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The orthopaedic management of lower limb deformity in hypophosphataemic rickets


Abstract and Figures

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.
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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
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.
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
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
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
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.
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.
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.
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-
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
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).
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.
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)
• Male
• Female
• 12
• 12
Mean age at initiation of medical
1 year 6 months (1 month to 3
Known family history 16 (66%)
PHEX mutation
• Confirmed
• Excluded
• Unknown
• 16
• 5
• 3
Direction of deformity (limbs)
• Valgus
• Varus
• Neutral
• 12
• 18
• 18
• 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)
• Male
• Female
Mean age at initiation of
medical therapy (mths)
16 24
Known family history 3 (37.5%) 6 (75%)
PHEX mutation
• Present
• Absent
• Unknown
Direction of deformity
• Varus
• Valgus
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
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-
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
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
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-
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.
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.
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
The authors thank Paul Bassett, Statistical Consultant, who provided additional sta-
tistical advice.
J Child Orthop 2017;11:298-305 305
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.
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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... Hypophosphatemic Rickets; HPR) -совокупность орфанных генетических заболеваний из группы первичных (наследственных) тубулопатий, характеризующихся дефектом реабсорбции фосфатов в проксимальных канальцах почек, проявляющихся гиперфосфатурией, гипофосфатемией и выраженными рахитическими изменениями, резистентными к обычным дозам витамина D [1][2][3]. Распространённость HPR составляет примерно 1 на 20 000 новорождённых [4]. Первое сообщение о рахите, устойчивом к витамину D, сделано Albright F., Butler M.A., Bloomberg E. в 1937 году [5]. ...
... Описанные молекулярно-генетические, биохимические изменения при XHPR приводят к нарушению минерализации костной ткани (остеомаляции), хрящевой ткани, в том числе хрящевой пластинки роста (зоны роста, эпифизарной пластинки) и, как следствие, к низкому росту, деформациям скелета, значительно более выраженным в наиболее нагружаемых его частях, то есть в нижних конечностях [2,4,6,9]. Стандартная терапия XHPR основана на одновременном назначении неорганических фосфатов и активных форм витамина D [1,7]. Однако оптимальные дозы фосфатов и препаратов 1,25(OH) 2 D 3 не определены, существует риск развития витамин D 3 -обусловленного нефрокальциноза [1,10]. ...
... На рентгенограммах деформированных костей нижних конечностей выявлены признаки остеомаляции, зоны перестройки Лоозера, остеоартритические изменения в области тазобедренных, коленных, голеностопных суставов, отсутствие зон роста. Для детальной оценки деформаций и решения задач предоперационного планирования были определены и документированы следующие параметры [4,13,16,17]: 1. положение фронтальных проекций механических осей нижних конечностей, проходящих от центров головок бедренных костей к серединам голеностопных суставов, относительно коленных суставов -справа и слева данные оси у па-циента проецировались снаружи от коленных суставов в зонах «+3», то есть имели место выраженные вальгусные смещения (референсный интервал -положение в медиальной зоне «-1», то есть кнутри от середины коленного сустава в пределах 50% ширины медиального мыщелка, или в латеральной зоне «+1», то есть кнаружи от середины коленного сустава в пределах 50% ширины латерального мыщелка [4,13,16]); 2. механические латеральные проксимальные бедренные углы -mLPFA -справа -129°, слева -131° (референсный интервал -85° -95°); 3. механические латеральные дистальные бедренные углы -mLDFA -справа -95°, слева -93° (референсный интервал -85° -90°); 4. механические задние дистальные бедренные углы -mPDFA -справа -97°, слева -71° (референсный интервал -79° -87°); 5. механические медиальные проксимальные тибиальные углы -mMPTA -справа -105°, слева -104° (референсный интервал -85° -90°); ...
