The orthopaedic management of lower limb deformity in hypophosphataemic rickets

Abstract

Background
Many patients with X-linked hypophosphataemic rickets (X-LHPR) demonstrate significant lower limb deformity despite optimal medical management. This study evaluates the use of guided growth by means of hemi-epiphysiodesis to address coronal plane deformity in the skeletally immature child.

Methods
Since 2005, 24 patients with X-LHPR have been referred to our orthopaedic unit for evaluation. All patients had standardised long leg radiographs that were analysed sequentially before and after surgery if any was performed. The rate of correction of deformity was calculated based on peri-articular angles and diaphyseal deformity angles measured at regular intervals using Traumacad software. Clinical records were reviewed to obtain relevant clinical and demographic details. Statistical analysis was performed using SPSS 23 (SPSS Inc., Chicago, IL, USA).

Results
The indication for surgical intervention was a mechanical axis progressing through Zone 2 or in Zone 3 despite one year of optimised medical treatment. The 15 patients underwent 16 episodes of guided growth (30 limbs, 38 segments) at a mean age of 10.3 years. In four limbs, surgery has only taken place recently; and in three limbs, correction is ongoing. Neutral mechanical axis was restored in 16/23 (70%) limbs: six improved and one limb (one segment) required osteotomy for residual deformity. The mean rate of angular correction per month was 0.3° for the proximal tibia and 0.7° for the distal femur. Patients with ≥ 3 years of growth remaining responded significantly better than older patients (p = 0.004). Guided growth was more successful in correcting valgus than varus deformity (p = 0.007). In younger patients, diaphyseal deformity corrected at a rate of 0.2° and 0.6° per month for the tibia and the femur, respectively. There has been one case of recurrent deformity. Patients with corrected coronal plane alignment did not complain of significant residual torsional malalignment. Serum phosphate and alkaline phosphatase levels did not affect response to surgery.

Conclusions
Guided growth is a successful, minimally invasive method of addressing coronal plane deformity in X-LHPR. If coronal plane deformity is corrected early in patients with good metabolic control, osteotomy can be avoided.

Full text

Original Clinical Article
The orthopaedic management of lower limb
deformity in hypophosphataemic rickets
A. Horn1
J. Wright2
D. Bockenhauer3
W. Van’t Hoff3
D. M. Eastwood2
Abstract
Background Many patients with X-linked hypophosphatae-
mic rickets (X-LHPR) demonstrate significant lower limb de-
formity despite optimal medical management. This study
evaluates the use of guided growth by means of hemi-
epiphysiodesis to address coronal plane deformity in the skel-
etally immature child.
Methods Since 2005, 24 patients with X-LHPR have been
referred to our orthopaedic unit for evaluation. All patients
had standardised long leg radiographs that were analysed
sequentially before and after surgery if any was performed.
The rate of correction of deformity was calculated based on
peri-articular angles and diaphyseal deformity angles meas-
ured at regular intervals using Traumacad software. Clinical
records were reviewed to obtain relevant clinical and demo-
graphic details. Statistical analysis was performed using SPSS
23 (SPSS Inc., Chicago, IL, USA).
Results The indication for surgical intervention was a me-
chanical axis progressing through Zone 2 or in Zone 3 despite
one year of optimised medical treatment. The 15 patients
underwent 16 episodes of guided growth (30 limbs, 38 seg-
ments) at a mean age of 10.3 years. In four limbs, surgery has
only taken place recently; and in three limbs, correction is on-
going. Neutral mechanical axis was restored in 16/23(70%)
limbs: six improved and one limb (one segment) required
osteotomy for residual deformity. The mean rate of angular
1 Department of Orthopaedic Surgery, Red Cross War Memorial
Hospital for Children, Cape Town, South Africa
2 Department of Orthopaedic Surgery, Great Ormond St Hospital
for Children, London, UK
3 Department of Nephro-Urology, Great Ormond St Hospital for
Children, London, UK
Correspondence should be sent to: Anria Horn, Department of
Orthopaedic Surgery, University of Cape Town. Room H49, Old
Main Building, Groote Schuur Hospital, Anzio Road, Observatory,
Cape Town, South Africa.
E-mail: 7701.anria.horn@uct.ac.za
correction per month was 0.3° for the proximal tibia and
0.7° for the distal femur. Patients with ≥ 3 years of growth
remaining responded significantly better than older patients
(p = 0.004).Guided growth was more successful in correcting
valgus than varus deformity (p = 0.007). In younger patients,
diaphyseal deformity corrected at a rate of 0.2° and 0.6° per
month for the tibia and the femur, respectively. There has
been one case of recurrent deformity. Patients with corrected
coronal plane alignment did not complain of significant re-
sidual torsional malalignment. Serum phosphate and alkaline
phosphatase levels did not affect response to surgery.
Conclusions Guided growth is a successful, minimally invasive
method of addressing coronal plane deformity in X-LHPR. If
coronal plane deformity is corrected early in patients with
good metabolic control, osteotomy can be avoided.
Cite this article: Horn A, Wright J, Bockenhauer D, Van’t Hoff
W, Eastwood DM, The orthopaedic management of lower
limb deformity in hypophosphataemic rickets. JChild Orthop
2017;11:298-305. DOI 10.1302/1863-2548.11.170003
Keywords: Guided growth; hypophosphataemic rickets;
lower limb deformity
Introduction
Following the initial reports of vitamin D resistant rickets
by Albright et al1 in 1937, much progress has been made
in understanding the genetic and pathological processes
involved in this disorder, which affects approximately 1 in
20 000 births.2 Eighty percent of cases are inherited in an
X-linked fashion with the remainder resulting from auto-
somal recessive inheritance or spontaneous mutations.
The mutation leading to the clinical picture of hypophos-
phataemic rickets (X-LHPR) affects the PHEX (phosphate
regulating gene homologous to endopeptidases on the
X-chromosome) gene and leads to increased production
of fibroblast growth factor-23 (FGF-23).3,4 Elevated levels
of FGF-23 in turn lead to decreased phosphate reabsorp-
tion in the proximal renal tubule as well as decreased renal
production of 1,25 (OH)2Vit-D.3,5
The biochemical picture of X-LHPR is that of low serum
phosphate, elevated urinary phosphate, increased alkaline
phosphatase (ALP) levels and low or low normal circulat-
ing 1,25 (OH)2Vit-D. Parathyroid hormone (PTH) levels are

