Mineralized tissues in hypophosphatemic rickets.

Hypophosphatemic rickets is caused by renal phosphate wasting that is most commonly due to X-linked dominant mutations in PHEX. PHEX mutations cause hypophosphatemia indirectly, through the increased expression of fibroblast growth factor 23 (FGF23) by osteocytes. FGF23 decreases renal phosphate reabsorption and thereby increases phosphate excretion. The lack of phosphate leads to a mineralization defect at the level of growth plates (rickets), bone tissue (osteomalacia), and teeth, where the defect facilitates the formation of abscesses. The bone tissue immediately adjacent to osteocytes often remains unmineralized ("periosteocytic lesions"), highlighting the osteocyte defect in this disorder. Common clinical features of XLH include deformities of the lower extremities, short stature, enthesopathies, dental abscesses, as well as skull abnormalities such as craniosynostosis and Chiari I malformation. For the past four decades, XLH has been treated by oral phosphate supplementation and calcitriol, which improves rickets and osteomalacia and the dental manifestations, but often does not resolve all aspects of the mineralization defects. A newer treatment approach using inactivating FGF23 antibodies leads to more stable control of serum inorganic phosphorus levels and seems to heal rickets more reliably. However, the long-term benefits of FGF23 antibody treatment remain to be elucidated.

Polydopamine coated copper nanoclusters with aggregation-induced emission for fluorometric determination of phosphate ion and acid phosphatase activity.

The preparation of aggregation-induced emission-type copper nanoclusters (CuNCs) capped with polydopamine (PDA) is described. PDA was formed via in situ polymerization of dopamine in the presence of alkaline polyethylenimine. The PDA-capped CuNCs (PDA-CuNCs) exhibit orange fluorescence with maximal emission at 580 nm upon excitation at 340 nm, a storage stability of at least 2 weeks, and a quantum yield (QY) of 2.54% in aqueous solution. The QY is 28-fold higher than that of sole CuNCs. The fluorescence of the PDA-CuNCs is quenched by Fe3+ ion while it is recovered by PO43- due to its stronger affinity for Fe3+. On this basis, a fluorometric phosphate assay was developed that has a 1.5 nM detection limit and a linear range over 0.003-70 µM. The method was satisfactorily applied to the determination of phosphate in local tap water and human sera, and the results agreed well with those obtained by a colorimetric method. In the presence of acid phosphatase (ACP), PO43- is produced by the catalytic hydrolysis of adenosine triphosphate (ACP substrate). Thus, a fluorogenic assay for screening ACP activity was established. Response is linear over the activity range 0.0012-25 U L-1, with a detection limit of 0.001 U L-1 (at S/N = 3). Graphic abstract We proposed an effective polydopamine-templating strategy for the in situ synthesis of highly emissive and stable CuNCs and demonstrated its use as an ion-driven fluorescence switch for the determination of phosphate and acid phosphatase activity.

Effect of alendronate on the mandible and long bones: an experimental study in vivo.

BACKGROUND: Bisphosphonates are anticatabolic agents that inhibit bone resorption and are widely used to treat osteoporosis and bone metastases in adults. They are also used in young patients with diseases like osteogenesis imperfecta or juvenile osteoporosis. Bone modeling/remodeling is elevated in growing subjects, and inhibition of osteoclastic activity has been shown to interfere with growth. Thus, our objective was to evaluate the effect of alendronate (ALN) on growing animals. METHODS: Healthy male Wistar rats, aged 1 mo, received ALN or vehicle for 8 wk. Serum levels (calcemia, phosphatemia, and total alkaline phosphatase) were determined. Morphometric (rat: femur and tibia weight and length and hemimandible growth) and histomorphometric parameters (thickness of tibial epiphyseal cartilage and each cartilage zone, interradicular bone volume in the first lower molar, trabeculae volume, percentage of bone and cartilage, and osteoclast number in mandibular condyles) were assessed. RESULTS: ALN caused a significant decrease in femur and tibia length, tibial cartilage thickness, and longitudinal growth of hemimandibles. It increased interradicular bone volume and mandibular condyle trabeculae volume, increasing the percentage of cartilage and osteoclast number. CONCLUSION: These findings indicate that administration of ALN to growing animals alters the endochondral ossification process, and thus alters growth.

Feasibility study of colestipol as an oral phosphate binder in hemodialysis patients.