Relevance. Relapses of deformities of the lower extremities after their surgical correction in patients with hypophosphatemic rickets reach 95%, which requires improved approaches to the treatment of this pathology. The aim of the study was to study the efficacy and safety of staged surgical treatment, including osteotomy, sequential transosseous and intraosseous blocking osteosynthesis-reinforcement, in a patient with completed growth, suffering from X-linked dominant form of hypophosphatemic rickets. Materials and methods. A patient with completed growth with an X-linked dominant form of hypophosphatemic rickets at the age of 21–28 years underwent 11 operations on the lower extremities due to their pronounced multiplanar multiapical deformities, segment length inequality against the background of osteomalacia. Simultaneous corrections were made on the femurs using osteotomies and intraosseous blocking osteosynthesis-reinforcement. On the bones of the lower legs, staged corrections were performed using osteotomies, bone autoplasty, sequential transosseous and intraosseous blocking osteosynthesis-reinforcement. Results. The inequality of the lengths of the femurs and lower legs is eliminated. The axes of the lower extremities were corrected to normal. The patient's height has increased by 8 cm. He walks up to 25,000 steps a day without additional support. When observing the patient for 8 years, no relapses of deformities and other complications were noted. Conclusion. Our experience testifies to the high efficiency and safety of staged surgical treatment using osteotomies, transosseous and intraosseous blocking osteosynthesis-reinforcement for the correction of pronounced multiplanar multiapical deformities, inequality in the length of the bones of the lower extremities against the background of osteomalacia in the patient with completed growth, suffering from an X-linked dominant form of hypophosphatemic rickets.
... The deformities include bilateral genu varum or valgum, bowing of the femur 18:488 or tibia, torsional deformity of the tibia, and windswept deformity. These defects are usually noticeable after 1 or 2 years of age [2][3][4]. Typical radiological findings are widened and irregular physes, cupped and flared metaphyses, and generalized osteopenia [2]. ...
... These defects are usually noticeable after 1 or 2 years of age [2][3][4]. Typical radiological findings are widened and irregular physes, cupped and flared metaphyses, and generalized osteopenia [2]. The biochemical profile mainly consists of hypophosphatemia, hyperphosphaturia, decreased or slightly decreased 1,25-dihydroxy vitamin D levels, and increased alkaline phosphatase levels. ...
... The biochemical profile mainly consists of hypophosphatemia, hyperphosphaturia, decreased or slightly decreased 1,25-dihydroxy vitamin D levels, and increased alkaline phosphatase levels. However, calcium and parathyroid hormone (PTH) levels are frequently normal at presentation [2][3][4][5]. ...
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Background: Surgical treatment for severe lower limb deformities in patients with hypophosphatemic rickets has shown satisfactory outcomes. However, the rates of recurrence of deformities after surgical correction were high, and studies on predictive factors of recurrence were limited. This study aimed to determine the predictive factors for the recurrence of lower limb deformities after surgical correction in patients with hypophosphatemic rickets, and the effects of each predictor on the recurrence of deformities. Methods: We retrospectively reviewed the medical records of 16 patients with hypophosphatemic rickets aged 5-20 years and who had undergone corrective osteotomies between January 2005 and March 2019. Demographic data from the patients, biochemical profiles, and radiographic parameters were collected. Univariable Cox proportional hazard analyses of recurrence were performed. Kaplan-Meier failure estimation curves for deformity recurrences of potential predictors were created. Results: A total of 38 bone segments were divided into 2 groups: 8 segments with recurrent deformities and 30 segments without recurrent. The average follow-up time was 5.5 ± 4.6 years. Univariable Cox proportional hazard analyses of recurrence found that an age < 10 years (hazard ratio [HR], 5.5; 95% CI, 1.1-27.1; p = 0.04), and gradual correction by hemiepiphysiodesis (HR, 7.0; 95% CI, 1.2-42.7; p = 0.03) were associated with recurrence after surgery. The Kaplan-Meier failure estimation for deformity recurrences by age at the time of surgery also achieved a statistically significant difference between ages < 10 years and those > 10 years (p = 0.02). Conclusions: Identifying predictive factors for the recurrence of lower limb deformities after surgical correction in hypophosphatemic rickets can assist in early recognition, proper intervention, and prevention. We found that an age < 10 years at the time of surgery was associated with recurrence after deformity correction and gradual correction with hemiepiphysiodesis may also be a potential factor affecting the recurrence.
