Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease).

The neurofibromatosis type 1 (NF1) is characterized by specific cutaneous features (neurofibromas, "café-au-lait" spots of the skin) and alterations of several tissue (nervous, vascular) and bone deformities, such as scoliosis, congenital pseudoarthrosis and bone dysplasia of tibia. Moreover, several studies have shown systemic involvement of bone tissue in NF1 patients, leading to reduced bone mass. The aim of our study was to evaluate some bone mineral metabolism parameters before and after calcium and vitamin D supplementation in NF1 patients. We evaluated in 70 NF1 consecutive patients the mineral metabolism and bone mineral density compared with 40 normal subjects. We showed bone alterations in 35% of patients and the increase of bone formation markers, such as bone isoenzyme of alkaline phosphatase (41.2 ± 15.5 vs. 25.6 ± 8.7 UI; P < 0.05, respectively) and osteocalcin (18.1 ± 5.6 vs. 7.6 ± 1.9 ng/ml; P < 0.05) and reduction of circulating levels of (25OH)-vitamin D (21.8 ± 12.3 ng/ml) with an high percentage of hypovitaminosys D (>60%). Moreover, we revealed a significant reduction of bone mass density at spine (L1-L4) (0.935 ± 0.13 vs. 1.110 ± 0.17 g/cm(2); P < 0.001) and femoral neck side (0.765 ± 0.09 vs. 0.839 ± 0.12 g/cm(2); P < 0.02), with high prevalence of osteopenia (44%) and osteoporosis (18%). After 12 months of calcium (1,200 mg/die) and cholecalciferol (800 UI/die) supplementation, we found a significant increase of (25) OH-vitamin D level (21.8 ± 12.3 vs. 35 ± 13 ng/ml; P < 0.01), without changes in bone mass density. In conclusion, NF1 patients may present a mineral bone involvement, with vitamin D deficiency; calcium and vitamin D supplementation is necessary to restore these bone mineral metabolic alterations.

Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly.

CONTEXT: In humans, few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status. OBJECTIVE: Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], ionized calcium, and parathyroid hormone (PTH) at baseline, and at 3, 7, 30, and 60 d. DESIGN: This was a prospective randomized intervention study. SETTING: The study was performed in a nursing home residence. PARTICIPANTS: A total of 32 elderly female patients (age range 66-97 yr), with vitamin D deficiency was included in the study. INTERVENTION: Participants were randomized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral (os) or im route. RESULTS: 25(OH)D levels sharply increased at d 3 only when vitamins were given os. The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration (47.8 +/- 7.3 ng/ml) compared with other forms (D(3) im: 15.9 +/- 11.3; D(2) os: 17.3 +/- 4.7; D(2) im: 5 +/- 4.4; all P < 0.001). The area under the curve (AUC) of the serum 25(OH)D against time (AUC(60)) was: D(3) os, 3193 +/- 759 ng x d/ml vs. D(2) os, 1820 +/- 512, P < 0.001; and D(3) im, 1361 +/- 492 vs. D(2) im, 728 +/- 195, P < 0.01. 25(OH)D significantly influences PTH levels at 3 (P < 0.03), 7 (P < 0.01), 30 (P < 0.01), and 60 d (P < 0.05). At 60 d, the form of vitamin (cholecalciferol) significantly lowers PTH levels (P = 0.037). CONCLUSIONS: Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D, when administered either by mouth or im. 25(OH)D plays a role in modulating serum PTH.

Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.

The functional HERG variant 897T is associated with Conn's adenoma.