BACKGROUND: Currently available calcium- and aluminium-based phosphate binders are dose limited because of potential toxicity, and newer proprietary phosphate binders are expensive. We examined phosphate-binding effects of the bile acid sequestrant colestipol, a non-proprietary drug that is in the same class as sevelamer. METHODS: The trial was an 8 week prospective feasibility study in stable hemodialysis patients using colestipol as the only phosphate binder, preceded and followed by a washout phase of all other phosphate binders. The primary study endpoint was weekly measurements of serum phosphate. Secondary endpoints were serum calcium, lipids and coagulation status. Analyses used random effects mixed models. RESULTS: Thirty patients were screened for participation of which 26 met criteria for treatment. At a mean dose of 8.8 g/24 h of colestipol by study end, serum phosphate dropped from 2.24 to 1.96 mmol/L (P < 0.001). Three patients required calcium supplementation. LDL cholesterol dropped from 1.75 to 1.2 mmol/L (P < 0.001). Three patients dropped out because of side effects or intolerance of the required dose. CONCLUSION: The results support the feasibility of a larger trial to determine the efficacy of colestipol as a phosphate binder and that other non-proprietary anion-exchange resins may also warrant investigation.

Long-term clinical outcome and phenotypic variability in hyperphosphatemic familial tumoral calcinosis and hyperphosphatemic hyperostosis syndrome caused by a novel GALNT3 mutation; case report and review of the literature.

BACKGROUND: Hyperphosphatemic Familial Tumoral Calcinosis (HFTC) and Hyperphosphatemic Hyperostosis Syndrome (HHS) are associated with autosomal recessive mutations in three different genes, FGF23, GALNT3 and KL, leading to reduced levels of fibroblast growth factor 23 (FGF23) and subsequent clinical effects. RESULTS: We describe a consanguineous family with two affected siblings with HFTC and HHS caused by a novel homozygous G-to T substitution in exon 3 of GALNT3 (c.767 G > T; p.Gly256Val), demonstrating great phenotypic variation and long asymptomatic intervals. Calcific tumors appeared at 14 years of age in the male, and the female displayed episodic diaphysitis from age 9 years. Symptoms of eye involvement were present in both from childhood, and progressed into band keratopathy in the female. Abnormal dental roots and tooth loss, as well as myalgia were present in both from their mid-twenties, while the female also had calcifications in the placenta, the iliac vessels and thyroid cartilage. New calcific tumors appeared more than 20 years after the initial episodes, delaying diagnosis and treatment until the ages of 37 and 50 years, respectively. Both siblings had elevated serum phosphate levels, inappropriately elevated tubular maximum phosphate reabsorption per unit glomerular filtration rate (TmP/GFR), reduced levels of intact FGF23 and increased levels of c-terminal FGF23. Review of all 54 previously published cases of GALNT3, FGF23, and KL associated HFTC and HHS demonstrated that more subjects than previously recognized have a combined phenotype. CONCLUSION: We have described HFTC and HHS in a consanguineous Caucasian family with a novel GALNT3 mutation, demonstrating new phenotypic features and significant variability in the natural course of the disease. A review of the literature, show that more subjects than previously recognized have a combined phenotype of HFTC and HHS. HHS and HFTC are two distinct phenotypes in a spectrum of GALNT3 mutation related calcification disorders, where the additional factors determining the phenotypic expression, are yet to be clarified.

Evaluation of oral health status in pregnant women and its correlation with calcium and phosphate levels.

AIM: This study aimed to analyze the oral health conditions of pregnant women. The analysis involves evaluating two key indices: the decayed, missing, and filled teeth (DMFT) index and the basic erosive wear examination (BEWE) index. Furthermore, this study investigated potential correlations between calcium (Ca) and phosphate (P) levels within specific time intervals and the aforementioned oral health indices.

The Fgfr2(S252W/+) mutation in mice retards mandible formation and reduces bone mass as in human Apert syndrome.

