A functional allelic variant of the FGF23 gene is associated with renal phosphate leak in calcium nephrolithiasis.

Background: A significant percentage of patients with calcium nephrolithiasis and normal parathyroid function have renal phosphate leak. This disorder is characterized by idiopathic hypophosphatemia and reduced renal phosphate threshold normalized for the glomerular filtration rate (TmPi/GFR). The majority of these patients harbor high or inappropriately normal circulating levels of fibroblast growth factor 23 (FGF23), a hormone regulating phosphate homeostasis.

A nonsynonymous TNFRSF11A variation increases NFκB activity and the severity of Paget's disease.

Mutations in the SQSTM1 gene were identified as a common cause of Paget's disease of bone (PDB) but experimental evidence demonstrated that SQSTM1 mutation is not sufficient to induce PDB in vivo. Here, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations. The largest effect was found for the T575C variant, yielding an odds ratio of 1.

The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis.

Background: Experimental evidence indicate that melatonin regulates some renal tubular functions via specific melatonin receptors (MTNRs) located in the kidney of several avian and mammalian species, including humans. We hypothesized that single nucleotide polymorphisms (SNPs) in the melatonin receptor 1A gene (MTNR1A) might influence the risk of calcium nephrolithiasis.

Methods: We performed a systematic analysis of the MTNR1A gene in 246 recurrent calcium stone formers (136 men, 110 women; mean age 40.

Characteristic clinical and biochemical profile of recurrent calcium-oxalate nephrolithiasis in patients with metabolic syndrome.

Background: Metabolic syndrome is a risk factor for nephrolithiasis. This study was performed to evaluate the clinical and biochemical profile of calcium-oxalate nephrolithiasis in stone formers with metabolic syndrome.

Methods: A total of 526 recurrent stone formers, 184 of them with metabolic syndrome, and 214 controls were examined on a free diet and after a sodium-restricted diet (sodium intake < 100 mmol/24 h).

Comparison of intravenous and intramuscular neridronate regimens for the treatment of Paget disease of bone.

Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar short-term efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB.

[Diagnostic and therapeutic approach in patients with urinary calculi].

The natural history of urolithiasis includes the risk of recurrence and of the development of chronic kidney and/or bone disease, which is why a thorough clinical and metabolic evaluation of these patients is of the utmost importance at disease onset. This paper is aimed at identifying the type of urolithiasis, the related risk factors, and the corresponding treatment options. The diagnostic and therapeutic approach described here includes 1) accurate history taking to detect secondary nephrolithiasis and screen for the main risk factors for kidney and bone disease; 2) metabolic evaluation graded according to different complexity levels based on the severity of the disease and the presence of risk factors; 3) carrying out appropriate imaging procedures.

FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women.

Objective: FSH, via its receptor (FSHR), influences bone remodeling and osteoclast proliferation and activity. The aim of this study was to evaluate the influence of two single nucleotide polymorphisms (SNPs) of the FSHR gene on bone mineral density (BMD) and bone turnover markers (bone alkaline phosphatase and type I collagen C-telopeptides) in postmenopausal women.

Methods: Two hundred and eighty-nine unrelated postmenopausal women were genotyped for the SNPs rs1394205 and rs6166.

SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone.

Even though SQSTM1 gene mutations have been identified in a consistent number of patients, the etiology of Paget's disease of bone (PDB) remains in part unknown. In this study we analyzed SQSTM1 mutations in 533 of 608 consecutive PDB patients from several regions, including the high-prevalence area of Campania (also characterized by increased severity of PDB, higher number of familial cases, and peculiar phenotypic characteristics as giant cell tumor). Eleven different mutations (Y383X, P387L, P392L, E396X, M401V, M404V, G411S, D423X, G425E, G425R, and A427D) were observed in 34 of 92 (37%) and 43 of 441 (10%) of familial and sporadic PDB patients, respectively.

Clinical, historical and diagnostic findings associated with right ventricular dysfunction in patients with central and non-massive pulmonary embolism.

Right ventricular dysfunction during acute pulmonary embolism (PE) predisposes to hemodynamic instability and cardiogenic shock. Aim of this case-control study was to determine the clinical, historical and diagnostic findings associated with right ventricular dysfunction in patients with acute PE involving the main or segmental pulmonary arteries (central PE) and without hemodynamic instability on admission to the Emergency Department (ED) (non-massive PE). From January 1, 2002 to December 31, 2005, 211 patients with central PE were admitted to the Department of Emergency Medicine of the "Antonio Cardarelli" Hospital (Naples, Italy).

Bone turnover and the osteoprotegerin-RANKL pathway in tumor-induced osteomalacia: a longitudinal study of five cases.

To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-kappaB (RANKL), and their relationship with FGF-23, lumbar bone mineral density (BMD), and bone turnover markers, five patients with tumor-induced osteomalacia (TIO) and 40 healthy controls were studied. TIO patients were followed for 360 days after surgical removal of underlying tumor (n = 2) or beginning of therapy with phosphate and calcitriol when surgical treatment was impossible (n = 3). At diagnosis, TIO patients had higher levels of FGF-23 and bone-specific alkaline phosphatase (bALP) and lower levels of cathepsin K (CathK), RANKL, and RANKL/OPG ratio compared to controls.

