cholecalciferol and Hypophosphatemia

Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome induced by tumor produced phosphaturic factors, i.e. phosphatonins. The disorder is characterized by renal tubular phosphate loss, secondary to this process hypophosphatemia and defective production of active form of vitamin D. The clinical course of oncogenic osteomalacia is characterized by bone pain, pathological fractures, muscle weakness and general fatigue. Osteomalacia-associated tumors are usually located in the upper and lower limbs, with half of the lesions primarily situated in the bones. Most of them are small, slow-growing tumors. Their insignificant size and various location coupled with rare occurrence of the disease and non-specificity of clinical symptoms lead to difficulties in reaching a diagnosis, which is often time-consuming and requires a number of additional tests. The average time between the appearance of the first symptoms and the establishment of an accurate diagnosis and the beginning of treatment is over 2.5 years. The aim of this study is to discuss the pathophysiology of disease symptoms, pathomorphology of tumors, diagnostic methods and treatment of oncogenic osteomalacia.

Topics: Biopsy; Bone and Bones; Cholecalciferol; Diagnostic Imaging; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fractures, Spontaneous; Humans; Hypophosphatemia; Neoplasms, Connective Tissue; Osteomalacia; Pain; Paraneoplastic Syndromes; Somatostatin

Topics: Cholecalciferol; Diagnosis, Differential; Humans; Hypophosphatemia; Orthopedic Procedures; Osteomalacia; Prognosis; Receptors, Calcitriol; Sunlight; Vitamin D Deficiency

Topics: Cholecalciferol; Diagnosis, Differential; Fractures, Spontaneous; Humans; Hypophosphatemia; Osteomalacia; Phosphates; Prognosis; Rickets; Syndrome; Vitamin D Deficiency

Topics: Animals; Cholecalciferol; Diagnosis, Differential; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypophosphatemia; Neoplasms; Osteomalacia; Paraneoplastic Syndromes; Prognosis; Rickets

Hungry Bone Syndrome (HBS) refers to rapid, profound, and prolonged hypocalcemia associated with hypophosphatemia and hypomagnesemia occurring in patients with increased bone turnover after successful management of the underlying disorder. We describe a male patient with primary hyperparathyroidism (PHPT), in whom HBS was diagnosed 6 months after parathyroidectomy. Histopathologic examination revealed an atypical parathyroid adenoma (APA), while immunohistochemistry showed cell proliferation index Ki-67 10% and overexpression of cyclin D1 (>90%). Preoperative treatment with vitamin D3 had normalized 25OHD and alkaline phosphatase levels, reflected in an improvement in bone turnover prior to surgery. Postoperative treatment for HBS with alfacalcidol, calcium, vitamin D3 and magnesium was administered for a long period. This treatment prevented severe postoperative hypocalcemia and he was discharged two days later. Preoperative cinacalcet treatment did not reduce hypercalcemia implying that the tumor had lack of calciumsensing receptors (CaSR). In conclusion, preoperative restoration of low 25OHD levels is essential for prevention of HBS. Postoperative treatment with active metabolites of vitamin D must be initiated as early as possible, in order to prevent or minimize the development of HBS, and to reduce the duration of hospitalization.

Topics: Adenoma; Adult; Bone Density Conservation Agents; Calcium; Calcium-Regulating Hormones and Agents; Cholecalciferol; Cinacalcet; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypocalcemia; Hypophosphatemia; Magnesium; Male; Parathyroid Neoplasms; Parathyroidectomy; Postoperative Complications; Syndrome

There is clinical uncertainty as to the testing of serum 25--Hydroxy vitamin D (25[OH]D) concentrations and when to use high-dose supplementation. Data show that there has been a rapid increase in the number of tests performed within the Northumbria Healthcare NHS Foundation Trust over the past 8 years and an increase in high-dose supplementation over the past 5 years. We performed a retrospective analysis of the 25(OH)D test requests over the period from January to -October 2017. A total of 17,405 tests were performed in this time period. The overall average concentration was 57.5 nmol/L and this figure was similar across age groups, although a larger proportion of patients aged over 75 had a concentration <25 nmol/L. Test requests were classified into 'appropriate', 'inappropriate' and 'uncertain' categories based on current expert opinion. We found that between 70.4% and 77.5% of tests could be inappropriate, depending on whether the 'uncertain' categories of falls and osteoporosis are considered to be justified. Tiredness, fatigue or exhaustion was the reason for testing in 22.4% of requests. We suggest that a more rational approach to testing, and subsequent treating, could lead to reductions in costs to the healthcare system and patients.

Topics: Accidental Falls; Adult; Aged; Alkaline Phosphatase; Cholecalciferol; Clinical Laboratory Techniques; Dietary Supplements; Female; Humans; Hypocalcemia; Hypophosphatemia; Male; Medical Overuse; Middle Aged; Osteoporosis; Retrospective Studies; State Medicine; United Kingdom; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Agammaglobulinemia; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Bacterial Infections; Calcium; Cholecalciferol; Electrolytes; Female; Humans; Hypocalcemia; Hypokalemia; Hypoparathyroidism; Hypophosphatemia; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Magnesium; Middle Aged; Thymoma; Weight Loss