... Lower-extremity deformity was reported as the most frequent clinical manifestation in patients of all ages, which delays the growth of the long bones and then worsens the reduction in height (8). As shown in the literature, 24%-65% of patients with XLH required surgical intervention for lower-extremity deformities (9,10). Some of them underwent orthopedic surgeries to obtain a neutral axis of the lower limbs. ...
... Considering the high recurrence rate of the surgery, it may not be appropriate to perform orthopedic surgery before puberty unless serious complications occur. It was suggested that close to the end of puberty with the epiphysis nearly closed would be the best timing for corrective surgeries, which was consistent with previous studies (8,9,25,26). From our study, four adult patients with satisfactory orthopedic surgery underwent their surgeries at the ages of 13, 16, 22, and 30 years, respectively, further supporting our suggestion. ...
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Objective The aim of this study was to fully describe the clinical and genetic characteristics, including clinical manifestations, intact fibroblast growth factor 23 (iFGF23) levels, and presence of PHEX gene mutations, of 22 and 7 patients with familial and sporadic X-linked dominant hypophosphatemia (XLH), respectively. Methods Demographic data, clinical features, biochemical indicators, and imaging data of 29 patients were collected. All 22 exons and exon–intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The serum level of iFGF23 was measured in 15 of the patients. Results Twenty-nine patients (male/female: 13:16, juvenile/adult: 15:14) with XLH were included. The main symptoms were bowed lower extremities (89.7%), abnormal gait (89.7%), and short stature/growth retardation (78.6%). Hypophosphatemia with a high alkaline phosphatase level was the main biochemical feature and the median value of serum iFGF23 was 55.7 pg/ml (reference range: 16.1–42.2 pg/ml). Eight novel mutations in the PHEX gene were identified by Sanger sequencing, including two missense mutations (p. Gln682Leu and p. Phe312Ser), two deletions (c.350_356del and c.755_761del), one insertion (c.1985_1986insTGAC), and three splice mutations (c.1700+5G>C, c.1966-1G>T, and c.350-14_350-1del). Additionally, the recurrence rate after the first orthopedic surgery was 77.8% (7/9), and five of them had their first surgery before puberty. Conclusion Our study expanded the clinical phenotypes and gene mutation spectrum of XLH and provided a reference for the optimal timing of orthopedic surgeries.
... Surgical treatment should be delayed until the end of growth and closure of the physis to avoid the recurrence of deformities and therefore the need for new interventions (33), although special emphasis has been placed on the early follow-up of varus or valgum knee and analysis of proximal joints, foreseeing complications with presentation of deformities in the future such as foot and ankle valgum or femoral antecurvatum (44). Elective surgical treatment has been recommended in the pediatric population with intensive medical treatment for at least 12 months (8), including guided growth in cases of persistence of deformities despite the medical management (45). ...
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Background: X-linked hypophosphatemic rickets is a hereditary disease that generates alterations in bone mineral homeostasis. The morbidity of the condition has been variable in previous decades and even contradictory, probably due to the definition of the case and the diagnostic confirmation. Our propose was to generate evidence-informed recommendations for the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR. Results: After the screening and selection process for 1041 documents, 38 were included to answer the questions raised by the developer group. 97 recommendations about the diagnosis, treatment, and follow-up of patients with suspected or diagnosed XLHR were approved by the experts consulted through modified Delphi consensus. The quality of the evidence was low. Conclusions: The recommendations proposed here will allow early and timely diagnosis of X-linked hypophosphatemic rickets, while optimizing resources for its treatment and follow-up and help clarify the burden of disease and improve health outcomes for this population.
... Long bone deformities, including bowing and maltorsion of the lower limbs, are common in patients with XLH, with many of these patients requiring multiple surgical procedures to correct these deformities [31,32]. A cross-sectional study in East Asian patients with XLH showed that 59.4% of adult XLH patients complained walking difficulties and that 25.0% required a walking device [33]. ...
