Tumor(s) induced osteomalacia--a curious case of double trouble.

CONTEXT: We report a case of tumor-induced osteomalacia with evidence of synchronous multifocal fibroblast growth factor 23 (FGF23) production. OBJECTIVE: The aim is to present a case of tumor-induced osteomalacia and to highlight the fact that incomplete removal of multifocal FGF23-producing tumors, which are not entirely picked up by functional imaging, could be the cause of treatment failure. SETTING: The patient was treated in the Department of Endocrinology of a tertiary care center in India. PATIENT: We report the case of a 42-year-old male with tumor-induced osteomalacia. INTERVENTION: We treated the tumor-induced osteomalacia with staged surgery of the two tumors. The 18F-fluorodeoxyglucose (FDG)-avid lesion (considered the sole culprit lesion after functional imaging) was resected first, followed by the non-FDG-avid lesion. The sequential removal of both tumors resulted in complete cure. RESULTS: The patient had hypophosphatemia and hyperphosphaturia. C-Terminal FGF23 level was elevated. Positron emission tomography-computed tomography showed two lesions-an FDG-avid lesion in the right leg, and a non-avid lesion in the left thigh. After removal of the FDG-avid lesion, the hypophosphatemia persisted, and the FGF23 level showed only modest reduction. The patient had complete clinical and biochemical resolution only after removal of the second non-FDG-avid tumor. CONCLUSIONS: We present the case of a tumor-induced osteomalacia whose biochemical parameters did not improve after removal of the FDG-avid tumor initially. The possibility of multifocal FGF23 production was considered, and the second, non-FDG-avid lesion was resected, which resulted in complete cure. Thorough clinical examination and meticulous follow-up with documentation of the biochemical resolution are necessary for management of all patients with this rare disorder.

[Locking plates for osteosyntheses of corrective osteotomies in paediatric orthopaedic and neuroorthopaedic patients]. / Winkelstabile Implantate zur Osteosynthese nach Korrekturosteotomien in der Kinder- und Neuroorthopädie.

BACKGROUND: Modern locking plates are widely used for the treatment of adult orthopaedic and trauma patients. Sporadic descriptions of their advantages now exist for paediatric trauma patients. Publications concerning their implantation in paediatric orthopaedic and neuroorthopaedic patients are still scarce even though it is well known that the compliance of children and adolescents is limited and that rapid mobilisation is essential for patients with disorders of neurological origin or bone metabolism to avoid developmental setbacks and perioperative fractures. PATIENTS AND METHODS: The principle of the locking plate system also described as internal fixateur is based on the thread bolting of the screwheads within the plate. This results in high initial stability and thus high initial loading capacity. Furthermore, it is possible to preserve soft tissue and periosteum which leads to less impaired biological bone healing. Between February 2008 and March 2010 locking plates were used for osteosynthesis in our department in 16 paediatric patients with 20 corrective osteotomies. All patients suffered from either neurological disorders or diseases with alteration of the bone metabolism. The outcome was analysed concerning safety, complications, practicability, mobilisation, consolidation of the osteotomy, loss of correction, as well as complications with the removal of the implants. RESULTS: Seven of the treated patients suffered from neurological disorders such as cerebral palsy or spina bifida, 9 patients had diseases with local or systemic alteration of their bone metabolism such as vitamin D deficiency and phosphate diabetes. The average age of the patients at the time of surgery was 11.18 (5-18) years. Implant-associated complications were not seen in this patient group, especially no implant failures. Mobilisation was achieved without cast treatment with at least partial weight-bearing within the first postoperative week in most cases. Loss of correction or problems with implant removal did not occur. 18 of the 20 osteotomy sites were completely healed at the 12 week follow-up. CONCLUSION: Locking plates are a safe and effective treatment device not only for adult trauma patients but also for the treatment of children and adolescents. When stabilisation of corrective osteotomies is performed with locking plates especially young patients benefit from this technique since mobilisation can be started earlier as compared to the use of non-angle stable plates or wires and cast immobilisation becomes unneccessary. The surgeon needs to know the range of products to pick the best implant regarding the growing skeleton's special anatomy. When choosing implants for patients with reduced bone density or impaired motor abilities as in cerebral palsy, spina bifida, and other systemic disorders, locking plates have to be taken into account to facilitate mobilisation and to avoid setbacks in motor development as well as pressure ulcers from casts. Clinical studies have to evaluate if early mobilisation combined with shorter inpatient treatment and less time and cost consuming postoperative physiotherapy or rehabilitation justify the use of the more expensive locking plates for the treatment of otherwise healthy patients.

Deformity correction by external fixation and/or intramedullary nailing in hypophosphatemic rickets.