Apert syndrome is a common craniosynostosis caused by gain-of-function missense mutations of fibroblast growth factor receptor 2 (FGFR2). Mice with the FGFR2 S252W mutation can elucidate the mechanism by which the human Apert syndrome phenotypes arise. However, many studies have focused on mutant skull and long bone malformation, only few studies have focused on mandible changes. Bone formation and micro-architecture between 28- and 56-day-old mutant mice and controls were compared to investigate the changes in the mandibular micro-architecture caused by the Fgfr2(S252W/+) mutation to provide a basis for exploring the pathogenesis and therapeutic measures of human Apert syndrome. Fgfr2(S252W/+) mutant mice were established, and their general characteristics, including weight, naso-anal length, and calcium and phosphate content in serum and bone were tested. Calcein labeling, tartrate-resistant acid phosphatase staining and toluidine blue staining were used to detect osteoblast and osteoclast activities. H&E staining and micro-CT detection were used to test micro-architecture changes. The changes in mineral apposition rate and micro-architecture of the Fgfr2(S252W/+) mice were statistically significant; however, the magnitude of the micro-architecture became less with age. The Fgfr2(S252W/+) mutation may retard mandibular bone formation, decreased bone volume, and compromised skeletal architecture by regulating both osteoblastogenesis and osteoclastogenesis.

Effect of a non-calcium-based phosphate binder on fibroblast growth factor 23 in chronic kidney disease.

BACKGROUND: Elevated fibroblast growth factor 23 (FGF23) levels are associated with progression of chronic kidney disease (CKD) and increased mortality. Studies in individuals without CKD suggest that FGF23 levels are regulated by dietary phosphorus; however, the effect of pharmacologic phosphorus restriction on FGF23 in CKD patients is uncertain. METHODS: We performed a prospective cohort study examining the effect of phosphorus reduction with sevelamer carbonate on FGF23 levels in CKD patients. Adults with an estimated glomerular filtration rate <60 ml/min/1.73 m(2) according to MDRD (Modification of Diet in Renal Disease) and hyperphosphatemia were enrolled. Subjects were started on sevelamer carbonate 800 mg by mouth with meals and the dose was titrated to achieve a serum phosphorus between 2.7 and 4.6 mg/dl for those with CKD stages III and IV, and between 3.5 and 5.5 mg/dl for CKD stage V. FGF23 levels were measured at baseline and 3 months. Results were analyzed as percent change from baseline. RESULTS: 40 patients completed the study. Mean estimated glomerular filtration rate by MDRD at entry was 21.2 ± 10.5, serum phosphorus 4.8 ± 0.8, and FGF23 level 602.3 ± 1,074.6. Mean serum phosphorus and FGF23 levels after 3 months were 4.4 ± 0.9 and 599.2 ± 720.9, respectively. No significant difference was seen in FGF23 (p = 0.76) despite a significant difference in phosphorus (p = 0.001). CONCLUSION: The patients treated with sevelamer carbonate did not have a significant change in plasma FGF23 levels despite a significant reduction in phosphorus. It is possible that once overt hyperphosphatemia develops, FGF23 levels may not be reduced by phosphorus reduction alone in CKD patients.

Effect of salivary phosphate-binding chewing gum on serum phosphate in chronic kidney disease.

BACKGROUND/AIMS: Serum phosphate (P) has been linked to adverse events in patients with chronic kidney disease. Salivary phosphate (Psal) has been proposed as a potential target of therapy with a chitosan-containing chewing gum. METHODS: We conducted several pilot studies to characterize Psal and its relationship with kidney function and subsequently conducted two clinical efficacy studies: a double-blind placebo-controlled trial in patients with end-stage renal disease (ESRD) and an open-label trial in those with stage 3-4 CKD. RESULTS: Pilot studies demonstrated no relationship between the level of kidney function and Psal. Mean Psal was approximately 6.46 mmol/l across the entire spectrum of kidney function. Passive saliva collection demonstrated higher Psal concentration as compared to active collection. There was no evidence of diurnal variation in Psal. Twice daily 20 mg chitosan gum over 4 weeks reduced serum P by 0.065 mmol/l in the double-blind, placebo-controlled trial in ESRD (p = NS vs. placebo). In an open-label extension in these subjects, 40 mg chitosan gum three times daily reduced serum P by 0.065 mmol/l (p = 0.03 vs. end of washout). In a 2-week open-label trial in patients with CKD not on dialysis, 20 mg chitosan gum given three times daily reduced serum P by 0.05 mmol/l (p = 0.003 vs. day 1). Neither trial demonstrated any significant change in Psal with chitosan gum. CONCLUSIONS: Psal concentration is approximately 4-5 times that of serum P and is not related to glomerular filtration rate. Chitosan chewing gum resulted in a reduction of serum P by approximately 0.05-0.065 mmol/l but had no effect on Psal concentration.

