Recombinant Osteoprotegerin for Juvenile Paget's Disease

Cundy, Tim; Davidson, James S.; Rutland, M. D.; Stewart, Carolyn; DePaoli, Alex M.

doi:10.1056/nejmoa050893

Cited by 87 publications

(35 citation statements)

References 15 publications

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“…Other studies have shown that increased bone metabolism may be associated with TNFRSF11B sequence variants which downregulate or block the expression of the osteoprotegerin gene [22, 23]. In a recent paper, Xue et al [24] showed that OPG serum levels were significantly higher in patients with intervertebral disc degeneration and the TC or CC genotype at the c.- 223C > T polymorphic locus (rs2073617) than those carrying the wild-type homozygous (TT) genotype.…”

Section: Introductionmentioning

confidence: 99%

Bone Metabolism and the c.-223C > T Polymorphism in the 5′UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease

et al. 2016

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Osteoporosis is more frequent in inflammatory bowel disease (IBD) patients. A reduction in bone mineral mass in these individuals is caused not only by inflammatory processes in the bowel, because osteoporosis occurs already in very young IBD patients and in newly diagnosed individuals who have not yet undergone any pharmacological treatment. One of individual determinants of the bone turnover parameters is osteoprotegerin (OPG) encoded by the TNFRSF11B gene. The c.-223C > T polymorphism in this gene has been extensively studied in post-menopausal osteoporosis patients. However, no such studies exist for osteoporosis related to IBD. The aim of our study was to determine whether the c.-223C > T (rs2073617) polymorphism in the 5′UTR region of the gene encoding osteoprotegerin is a functional polymorphism which may change the gene expression and resulting OPG levels, and so be associated with osteopenia and osteoporosis, and impaired bone metabolism in Crohn’s disease and ulcerative colitis patients. Our study included 198 IBD patients and 41 healthy controls. Lumbar spine and femoral neck bone mineral density, T-score, Z-score as well as OPG, RANKL, vitamin D, calcium and interleukin 4 and 10 concentrations were determined for all study subjects. Genotyping of the TNFRSF11B polymorphic site was performed by restriction fragment length polymorphism technique. Statistical analyses were conducted using Statistica software. Odds ratios, 95 % confidence intervals, and P values were calculated using the HWE calculator. Our results did not allow determining an unequivocal association between the polymorphic variants of the TNFRSF11B 5′UTR region and a susceptibility to osteoporosis in IBD patients. We have shown, however, that the c.-223T allele was twice as more frequent in Crohn’s disease (CD) patients than among controls (OR = 1.99, P value = 0.009). Interestingly, average osteoprotegerin levels in CD patients did not significantly differ from those in controls, whereas in ulcerative colitis patients, OPG levels were significantly lower. We have concluded that low OPG levels may be associated with osteoporosis in ulcerative colitis, but it is not correlated with the c.-223C > T polymorphism in the TNFRSF11B gene. In CD patients, in turn, we observed increased RANKL levels. Our observations confirm different pathogeneses of Crohn’s disease and ulcerative colitis as well as different molecular backgrounds of osteoporosis associated with these two diseases.

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Section: Introductionmentioning

confidence: 99%

Bone Metabolism and the c.-223C > T Polymorphism in the 5′UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease

et al. 2016

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“…Mice lacking functional osteoprotegerin show growth plate abnormalities (12). In humans, inactivating mutations of the gene encoding osteoprotegerin result in juvenile Paget's disease, which is primarily characterized by excessive bone resorption but also causes short stature (13). Secreted frizzled-related protein 4 inhibits action of the Wnt system (14), which is critical for normal growth plate function (15,16).…”

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confidence: 99%

Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

et al. 2008

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Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.

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“…The effect of recombinant osteoprotegerin was studied in patients with juvenile Paget's disease (33). This disease is characterized by an accelerated bone turnover due to inactivating mutations in the gene encoding osteoprotegerin.…”

Section: Recent Advancesmentioning

confidence: 99%

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Pathway and Its Therapeutic Implications

Vries

Gietema

Jong

2006

Clinical Cancer Research

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Recombinant Osteoprotegerin for Juvenile Paget's Disease

Cited by 87 publications

References 15 publications

Bone Metabolism and the c.-223C > T Polymorphism in the 5′UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease

Bone Metabolism and the c.-223C > T Polymorphism in the 5′UTR Region of the Osteoprotegerin Gene in Patients with Inflammatory Bowel Disease

Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Pathway and Its Therapeutic Implications

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