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X-linked hypophosphatemia (XLH) is a rare inherited disorder involving elevated levels of fibroblast growth factor (FGF) 23, and is caused by loss-of-function mutations in the PHEX gene. FGF23 induces renal phosphate wasting and suppresses the activation of vitamin D, resulting in defective bone mineralization and rachitic changes in the growth plate and osteomalacia. Conventional treatment with combinations of oral inorganic phosphate and active vitamin D analogs enhances bone calcification, but the efficacy of conventional treatment is insufficient for adult XLH patients to achieve an acceptable quality of life. Burosumab, a fully human monoclonal anti-FGF23 antibody, binds and inhibits FGF23, correcting hypophosphatemia and hypovitaminosis D. This review describes a typical adult with XLH and summarizes the results of clinical trials of burosumab in adults with XLH.
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Introduction: X-linked hypophosphatemic rachitis (XLHR) is the most common cause of hereditary rickets that can lead to long bone deformities requiring multiple surgical correction procedures. In addition, high rates of fractures are reported in adult XLHR patients. This study aimed to report a case of femoral neck stress fracture in XLHR patient treated with mechanical axis correction. No previous studies demonstrating a combined valgus correction and cephalomedullary nail fixation were identified in the literature. Case report: A 47-year-old male patient with XLHR attended the outpatient clinic with severe left hip pain. X-rays revealed a left proximal femoral varus deformity and a femoral neck stress fracture. After 1 month without improvement of pain, and no radiographic sign of healing, correction of the proximal femoral varus deformity and fixation of the cervical neck fracture was achieved by a cephalomedullary nail. At 8 months follow-up, hip pain relief was achieved with radiographic healing of the femoral neck stress fracture and the proximal femoral osteotomy. Conclusion: A review of the literature was performed to identify any case report of femoral neck fractures fixation due to coxa vara in an adult. Both coxa vara and XLHR can cause femoral neck stress fracture. This study presented the surgical technique for treating a rare case of femoral neck stress fracture in a XLHR patient with coxa vara. Pain relief and bone healing were achieved by combined deformity correction and fracture fixation with a femoral cephalomedullary nail. The technique for deformity correction and cephalomedullary nail insertion in the patient with coxa vara is shown.
In the past decade, research in genetic disorders of hypophosphatemic disorders has significantly expanded our understanding of phosphate metabolism. X-linked hypophosphatemic rickets is the most common inherited form of rickets due to renal phosphate wasting. The common denominator for all types of rickets is hypophosphatemia, leading to inadequate supply of the mineral to the growing bone. Recent understanding of the mechanisms of disease and role of fibroblast growth factor 23 (FGF23) in hypophosphatemic disorders have opened new therapeutic avenues such as FGF23 blockade. We will discuss the genetic and clinical features of hypophosphatemic disorders and provide understanding and treatment options.KeywordsX-linked hypophosphatemic ricketsFibroblast growth factor 23Vitamin DRicketsOsteomalacia—burosumabNephrocalcinosisRenal phosphate wasting
Purpose: Patients with X-linked hypophosphatemic rickets (XLH) often develop coronal plane knee deformities despite medical treatment. Hemiepiphysiodesis is an effective way to correct coronal plane knee deformities in skeletally immature patients, but a full understanding of the rate of angular correction after hemiepiphysiodesis in XLH patients, compared with idiopathic cases is lacking. Methods: We retrospectively reviewed charts of 24 XLH patients and 37 control patients without metabolic bone disease who underwent hemiepiphysiodesis. All patients were treated with standard-of-care medical therapy (SOC=active vitamin D and phosphate salt supplementation) in our clinical research center and had a minimum of 2-year follow-up after hemiepiphysiodesis. Demographic data as well as complications, repeat procedures, or recurrence/overcorrection were recorded. Standing lower extremity radiographs were evaluated before the surgical intervention and at subsequent hardware removal or skeletal maturity, whichever came first. Mean axis deviation, knee zone, mechanical lateral distal femoral angle (mLDFA), and medial proximal tibial angle were measured on each radiograph. The rate of angular correction was calculated as the change in mLDFA and medial proximal tibial angle over the duration of treatment. Results: The magnitude of the initial deformity of the distal femur was greater in XLH patients as compared with control for varus (XLH mLDFA 97.7 +/- 4.9 vs. Control mLDFA 92.0 +/- 2.0 degrees) and valgus (XLH mLDFA 78.7 +/- 6.2 vs. Controls mLDFA 83.6 +/- 3.2 degrees). The rate of correction was dependent on age. When correcting for age, XLH patients corrected femoral deformity at a 15% to 36% slower rate than control patients for the mLDFA (>3 y growth remaining XLH 0.71 +/- 0.46 vs. control 0.84 +/- 0.27 degrees/month, <3 y growth remaining XLH 0.37 +/- 0.33 vs. control 0.58 +/- 0.41 degrees/month). No