The effect of sea buckthorn supplement on oral health, inflammation, and DNA damage in hemodialysis patients: a double-blinded, randomized crossover study.

OBJECTIVE: Chronic kidney disease is associated with inflammation, oxidative stress, malnutrition, poor oral health, and mouth dryness. The objective of this study was to evaluate effects of sea buckthorn oil (SBO) extract, which is rich in vitamins, phytochemicals, and polyunsaturated fatty acids, on oxidative stress, saliva production, and inflammation in hemodialysis patients. DESIGN SETTING AND SUBJECTS: This was a randomized, double-blinded, and placebo-controlled crossover study (2 × 8 weeks, 4-week washout). The study subjects were hemodialysis patients (n = 45) recruited from the Department of Renal Medicine at Karolinska University Hospital in Stockholm. INTERVENTION AND MAIN OUTCOME MEASURES: The patients received 4 capsules per day, each containing 500 mg of SBO or placebo, for 8 weeks. They were then crossed over to the other treatment after a 4-week washout period. Salivary gland biopsies, saliva, and blood samples were collected before and after each treatment period. Main outcomes were DNA breaks and oxidative DNA lesions in minor accessory salivary glands, salivary flow rates, and inflammation markers in blood (high-sensitivity C-reactive protein, antitrypsin, orosomucoid in plasma, leukocytes in blood). Blood markers including creatinine, urea in plasma, and hemoglobin in blood were investigated. RESULTS: The results showed no significant changes in DNA breaks, oxidative DNA lesions, salivary flow rates, or inflammation after SBO supplementation. However, plasma levels of phosphate and sodium increased and plasma levels of iron decreased. CONCLUSION: In conclusion, SBO supplementation as performed in this study did not protect against oxidative stress, nor improve oral health or inflammation status in hemodialysis patients.

Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23.

In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper.

Can features of phosphate toxicity appear in normophosphatemia?

Phosphate is an indispensable nutrient for the formation of nucleic acids and the cell membrane. Adequate phosphate balance is a prerequisite for basic cellular functions ranging from energy metabolism to cell signaling. More than 85% of body phosphate is present in the bones and teeth. The remaining phosphate is distributed in various soft tissues, including skeletal muscle. A tiny amount, around 1% of total body phosphate, is distributed both in the extracellular fluids and within the cells. Impaired phosphate balance can affect the functionality of almost all human systems, including muscular, skeletal, and vascular systems, leading to an increase in morbidity and mortality of the involved patients. Currently, measuring serum phosphate level is the gold standard to estimate the overall phosphate status of the body. Despite the biological and clinical significance of maintaining delicate phosphate balance, serum levels do not always reflect the amount of phosphate uptake and its distribution. This article briefly discusses the potential that some of the early consequences of phosphate toxicity might not be evident from serum phosphate levels.

A sad but forgotten truth: the story of slow-moving solutes in fast hemodialysis.

When trying to optimize hemodialysis adequacy, it can be questioned whether one should focus on the dialyzer or on the patient. Another crucial question is whether the currently applied dialysis adequacy parameter, Kt/V(urea) , is a reliable marker. For the small and water-soluble solutes, recent advances in convective strategies and/or new dialyzer designs do not add much removal capacity. Depending on their specific kinetics, generally quite different from those of urea, small solute removal benefits from longer or more frequent dialysis. Clearance of beta-2-microglobulin (ß(2) M), a marker of middle molecule removal pattern, is improved with dialysis using more open and permselective membranes, as well as by using high convective volume strategies. Furthermore, longer and more frequent dialyses have highly favorable removal characteristics because they facilitate the retarded transport between plasmatic and extraplasmatic compartments over which these molecules are distributed. As ß(2) M may not be representative of other middle molecules, future kinetic analyses of alternative middle molecules will be of the utmost interest. Protein-bound solute clearance is improved by convective techniques, but not by more open dialyzer pores. Knowledge of their kinetics should be helpful in interpreting the observation that frequent (but not longer) dialysis enhances protein-bound solute removal. Hence, further technical improvements in dialyzers will have only a minor impact on dialysis adequacy, as retarded solute movement in the patient plays a decisive role. As urea kinetics is not representative of the kinetics of protein-bound compounds, middle molecules, nor even of other small and water-soluble solutes, it becomes self-evident that urea clearance is a poor predictor of many aspects of dialysis adequacy.

