Chronic hypophosphatemia caused by decreased intestinal absorption or increased renal clearance, may lead to rickets or osteomalacia independently of other predisposing abnormalities. The conditions commonly associated with increased renal clearance of phosphate are X-linked hypophosphatemic rickets, tumor associated rickets/osteomalacia, RTA and Fanconi syndrome. Recently we experienced 3 men with adult-onset, histologically proven osteomalacia associated with increased renal clearance of phosphate. None of them had a family history of bone disease, tumors or other tubular defects. All of these had remarkable biochemical and clinical improvement with medical treatment such as 1, 25-dihydroxyvitamin D and phosphate supplementation. Although we did not find tumors yet, we could not rule out the possibility of tumor-associated osteomalcia since it often takes several years to make a diagnosis because of small size, benign nature and unusual location of tumors. Thus, careful long-term follow up for tumor occurrence will be maintained in these patients with sporadic nonfamilial hypophosphatemic osteomalacia.
Bone Diseases ; Diagnosis ; Familial Hypophosphatemic Rickets ; Fanconi Syndrome ; Follow-Up Studies ; Humans ; Hypophosphatemia ; Intestinal Absorption ; Male ; Osteomalacia ; Rickets

PURPOSE: Hypophosphatemic rickets is a hereditary disease, characterized by hypophosphatemia due to renal phosphate wasting, impaired renal production of 1,25-dihydroxyvitamin D3, rachitic bone deformities and impaired growth. The purpose of this study is to provide clinical profiles of patients with hypophosphatemic rickets in our hospital. METHODS: Between July 1983 and February 2004, 56 patients were diagnosed as having hypophosphatemic rickets. The medical records of these patients were reviewed retrospectively. Clinical manifestations, family histories, laboratory data, treatment outcomes were described. RESULTS: Fifty six patients were enrolled in this study. The average age at symptom onset and diagnosis were 20 months and 5 years respectively. Fourteen patients had family histories. The main clinical manifestations were bow legs and short stature. There was a significant negative correlation between the ages and the height z-scores at the time of diagnosis(r=-0.47, P=0.005). Initial laboratory data showed normocalcemia, hypophosphatemia, elevated serum alkaline phosphatase, decreased tubular reabsorption of phosphate and a normal range of 1,25-dihydroxyvitamin D3. Radiographic examinations of bone revealed fraying, widening and cupping of the metaphyseal ends. Treatment consisted of Joulie solution and vitamin D metabolites, and resulted in improved biochemical and radiographic findings. However, height z-scores remained essentially unchanged(P=0.224). Complications of treatment were frequently observed, including hyperparathyroidism, nephrocalcinosis, and hypercalciuria. Sixteen patients had corrective osteotomy and 4 of them underwent leg lengthening together. CONCLUSION: There was a gap of several years between the onset of symptoms and the diagnosis. Early treatment seems to be essential to growth. For the earlier treatment, the offsprings of affected parents should be followed up closely.
Alkaline Phosphatase ; Calcitriol ; Congenital Abnormalities ; Diagnosis ; Familial Hypophosphatemic Rickets ; Genetic Diseases, Inborn ; Genu Varum ; Humans ; Hypercalciuria ; Hyperparathyroidism ; Hypophosphatemia ; Hypophosphatemia, Familial ; Leg ; Medical Records ; Nephrocalcinosis ; Osteotomy ; Parents ; Reference Values ; Retrospective Studies ; Rickets, Hypophosphatemic* ; Vitamin D