significant differences were seen in the rate of proximal tibia correction. XLH patients were less likely to end treatment in zone 1 (55.0% XLH vs. 77.8% control). XLH patients had longer treatment times than controls (19.5 +/- 10.7 vs. 12.6 +/- 7.0 mu, P value <0.001), a higher average number of secondary procedures than controls (1.33 +/- 1.44 vs. 0.62 +/- 0.92 number of procedures), a higher rate of overcorrection than controls (29.2% vs. 5.4%), and a higher rate of subsequent corrective osteotomy than controls (37.5% vs. 8.1%). There was no significant difference in the rate of complications between groups (8.3% vs. 5.4%). Conclusions: Patients with XLH undergoing hemiepiphysiodesis have a 15% to 36% slower rate of femoral deformity correction that results in longer treatment times, a higher likelihood to undergo more secondary procedures, and a lower likelihood to reach neutral mechanical alignment. Significance: This study provides important information to guide the timing and treatment of patients with XLH and coronal plane knee deformities. In addition, results from this study can be educational for families and patients with respect to anticipated treatment times, success rates of the procedure, complication rate, and likelihood of needing repeat procedures.
Fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets (HPR) are characterized by excess circulating FGF23 and low concentrations of serum phosphorus, leading to skeletal manifestations of rickets, including lower limb deformities in children. The objective of this study was to prospectively evaluate whether treatment with burosumab, a monoclonal antibody neutralizing FGF23, changes lower limb deformities in HPR. Patients who were 15 years of age or younger with a documented clinical diagnosis of HPR, receiving burosumab treatment, and had a minimum follow-up period of one year were included in the study. Various radiological parameters were measured from anteroposterior and lateral radiographs of the bilateral lower limbs taken before administration of burosumab and at 3, 6, 9, and 12 months after treatment for evaluation of lower limb alignment. Outcome was classified as 'improvement', 'no change', or 'deterioration' after 12 months treatment. Five patients (10 limbs), with a mean age of 7.2 years were included in this study. The outcome was 'improvement' in six limbs and 'no change' in four limbs. There were no limbs of 'deterioration'. The improvement in deformities after treatment was more significant in younger patients who originally showed severe lower limb deformities. Older patients with milder deformities, on the other hand, showed less improvement. Burosumab therapy favorably changed lower-limb malalignment in children with FGF23-related HPR.
Purposes: Temporary hemiepiphysiodesis (TH) using eight-plates is one of the most frequently performed surgeries for correcting angular deformities of the lower extremities in adolescents. Rarely have studies examined children with X-linked hypophosphataemic rickets (X-LHPR) treated with TH using eight-plates. This study was conducted to investigate the efficacy, the endpoint, and the complications of TH using eight-plates to correct angular deformities of the lower extremities in skeletally immature children. Methods: We reviewed a total of 26 children (86 physes, 52 knees) with X-LHPR (mean age of 6.2 years, range from 2 to 13 years) who underwent TH using eight-plate to correct angular deformities of the lower extremities. Radiographs and clinical records of these patients were evaluated for demographic data and related clinical factors. Results: The average correction of the mechanical lateral distal femoral angle (mLDFA) was 11.7 ± 8.7° (range from 1.0 to 29.7°), and the average correction of the mechanical medial proximal tibial angle (mMPTA) was 8.4 ± 5.0° (range from 0.3 to 16.7°). The mean deformity correction time was 22.7 months (range from 7 to 60 months), and the mean follow-up after eight-plate removal was 43.9 months (range from 24 to 101 months). Overall, 76.9% (20/26 patients) of the angular deformities of the knee were completely corrected and 15.4% (4/26) of the patients received osteotomy surgery. The femoral correction velocity (0.9° per month) was significantly higher than the proximal tibial (0.6° per month) (p = 0.02). The correction velocity of the mLDFA and mMPTA with the TH procedure was faster than that in the absence of intervention (0.9° vs. 0.2°, 0.7° vs. 0.4° per month, p < 0.05). The correction velocity of the mLDFA (1.2° vs. 0.5° per month, [Formula: see text]) and mMPTA (0.7° vs. 0.5° per month, p = 0.04) of patients whose age ≤ five years old was faster than that of patients whose age > five years old. A total of 69.2% (18/26) patients experienced one TH procedure using eight-plates only. Two patients had screw loosening (2/26, 7.7%). One patient (1/26, 3.8%) had a rebound phenomenon after the removal of eight-plate and had the TH procedure again. There was no breakage, infection, physis preclosure, or limited range of movement found in the follow-up. Conclusion: TH using eight-plates is a safe and effective procedure with a relatively low incidence of complication and rebound, and it could be used as part of a streamlined treatment for younger X-LHPR patients with resistant or progressive lower limb deformity despite optimal medical treatment. Early intervention can achieve better results.
