Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

Juvenile onset systemic sclerosis (JoSSc) is a rare disease, and there are no studies focusing in bone mineral density and biochemical bone parameters. Ten consecutive patients with JoSSc and 10 controls gender, age, menarche age, and physical activity matched were selected. Clinical data were obtained at the medical visit and chart review. Laboratorial analysis included autoantibodies, 25-hydroxyvitamin D (25OHD), intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase and albumin sera levels. Bone mineral density was analyzed by dual-energy X-ray absorptiometry, and bone mineral apparent density (BMAD) was calculated. A lower BMAD in femoral neck (0.294 +/- A 0.060 vs. 0.395 +/- A 0.048 g/cm(3), P = 0.001) and total femur (0.134 +/- A 0.021 vs. 0.171 +/- A 0.022 g/cm(3), P = 0.002) was observed in JoSSc compared to controls. Likewise, a trend to lower BMAD in lumbar spine (0.117 +/- A 0.013 vs. 0.119 +/- A 0.012 g/cm(3), P = 0.06) was also found in these patients. Serum levels of 25OHD were significantly lower in JoSSc compared to controls (18.1 +/- A 6.4 vs. 25.1 +/- A 6.6 ng/mL, P = 0.04), and all patients had vitamin D insufficiency (< 20 ng/mL) compared to 40% of controls (P = 0.01). All other biochemical parameters were within normal range and alike in both groups. BMAD in femoral neck and total femur was correlated with 25OHD levels in JoSSc (r = 0.82, P = 0.004; r = 0.707, P = 0.02; respectively). We have identified a remarkable high prevalence of 25OHD insufficiency in JoSSc. Its correlation with hip BMAD suggests a causal effect and reinforces the need to incorporate this hormone evaluation in this disease management.

The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking. Clin J Am Soc Nephrol 5: S31-S40, 2010. doi: 10.2215/CJN.05880809

Characterization of acid-base status in maintenance hemodialysis: physicochemical approach

Acidosis is a common and deleterious aspect of maintenance dialysis. Traditionally, it is considered to be an elevated anion gap acidosis caused by the inability to excrete nonvolatile anions. Stewart`s approach made it possible to identify real determinants of the acid-base status and allowed quantification of the components of these disturbances, especially the unmeasured anions. We performed a cross-sectional study to identify and quantify each component of acidosis in hemodialysis maintenance patients. Sixty-four maintenance hemodialysis patients and 14 controls were enrolled in this study. Gasometrical and biochemical analysis were performed before the midweek dialysis session. Quantitative physicochemical analysis was carried out using the Stewart methodology. Hemodialysis patients were found to have mild acidemia (mean pH: 7.33 +/- 0.06 versus 7.41 +/- 0.05) secondary to metabolic acidosis (serum bicarbonate: 18.8 +/- 0.26 versus 25.2 +/- 0.48 mEq/l). The metabolic acidosis was due to retention of unmeasured anions (6.5 +/- 0.29 versus 3.1 +/- 0.62 mEq/l), hyperchloremia (105.1 +/- 0.5 versus 101.8 +/- 0.7 mEq/l), and hyperphosphatemia (5.90 +/- 0.19 versus 3.66 +/- 0.14 mg/dl). Compared with control values, the unmeasured anions and hyperchloremia had a similar acidifying effect (3.4 and 3.3 mEq/l), corresponding to almost 90% of the metabolic acidosis. Unmeasured anions and hyperchloremia are important components of acidosis in maintenance hemodialysis, in addition to phosphorus. Future studies to determine the etiology and consequences of hyperchloremic acidosis are warranted.