X-linked hypophosphatemia (XLH) is a hereditary metabolic disease caused by the loss of phosphate through the renal tubules into the urine, and an associated decrease in serum calcium and potassium phosphate. Its dental features include spontaneous dental abscesses that occur in the absence of trauma or dental caries. The aim of this case report was to describe the dental problems of XLH patients and to evaluate limitations in their treatment. A 14 year old male and a 38 year old female with XLH were referred to the Department of Conservative Dentistry for endodontic treatment. The dental findings were periapical abscesses without obvious trauma or caries. Conservative endodontic treatment was performed in teeth with pulp necrosis and abscess. In case 1, the treated teeth showed improvements in bone healing, without clinical symptoms. However, in case 2, the implants and the treated tooth showed hypermobility, and the final restoration was therefore postponed. Early diagnosis, periodic examinations, and communication with the patient's pediatrician are important in the dental management of patients with XLH.
Abscess ; Calcium ; Dental Caries ; Dental Pulp Necrosis ; Dentistry ; Early Diagnosis ; Familial Hypophosphatemic Rickets* ; Female ; Humans ; Hypophosphatemia ; Male ; Metabolic Diseases ; Periapical Abscess ; Potassium ; Tooth

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.
Absorption ; Alkaline Phosphatase ; Calcium ; Chondrocytes ; Collagen ; Diagnosis ; Durapatite ; Enzyme Replacement Therapy ; Extracellular Matrix ; Extracellular Vesicles ; Familial Hypophosphatemic Rickets ; Fibroblast Growth Factors ; Gene Expression ; Humans ; Hypophosphatasia ; Hypophosphatemia ; Metabolism ; Miners ; Osteoblasts ; Osteocytes ; Prognosis ; Quality of Life ; Receptors, Fibroblast Growth Factor ; Rickets ; Signal Transduction ; Vitamin D ; Vitamin D Deficiency

Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, decreased 1,25-dihydroxyvitamin D level and specific signs and symptoms of osteomalacia. It is associated with the presence of neoplasm originated from mesenchyme. Until now, less than 100 cases of oncogenic osteomalacia have been reported. The pathophysiology of oncogenic osteomalacia has not been fully understood, but it has been suggested that a certain substance released by tumor may inhibit not only la-hydroxylase activity and reduce 1,25-dihydroxyvitamin D level in part, but directly inhibit reabsorption of phosphate. And then, reduced phosphaturia, hypophosphatemia and eventually osteomalacia develop. We report a case of osteosarcoma induced oncogenic osteomalacia detected by MRI in 59 year old woman.
Female ; Humans ; Hypophosphatemia ; Hypophosphatemia, Familial ; Magnetic Resonance Imaging* ; Mesoderm ; Middle Aged ; Osteomalacia* ; Osteosarcoma*

Adefovir dipivoxil is used antiviral agent in the treatment of chronic hepatitis B virus infection. This drug is recommended for patients infected with lamivudine-refractory hepatitis B. Many studies of low-dose adefovir have shown little evidence of renal tubular dysfunction. However, hypophosphatemic osteomalacia has recently been reported in patients treated with adefovir. We report three cases of low dose adefovir-induced hypophosphatemic osteomalacia with fractures. All three patients had been receiving adefovir due to lamivudine-refractory hepatitis B, presented multiple bone pain. The laboratory tests revealed hypophosphatemia and phosphaturia. Bone scintigraphy showed increased uptake in multiple lesions. They were diagnosed as adefovir induced hypophophatemic osteomalacia. Changing the antiviral agent and administration of calcitriol and phosphates improved hypophosphatemia and clinical symptoms. Patients with hepatitis B virus treated with adefovir should be monitored with the serum phosphate levels and presenting symptoms of diffuse bone pain, clinicians need to suspect this infrequent complication.
Calcitriol ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Hypophosphatemia ; Hypophosphatemia, Familial ; Osteomalacia ; Phosphates ; Radionuclide Imaging

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, which is characterized by overproduction of FGF23 as a phosphaturic agent leading to chronic phosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of vitamin D. We describe a rare case of a 57-year-old Indian female who presented with bone pains, muscle pains and lower limb weakness. On examination she was found to have hypophosphatemia. Our work up led to the identification of a FGF23 secreting parotid tumour. The tumour responsible for symptoms was a pleomorphic adenoma of the parotid gland. Its complete resection resulted in normalisation of patient's symptoms. Laboratory parameters and microsopic examination further revealed a mesenchymal tumour of mixed connective tissue type.