We previously found that the lack of nuclear xenobiotic receptor, PXR, decreases femoral bone mineral density (BMD) in Pxr-/- mice. Our present study aims to elucidate the inherited phenotype that correlates with the decreased BMD and to identify the PXR-regulated gene that may link with this phenotype.. Pxr+/+ and Pxr-/- mice were used to measure the serum levels of inorganic phosphate (Pi), calcium and vitamin D3. Real time PCR and western blots were used to determine the intestinal and renal expressions of Pi and calcium transporters and various other genes involved in bone homeostasis. Cell-based reporter and gel shift assays were performed to characterize the promoter of the identified PXR-regulated gene.. In both Pxr-/- male and female mice, lumbar, sternum, and skull were all also found to have decreased their BMD values. Serum Pi levels, but not calcium levels, are attenuated in Pxr-/- mice, exhibiting a phenotype of hypophosphatemia. Among the members of the Na/Pi contransporter family, only the SLC34A2 mRNA and protein are repressed in Pxr-/- mice. PXR can directly activate the transcription of the SLC34A2 gene through an ER6 motif on its promoter.. Pxr-/- mice show the inherited phenotype of hypophosphatemia. The lack of PXR results in a severe repression of the Na/Pi cotransporter NaPi-IIb/Npt2b (SLC34A2), thus leading Pxr-/- males and females to develop a type of hypophosphatemia.

Topics: Animals; Blotting, Western; Bone Density; Calcium; Cholecalciferol; Female; Gene Expression Regulation; Hypophosphatemia; Male; Mice; Mice, Mutant Strains; Phenotype; Phosphates; Pregnane X Receptor; Promoter Regions, Genetic; Receptors, Steroid; Sodium-Phosphate Cotransporter Proteins, Type IIb; Transcriptional Activation

A 60-year-old Caucasian woman with a 1-year history of pain at the ribs, spine, and pelvis consulted at our Institute in March 1999. She brought a bone densitometry performed using a Lunar DPX densitometer that showed bone mineral density (BMD) measurements in the osteoporotic range at both the lumbar spine and the femoral neck. As a child she had had bowed legs and had been treated with ultraviolet radiation. Results of the laboratory test performed at our institute showed normal total serum calcium, repeated low serum P levels, and a low renal phosphate threshold with elevated total and bone fraction of alkaline phosphatase with normal intact parathyroid hormone (PTH). A diagnosis of hypophosphatemic osteomalacia due to renal phosphate leak was made. She began treatment with neutral sodium phosphate at 1.5 g/day and calcitriol 0.5 microg/day. Her serum P levels normalized, and there was a progressive decrease in alkaline phosphatase levels. The densitometry showed a very rapid increase in BMD values with normalization at the lumbar spine after 10 months of treatment. This case shows the importance of bone densitometry in the follow-up of patients with suspected osteomalacia.

Topics: Alkaline Phosphatase; Bone Density; Calcium; Cholecalciferol; Female; Humans; Hypophosphatemia; Middle Aged; Osteomalacia; PHEX Phosphate Regulating Neutral Endopeptidase; Phosphates; Phosphorus; Proteins

We report a 28-year-old woman who presented with severe proximal muscle weakness secondary to paraneoplastic hypophosphatemia and associated with recurrent neuroblastoma. The biochemical findings included hyperphosphaturia, a reduced serum level of 1,25-dihydroxyvitamin-D3, elevated alkaline phosphatase and normocalcemia which are pathognomic for paraneoplastic hypophosphatemia. Following systemic chemotherapy and supplementation of 1,25-dihydroxyvitamin-D3 a complete remission of the neuroblastoma was achieved and all features of the paraneoplastic hypophosphatemia gradually disappeared. In the differential diagnosis of muscle weakness, hypophosphatemia should be included. Paraneoplastic hypophosphatemia associated with metastatic neuroblastoma has not been reported previously. Diagnosis, mechanism and therapy of paraneoplastic hypophosphatemia are shortly reviewed.

Topics: Adult; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Calcium; Cholecalciferol; Female; Follow-Up Studies; Humans; Hypophosphatemia; Magnetic Resonance Imaging; Muscle Weakness; Neoplasm Recurrence, Local; Neuroblastoma; Paraneoplastic Syndromes; Spinal Neoplasms

To determine whether 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] exerts unique biologic effects on bone, we examined the effects of the vitamin D metabolites, 24R,25(OH)2D3 and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], on the hypophosphatemic (Hyp) mouse, a model for X-linked hypophosphatemic rickets in humans. The Hyp mice were administered 1-10,000 micrograms/kg/day of 24R,25(OH)2D3, 0.01-10 micrograms/kg/day of 1 alpha,25(OH)2D3, or vehicle alone, given daily for 28 days by intraperitoneal injection. 24R,25(OH)2D3 at doses of 1-1000 micrograms/kg/day had dose-dependent effects in increasing bone size, dry bone weight, and bone mineral content without causing hypercalcemia. 1 alpha,25(OH)2D3 at doses of 1 or 10 micrograms/kg/day, which we considered to have activity similar to that of 1000 micrograms/kg/day of 24R,25(OH)2D3 with respect to cell differentiation activity, caused severe bone resorption and hypercalcemia. At 0.1 microgram/kg/day, 1 alpha,25(OH)2D3 increased bone size, similarly to a dose of 1000 micrograms/kg/day of 24R,25(OH)2D3, without significantly affecting dry bone weight or bone mineral content, as did 1000 micrograms/kg/day of 24R,25(OH)2D3. These findings suggest that 24R,25(OH)2D3 exerts unique activity in the Hyp mouse rather than merely mimicking the activity of 1 alpha,25(OH)2D3.

Topics: Animals; Bone Density; Bone Development; Calcitriol; Cholecalciferol; Disease Models, Animal; Drug Administration Schedule; Hypercalcemia; Hypophosphatemia; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Radiography