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Purpose Renal osteodystrophy (ROD) may cause severe lower limb deformities in children. The purpose of this study is to evaluate the efficacy of the temporary hemiepiphysiodesis for the correction of lower limb deformities in children with ROD. Methods Guided growth correction by hemiepiphysiodesis has been performed in skeletally immature patients with deformities of the lower limbs caused by ROD. The correction of the mechanical axes of the lower limbs and its correction speed have been evaluated. Results A total of seven patients with ROD, five males and two females, were treated with the above technique. The average age of the patients at their first surgery was 7.8 years (2.9 to 13.6). The average follow-up time 5.2 years (2.3 to 8). There were 13 valgus deformities and one varus deformity of the knee. The measure of the lower limb angular deformity was in the range of 10° to 47°. Restoration of normal mechanical axis was achieved in all patients at the final follow-up. Three patients relapsed and required further hemiepiphysiodesis. The average time for correction was 20 months (7 to 30). The average speed of correction was 0.49° per month for a tibia and 1.73° per month for a femur. There were two minor complications: a screw mobilisation and a screw breakage occurred during removal. Conclusion Guided growth technique by hemiepiphysiodesis is a mini-invasive surgical procedure that has been found to be effective for the correction of misalignment due to ROD in skeletally immature patients. The method has allowed progressive correction of the deformities at any age in childhood. These patients are predisposed to relapse to their deformities, thus a strict follow-up is required.
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The operative procedures to correct multiplanar bone deformities may be indicated for prevention of secondary orthopaedic complications in children with X-linked hereditary hypophosphatemic rickets (XHPR). Different problems related to surgical correction were reported: increased rate of non-union, delayed union, recurrent deformity, deep intramedullary infection, refracture, nerve palsy, and pin tract infection. The aim of this retrospective study was comparison of results of correction in children with XHPR who underwent the treatment with either the Ilizarov device alone or a combined technique: the Ilizarov fixator with flexible intramedullary nailing (FIN) with hydroxyapatite bioactive coating and FIN. We retrospectively analysed 47 cases (children of age under 14 years) affected by XHPR. Simultaneous deformity correction in femur and tibia was performed with the Ilizarov device (group I) or the combined method (group II). This article is based on the results of a historical comparative retrospective study from the same institution. The duration of external fixation is noted to be shorter applying the combined technique: 124.7 days (group I) vs 87.4 days (group II). In both groups deformity correction was achieved with a proper alignment. Nevertheless, while a child continues to grow during long-term follow-up, deviations of the mechanic axis from the centre of the knee joint have been developing again and values of mLDFA, mMPTA have become pathologic in the most of the cases. In group I location of a newly developed deformity resembled a pre-operative one, whereby both diaphyseal and metaphyseal parts were deformed. In group II in all the cases an apex of deformity was located in distal metadiaphyseal zone of the femur and proximal metadiaphyseal zone of the tibia. It is important to note that all of those in group II were out of the zone of the intramedullary nail. Simultaneous correction of femoral and tibial deformities by means of circular external fixators is preferable. Application of a combined osteosynthesis allows to considerably reduce the duration of external fixation and decrease the number of complications. There were no recurrent deformities in parts of bone reinforced by intramedullary nails.
