilizarov technique with external fixation using the Ilizarov
device.15 Twenty-two individuals had achondroplasia or hypochondroplasia. The remaining
individuals had limb length discrepancy (n=21) or short stature (n=15) due to another cause
(i.e., Turner Syndrome, Noonan Syndrome or constitutional short stature). A number of
individuals with short stature underwent simultaneous lengthening of the opposite femur and
tibia. It was not reported whether correction of a deformity was part of the operative procedure.
Outcomes in achondroplasia were not reported separately but were included in the short stature
group (n=37). For short stature, the average age at the time of surgery was 21 years old. The
average tibial lengthening was 9.1 cm. On average, lengthening occurred over 152 days and
the average healing index was 54.2 days per centimeter of lengthening. A total of 54
complications were observed in the short stature group. The authors did not provide a detailed
report of specific complications, but 36 complications were reported as minor, while 18
complications required additional surgical intervention.
While these case series reports may be useful from a descriptive perspective, they lacked
methodological rigor. For instance, the reports included small patient populations that were
heterogeneous in terms of surgical procedure and pathology. Some individuals had the tibiae
and femora lengthened while others had only the tibia lengthened.14,15 The overall outcome of
lengthening both tibiae and femora was not reported. This question may be of interest given that
combined lengthenings could increase the total gain in height and possibly function. Further, the
second case report presented the results of individuals with short stature of different etiologies
as a single group.15 This makes interpretation challenging as that the authors stated in their
discussion that individuals with Turner Syndrome had more complications than short stature of
other etiologies. The usefulness of these reports was also limited by their focus on the effect on
bone, rather than on longer term outcomes such as quality of life, function, spinal stenosis and
other neurological complications of achondroplasia.14,15 The duration of follow-up, however,
Limb Lengthening in Achondroplasia
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was likely insufficient to assess the impact of limb lengthening on these outcomes.14 Finally,
both reports lacked sufficient detail with respect to methods. Details about the patient
populations were limited to age and indication for lengthening.14,15 Vargas Barreto et al. did not
report the duration of follow-up or whether deformities were also corrected.15 Neither report
gave details of the surgical technique or device that was used for lengthening of the femur.14,15
Conclusions and implications for decision or policy making:
Given the quality of these studies14,15, the outcomes measured and the duration of follow-up, it
is difficult to draw any conclusions with respect to the long-term impact of limb lengthening in
achondroplasia. While there is evidence that gains in height can be attained, it is not clear how
this would impact function, quality of life or common complications of achondroplasia. Because
of the lack of long-term data, the potential for complications, and physical demands of the
procedure, limb lengthening in achondroplasia remains controversial.
Prepared by:
Sheri Pohar, BScPharm, PhD, Research Officer
Melissa Severn, MISt, Information Specialist
Health Technology Inquiry Service
Email: [email protected]
Tel: 1-866-898-8439
Limb Lengthening in Achondroplasia
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References:
1. Carter EM, Davis JG, Raggio CL. Advances in understanding etiology of achondroplasia
and review of management. Curr Opin Pediatr 2007;19(1):32-7.
2. Haga N. Management of disabilities associated with achondroplasia. J Orthop Sci
2004;9(1):103-7.
3. Kashiwagi N, Suzuki S, Seto Y, Futami T. Bilateral humeral lengthening in achondroplasia.
Clin Orthop Relat Res 2001;(391):251-7.
4. Savarirayan R, Rimoin DL. The skeletal dysplasias. Best Practice & Research Clinical
Endocrinology & Metabolism 2002;16(3):547-60.
5. Hamdy RC, Fassier F, Lachapelle D, Gibis J, Gervais N, Duhaime M. The Use Of The
Ilizarov Method In Children for Limb Lengthening. MedGenMed 1999;1(1).
6. Di Russo F, Committeri G, Pitzalis S, Spitoni G, Piccardi L, Galati G, et al. Cortical
plasticity following surgical extension of lower limbs. Neuroimage 2006;30(1):172-83.
7. Herzenberg JE, Paley D. Leg lengthening in children. Curr Opin Pediatr 1998;10(1):95-7.
8. Bone Lengthening for Congenital Conditions, Limb Discrepancies and Angular Deformities
of Long Bones. In: BlueCross BlueShield of Tennessee Medical Policy Manual; 2005.
Available:http://www.bcbst.com/mpmanual/bone_lengthening_for_congenital_conditions_li
mb_discrepancies_and_angular_deformities_of_long_bones.htm. (accessed 2007 May
22).
9. Ilizarov Method for Distraction Osteosynthesis. [Clinical Policy Bulletin no. 0220]. Hartford
(CT): Aetna; 2007. Available: http://www.aetna.com/cpb/medical/data/200_299/0220.html.
(accessed 2007 May 23).
10. Illizarov procedure. In: CIGNA Healthcare Coverage Position [Coverage Position no.
0397]: CIGNA Health Corporation; 2006. Available:
http://www.cigna.com/customer_care/healthcare_professional/coverage_positions/medical
/mm_0397_coveragepositioncriteria_ilizarov_distraction_procedure.pdf. (accessed 2007
May 23).