THE ORTHOPAEDIC MANAGEMENT OF LOWER LIMB DEFORMITY IN HYPOPHOSPHATAEMIC RICKETS
J Child Orthop 2017;11:298-305 299
usually normal on presentation but need to be monitored
throughout growth.5
Patients present with delayed linear growth and lower
limb deformity. In cases of high clinical suspicion or if the
genetic cause is known, the diagnosis can be made in
infancy.3
The typical skeletal manifestations include genu varum
or valgum and radiographic features of rickets including
generalised osteopaenia, widened, irregular physes and
cupped and flared metaphyses (Fig. 1).
Historically, patients frequently presented late or were
initially misdiagnosed, and treatment failed to achieve the
goals of limiting or improving skeletal deformity. Osteot-
omies performed early in childhood were associated with
a high rate of recurrent deformity.6,7 More recently, with
earlier and better medical care, not all patients develop
severe deformity. This, combined with the development
of guided growth techniques, suggests that extensive
surgery and the associated risks may be avoidable. At our
institution, the use of eight-plate (Orthofix, Verona, Italy)
hemi-epiphysiodesis for guided growth in these patients
was introduced ten years ago as the preferred primary sur-
gical treatment. This study evaluates the effect of this tech-
nique on coronal plane lower limb deformity in X-LHPR
and determines which factors influence the patient’s
response to surgical treatment.
Patients and methods
A search of the electronic database at our institution iden-
tified 24 patients suffering from X-LHPR who were referred
to the orthopaedic clinic for evaluation of their lower limb
deformity. The clinical records and radiographs of these
patients were obtained and demographic data gathered,
including clinical and laboratory findings, deformity
change over time, type and timing of surgical interven-
tions and response to surgery.
All patients completed at least 12 months of optimised
medical treatment consisting of phosphate and 1-alfacal-
cidol supplementation before being considered for sur-
gery (Fig. 2).6 Patients were reviewed every three months,
more frequently if necessary. The biochemical treatment
goals were normalisation of plasma PTH and ALP levels:
subnormal plasma phosphate levels were accepted to
avoid high dose phosphate supplementation. The clinical
goal was an improvement in linear growth and deformity
correction, concurrent with radiological healing.
Our patients underwent regular standardised long leg
alignment radiographs (Fig. 1) at ages 5, 8, 10 and 12
years, in addition to those performed for a specific clinical
indication. On each occasion, for each limb, the mechan-
ical axis was determined according to Stevens’ method;8
an axis outside Zone 1 at knee joint level (Fig. 3) was
considered abnormal. A mechanical axis in Zone 3 or a
progressively deteriorating Zone 2 alignment, despite 12
months of optimised medical management, was an indi-
cation for surgery.
Sagittal plane deformity was evaluated clinically and
radiographs were only taken when the deformity was
deemed to be contributing significantly to gait distur-
bance or cosmetic deformity. In our patient cohort, sagit-
tal plane deformity was not a significant clinical concern
in any patient at the time of initial surgery; therefore,
only the coronal plane deformity was addressed and
reported on.
The pre-operative radiograph defines the site(s) of
deformity and orientation of the knee joint axis to allow
selection of the ideal site(s) for eight-plate placement.
Diaphyseal deformity was not addressed directly.
For each patient, the long leg radiographs taken at reg-
ular intervals during surveillance and treatment periods
were analysed for the following parameters: mechanical
axis deviation (MAD); the mechanical lateral proximal
femoral angle (mLPFA); the mechanical lateral distal fem-
oral angle (mLDFA); the mechanical medial proximal tib-
ial angle (mMPTA); and the mechanical lateral distal tibial
angle (mLDTA). The peri-articular angles were measured
using Traumacad software (TraumaCAD, Voyant Health,
Tel Aviv, Israel) (Fig. 4). Following guided growth sur-
gery, alignment films were taken within one month of
surgery and at intervals of four to six months thereafter
Fig. 1 Anteroposterior standing leg alignment radiographs of a
four-year-old girl with X-linked hypophosphataemic rickets after
2.2 years of medical treatment.