OBJECTIVE: Aldosterone secreting adenomas (aldosteronomas) have an unknown molecular origin. Ion channel currents are involved in signal transduction leading to aldosterone synthesis and secretion. HERG (human-ether-a-go-go-related gene) encodes for a potassium channel responsible for the outward rectifying delayed current and it is mutation prone. When mutated it causes most of the familial forms of both long QT and short QT syndromes. Abnormal repolarization in glomerulosa cells might increase aldosterone secretion or induce a proliferative advantage. The aims of this study were to: (1) evaluate HERG expression in aldosteronomas; (2) search for HERG somatic mutations; and (3) determine whether there is any relationship between the common HERG functional variant (A2690C, leading from lysine 897 to threonine, K897T) and aldosteronoma. DESIGN AND METHODS: Aldosteronoma and blood samples from 17 patients were studied to evaluate HERG expression, full-length HERG complementary DNA sequencing, and genotyping for K897T alleles. The prevalence of HERG 897 alleles was also tested in a control population and a population consisting entirely of hypertensive individuals. RESULTS: HERG was expressed in all aldosteronomas analysed. HERG somatic mutations were not detected. The 897T variant of HERG was significantly more common among patients with aldosteronoma (897T allele 41%) than in patients with moderate-severe essential hypertension (897T allele 20%, P = 0.007) or in the control population (897T allele 12%, P < 0.0001). The 897T/T genotype was present in 24% of the aldosteronoma patients versus 7% (P = 0.040) and 3% (P = 0.001) in essential hypertension and in the control population, respectively. When the chi test was performed considering the three groups together, the significance was similar (for alleles P < 0.0001 and for genotypes P = 0.004). CONCLUSION: The common functional HERG variant 897T may predispose to the development of aldosteronoma.

[The use of parenteral clodronate in elderly women with postmenopausal osteoporosis: compliance, effects on bone mineral density and on bone turnover]. / L'uso del clodronato per via parenterale in donne anziane affette da osteoporosi postmenopausale: compliance, effetti sulla densità minerale ossea e sul turnover scheletrico.

The aim of the study was to evaluate parenteral clodronate (CLD) compliance in patients with postmenopausal osteoporosis and intolerance to aminobisphosphonates. Moreover, we have also assessed the effects of CLD on bone mineral density (BMD) and bone turnover. Eighty-four consecutive postmenopausal women with osteoporosis (range 62-74 years) were enrolled and randomly allocated to three groups: group A included 26 women who received CLD i.v., 300 mg/2 weeks and oral supplemental calcium carbonate (500 mg x 2/day) and vitamin D3 (400 IU x 2/day); group B included 28 women who received CLD i.m., 100 mg/week, and the same dose of calcium and vitamin D3 administered to group A; group C, the control group, included 30 women receiving only calcium and vitamin D3 at the same doses as the other two groups. The lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorbiometry at time 0 (T0) and after 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months. At the same time, the serum bone specific alkaline phosphatase and amino-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6, T12, T18, and T24. Eighty (95.2%) women completed the study, 24 in group A, 27 in group B and 29 in group C. In groups A and B, after 6 months of treatment we found a significantly greater (p < 0.05) increase in the L1-L4 BMD with respect to group C. After 12 months of therapy, in group A the L1-L4 BMD (1.8 +/- 0.5%) was significantly higher (p < 0.05) than that in group B (0.9 +/- 0.3%). At the end of the study, in groups A (1.2 +/- 0.5%) and B (1.1 +/- 0.4%) the percentage increase in the FN BMD was significantly greater (p < 0.05) than in group C (0.6 +/- 0.5%). After 24 months of therapy, there was no difference in the FN BMD between groups A and B. Since the sixth month, both the bone specific alkaline phosphatase and NTx/cr were found to be more markedly and significantly decreased (p < 0.05) in groups A and B with respect to group C. After 18 months, in group A (NTx/cr -16.7 +/- 0.8%) we observed a significantly reduced (p < 0.05) bone resorption with respect to group B (NTx/cr -11.0 +/- 0.5%). In group B, only 3 patients (11.2%) referred pain at the site of drug administration. Our data demonstrate that compliance to parenteral CLD is satisfactory and that this drug reduces bone turnover, increases the L1-L4 BMD and decreases the FN BMD loss. Parenteral CLD administration can represent an effective alternative treatment for postmenopausal women with osteoporosis, especially those who do not tolerate oral aminobisphosphonates.