Predictive factors for recurrence after lower limb deformity correction in hypophosphatemic rickets.

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.

Temporary hemiepiphysiodesis using eight-plates for angular deformities of the lower extremities in children with X-linked hypophosphataemic rickets.

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.

Genetic analysis combined with 3D-printing assistant surgery in diagnosis and treatment for an X-linked hypophosphatemia patient.

BACKGROUND: Hypophosphatemia is mainly characterized by hypophosphatemia and a low level of 1alpha,25-Dihydroxyvitamin D2 (1,25-(OH)2 D2) and/or 1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2 D3) in the blood. Previous studies have demonstrated that variants in PHEX and FGF23 are primarily responsible for this disease. Although patients with variants of these two genes share almost the same symptoms, they exhibit the different hereditary pattern, X-link dominant and autosome dominant, respectively. Three-dimensional (3D) printing is a method which can accurately reconstruct physical objects, and its applications in orthopedics can contribute to realizing a more accurate surgical performance and a better outcome. METHODS: An X-linked hypophosphatemia (XLH) family was recruited, with four patients across three generations. We screened candidate genes and filtered a duplication variant in PHEX. Variant analysis and co-segregation confirmation were then performed. Before the operation of our patient, a digital model of our patient's leg had been rebuilt upon the CT scan data, and a polylactic acid (PLA) model had been 3D-printed. RESULTS: A novel duplication PHEX variant c.574dupG (p.A192GfsX20) was identified in a family with XLH. Its pathogenicity was confirmed by the co-segregation assay and online bioinformatics database. The preoperative plan was made with the help of the PLA model. Then, arch osteotomy and transverse osteotomy were performed under the guidance of the previous simulation. The appearance of the surgical-intervened leg was satisfactory. CONCLUSIONS: This study identified a novel PHEX variant and showed that 3D printing tech is a very promising approach for corrective osteotomies.

Orthopedic and neurosurgical care of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is due to mutations in the PHEX gene leading to unregulated production of FGF23 and uncontrollable hypophosphatemia. XLH is characterized in children by rickets, short stature, waddling gait, and leg bowing of variable morphology and severity. Phosphate supplements and oral vitamin D analogs partially or, in some cases, fully restore the limb straightness. XLH patients may also be affected by premature, complete, or partial ossification of sutures between cranial bone, which could eventually result in cranial dysmorphia, decreased intracranial volume, and secondary abnormally high intracranial pressure with a cerebral compression. Our goal is to address the criteria and the management of the skeletal complications associated with XLH, mainly orthopedic and neurosurgical care, and reflect on decision-making and follow-up complexities.

Minimally Invasive Surgical Management of Thoracic Ossification of the Ligamentum Flavum Associated with X-linked Hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia (XLH) is the most common inherited form of renal phosphate wasting and inherited rickets. Patients have hyperplasia of fibrochondrocytes in tendons and ligaments, causing the structures to thicken and calcify. Thickening of the lamina, hypertrophy of facet joints, and calcification of spinal ligaments are sequelae of this condition and can result in central or foraminal stenosis that compresses nerve roots or the spinal cord. We present a case of XLH with calcification of the ligamentum flavum in which the patient was operated on using minimally invasive posterior decompression. CASE DESCRIPTION: A 49-year-old man with a history of XLH presented to our emergency department with symptomatic myelopathy from multilevel thoracic stenosis. Radiographically, the calcified ligamentum flavum appeared to be the cause of the stenosis at various levels. The patient underwent a posterior decompression at the levels of compression, T4-T5, T8-T9, T9-T10, and T11-T12, via a minimally invasive spine surgery approach. Intraoperatively, the ligamentum flavum appeared to be both calcified and the source of spinal compression. Postoperatively, the patient experienced neurologic and radiographic improvement. CONCLUSION: Patients with a history of XLH and multilevel symptomatic spine stenosis can be treated successfully and safely with a minimally invasive posterior decompression.

Age at initial consultation for craniosynostosis: comparison across different patient characteristics.

BACKGROUND: The severity and dysmorphology that results from the premature fusion of one or more cranial sutures is not uniform. Less striking phenotypes may be more easily missed on routine screening, possibly leading to delayed diagnosis and treatment. The purpose of this study was to compare the age at initial presentation for the different forms of craniosynostosis. METHODS: The authors reviewed the records of all patients who underwent open craniofacial repair of craniosynostosis at a single institution from 1996 to 2009. Relationships between type of suture fusion and age at initial consultation were compared. RESULTS: Two hundred eleven patients (136 males, 75 females) were identified. Indications included sagittal (n = 96), metopic (n = 39), unicoronal (n = 33), bicoronal (n = 24), multisutural (n = 15), bilambdoidal (n = 3), and unilambdoidal (n = 1) synostoses. Seventeen patients (8.1%) had a craniosynostosis syndrome and 5 (2.4%) had a syndrome or disorder not typically associated with craniosynostosis [X-linked hypophosphatemic rickets (n = 3), achondroplasia (n = 1), and Beckwith Wiedemann (n = 1)]. Median age at initial consultation was 4.1 months; there was no gender difference. Patients with X-linked hypophosphatemic rickets presented at a significantly older age than nonsyndromic patients or those with a known craniosynostosis syndrome. Those with multisutural synostosis presented at a significantly older age than patients with sagittal or bicoronal synostosis. CONCLUSIONS: Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. The latter group of patients may especially benefit from routine surveillance for craniosynostosis given their advanced age at diagnosis.

Experience with the Fassier-Duval telescopic rod: first 24 consecutive cases with a minimum of 1-year follow-up.