THE ORTHOPAEDIC MANAGEMENT OF LOWER LIMB DEFORMITY IN HYPOPHOSPHATAEMIC RICKETS
300 J Child Orthop 2017;11:298-305
as the deformity corrected. These radiographs determined
the rate of correction. In order to quantify the diaphyseal
deformity in the coronal plane, the centre of rotation of
angulation (CORA) was determined and the deformity
recorded (Fig. 5).
In skeletally immature patients, eight plates were
removed once the deformity corrected to central Zone 1
(i.e. Zone ‘0’). Clinical and radiographic follow-up was
continued until skeletal maturity.
For analysis, patients were divided into two groups
depending on their age at the time of surgery for guided
growth. The young cohort were patients that were > 3
years from skeletal maturity (< 11 years in girls, < 13 years
in boys). The older cohort were < 3 years from skeletal
maturity at the time of surgery.
Statistical analysis was performed using SPSS 23 (SPSS
Inc., Chicago, IL, USA). The Mann-Whitney U test was
used for analysis of continuous data and Fisher’s exact test
for categorical data. Categorical variables are expressed
as frequency (percent) and continuous variables are
expressed as mean (range), unless otherwise stated. Sta-
tistical significance was considered at p < 0.05.
Results
The presenting features of this patient cohort are sum-
marised in Tables 1 and 2. Fourteen of our patients started
medical treatment before the age of 2 years, and none
after the age of 3 years. Compliance with medical treat-
ment was defined as attendance of three out of the four
planned renal clinics per year.9
In all patients, serum phosphate levels were low (nor-
mal range 1.2 to 1.8 mmol/L) throughout their clinical
course. Metabolic control and compliance to med-
ical treatment was good in all our patients and we can
Fig. 2 Flow diagram that details management of this patient cohort. *One patient underwent two episodes of treatment: left leg varus
and subsequently right leg varus.