Dynamics of Parathyroid Hormone Secretion After Total Parathyroidectomy and Autotransplantation

Secondary hyperparathyroidism is a common complication in uremic patients. Total parathyroidectomy combined with partial autotransplantation into brachioradialis muscle has been the preference among the options for surgical treatment. This study was designed to evaluate the reserve and ability of suppression of autotransplanted parathyroid tissue using dynamics tests. We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative of total parathyroidectomy with autotransplantation. For analysis of the secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid hormone (PTH) suppression, the hypercalcemia test was used, by intravenous administration of calcium in LP. In RP, there was a decrease in the average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged from 13 to 231 (87 +/- A 65) pg/ml, 2.3 to 6.2 (3.3 +/- A 1.1) mg/dl, and 77 to 504 (250 +/- A 135) U/L, respectively, similar to that observed in LP. The analysis of the average curve of variations in PTH during testing of the stimulus with EDTA showed lack of secretion in RP and partial response in LP. Impaired suppression ability of the graft in LP was observed in the test with intravenous calcium. Total parathyroidectomy followed by partial autotransplantation was effective in reducing PTH serum levels in patients with terminal kidney disease. The elevation of serum calcium during the suppression test was not able to inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft function demonstrated an inability to respond to the stimulus of hypocalcemia induced by EDTA, although there was a partial recovery, in late postoperative period.

Transcriptional changes in the nuc-2A mutant strain of Neurospora crassa cultivated under conditions of phosphate shortage

The molecular mechanism that controls the response to phosphate shortage in Neurospora crassa involves four regulatory genes - nuc-2, preg, pgov, and nuc-1. Phosphate shortage is sensed by the nuc-2 gene, the product of which inhibits the functioning of the PREG-PGOV complex. This allows the translocation of the transcriptional factor NUC-1 into the nucleus, which activates the transcription of phosphate-repressible phosphatases. The nuc-2A mutant strain of N. crassa carries a loss-of-function mutation in the nuc-2 gene, which encodes an ankyrin-like repeat protein. In this study, we identified transcripts that are downregutated in the nuc-2A mutant strain. Functional grouping of these expressed sequence tags allowed the identification of genes that play essential roles in different cellular processes such as transport, transcriptional regulation, signal transduction, metabolism, protein synthesis, protein fate, and development. These results reveal novel aspects of the phosphorus-sensing network in N. crassa. (C) 2009 Elsevier GmbH. All rights reserved.

Orbital Involvement in Craniofacial Brown Tumors

Purpose: To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. Methods: A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. Results: Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. Conclusions: Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism.

Dentine caries inhibition through CO(2) laser (10.6 mu m) irradiation and fluoride application, in vitro

Objective: The purpose of the study was to investigate whether dentine irradiation with a pulsed CO(2) laser (10.6 mu m) emitting pulses of 10 ms is capable of reducing dentine calcium and phosphorus losses in an artificial caries model. Design: The 90 dentine slabs obtained from bovine teeth were randomly divided into six groups (n = 15): negative control group (GC); positive control group, treated with fluoride 1.23% (GF); and laser groups irradiated with 8 J/cm(2) (L8); irradiated as in L8 + fluoride 1.23% (L8F); irradiated with 11j/cm(2) (L11); irradiated as in L11 + fluoride 1.23% (L11F). After laser irradiation the samples were submitted to a pH-cycling model for 9 days. The calcium and phosphorous contents in the de- and remineralization solutions were measured by means of inductively coupled plasma optical emission spectrometer - ICP-OES. Additionally intra-pulpal temperature measurements were performed. The obtained data were analysed by means of ANOVA and Tukey`s test (alpha = 0.05). Results: In the demineralization solutions the groups L11F and GF presented significantly lower means of calcium and phosphorous losses than the control group; and in L11F means were significantly lower than in the fluoride group. Both irradiation parameters tested caused intrapulpal temperature increase below 2 degrees C. Conclusion: It can be concluded that under the conditions of this study, CO(2) laser irradiation (10.6 mu m) with 11J/cm(2) (540 mJ and 10 Hz) of fluoride treated dentine surfaces decreases the loss of calcium and phosphorous in the demineralization process and does not cause excessive temperature increase inside the pulp chamber. (C) 2010 Elsevier Ltd. All rights reserved.

