Paget disease of bone

Paget disease of bone are rare inherited osteolytic disorders that show phenotypic overlap. Patients with these diseases carry mutations in RANK/TNFRSF11A, OPG/TNFRSF11B or SQSTM1, resulting in activation of RANKL-RANK signaling axis with increases in bone resorption. Hearing impairment and tooth loss is common. Apart from juvenile-onset Paget's disease (PDB5), the condition is inherited as an autosomal dominant trait.

Musculoskeletal disease

(PDB2) TNFRSF11A [HSA:8792] [KO:K05147]
(PDB3) SQSTM1 [HSA:8878] [KO:K14381]
(PDB5) TNFRSF11B [HSA:4982] [KO:K05148]
(PDB6) ZNF687 [HSA:57592]

Etidronate disodium [DR:D00314]
Pamidronate disodium [DR:D00941]
Alendronate sodium [DR:D00939]
Risedronate sodium [DR:D00942]
Sodium risedronate hydrate [DR:D03234]
Zoledronic acid [DR:D01968]

PMID:16831914

Whyte MP

Paget's disease of bone and genetic disorders of RANKL/OPG/RANK/NF-kappaB signaling.

Ann N Y Acad Sci 1068:143-64 (2006)
DOI:10.1196/annals.1346.016

PMID:12929927

Nakatsuka K, Nishizawa Y, Ralston SH

Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene.

J Bone Miner Res 18:1381-5 (2003)
DOI:10.1359/jbmr.2003.18.8.1381

PMID:10615125

Hughes AE, Ralston SH, Marken J, Bell C, MacPherson H, Wallace RG, van Hul W, Whyte MP, Nakatsuka K, Hovy L, Anderson DM

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.

Nat Genet 24:45-8 (2000)
DOI:10.1038/71667

PMID:12362049

Palenzuela L, Vives-Bauza C, Fernandez-Cadenas I, Meseguer A, Font N, Sarret E, Schwartz S, Andreu AL

Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene.

J Med Genet 39:E67 (2002)
DOI:10.1136/jmg.39.10.E67

PMID:11771666

Whyte MP, Hughes AE

Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis.

J Bone Miner Res 17:26-9 (2002)
DOI:10.1359/jbmr.2002.17.1.26

PMID:12124406

Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S

Osteoprotegerin deficiency and juvenile Paget's disease.

N Engl J Med 347:175-84 (2002)
DOI:10.1056/NEJMoa013096

PMID:18328984

Ralston SH

Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders.

Best Pract Res Clin Rheumatol 22:101-11 (2008)
DOI:10.1016/j.berh.2007.11.005

PMID:20875342 (drug)

Brandi ML

Current treatment approaches for Paget's Disease of Bone.

Discov Med 10:209-12 (2010)

PMID:2460988

Carey PO, Lippert MC

Treatment of painful prostatic bone metastases with oral etidronate disodium.

Urology 32:403-7 (1988)
DOI:10.1016/0090-4295(88)90410-4

PMID:26849110

Divisato G, Formicola D, Esposito T, Merlotti D, Pazzaglia L, Del Fattore A, Siris E, Orcel P, Brown JP, Nuti R, Strazzullo P, Benassi MS, Cancela ML, Michou L, Rendina D, Gennari L, Gianfrancesco F

ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor.

Am J Hum Genet 98:275-86 (2016)
DOI:10.1016/j.ajhg.2015.12.016