THE ORTHOPAEDIC MANAGEMENT OF LOWER LIMB DEFORMITY IN HYPOPHOSPHATAEMIC RICKETS
J Child Orthop 2017;11:298-305 301
therefore not comment on the effect of poor metabolic
control on the response to guided growth. The presence
of a mutation of the PHEX gene did not predict require-
ment for surgery (NS; Fisher’s exact test). Similarly, neither
gender nor a positive family history were predictors for
deformity requiring surgery.
In total, 15 patients (62.5%) had deformity severe
enough to warrant surgical intervention. In total, 38 limb
segments (21 distal femora and 17 proximal tibiae) were
treated in 30 limbs; 12 limbs were in valgus and 18 in
varus. The mean age at treatment was 10.3 years (4.8 to
14.75). One patient underwent two surgical procedures:
initially a unilateral varus deformity was corrected, and
then six years later he developed a contralateral deformity
which required treatment. All other patients underwent
bilateral treatment: in all limbs, the deformity was in the
same direction although severity was sometimes asym-
metrical.
Two patients (four limbs) underwent surgery within
the last three months and therefore have been excluded
from further analysis. In the remaining 13 patients (26
limbs), there have been no significant complications fol-
lowing surgery but one prominent screw required early
revision.
In 3/26 limbs, deformity correction is ongoing. Fif-
teen of the remaining 23 limbs (65%) have achieved a
neutral limb alignment with a mean correction time of
16 months (9 to 27) (Fig. 6). Seven limbs in four patients
improved, but not sufficiently to restore a neutral axis at
skeletal maturity. These patients all had varus deformities
and all were in the older cohort. One limb (one segment)
has required further surgery to address residual deformity
and was successfully treated by means of gradual correc-
tion with a Taylor Spatial Frame (Smith & Nephew, TX,
USA). The median follow-up for patients who have not yet
reached skeletal maturity is 48 months (8 to 90).
One patient treated successfully for bilateral varus
knees was overcorrected to Zone 2 on one side at plate
removal: this has not improved at two-year follow-up.
In the corrected group, there has been no case of recur-
rent deformity in the ten limbs that have reached skeletal
maturity. One patient has developed bilateral recurrent
varus deformity at the age of ten years, four years after
plate removal (Fig. 2).
Fig. 3 Diagram of the knee demonstrating that a mechanical
axis may pass medial or lateral to the centre of the knee joint or
indeed pass outside the knee joint. The degree of displacement
of the mechanical axis can be defined in terms of Zones 1, 2 and 3
(medial or lateral). An axis within either medial or lateral Zone 1 is
considered to be within normal limits: surgically induced guided
growth defined central Zone 1 as fully corrected.
Fig. 4 Anteroposterior standing long leg radiographs of
a 12-year-old by showing the measurements made by the
TraumaCad software (Voyant Health, Tel Aviv, Israel).

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302 J Child Orthop 2017;11:298-305
Table 3 contains a summary of the rate of correction
(degrees/month) for all measured indices following appli-
cation of eight plates for guided growth for the two age
groups. Overall, femoral indices improved at a faster rate
than tibial indices, in keeping with the growth rates of the
respective physes.10 Use of this technique around the knee
resulted in an improvement in abnormal peri-articular
angles at the hip and ankle at a rate similar to that in the
proximal tibia.
Patients undergoing surgery for guided growth three
or more years prior to skeletal maturity had a higher rate
of successful mechanical axis restoration (10/11 (90%) vs
5/15 (33%); Fisher’s exact test, p = 0.004). Significantly
greater rates of correction at the operated physes were
seen in the younger age group in comparison to those
undergoing surgery less than three years prior to skeletal
maturity (Mann-Whitney U test, p = 0.007). Table 4 sum-
marises the time to correction of deformity for the respec-
tive groups.
Of the 23 limbs that have completed correction, those
with a varus deformity had less satisfactory outcome with
guided growth than those with valgus deformity. Eight
out of 15 (53%) varus limbs were considered fully cor-
rected at the end of treatment compared with eight out of
eight (100%) of valgus limbs (Fisher’s exact test p = 0.004).
Overall, the age at time of surgery was similar for the varus
(ten years) and the valgus (10.5 years) groups, but five of
seven varus limbs in four patients that failed to correct had
been straight until the sudden development of lower limb
deformity at the time of the adolescent growth spurt.
Discussion
The literature suggests that 24% to 65% of patients will
require surgical intervention for lower limb deformity
resulting from X-LHPR, despite optimal medical treat-
ment.11 This fact was confirmed by our study where 62.5%
had a persistent or worsening coronal plane deformity
that merited surgery. The presence of a defined mutation
on the PHEX gene did not predict requirement for surgery,
nor did gender or family history. Serum phosphate levels
were below normal levels in all patients and therefore not
predictive of requirement for surgery. Serum phosphate
Fig. 5 Anteroposterior view of the left femur of a skeletally
mature girl with the diaphyseal deformity of measured at 18°.
Table 1. Clinical variables of the 24 patients included in the study.
Patients (n) 24 (48 limbs)
Gender
• Male
• Female
• 12
• 12
Mean age at initiation of medical
therapy
1 year 6 months (1 month to 3
years)
Known family history 16 (66%)
PHEX mutation
• Confirmed
• Excluded
• Unknown
• 16
• 5
• 3
Direction of deformity (limbs)
• Valgus
• Varus
• Neutral
• 12
• 18
• 18
Treatment
• Medical only
• Guided growth
• 11
• 13
Table 2. Comparison between patients that underwent guided growth
more or less than three years prior to skeletal maturity.
Younger cohort Older cohort
Patients (n (limbs))* 8* (15) 8* (15)
Gender
• Male
• Female
4
4
4
4
Mean age at initiation of
medical therapy (mths)
16 24
Known family history 3 (37.5%) 6 (75%)
PHEX mutation
• Present
• Absent
• Unknown
4
2
2
5
2
1
Direction of deformity
• Varus
• Valgus
9
6
9
6
Mean age at surgery 7 years 6 months 13 years 0 months
* One patient had two separate episodes of surgery for guided growth, one at
nine years and the other at 15 years

