Guidelines on the management of Paget’s disease of bone*

Selby, Peter L.; Davie, M.W.J.; Ralston, Stuart H.; Stone, Mike

doi:10.1016/s8756-3282(02)00817-7

Cited by 196 publications

(163 citation statements)

References 115 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…(10)(11)(12) However, up to 70% of PDB patients are asymptomatic. (4,7,13) At the histologic level, osteoclasts are most likely the primary defective cells. Osteoclasts in PDB patients are more numerous and larger in size and have more nuclei (>100) and a significantly higher activity than osteoclasts in healthy individuals.…”

mentioning

confidence: 99%

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Chung

Beyens

Riches

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

RANK (receptor activator of nuclear factor-kB), encoded by TNFRSF11A, is a key protein in osteoclastogenesis. TNFRSF11A mutations cause Paget's disease of bone (PDB)-like diseases (ie, familial expansile osteolysis, expansile skeletal hyperphosphatasia, and early-onset PDB) and an osteoclast-poor form of osteopetrosis. However, no TNFRSF11A mutations have been found in classic PDB, neither in familial nor in isolated cases. To investigate the possible relationship between TNFRSF11A polymorphisms and sporadic PDB, we conducted an association study including 32 single-nucleotide polymorphisms (SNPs) in 196 Belgian sporadic PDB patients and 212 control individuals. Thirteen SNPs and 3 multimarker tests (MMTs) turned out to have a p value of between .036 and 3.17 Â 10 À4 , with the major effect coming from females. Moreover, 6 SNPs and 1 MMT withstood the Bonferroni correction ( p < .002). Replication studies were performed for 2 nonsynonymous SNPs (rs35211496 and rs1805034) in a Dutch and a British cohort. Interestingly, both SNPs resulted in p values ranging from .013 to 8.38 Â 10 À5 in both populations. Meta-analysis over three populations resulted in p ¼ .002 for rs35211496 and p ¼ 1.27 Â 10 À8 for rs1805034, again mainly coming from the female subgroups. In an attempt to identify the underlying causative SNP, we performed functional studies for the coding SNPs as well as resequencing efforts of a 31-kb region harboring a risk haplotype within the Belgian females. However, neither approach resulted in significant evidence for the causality of any of the tested genetic variants. Therefore, further studies are needed to identify the real cause of the increased risk to develop PDB shown to be present within TNFRSF11A. ß

show abstract

mentioning

confidence: 99%

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Chung

Beyens

Riches

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Los más utilizados son la fosfatasa alcalina sérica (marcador de formación ósea) y la hidroxiprolina en orina de 24 horas (marcador de resorción). La fosfatasa alcalina sérica es el marcador de referencia por su sensibilidad, coste y disponibilidad en todos los ámbitos médicos (11). Normalmente esta elevado en pacientes con EP que no han recibido tratamiento.…”

Section: Acta Reumatológica Issn 2386-6861unclassified

Enfermedad de Paget. Actualización en el tratamiento médico

Bachiller‐Corral

2015

acta reuma

View full text Add to dashboard Cite

ResumenLa enfermedad de Paget del hueso (EP) se caracteriza por un aumento del metabolismo óseo localizado en uno o varios focos del esqueleto. El mecanismo fisiopatológico inicial es el aumento de la resorción ósea osteoclástica, y los bifosfonatos son el tratamiento de elección. Las indicaciones aceptadas para el tratamiento de la EP incluyen el dolor óseo y las manifestaciones del sistema nervioso. También se recomienda el tratamiento antes de una cirugía ósea para prevenir el sangrado excesivo o la hipercalcemia. Los pacientes con una alta actividad metabólica (nivel de fosfatasa alcalina más de dos veces el límite superior normal) también deben ser tratados. Una indicación controvertida es el tratamiento en pacientes asintomáticos para prevenir las complicaciones evolutivas.Los nuevos bifosfonatos, como el ácido zoledrónico, con una gran potencia y afinidad de unión a la hidroxiapatita, son muy útiles para el control de la actividad de la enfermedad a corto y largo plazo. El ácido zoledrónico está indicado para EP en Europa y América en una sola dosis de 5 mg, administrado por vía intravenosa. En 2005, un ensayo controlado con risedronato, demostró una respuesta terapéu-tica en el 96% de los pacientes tratados con ácido zoledrónico, que es significativamente mayor que los resultados obtuvieron por otros bisfosfonatos. En el estudio de extensión, se demostró que la duración de la respuesta era de al menos 6 años y medio tras la infusión del fármaco.El ácido zoledrónico ha cambiado el manejo de la enfermedad de Paget. Queda pendiente demostrar si el control metabólico eficaz y prolongado que se consigue con los nuevos fármacos, reducirá el riesgo de complicaciones tales como la deformidad, las fracturas, la sordera y la artropatía secundaria.

show abstract

“…Subjects were evaluated at baseline and after 3,6,12,18,24,30 The primary efficacy endpoint was the rate of therapeutic response assessed at 6, 12, 24, and 36 months and defined as the normalization of ALP levels or a reduction of at least 75% in total ALP excess (the difference from the midpoint of the reference range). Secondary endpoints were the reduction of bone pain, time of nadir of ALP (defined as the number of days from the beginning of the treatment to the time when the lowest value was observed), time to a therapeutic response (defined as the number of days between the onset of treatment and the visit at which a response was observed), and the average percent decrease in ALP or the other bone turnover markers at each time point compared with baseline levels.…”

Section: Biochemical Evaluation and Efficacy Endpointsmentioning

confidence: 99%

“…Specific therapy for PDB is aimed at decreasing the abnormal bone remodeling, and different bisphosphonates are currently considered the treatment of choice. (6,7) These treatments are associated with a reduction in bone turnover markers and an improvement in radiologic and scintigraphic appearance, as well as a reduction in bone pain and bone deformity, whereas the effects of treatment on the development or progression of other PDB complications are poorly understood. (6)(7)(8) Different bisphosphonates have been used successfully for the treatment of PDB.…”

mentioning

confidence: 99%

“…(6,7) These treatments are associated with a reduction in bone turnover markers and an improvement in radiologic and scintigraphic appearance, as well as a reduction in bone pain and bone deformity, whereas the effects of treatment on the development or progression of other PDB complications are poorly understood. (6)(7)(8) Different bisphosphonates have been used successfully for the treatment of PDB. Compounds such as etidronate and clodronate were used initially and were associated with about 50% reduction in levels of serum alkaline phosphatase (ALP) or other bone turnover markers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Merlotti

Rendina

Gennari

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

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 shortterm 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. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bonespecific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions. ß

show abstract

Guidelines on the management of Paget’s disease of bone*

Cited by 196 publications

References 115 publications

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget's disease of bone

Enfermedad de Paget. Actualización en el tratamiento médico

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

Contact Info

Product

Resources

About