BACKGROUND: The new Fassier-Duval Telescopic IM System (FD-rod) has the advantage of a single entry point over the traditional telescopic rods such as the Bailey-Dubow or Sheffield rods. Although encouraging early results were presented by the originators of the technique at international meetings, there is no formal publication in the literature as yet. METHODS: We performed a chart and x-ray review of the first 24 consecutive FD-rod insertions in 15 patients (age, 1.5 to 12.5 y) with a minimum of 1-year follow up (1 to 2.4 y) after implantation of femoral and/or tibial FD-rods. Diagnoses included with osteogenesis imperfecta (OI) (15 cases, 9 patients), and other conditions such as congenital tibial pseudarthrosis (CPT) in neurofibromatosis type 1 (NF1) (2 cases), and epidermal naevus syndrome (1 case). In patients with hypophosphataemic rickets (6 cases, 2 patients) the FD-rods were combined with an Ilizarov frame. RESULTS: We found the OI patient group associated with a 13% reoperation rate (2 of 15 cases) for proximal rod migration and a 40% complication rate (6 of 15 cases): rod migration and limited telescoping (5) and intraoperative joint intrusion (1). There were no infections. All the NF1 CPT (2) and epidermal naevus syndrome (1) cases required several reoperations for nonunion, loss of fixation, shortening (negative telescoping), migration, and/or joint intrusion-mainly due to the severe underlying pathology with insufficient longitudinal or torsional stability and diminished healing capacity. In hypophosphataemic rickets (combined with Ilizarov frame fixation) we found a 50% complication rate (3 of 6 cases) and a 17% reoperation rate (1 of 6): 2 FD-rods did not telescope and 1 case of peroneal neuropraxia required neurolysis. CONCLUSIONS: In our experience the technique of using FD rods is demanding and associated with some intraoperative and postoperative pitfalls. We are happy to continue its use in OI patients when there is longitudinal stability and sufficient bone healing. However, in circumstances of insufficient stability and bone healing potential, further stabilization that can be achieved with an Ilizarov frame may be beneficial.

Combined technique for the correction of lower-limb deformities resulting from metabolic bone disease.

We present the results of the surgical correction of lower-limb deformities caused by metabolic bone disease. Our series consisted of 17 patients with a diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and 16 tibiae) were osteotomised and the deformity corrected using a monolateral external fixator. The segment was then stabilised with locked intramedullary nailing. In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The frontal alignment parameters (the mechanical axis deviation, the lateral distal femoral angle and the medial proximal tibial angle) and the sagittal alignment parameters (the posterior distal femoral angle and the posterior proximal tibial angle) improved post-operatively. The external fixator was removed either at the end of surgery or at the end of the lengthening period, allowing for early mobilisation and weight-bearing. We encountered five problems and four obstacles in the programme of treatment. The use of intramedullary nails prevented recurrence of deformity and refracture.

Tumor-induced hypophosphatemic rickets in an adolescent boy--clinical presentation, diagnosis, and histological findings in growth plate and muscle tissue.

CONTEXT: The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported. PATIENT: A mesenchymal tumor was detected in the left distal fibula by (68)Ga-DOTATOC in a 17-yr-old boy with adolescent onset of severe hypophosphatemic rickets. Disabling muscle weakness improved within days after surgery, and normal mobility was restored within months. METHODS AND RESULTS: The resected tissue included part of the growth plate allowing immunohistochemical investigation. Positive staining of FGF23 was found in the tumor cells and in hypertrophic chondrocytes, osteoblasts, and osteoclasts of the adjacent growth plate. This distribution matched that found in growth plate tissue of a healthy control. We found positive staining for the somatostatin receptor not only in the tumor but also within the growth plate and adjacent bony tissue in the patient and the healthy control. Muscle tissue provided evidence for a partial defect in respiratory chain complexes I-IV. Biochemical markers were nearly or completely restored to normal 12 months after surgery. CONCLUSIONS: Hypertrophic growth plate chondrocytes are a target or source of FGF23 in tumor-induced osteomalacia. Low serum phosphate, FGF23, or other factors produced by the tumor may interfere with mitochondrial function.

Deformity correction for vitamin D-resistant hypophosphatemic rickets of adults.

We performed correction for bowing deformity of the lower extremities due to vitamin D-resistant hypophosphatemic rickets of three adults, six segments. The operative method was gradual correction and lengthening using distraction osteogenesis by Ilizarov external fixator or Heidelberg external fixator. The orders of the corrections were simultaneous correction of the bilateral femur for one patient, simultaneous correction of the ipsilateral leg for one patient, and diagonal correction of the bilateral leg for one patient. The mean correction angle was 30.5 degrees. The mean external fixation period was 146 days. Each orders of the corrections had its merits and demerits. All patients obtained a physiological alignment and good bone formation by taking Vitamin D and oral phosphate supplements even an adult patient. All the patients had articular pain, such as hip, knee, and ankle, however, these pains healed up. All the patients were satisfied with the outcomes at the time of the final follow-up interview in terms of their cosmetic improvement. Distraction osteogenesis for bowing deformity of the lower extremities due to vitamin D-resistant hypophosphatemic rickets was very effective method and could be applied to adult patients. However, the order of the corrections should be considered carefully depending on each patient.

[Hyperphosphatasia and hypophosphatasia in childhood]. / Hyperphosphatasie und Hypophosphatasie im Kindesalter.

The treatment of phosphate diabetes and hyperphosphatasia requires an interdisciplinary therapy concept between paediatricians and orthopaedic surgeons. The surgical challenge is the correction of the multiplanar bending deformities and the pathological fractures. Different techniques are discussed in the literature without an outstanding recommendation for a special approach. This contribution gives an overview of the published methods and discusses various surgical concepts in view of our own clinical experience.