THE ORTHOPAEDIC MANAGEMENT OF LOWER LIMB DEFORMITY IN HYPOPHOSPHATAEMIC RICKETS
J Child Orthop 2017;11:298-305 303
levels below 2.5 mg/dL (0.81 mmol/L) have been reported
to be predictive of worse outcome after surgery;12 but this
was not reflected in our cohort.
Historically, at our institution and elsewhere, surgery
for rachitic bone consisted of osteotomy, preferably at
skeletal maturity, using a variety of internal and external
fixation devices. Published results of corrective osteot-
omies for these patients are varied and consist mostly
of small case series reporting on a variety of surgical
techniques.6,12-19 Reported recurrent deformity is in the
range of 0% to 90%6,16-18 and appears to be related to
age at time of surgery and the fixation method used.
External fixation over an intramedullary rod appears
to have reliably fair outcome,12,15,19 although recurrent
deformity above and below the intramedullary device
has been noted by some authors in a large proportion
of patients.16 Patients who had surgery before skeletal
maturity generally had a higher rate of recurrent defor-
mity, and several authors also emphasised the impor-
tance of medical compliance, both for maintenance of
correction and prevention of complications such as non-
union.6,12-14,17
Fig. 6 (a)Long leg standing films of a ten-year-old girl with bilateral genu valgum and a mechanical axis in Zone 2. (b) Four months
after insertion of medial distal femoral eight plates. The mechanical axis is still in Zone 2, but improving. (c) Mechanical axis in Zone 1
ten months after insertion of eight plates.
Table 3. Rate of correction of all physes in patients who had surgery around the knee for guided growth.
Angle Mean rate of correction for all patients
(degrees/mth) (range)
Mean rate of correction in young
cohort (degrees/mth)
Mean rate of correction in older
cohort (degrees/mth)
mLPFA 0.3 (0 to 1.1) 0.4 0. 11
mLDFA 0.6 (0 to 1.7) 0.8 0.32
Operated*0.7 (0.1 to 1.7) 0.8 0.35
Non-operated 0.3 (0 to 0.64) n/a 0.30
mMPTA 0.3 (0 to 1.4) 0.46 0.19
Operated*0.3 (0 to 1.4) 0.6 0.2
Non-operated 0.31 (0 to 0.78) 0.39 0.19
mLDTA 0.4 (0 to 1.6) 0.48 0.21
Femoral diaphyseal bow 0.3 (0 to 1.4) 0.62 0.07
Tibial diaphyseal bow 0.2 (0 to 0.8)] 0.25 0.07
* Operated physes refers to the physes (distal femoral or proximal tibial) to which the eight-plate was applied
Table 4. Time to correction in successfully treated patients (months).
Young cohort Old cohort
Varus limbs 14 n/a: all failed to correct
Valgus limbs 11 .8 16.5