Human ; Female ; Middle Aged ; Adenoma, Pleomorphic ; Connective Tissue ; Hypophosphatemia ; Hypophosphatemia, Familial ; Lower Extremity ; Neoplasms, Connective Tissue ; Paraneoplastic Syndromes ; Parotid Gland ; Parotid Neoplasms ; Vitamin D ; Hypophosphatemia

Oncogenic osteomalacia is a rare clinicopathological condition. The syndrome is characterized by hypophosphataemic osteomalacia with hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D and normal plasma calcaemia and parathyroid hormone, associated with a tumor, generally of mesenchymal origin. Complete excision of the tumour results in cure of the whole syndrome. Recently we experienced 56-year-old woman with oncogenic osteomalacia caused by a chondromyxoid fibroma of the left foot. We report this case with the review of literatures.
Female ; Fibroma* ; Foot ; Humans ; Hypophosphatemia, Familial ; Middle Aged ; Osteomalacia* ; Parathyroid Hormone ; Plasma

PURPOSE: Recent studies have suggested that renal phosphate leakage and the associated phosphaturia are significant underlying causes of calcium urolithiasis. The aims of this study were to assess whether phosphaturia relates to urinary metabolic abnormalities and recurrent stone formation. MATERIALS AND METHODS: A database of patient histories and urine chemistries was analyzed for 1,068 consecutive stone formers (SFs) and 106 normal controls. Urine values for phosphaturia that were higher than 95% of the normal control values were defined as indicating hyperphosphaturia, and the effect of phosphaturia on urinary metabolites and stone recurrence was determined. Of these patients, 247 patients (23.1%) who had been followed up for more than 36 months or had a recurrence of stones during follow-up (median, 46.0 months; range, 5-151) were included in the analyses for stone recurrence. RESULTS: Of the SFs, 19.9% (212/1,068) had increased urinary phosphate excretion. SFs with hyperphosphaturia had a greater urinary volume and higher levels of calcium, uric acid, oxalate, and citrate than did SFs with normophosphaturia. A multivariate Cox regression model, stratified by stone episodes, revealed that hyperphosphaturia was an independent predictor of recurrent stone formation in first-time SFs (hazard ratio [HR]: 2.122; 95% confidence interval [CI]: 1.100-4.097; p=0.025). No association was detected between hyperphosphaturia and recurrent stone formation in recurrent SFs. Kaplan-Meier curves showed identical results. CONCLUSIONS: This study demonstrates that hyperphosphaturia is closely associated with urinary metabolic abnormalities. Furthermore, hyperphosphaturia is a significant risk factor for stone recurrence in first-time SFs.
Calcium ; Citric Acid ; Follow-Up Studies ; Humans ; Hypophosphatemia, Familial ; Phosphates ; Recurrence ; Risk Factors ; Uric Acid ; Urolithiasis

Fanconi syndrome is a complex of renal tubular dysfunction defined by glycosuria without diabetes, generalized aminoaciduria, phosphaturia, bicarbonaturia, uric aciduria, and renal tubular acidosis. It is often associated with hypokalemia, hypophosphatemia, rickets and osteomalacia. We have experienced one case of Fanconi syndrome with chronic tubulointerstitial nephritis. The patient was a 4 year old and his chief complaints were polyuria, polydipsia, and poor weight gain. There were hyperchloremic metabolic acidosis, hypokalemia, glycosuria, generalized aminoaciduria and phosphaturia. We report a case of Fanconi syndrome with brief review of the literatures.
Acidosis ; Acidosis, Renal Tubular ; Child, Preschool ; Fanconi Syndrome* ; Glycosuria ; Humans ; Hypokalemia ; Hypophosphatemia ; Hypophosphatemia, Familial ; Nephritis, Interstitial ; Osteomalacia ; Polydipsia ; Polyuria ; Rickets ; Weight Gain