[Bone and tooth in calcium and phosphate metabolism].

Tight regulation of serum concentrations of calcium and phosphate is indispensable for maintaining normal physiological condition. Imbalance of this regulation leads to pathophysiological disorders including heart disease, chronic kidney disease, and ectopic calcification. Formation and mineralization of bone and tooth are greatly influenced by calcium and phosphate metabolism since both organs are mainly consist of calcium-phosphate. Calcium and phosphate homeostasis is under hormonal control on its target organs such as kidney, bone and intestine. Calcium and phosphate are absorbed in intestine and reabsorbed and excreted in kidney. Bone store and release them in response to changing physiological demand by osteoblastic bone formation and osteoclastic bone resorption. Bone is also important as an endocrine organ that releases FGF23 from osteocytes, a novel hormone that targets the kidney to inhibit phosphate reabsorption and 1α, 25 (OH) (2)D(3) production.

Clinical and molecular findings in children and young adults with persistent low alkaline phosphatase concentrations.

BACKGROUND: Hypophosphatasia is a rare inherited metabolic disease resulted by ALPL gene mutations. It is characterized by defective bone and teeth mineralization. The phenotypic spectrum is highly variable ranging from lethal perinatal form to mild forms which are only diagnosed in adulthood or remain undiagnosed despite persistently low concentrations of ALP. The aim of this study is to evaluate the clinical phenotype and frequency of ALPL mutations in a group of patient with hypophosphatasaemia. METHODS: Thirty individuals with alkaline phosphatase values below 40 IU/L in at least two assessments and having no alternative explanation for their low ALP concentrations were included in the study. The clinical features and radiological data of the study group were re-investigated for hypophosphatasia-related findings. ALPL sequence analysis was performed using Sanger sequencing. RESULTS: No patient in the study group had severe symptoms, nor had they initially been diagnosed as having hypophosphatasia. Four different heterozygous ALPL mutations (c.542C>T, c.648 + 1G>A, c.657G>T and c.862 + 1G>C) were found in four patients. One splice site mutation (c.862 + 1G>C) was reported for the first time in this study. CONCLUSION: ALPL sequence analysis may help to diagnosing genetic defects in individuals with persistently low ALP concentrations and provide to take preventive measures before symptoms appear. As in the other populations, HPP displays allelic heterogeneity in our population.

Prolonged Hypophosphatemia and Intensive Care After Curative Surgery of Tumor Induced Osteomalacia: A Case Report.

Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.

Biochemical markers of particle induced osteolysis in C57BL/6 mice.

BACKGROUND: Micro-structural changes associated with ultra high molecular weight polyethylene particle (UHMWPE) induced osteolysis, the most frequent cause of aseptic loosening, have been intensively investigated in the mammalian calvarian model by histomorphometry and micro-computed tomography. However, little is known regarding the serological changes that occur during this process. METHODS: Serological parameters for bone metabolism [calcium, phosphate, osteocalcin (OCN), deoxypyridinoline (DPD)/creatinine, alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor-κB] were analyzed in this animal model for particle induced osteolysis. Ten C57BL/6 mice were divided at random into sham operated and UHM-WPE implanted groups. Blood and urine samples were collected prior to and at 14 days after surgery. RESULTS: Implantation of UHMWPE lead to a significant decrease in bone volume (p=0.027). Both groups (sham/UHMWPE) showed a significant increase in calcium (p=0.004/p=0.027) and phosphate (p=0.001/p=0.001), without correlation to particle implantation. Significantly higher concentrations of DPD/creatinine (p=0.034) and OCN (p=0.022) were found after implantation of UHM-WPE. In addition, parameters could not be correlated to particle induced osteolysis. CONCLUSIONS: DPD can be regarded as a valuable parameter for detecting UHMWPE induced osteolysis in the calvarian model. Further studies of serum parameters should focus on the clinical relevance in aseptic prosthetic loosening.

Salivary phosphate-binding chewing gum reduces hyperphosphatemia in dialysis patients.