BACKGROUND: There are many modalities of treatment for complex lower extremity deformity in hypophosphatemic rickets. We evaluated the outcomes of deformity correction using an external fixation and/or intramedullary nailing in hypophosphatemic rickets. PATIENTS AND METHODS: 55 segmental deformities (20 femora, 35 tibiae) from 20 patients were examined retrospectively. There were 9 children and 11 adults. Distraction osteogenesis was used in 28 segments and acute deformity correction in 27. External fixation was applied in 24 segments, intramedullary nailing in 6, and external fixation and intramedullary nailing in 25. RESULTS: There were 18 major and 13 minor complications in 26 of 28 segments with distraction osteogenesis, and 13 major and 10 minor complications in 19 of 27 segments with acute correction. Recurrent deformity or refracture occurred in 10 of 21 segments with distraction osteogenesis by external fixation only, 4 of 6 with acute correction by intramedullary nailing, and 1 of 25 with distraction osteogenesis or acute correction by external fixation and intramedullary nailing. Nail-related complications occurred in 3 of 6 with intramedullary nailing and 2 of 25 with external fixation and intramedullary nailing. INTERPRETATION: External fixation and intramedullary nailing can be recommended to prevent complications during or after deformity correction in hypophosphatemic rickets.

Hypophosphatemic rickets: the role of hemiepiphysiodesis.

Despite early medical intervention, children with hypophosphatemic rickets often have progressive deformities in the lower extremities. With the forces imparted by gravity and weight bearing, varus or valgus deformities that might otherwise have been physiological are likely to progress, causing gait disturbance and pain. Proper medical management is important and may theoretically slow or prevent the progression of varus or valgus, but is ineffective at correcting deformity once established. We have reviewed the literature and gathered a series of 10 patients, most of whom underwent hemiepiphysiodesis. We are presenting the rationale for, and the results of, that surgery, in an effort to define the role of this minimally invasive procedure.

Surgical treatment of femoral bending deformity in a patient with vitamin D-resistant rickets.

Surgical treatment of patients with vitamin D-resistant rickets is reserved for management of severe deformities or pathological fractures of the lower limbs. This case report describes the operative management of a child with vitamin D-resistant rickets suffering from a pathological fracture and a bending deformity of the right femoral bone. A modified technique of fragmentation and realignment by intramedullary fixation was performed using an unreamed humerus nail. We corrected the anatomical proximal femoral shaft angle (aMPFA) from 68 degrees to 84 degrees and achieved three more centimetres of femoral length. The same procedure was performed on the left femur and corrected the aMPFA from 108 degrees to 89 degrees and gained 2.5 more centimetres of femoral length. Thus the legs were almost equal in length. We preferred the modified technique of multiple osteotomies and intramedullary fixation by nailing (originally described by Sofield and Millar) because the correction of angulation and rotation of the femoral shaft in one step appeared to be much easier than with plate fixation. Moreover, this method seems to reduce the number of refractures and enables the patients to approach the normal activities of growing children.

Genetic advances, biochemical and clinical features and critical approach to treatment of patients with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is an hereditary form of rickets due to isolated renal tubular phosphate wasting and impaired production of 1,25-dihydroxyvitamin D [1,25(OH)2D]. XLH is caused by mutations in the PHEX (phosphate regulating gene with homology to endopeptidases) gene, which is located on Xp22.1. The pathogenetic mechanisms by which mutations in the PHEX gene cause XLH are not completely known. Hypophosphatemia associated with disproportionate short stature and bone deformities of the lower limbs are the main findings in XLH patients. Some studies have shown that conventional treatment with vitamin D metabolites, such as 1,25(OH)2D3 or 1 alpha-hydroxyvitamin D3, combined with inorganic phosphate salts is able to improve serum phosphate concentrations and linear growth, as well as healing rickets. However, some patients may have poor beneficial effects by this therapy. On the other hand, some important treatment complications, such as hypervitaminosis D, nephrocalcinosis and secondary/tertiary hyperparathyroidism may occur during the current therapy. Despite conventional treatment, some patients may require surgical correction of bone deformities. In the light of the recent genetic advances the mechanisms that could be involved in the pathogenesis of XLH are discussed. Furthermore, the article reviews the effects of the medical treatment providing current recommendations for the management of XLH patients.

Deformity correction of knee and leg lengthening by Ilizarov method in hypophosphatemic rickets: outcomes and significance of serum phosphate level.

The authors evaluated 14 patients with hypophosphatemic rickets who underwent correction of a knee deformity along with a leg lengthening by the Ilizarov 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.

Cervical spinal cord compression attributable to a calcified intervertebral disc in a patient with X-linked hypophosphatemic rickets: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: X-linked hypophosphatemic rickets is a common inherited phosphate-wasting disorder, but it is a rare cause of spinal cord compression. We present the first reported case of a calcified intervertebral disc causing spinal canal stenosis in X-linked hypophosphatemic rickets. CLINICAL PRESENTATION: A 44-year-old woman presented with paresthesia of her left arm and a loss of grip in both hands. Magnetic resonance imaging revealed a calcified intervertebral disc, as well as a posterior osteophytic bar causing marked cervical cord compression at C6/C7. INTERVENTION: An anterior cervical discectomy at C6/C7 and fusion with autologous bone graft were performed. The patient then exhibited significant improvement. CONCLUSION: A review of the 16 published cases demonstrates that thickening of the vertebral laminae, facet joint hypertrophy, and ossification of the intervertebral discs, posterior longitudinal ligament, and/or ligamentum flavum contribute to spinal canal stenosis in X-linked hypophosphatemic rickets. Those changes are caused by the disease itself and are unlikely to be related to long-term vitamin D treatment. Eleven of 16 patients were reported to have experienced favorable outcomes after surgery.

