Tim Cundy

..To review recent advance in understanding the causation and management of Paget's disease...

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..Given the many reservations about the new criteria an urgent but dispassionate debate is required on the risks, costs and benefits of their introduction...

..To review recent advance in understanding the causation and management of Paget's disease...

..Our data demonstrate that, on average, newly referred patients with Paget's disease have less severe disease and are significantly older at diagnosis than was the case two decades ago...

..Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability...

..005). SQSTM1 mutations were found in 10.5% of patients with early onset and/or severe disease but no family history...

..To explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs)...

..Women with type 2 and type 1 diabetes have differing risk factors for pregnancy loss. We compared the rates and causes of pregnancy loss in women with type 1 and type 2 diabetes...

..Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease...

..Most observations seem to fit best with the idea that Paget disease behaves as a multifocal benign neoplasm...

..We reviewed all the cases published to date in peer-reviewed journals to summarize what is known of the epidemiology, risk factors, cause and treatment...

..Plasma concentrations of procollagen peptides are decreased in osteogenesis imperfecta (OI), whereas other bone formation markers may be increased. We examined the utility of combining these markers in the diagnosis of OI in adults...

..Treatment with inhibitors of bone resorption (calcitonin or bisphosphonates) is successful in ameliorating some aspects of the disorder...

..0%, P = 0.029). There were no major adverse events. These data support the view that the likely cause of DMPA-associated bone loss is estrogen deficiency and demonstrate that it can be arrested by estrogen replacement therapy...

..This description of abnormal OPG function in humans expands the spectrum of genetic bone diseases arising from perturbations of the OPG/RANK-L/RANK system that regulates osteoclastogenesis...

..The aim of this study was to compare the incidence and outcomes of, and risk factors for, hypertension in pregnancy in women with Type 1 and Type 2 diabetes...

..The purpose of this study was to determine the rate of early postmenopausal bone loss in women who had used depot medroxyprogesterone acetate contraception through to menopause...

..To determine factors possibly associated with reduced bone density in women using the injectable contraceptive depot medroxyprogesterone acetate...

..This study reports observational data on perinatal mortality in Type 2 DM from a population with a high background rate of this disorder...

..Therefore, we examined the possibility that somatic mutations in the SQSTM1 gene are present in the local lesions, using RNA collected from primary osteoblast and bone marrow cell cultures of patients with this condition...

..EXPERIMENTAL SUBJECTS: Subjects included 80 women with postmenopausal osteoporosis who had been taking estrogen for at least 1 yr...

..We have tested for measles virus sequences in osteoblasts and bone marrow cells collected from pagetic lesions and healthy bone...

..Apart from mild hypocalcemia and hypophosphatemia, no apparent adverse events occurred...

..001), with marked differences evident even in the youngest group (mean age 23 years). Compared to other racial groups, women of Indian origin preferentially accumulate abdominal fat--a trait that is well established in young adulthood...

..At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents...

..Therefore, a move away from routine vitamin D measurements seems sensible, though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia...

..To determine if insulin sensitivity is altered in prepubertal offspring exposed to a diabetic intrauterine environment...

..Obvious abnormalities are apparent with a variety of radiologic modalities, and it is not clear that radiographs are inferior to other approaches. Most authors favor a conservative approach to surgical debridement of the lesions...

..The aim of this article is to put the risks of osteonecrosis of the jaw into context with the benefits of bisphosphonate treatment in these clinical scenarios...

..Although there are a number of potential biases, these data are consistent with a continued secular trend to presentation in older subjects with less extensive skeletal involvement, and a declining prevalence of Paget's disease...

..For patients whose HbA1c is less than and equal to 40 mmol/mol, repeat screening (including for CVD risk) at intermittent intervals is recommended as per published guidelines...

..There is no clear evidence from this study that any of these newer markers are superior to total AP in assessing patients with this severity of Paget's disease...

..We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions...

..We undertook a radiographic survey to determine the current prevalence of Paget's disease in New Zealand (previously recognized as a high prevalence area)...

..Birth weight and prematurity predict adult height, but it is slower fetal growth, rather than prematurity, that predicts lower peak bone mass. The lower peak bone mass in those born small is appropriate for their adult height...

..Adverse cardiovascular risk factors are prevalent in this population. Public health measures to curtail the rise of obesity in childhood and adolescence are required urgently...

..Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking...

..In the remainder of the GDM group, the rate does not differ from the non-diabetic background rate...

..It also implies that the apparent reduction in Paget's disease prevalence in western cities is unlikely to be explicable by the rising Asian population of these cities...

..This study examined the effect of an apparent medication formulation change on subjective and objective measures of medication effectiveness and medication side effects...

..To determine the prevalence and spectrum of retinal changes in juvenile Paget disease...

..To determine the lifetime risk of developing symptomatic carpal tunnel syndrome (CTS) in subjects with Type 1 diabetes and to investigate the effect of glycaemic control, body mass index (BMI), gender and age of onset of diabetes...

..Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement...

..This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies...

..TAFII-17 can bind VDR at low concentrations of 1,25(OH)2D3. These results suggest that MVNP expression in Paget's OCL precursors increases expression of a component(s) of the VDR transcription complex that can increase OCL formation...

..These results demonstrate that TEI-9647 can suppress the excessive bone resorption and OCL formation seen in marrow cultures from patients with PD...

..These results suggest that TEI-9647 acts directly on osteoclast precursors and osteoclasts, and that TEI-9647 may be a novel agent to suppress the excessive bone resorption and osteoclast formation in patients with Paget's disease...

..We found that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to both sporadic and familial PDB...

..Genetic variation in VCP does not appear to be a common cause of familial or sporadic PDB in the absence of myopathy and dementia...

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..These findings are consistent with the presence of a chronic MV infection in affected sites from these patients with Paget's disease...

..0001). These studies confirm that mutations affecting the ubiquitin-binding domain of SQSTM1 are a common cause of familial and sporadic Paget's disease of bone...

..Thus, the DCC 201 R --> G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested...

..Functional and structural analysis showed that disease severity was related to the type of mutation but was unrelated to the polyubiquitin-binding properties of the mutant UBA domain peptides...

..A major susceptibility locus for PDB was identified on chromosome 10p13 by a genome-wide linkage scan in families of British descent, which accounted for the vast majority of cases not caused by SQSTM1 mutations...

..Here we show that the most common disease-causing mutation (P392L) is carried on a shared haplotype, consistent with a founder effect and a common ancestral origin...