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Hypophosphatemic rickets (HR) is a genetic disorder, which prevents sufficient reabsorption of phosphate in the proximal renal tubule, with increased phosphate excretion, resulting in rickets. The more common form of HR is an X-linked inherited trait, with a prevalence of 1/20,000. The defective gene is located on the X chromosome, but females may present with a wide variety of clinical manifestations. The less common form of HR is caused by autosomal-dominant transmission. Activating mutations of the fibroblast growth factor 23 (FGF-23) gene and inactivating mutations in the phosphate regulating gene (PHEX gene with homologies to endopeptidases on the X chromosome), involved in the regulation of FGF-23, have been identified and have been implicated in the pathogenesis of these disturbances. A review of etiopathogenesis and clinical, differential diagnostic and therapeutic aspects of HR, with a particular emphasis on bone impairment, is reported.
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Inactivating mutations in phosphate-regulating endopeptidase (PHEX) cause X-linked hypophosphatemic rickets (XLHR) characterized by phosphaturia, hypophosphatemia, bony deformities, and growth retardation. We assessed the efficacy of combined calcitriol and orally administered phosphate (Pi) therapy on longitudinal growth in relation to age at treatment onset in a retrospective, single-center review of children with XLHR and documented PHEX mutations. Growth was compared in those who started treatment before (G1; N = 10; six boys) and after (G2; N = 13; five boys) 1 year old. Median height standard deviation score (HSDS) at treatment onset was normal in G1: 0.1 [interquartile range (IR) -1.3 to 0.4) and significantly (p = 0.004) lower in G2 (IR -2.1 (-2.8 to -1.4). Treatment duration was similar [G1 8.5 (4.0-15.2) vs G2 11.9 (6.2-14.3) years; p = 0.56], as were prescribed phosphate and calcitriol doses. Recent HSDS was significantly (p = 0.009) better in G1 [-0.7 (-1.5 to 0.3)] vs G2 [-2.0 (-2.3 to -1.0)]. No effects of gender or genotype on growth could be identified. Children with PHEX-associated XLHR benefit from early treatment and can achieve normal growth. Minimal catchup growth was seen in those who started treatment later. Our findings emphasize the importance of early diagnosis to allow treatment before growth has been compromised.
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The between-observer reliability of repeated anatomic assessments in pediatric orthopedics relies on the precise definition of bony landmarks for measuring angles, indexes, and lengths of joints, limbs, and spine. We have analyzed intra- and interobserver reliability with a new digital measurement system (TraumaCad Wizard™). Five pediatric orthopedic surgeons measured 50 digital radiographs on three separate days using the TraumaCad system. There were 10 anterior-posterior (AP) pelvic views from developmental dysplasia of the hip (DDH) patients, 10 AP pelvic views from cerebral palsy (CP) patients, 10 AP standing view of the lower limb radiographs from leg length discrepancy (LLD) patients, and 10 AP and 10 lateral spine X-rays from scoliosis patients. All standing view of the lower limb radiographs were calibrated by the software to allow for accurate length measurements, using as reference a 1-inch metal ball placed at the level of the bone. Each observer performed 540 measurements (totaling 2,700). We estimated intra- and interobserver standard deviations for measurements in all categories by specialists and nonspecialists. The intraclass correlation coefficient (ICC) summarized the overall accuracy and precision of the measurement process relative to subject variation. We examined whether the relative accuracy of a measurement is adversely affected by the number of bony landmarks required for making the measurement. The overall ICC was >0.74 for 13 out of 18 measurements. Accuracy of the acetabular index for DDH was greater than for CP and relatively low for the center-edge angle in CP. Accuracy for bone length was better than for joint angulations in LLD and for the Cobb angle in AP views compared to lateral views for scoliosis. There were no clinically important biases, and most of the differences between specialists and nonspecialists were nonsignificant. The correlation between the results according to the number of bony landmarks that needed to be identified was also nonsignificant. Digital measurements with the TraumaCad system are reliable in terms of intra- and interobserver variability, making it a useful method for the analysis of pathology on radiographs in pediatric orthopedics.