11. Trotter TL, Hall JG. Health supervision for children with achondroplasia. Pediatrics
2005;116(3):771-83.
12. Little People of America Medical Advisory Board. Extended Limb Lengthening. Hillsboro
(OR): Little People of America, Inc; 2006. Available:
http://medical.lpaonline.org/MRCFileManager/doc.php?doc_id=31&action=inline.
(accessed 2007 June 5).
13. Dwarfism: Achondroplasia and Hypochondroplasia [website]. In: The International Center
for Limb Lengthening. Baltimore: Sinai Hospital of Baltimore; 2007. Available:
http://www.lifebridgehealth.org/2187.cfm. (accessed 2007 May 22).
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14. Vaidya SV, Song HR, Lee SH, Suh SW, Keny SM, Telang SS. Bifocal tibial corrective
osteotomy with lengthening in achondroplasia: an analysis of results and complications. J
Pediatr Orthop 2006;26(6):788-93.
15. Vargas BB, Caton J, Merabet Z, Panisset JC, Pracros JP. Complications of Ilizarov leg
lengthening: a comparative study between patients with leg length discrepancy and short
stature. Int Orthop 2006.
16. Aldegheri R, Dall'Oca C. Limb lengthening in short stature patients. J Pediatr Orthop Part
B 2001;10(3):238-47.
17. Aldegheri R. Distraction osteogenesis for lengthening of the tibia in patients who have
limb-length discrepancy or short stature. J Bone Joint Surg Am 1999;81(5):624-34.
18. Polo A, Aldegheri R, Zambito A, Trivella G, Manganotti P, De Grandis D, et al. Lower-limb
lengthening in short stature. An electrophysiological and clinical assessment of peripheral
nerve function. J Bone Joint Surg Br 1997;79(6):1014-8.
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Appendix12:
Extended Limb Lengthening
Little People of America Medical Advisory Board
Position Summary, 2006
The following position summary is not intended to either advocate for or condemn extended limb
lengthening. It is meant to be a measured summary of information that may be of value to
members of the small stature community and members of Little People of America.
The techniques for leg lengthening were originally developed for correction of limb length
discrepancy and are an accepted therapy for this. Over the past two decades the procedure has
been expanded to allow for symmetric lengthening in individuals of short stature. Although this
newer application has generated widespread interest, it has also created controversy among
both medical professions, and persons of short stature and their families.
There are no established medical indications for symmetric extended limb lengthening (ELL).
While it may have benefit in preventing certain orthopedic and neurological complications in
some skeletal dysplasias, the procedure is primarily being performed for adaptive, cosmetic,
and psychosocial reasons.
Research is being done on the safety and long-term functional outcome of this procedure.
Currently no prospective, randomized studies have yet been completed.
The possible complications of ELL are numerous, These include:
•
Nerve injury (usually temporary);
•
Infection;
•
Angulation;
•
Non-union;
•
Increased contractures (of the hip, knee and/or ankle);
•
Fractures;
•
Unequal limb lengths;
•
Increased risk for late onset osteoarthritis.
Although the acute complication rate associated with ELL has been reduced, it is still
substantial.
This is what patients should have prior to initiation of ELL:
•
Confirmation of a specific short-stature diagnosis. The relative risks and benefits of
ELL are different in different types of skeletal dysplasias.
•
Counseling concerning the natural history and genetic implications of the relevant
skeletal dysplasia, independent of ELL.
•
Adequate discussion of the benefits and risks of ELL (including medical
complications, financial issues, educational and psychological concerns).
Prospective patients should be of an age to participate fully in these discussions and in the
decision-making process.
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We recommend that before, during and after ELL operative procedures, evaluation should
include:
•
Orthopedic assessment;
•
Physical therapy assessment, including evaluation of mobility, activity, functional
limitations, etc.;
•
Clinical neurological evaluation;
•
Peripheral vascular assessment;
•
Psychological evaluation, including self-image, body image, peer relationships, and
family relationships.
All of these evaluations will require the cooperative involvement of orthopedic surgeons,
physical and occupational therapists, medical geneticists, radiologists, psychologists and/or
psychiatrists, and social workers in longitudinal management. We caution prospective patients
and their families to seek out institutions that offer the broad multidisciplinary approach that is
needed. An institution should have a program with special emphasis and expertise in skeletal
dysplasia. The institution should be equipped to follow the patient for a decade or more.
Complete success of ELL is not guaranteed. Furthermore, ELL will not change other health
related needs of individuals of short stature. They will still need to have ongoing care by
someone knowledgeable about the natural history of their specific diagnosis.
ELL is a complex procedure with far-reaching implications. Interested individuals should
carefully assess the institution and personnel, as well as all risks and benefits of ELL prior to
committing to this procedure.
Approved by the LPA Medical Advisory Board and LPA Board of Directors July 2006.
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