The use of intravenous aminobisphosphonates for the treatment of Paget's disease of bone.

Paget's disease of bone is a focal skeletal disorder characterized by the formation of structurally abnormal bone, deformity and other complications leading to significant disability and bone pain. Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this disorder.

Vitamin D receptor gene polymorphisms predict acquired resistance to clodronate treatment in patients with Paget's disease of bone.

Bisphosphonates are first-choice drugs for treatment of Paget's disease of bone (PDB); nevertheless, acquired resistance to bisphosphonate therapy has been described in PDB patients. The 1,25(OH)(2)D(3)/vitamin D receptor (VDR) system influences the effectiveness of antiresorptive treatments in metabolic bone disorders. This study evaluated the relationship between acquired resistance to clodronate treatment and BsmI, TaqI, and FokI VDR polymorphisms in Caucasian patients with polyostotic PDB (n = 84).

Association between metabolic syndrome and nephrolithiasis in an inpatient population in southern Italy: role of gender, hypertension and abdominal obesity.

Background: Metabolic syndrome (MetS) and nephrolithiasis (NL) are quite common disorders. While some of the components of MetS have been proposed as precursors of NL in population studies, no data are available about the possible association between NL and MetS as such. The primary objective of the study was to evaluate the relationship between MetS and NL.

Metabolic syndrome and nephrolithiasis: can we hypotize a common background?

Metabolic syndrome and nephrolithiasis are quite common disorders presenting similar epidemiological characteristics. Belonging to genetic, environmental and hormonal interaction, they have high incidence and prevalence in the adult population of industrialised countries and are characterised by a high level of morbidity and mortality if not adequately identified and treated. Despite metabolic syndrome is considered a fundamental risk factor for chronic kidney diseases, is not actually known whether it is associated with nephrolithiasis beyond the effect of its individual components, in particular obesity, glucose intolerance, and hypertension.

Evidence for increased clinical severity of familial and sporadic Paget's disease of bone in Campania, southern Italy.

Unlabelled: The analysis of 236 Italian patients with Paget's bone disease showed higher clinical severity and greater frequency of neoplastic degeneration among patients who live or descend from individuals living in the Campania region (southern Italy). A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region.

Introduction: The Campania region in southern Italy has been recently indicated as a high prevalence area for Paget's disease of bone (PDB), and most pagetic families with multiple occurrence of neoplasms in affected members were from this geographical region.

Fibroblast growth factor 23 is increased in calcium nephrolithiasis with hypophosphatemia and renal phosphate leak.

Context: Nephrolithiasis affects about 10% of the population in industrialized countries, with calcium salts composing more than 80% of renal stones. A significant percentage of patients with calcium nephrolithiasis and normal parathyroid function show hypophosphatemia and reduced renal phosphate reabsorption (i.e.

Interleukin-6 and osteoprotegerin systems in Paget's disease of bone: relationship to risedronate treatment.

Serum concentrations of interleukin-6 (IL-6), IL-6-soluble receptor (sIL-6R), IL-6 gp130-soluble receptor (sgp130), ligand of receptor activator of nuclear factor (NF)-kappaB (RANKL), and osteoprotegerin (OPG) were determined in 42 patients with polyostotic Paget's disease of bone (PDB) and acquired resistance to clodronate (M/F ratio 23:19; mean age 58.5 +/- 9.4 years) in acute phase of disease and after oral risedronate treatment (30 mg/day for 8 weeks).

Association between vitamin D receptor gene polymorphisms and fasting idiopathic hypercalciuria in recurrent stone-forming patients.

Objectives: To investigate the association between fasting idiopathic hypercalciuria (IHc), defined as IHc in the fasting state associated with normal parathyroid function, and ApaI, BsmI, and FokI polymorphisms of the vitamin D receptor (VDR) gene in 159 hypercalciuric recurrent stone formers. IHc contributes to the formation of calcium kidney stones in more than one half of reported cases.

Methods: We examined 62 patients with fasting IHc (24 women, mean age 42.

The relationship of 3' vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis.

Background: Idiopathic hypercalciuria (IHc) and idiopathic hypocitraturia are frequently associated with calcium nephrolithiasis. We investigated the relationship of vitamin D receptor (VDR) polymorphisms (BsmI, TaqI and FokI) to urinary supersaturation of calcium oxalate salts in recurrent calcium oxalate stone formers with IHc and the clinical relevance of this relationship.

Methods: The study included 110 Caucasian stone formers with IHc and 127 unrelated healthy controls without history of nephrolithiasis.

Giant cell tumor and Paget's disease of bone in one family: geographic clustering.

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component.

Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes.

Objective: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes.

Design: Prospective baseline-controlled clinical trial.

Patients: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months.

Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes.

Background: The vitamin D receptor (VDR) gene polymorphism has been considered a factor influencing the effectiveness of the anti-osteoporotic treatments. The aim of this study was to correlate the effectiveness of raloxifene treatment in post-menopausal women with osteoporosis to BsmI VDR genotypes.

Methods: Between January and August 2000, 75 Italian osteoporotic women were enrolled and treated with raloxifene at a dose of 60 mg/day.