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Therapy of vitamin D-resistant hypophosphatemic rickets (VDXLR) consists of oral phosphate and vitamin D supplements. Bone deformities, pain, and small stature can occur even in children with good compliance, requiring surgical correction and bone lengthening. However, only few surgical reports are available. Twelve patients (three males) with VDXLR were followed at our institution. Median age at diagnosis was 3 9/12 years (range, birth to 11 10/12) with a follow-up period of 7 8/12 years (1 9/12-30) and age at last follow-up of 13 6/12 years (2-30). Eight patients underwent surgical correction, three of them in combination with bone lengthening. The corrections were performed at the end of growth in three patients. Clinical endpoints were height, leg axis, and pain. Single bilateral surgical correction was performed in six patients; one patient each had three and five corrections. Bone lengthening was performed in three patients. At last follow-up, the height of seven operated patients was within normal range. In addition, leg axis was normalized in six patients with mild genua vara in two. Only one patient complained of intermittent pain. Bone healing was excellent; surgical complications were rare. There was no radiological evidence of degenerative arthropathy. Medical treatment remains the main pillar of therapy in children with VDXLR. In case of bone deformity, surgery can safely be performed, independent of age or bone maturation. All patients were satisfied with the results of axial corrective surgery and bone lengthening, and in the majority only one corrective intervention was needed.
The authors evaluated 14 patients with hypophosphatemic rickets who underwent correction of a knee deformity along with a leg lengthening by the llizarov method. Deformity correction alone was performed in 8 femora and 4 tibiae-fibulae, and concomitant deformity correction and limb lengthening (>1.0 cm) in 9 femora and 19 tibiae-fibulae. The healing index correlated with the biochemical parameters. Knee deformities were satisfactorily corrected in all patients except one. There was a statistically significant negative correlation between the healing index and the serum phosphate level: those who had a serum phosphate level higher than 2.5 mg/dL showed a relatively rapid regenerate bone healing compared with those with less than 2.5 mg/dL. The authors conclude that a serum phosphate level of 2.5 mg/dL as a cut-off point should be considered in deciding whether deformity correction alone or with a concomitant leg lengthening should be undertaken.
X-linked hypophosphatemia is an inheritable disorder of renal phosphate wasting that clinically manifests with rachitic bone pathology. X-linked hypophosphatemia is frequently misdiagnosed and mismanaged. Optimized medical therapy is the cornerstone of treatment. Even with ideal medical management, progressive bony deformity may develop in some children and adults. Medical treatment is paramount to the success of orthopaedic surgical procedures in both children and adults with X-linked hypophosphatemia. Successful correction of complex, multiapical bone deformities found in patients with X-linked hypophosphatemia is possible with careful surgical planning and exacting surgical technique. Multiple methods of deformity correction are used, including acute and gradual correction. Treatment of some pediatric bony deformity with guided growth techniques may be possible. Copyright 2015 by the American Academy of Orthopaedic Surgeons.
X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines, which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the Advances in Rare Bone Diseases Scientific Conference held at the NIH in October 2008. We briefly review the clinical and pathophysiologic features of the disorder and offer this guide in response to the conference recommendation, based on our collective accumulated experience in the management of this complex disorder.
X-linked hereditary hypophosphatemic rickets can induce various multiplanar deformities of the lower limb. We evaluated our ability to correct these deformities and assessed complications and recurrence rates in 10 children (eight girls and a pair of twin boys) followed from early childhood to skeletal maturity. We performed 37 corrective operations in 10 children. Depending on the patient’s age, external fixation was used in 53 segments: Kirschner wires in 18, DynaFix® in three, the Taylor Spatial Frame® device in 13, and the Ilizarov device in 19. Internal fixation with intramedullary nailing was performed in 12. After bone consolidation, we radiographically determined the mechanical axis at an average distance of 0.5 cm medial to the center of the knee. The average mechanical lateral distal femoral angle was 85° (range, 83°–92°) and the average mechanical medial proximal tibial angle was 91° (range, 85°–92°). Deviation of the mechanical axis and knee orientation lines was increased at the followups conducted during a period of 5 to 12 months. Additional followups revealed a recurrence rate of 90% after the first corrective procedure and 60% after a second procedure. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.