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304 J Child Orthop 2017;11:298-305
Little has been published on the use of guided growth
for patients with hypophosphataemic rickets. Evans
et al13 employed stapling of the medial femoral physes
for correction of valgus deformity in one patient near-
ing skeletal maturity, but performed osteotomies for all
varus deformities. Gigante et al20 used guided growth in
seven patients with renal osteodystrophy and corrected
all deformities, but three recurred and required further
surgery. Novais and Stevens11 showed full or partial
deformity correction in 7/9 X-LHPR patients treated by
hemi-epiphysiodesis. Most complications were related
to staple migration and the failures were seen in adoles-
cent patients nearing the end of growth. We had sim-
ilar results with this intervention, with 7/30 limbs not
corrected fully, but only one that required further sur-
gery. We agree with these authors that younger age at
surgery predicts a better response to guided growth.11
We furthermore suggest that valgus deformity generally
responds better to guided growth than varus deformity;
particularly the adolescent onset varus deformity. Recur-
rent deformity has not been a significant concern in our
patients but we would not consider it a failure of man-
agement as we still believe that simple treatment, even
if repeated, may be more acceptable than an osteotomy.
Our single overcorrected patient remained overcorrected
at skeletal maturity, two years after plate removal. Due to
this, and the relative lack of recurrence in the corrected
patients, we do not recommend overcorrection with the
guided growth technique.
One of the theoretical benefits of guided growth for
deformity correction is that the deformity is addressed at
its site of origin, the pathological physes. The peri-articular
deformity corrected at a rate of 0.3° and 0.7° per month
for the mMPTA and mLDFA, respectively. Interestingly,
femoral and tibial diaphyseal bowing also improved, par-
ticularly in the younger children. Presumably, normal-
isation of loads across the physes would eliminate the
ongoing imbalance in relative growth, according to the
Heuter-Volkmann Principle, and thereby lead to gradual
correction of the meta-diaphyseal deformity. This phe-
nomenon was also observed by Novais and Stevens.11
Stevens and Klatt,7 in their series of 14 patients with patho-
logical physes, observed that the appearance of the physes
at the hip and the ankle normalised once the mechanical
axis was restored by means of guided growth. We did not
specifically evaluate the appearance of the physes, but we
did note that that the mLPFA and the mLDTA improved
or normalised with the application of eight plates around
the knee. By restoring joint orientation around the hip,
theoretically hip abductor function should improve with
resolution of the waddling gait typically seen in these
patients. Restoration of normal joint alignment at the
knee diminishes the abnormal strain placed on the col-
lateral ligaments in a varus or a valgus knee, and may
decrease the incidence of early arthrosis associated with
gross lower limb malalignment.21 In our cohort, although
the diaphyseal bowing was not always corrected fully, no
patient with a neutral mechanical axis in the coronal plane
has requested surgical correction of a torsional deformity.
The need for osteotomy with all its concomitant morbidity
has been minimised.
The main limitation of this study is the fact that only
coronal plane deformity was evaluated and addressed.
Deformity in the sagittal and axial plane was not a sig-
nificant problem in our patients, likely due to the early
initiation of medical therapy and good metabolic con-
trol. The study is retrospective and does not compare
different treatment modalities and the numbers are
small.
All analyses were performed using computer software
that has previously been verified.22 There are limitations
in using a statistical analysis ‘per knee’ as each knee is
not a fully independent variable. However, in a rare con-
dition such as this, where the number of data points is
limited, a multivariant analysis is not feasible. The anal-
ysis performed is the most appropriate option available,
although care must be taken not to overestimate signif-
icance.
Medical management remains the mainstay of treat-
ment for lower limb deformity in X-LHPR. For those
patients that require surgical intervention for resistant or
progressive deformity despite optimal medical treatment,
guided growth by means of hemi-epiphysiodesis using
eight plates is an attractive option. Successful deformity
correction is more likely if guided growth is initiated three
years or more before skeletal maturity: the adolescent
onset tibial varus deformity does not respond well to treat-
ment. Early treatment may facilitate improvement in the
diaphyseal bowing.
Received 11 January 2017; accepted after revision 6 June 2017.
COMPLIANCE WITH ETHICAL STANDARDS
FUNDING STATEMENT
No benets in any form have been received or will be received from a commercial
party related directly or indirectly to the subject of this article.
OA LICENCE TEXT
This article is distributed under the terms of the Creative Commons Attribution-Non
Commercial 4.0 International (CC BY-NC 4.0) licence (https://creativecommons.
org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and
distribution of the work without further permission provided the original work is
attributed.
ACKNOWLEDGEMENT
The authors thank Paul Bassett, Statistical Consultant, who provided additional sta-
tistical advice.

THE ORTHOPAEDIC MANAGEMENT OF LOWER LIMB DEFORMITY IN HYPOPHOSPHATAEMIC RICKETS
J Child Orthop 2017;11:298-305 305
ETHICAL STATEMENT
No funding was received for this study.
All procedures performed in studies involving human participants were in accordance
with the ethical standards of the institutional and/or national research committee
and with the 1964 Helsinki declaration and its later amendments or comparable
ethical standards.
As this was a retrospective cohort study, no informed consent was sought. Approval
was granted by the Institutional review board.
ICMJE CONFLICT OF INTEREST STATEMENT
WvH has received travel and accommodation reimbursement from Ultragenyx and
is receiving research funding, paid to his institution. DME receives royalties from the
Oxford Textbook of Orthopaedics and Trauma. All other authors declare that they
have no conicts of interest.
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