Fluoride uptake and acid resistance of enamel irradiated with Er : YAG laser

This study evaluated the resistance to demineralization and fluoride incorporation of enamel irradiated with Er:YAG. A total of 110 bovine teeth were selected and divided into eight groups: unlased, 37% phosphoric acid, and samples irradiated with the Er:YAG laser at several fluences (31.84 J/cm(2), 25.47 J/cm(2), 19.10 J/cm(2), 2.08 J/cm(2), 1.8 J/cm(2), and 0.9 J/cm(2)). The application of acidulated phosphate fluoride was performed after treatments. All samples were immersed in 2 ml of 2.0 M acetic-acetate acid solution at pH 4.5 for 8 h, and fluoride, calcium, and phosphorus ions dissolved were analyzed by atomic absorption spectrometry and spectrophotometry. The phosphoric acid and 31.84 J/cm(2) groups presented the lowest dissolution of calcium and phosphorus ions. Higher fluoride incorporation was observed on 1.8 J/cm(2) and 0.9 J/cm(2) groups. Based on these results, Er:YAG laser was able to decrease acid dissolution and increase fluoride uptake and can be a promissory alternative for preventive dentistry.

In vivo Dentin Remineralization by Calcium-Phosphate Cement

Minimally invasive caries-removal procedures remove only caries-infected dentin and preserve caries-affected dentin that becomes remineralized. Dental cements containing calcium phosphate promote remineralization. This study evaluated the in vivo remineralization capacity of resin-based calcium-phosphate cement (Ca-P) used for indirect pulp-capping. Carious and sound teeth indicated for extraction were randomly restored with the Ca-P base or without base (control), followed by adhesive restoration. Study teeth were extracted after three months, followed by elemental analysis of the cavity floor. Mineral content of affected or sound dentin at the cavity floor was quantified by electron probe micro-analysis to 100-mu m depth. After three months, caries-affected dentin underneath the Ca-P base showed significantly increased calcium and phosphorus content to a depth of 30 mu m. Mineral content of treated caries-affected dentin was in the range of healthy dentin, revealing the capacity of Ca-P base to promote remineralization of caries-affected dentin.

An in situ/ex vivo comparison of the ability of regular and light colas to induce enamel wear when erosion is combined with abrasion

Objective: To evaluate whether the type of cola drink (regular or diet) could influence the wear of enamel subjected to erosion followed by brushing abrasion, Method and !Materials: Ten volunteers wore intraoral devices that each had eight bovine enamel blocks divided into four groups; ER, erosion with regular cola; EAR, erosion with regular cola plus abrasion; EL, erosion with light cola; and EAL, erosion with light cola plus abrasion, Each day for 1 week, half of each device was immersed in regular cola for 5 minutes, Then, two blocks were brushed using a fluoridated toothpaste and electric toothbrush for 30 seconds four times daily, Immediately after, the other half of the device was subjected to the same procedure using a light cola, The pH, calcium, phosphorus, and fluoride concentrations of the colas were analyzed using standard procedures, Enamel alterations were measured by profilometry. Data were tested using two-way ANOVA and Bonferroni test (P < .05), Results: Regarding chemical characteristics, light cola presented pH 3.0, 13.7 mg Ca/L, 15.5 mg P/L, and 0.31 mg F/L, while regular cola had pH 2.6, 32.1 mg Ca/L, 1:8.1 mg P/L, and 0.26 mg F/L, The light cola promoted less enamel loss (EL, 0.36 pm; EAL, 0.39 pm) than its regular counterpart (ER, 0.72 pm; EAR, 0.95 pm) for both conditions, There was not a significant difference (P > .05) between erosion and erosion plus abrasion for light cola, However, for regular cola, erosion plus abrasion resulted in higher enamel loss than erosion alone,.nclusion: The data suggest that light cola promoted less enamel wear even when erosion was followed by brushing abrasion, (Quintessence Int 2011;42:xxx-xx)()