X-linked hypophosphatemic rickets--a report of 2 cases and review of literature.

We report two cases of x-linked dominant hypophosphatemic rickets involving a man and his daughter. The family tree consists of 44 members with 13 of them having short stature and bowing of the lower limbs. The study of this family tree strongly suggests an x-linked dominant inheritance.

A simple technique for correction of complicated tibial deformity including rotational deformity.

Although the simplest way to correct bone deformity is one-stage correction, the problem associated with that method is overstretching of the soft tissues, which limits the correction and leads to complications such as compartment syndrome or peripheral nerve palsy. If an adequate amount of tissue necessary for correction is formed in advance, the deformity can be corrected safely at one stage without overstretching of the tissues. A leg lengthening technique was employed to form the necessary tissues. After leg lengthening with an unilateral external fixator (Hifixator), deformities were corrected manually at one stage without anesthesia, and the corrected positions were again secured with the fixator. To correct rotational deformity, two sets of pins were inserted into the proximal bone fragment of the tibia at the time of the operation, and after lengthening the proximal pin clamp of the fixator was disconnected from one pin set and reconnected to the other set. We applied this method to four tibias of three patients without any complications. The tension of the tissues was monitored using a pressure sensor built into a Hifixator to prevent the tissues from overstretching. During and after the correction, the tension of the tissue was maintained at less than before the correction.

Spinal canal stenosis with hypophosphatemic vitamin D-resistant rickets: case report.

A 42-year-old woman with sex-linked hypophosphatemic vitamin D-resistant rickets presented with a 6-month history of progressive weakness and numbness in her lower extremities. Radiological studies revealed severe spinal canal stenosis extending from levels T4 to T10. Her symptoms improved markedly after extensive thoracic laminectomies.

Osteotomy and intramedullary nailing for the correction of progressive deformity in vitamin D-resistant hypophosphataemic rickets.

We have reviewed the results of surgical treatment of vitamin D-resistant hypophosphataemic rickets (VDRR) and describe a technique of corrective osteotomy and intramedullary nailing. From 1978 to 1986, epiphysiodesis (n = 4) and osteotomy (n = 8) was performed in 6 children (mean age 13, range 10-16 years) for the correction of progressive lower limb deformity. Realignment and internal fixation of a pathological fracture of the femur was performed in an adult (aged 24). Epiphysiodesis resulted in recurrent deformity in all patients and reapplication of staples for loosening was required in three. Corrective osteotomies were secured with staples (n = 3), plates (n = 4), or plaster alone (n = 1) and were complicated by non-union in one patient, and recurrent deformity in two patients. Double-plating of the femoral fracture resulted in union but recurrent deformity. Compliance to treatment with phosphate and vitamin D was variable. In order to manage progressive recurrent deformity, we have performed corrective osteotomy and closed intramedullary nailing of the tibia (n = 2) and femur (n = 3) in 4 skeletally mature patients (mean age 31). All osteotomies united and no complications were encountered. Deformity has been corrected in all cases and all patients are satisfied with the outcome at least 2 years after surgery. We conclude that rigid methods of fixation spanning the whole length of the bone are required to maintain limb alignment in skeletally mature patients with VDRR. Since the quality of bone in VDRR is variable, experience with intramedullary techniques is essential. We stress the importance of appropriate medical therapy throughout the treatment of these patients.

The orthopaedic management of hypophosphataemic rickets.

The orthopaedic management of 19 patients with hypophosphataemic rickets was reviewed. Three groups of patients could be identified: teenagers or young adults without knee problems, those with knee problems, and adults or elderly patients with stiff joints due to mineralisation of ligaments. Osteotomies were best staged. Diaphyseal osteotomies were performed at all ages with stabilisation over an intramedullary nail; metaphyseal osteotomies were most successful at or close to maturity. Early degeneration of the knees with shedding of the articular cartilage was seen in young adults, and osteochondritis-like lesions were seen in some teenagers. Stiffness and bone pain were a feature in elderly patients.

Surgically curable hypophosphatemic rickets. Diagnosis and management.

Childhood hypophosphatemic rickets (HR) is most often caused by a defect in renal tubular resorption of filtered phosphorus. However, HR can also be caused by secretion of a phosphaturetic factor from a tumor. The presentation of patients with the different HR syndromes may be identical. Distinguishing between the HR syndromes is essential, however, because HR caused by renal defect requires life-long therapy with Vitamin D and phosphate replacement, but tumor-associated HR is cured by removal of the tumor. A case of hemangiopericytoma occurring in bone and causing HR is reported. Children with HR typically have normal levels of serum calcium and parathyroid hormone but very low levels of serum phosphorus. In a child with HR, the following features should prompt a thorough evaluation for a causative tumor: lack of other family members who have hypophosphatemia; presence of aminoaciduria, particularly glycinuria. Causative lesions are most commonly found in the bone or skin.