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders, only half of hemodialysis (HD) patients achieve recommended serum phosphate levels. A hyperphosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients. We hypothesized that binding salivary phosphate during periods of fasting in addition to using phosphate binders with meals could improve the treatment of hyperphosphatemia. We assessed the phosphate-binding capacity of the natural polymer chitosan by (31)P nuclear magnetic resonance and established that 10 and 20% (wt/vol) middle viscosity chitosan solutions bind 30 and 50% of the phosphate contained in PBS, respectively. Thirteen HD patients with serum phosphate levels >6.0 mg/dl despite treatment with sevelamer hydrochloride chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 wk at fast in addition to their prescribed phosphate-binding regimen. Salivary phosphate and serum phosphate significantly decreased during the first week of chewing; by the end of 2 wk, salivary phosphate decreased 55% from baseline (73.21 +/- 19.19 to 33.19 +/- 6.53; P < 0.00001), and serum phosphate decreased 31% from baseline (7.60 +/- 0.91 to 5.25 +/- 0.89 mg/dl; P < 0.00001). Salivary phosphate returned to baseline by day 15 after discontinuing the chewing gum, whereas serum phosphate levels took 30 d to return to baseline. Parathyroid hormone and serum calcium concentrations were not affected by the gum. In conclusion, adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in HD patients.

Clinical responses to a mega-dose of vitamin D3 in infants and toddlers with vitamin D deficiency rickets.

OBJECTIVES: Was to investigate the effect of treatment with an IM injection, a mega dose of vitamin D3 (10,000 IU/kg) on the clinical, biochemical and radiological parameters of 40 rachitic children with vitamin D deficiency (VDD) over a period of 3 months. DESIGN: In this prospective study we evaluated the clinical, biochemical and radiological responses of an IM injection of cholecalciferol (10,000 IU/kg) for 3 months. RESULTS: At presentation, the most frequent manifestations were enlarged wrist joints, hypotonia, irritability, cranial bossing, wide anterior fontanel, bow legs, delayed teething and walking and Harrison's sulcus with chest rosaries. Short stature (length SDS < -2) was recorded in 30% of patients. Craniotabes and hypocalcemic tetany were the least common presentations. In VDD children the most frequent biochemical abnormality was high alkaline phosphatase (ALP) (100%), followed by low phosphate (PO(4)) (75%) and low calcium (Ca) (12.5%). One month after treatment, serum Ca, PO(4) and 25(OH)D concentrations were normal. Three months after the injection, serum level of ALP and parathormone (PTH) decreased to normal. The majority of patients (87.5%) had serum 25(OH)D level >or= 20 ng/ml, but some (12.5%) had level <20 ng/ml. Hypercalcemia was not recorded in any patient during the 3-month-period. Significant cure of all symptoms and signs related to vitamin D deficiency had been achieved in all children. Leg bowing showed significant improvement in all patients but was still evident in one third. Complete healing of the radiological evidence of rickets was achieved in 95% of all children. CONCLUSION: An IM injection of a mega dose of cholecalciferol is a safe and effective therapy for treatment of VDD rickets in infants and toddlers with normalization of all the biochemical parameters and healing of radiological manifestations. Measurement of serum 25(OH)D level is highly recommended in all short children with a clear need for a general vitamin D supplementation for all infants and young children in Qatar.

Panoramic radiography and its role in the diagnosis of systemic disorders.

This article presents a case report in which a systemic disease was first suspected by viewing a panoramic radiograph. A 49-year-old man sought prosthetic rehabilitation with implants. Panoramic radiography revealed an osteolysis of poorly defined limits in the apical region of teeth No. 26 to 28. The patient's medical history included the recent removal of a giant cell lesion from the left tibia. During palpation of the neck, a fixed nodule was detected on the superior portion of the left thyroid gland. Biochemical tests showed elevated levels of serum alkaline osphatase, serum calcium, and parathyroid hormone. As the serum phosphate was low, the final diagnosis was primary hyperparathyroidism. A CT scan showed a hypodense lesion involving teeth No. 26 to 28, with preserved cortical bone. A whole-body bone scintigraphy showed lesions in the mandible and other long bones. A high radiopharmaceutical capitation was present in the left parathyroid gland. The patient was referred to a head and neck surgeon, who removed the left thyroid lobule and the parathyroid gland. The microscopic diagnosis was parathyroid carcinoma. After eight months of follow-up, the mandibular lesion disappeared.