Details of Disease

General Information of Disease (ID: DISIPS4V)

• Disease Name: Bone Paget disease
• Synonyms: familial Paget's disease of bone; Paget's disease; bone Paget disease; Paget's disease of the bone; bone Paget's disease; Paget disease of bone; Paget's bone disease; osseous Paget's disease; osteitis deformans; Pagets disease (bone); Paget's disease of bone
• Definition: A disease of bone that initially results in the excessive resorption of bone (by osteoclasts) followed by the replacement of normal bone marrow with vascular and fibrous tissue.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DIS60EOE: Hyperostosis
  DISO7RI8: Metabolic bone disease
  DISIPS4V: Bone Paget disease
• Disease Identifiers:
  MONDO ID: MONDO_0005382
  MESH ID: D010001
  UMLS CUI: C0029401
  MedGen ID: 10493
  HPO ID: HP:0034159
  Orphanet ID: 280110
  SNOMED CT ID: 2089002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 6 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alendronate	DMY2KX9	Approved	Small molecular drug	[1]
Etidronic acid	DM1XHYJ	Approved	Small molecular drug	[2]
Pamidronate	DMB4AVP	Approved	Small molecular drug	[3]
Risedronate	DM5FLTY	Approved	Small molecular drug	[4]
Salmon Calcitonin	DMEWUPF	Approved	Small molecular drug	[5]
Zoledronate	DMIXC7G	Approved	Small molecular drug	[6]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PML	TTLH9NY	Limited	Genetic Variation	[7]
TNFRSF11A	TT3K9S2	Limited	Altered Expression	[8]
SOST	TTYRO4F	Disputed	Altered Expression	[9]
CSF1	TT0IQER	moderate	Biomarker	[10]
HNRNPA1	TTPJ9XK	moderate	Biomarker	[11]
GNE	TT4DP5S	Strong	Biomarker	[12]
HNRNPA2B1	TT8UPW6	Strong	Genetic Variation	[13]
INPP5D	TTTP2Z1	Strong	Biomarker	[14]
PDPK1	TTYMGWX	Strong	Altered Expression	[15]
TAF2	TTHMP8B	Strong	Altered Expression	[16]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ACP5	DESITDW	Strong	Biomarker	[17]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CFDP1	OTXY7J96	Limited	Genetic Variation	[18]
EIF4G2	OTEO98CR	Limited	Genetic Variation	[18]
GEMIN4	OTX7402E	Limited	Genetic Variation	[18]
NUP205	OTJKHCY6	Limited	Biomarker	[7]
PSMD2	OT6HZHN7	Limited	Genetic Variation	[18]
ACTA1	OTOVGLPG	Disputed	Altered Expression	[19]
KRT7	OTLT3JFN	Disputed	Altered Expression	[20]
DPYS	OTLTUIVL	moderate	Genetic Variation	[7]
PIGN	OTHHTJKX	moderate	Genetic Variation	[21]
SLC25A43	OTY6MWVD	moderate	Genetic Variation	[7]
AAAS	OTJT9T23	Strong	Genetic Variation	[22]
ATF7	OTM8T3OD	Strong	Biomarker	[23]
NFAM1	OT4PKH8L	Strong	Altered Expression	[24]
PABPN1	OT3MC5SE	Strong	Biomarker	[25]
RIN3	OT5Z6F8O	Strong	Genetic Variation	[26]
SMURF1	OT5UIZR8	Strong	Biomarker	[18]
TIA1	OTGPN3P8	Strong	Biomarker	[8]
TRIP6	OTIPA4ZR	Strong	Biomarker	[27]

References

• [1] Alendronate FDA Label
• [2] Etidronic acid. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs Aging. 1994 Dec;5(6):446-74. doi: 10.2165/00002512-199405060-00006.
• [3] Pamidronate FDA Label
• [4] Risedronate FDA Label
• [5] Calcitonin. 2023 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 JanC.
• [6] Paget's Disease of Bone: Diagnosis and Treatment. Am J Med. 2018 Nov;131(11):1298-1303.
• [7] Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.Nat Genet. 2011 May 29;43(7):685-9. doi: 10.1038/ng.845.
• [8] Rare Inherited forms of Paget's Disease and Related Syndromes.Calcif Tissue Int. 2019 May;104(5):501-516. doi: 10.1007/s00223-019-00520-5. Epub 2019 Feb 13.
• [9] Evaluation of Bone Metabolism Biomarkers in Paget's Disease of Bone.Cureus. 2019 May 31;11(5):e4791. doi: 10.7759/cureus.4791.
• [10] Paget's disease of bone: evidence for complex pathogenetic interactions.Semin Arthritis Rheum. 2012 Apr;41(5):619-41. doi: 10.1016/j.semarthrit.2011.07.005. Epub 2011 Sep 29.
• [11] Genetic and Pathological Assessment of hnRNPA1, hnRNPA2/B1, and hnRNPA3 in Familial and Sporadic Amyotrophic Lateral Sclerosis.Neurodegener Dis. 2017;17(6):304-312. doi: 10.1159/000481258. Epub 2017 Nov 11.
• [12] Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia.Mol Genet Metab. 2001 Dec;74(4):458-75. doi: 10.1006/mgme.2001.3256.
• [13] Familial Early-Onset Paget's Disease of Bone Associated with a Novel hnRNPA2B1 Mutation.Calcif Tissue Int. 2017 Aug;101(2):159-169. doi: 10.1007/s00223-017-0269-0. Epub 2017 Apr 7.
• [14] Involvement of SHIP in TLR2-induced neutrophil activation and acute lung injury.J Immunol. 2005 Jun 15;174(12):8064-71. doi: 10.4049/jimmunol.174.12.8064.
• [15] Autophagy and 3-Phosphoinositide-Dependent Kinase 1 (PDK1)-Related Kinome in Pagetic Osteoclasts.J Bone Miner Res. 2016 Jul;31(7):1334-43. doi: 10.1002/jbmr.2806.
• [16] Experimental models of Paget's disease.J Bone Miner Res. 2006 Dec;21 Suppl 2:P55-7. doi: 10.1359/jbmr.06s210.
• [17] Tartrate-resistant acid phosphatase 5b, but not periostin, is useful for assessing Paget's disease of bone.Bone. 2019 Jul;124:132-136. doi: 10.1016/j.bone.2019.04.023. Epub 2019 Apr 30.
• [18] VCP/p97 increases BMP signaling by accelerating ubiquitin ligase Smurf1 degradation.FASEB J. 2019 Feb;33(2):2928-2943. doi: 10.1096/fj.201801173R. Epub 2018 Oct 18.
• [19] VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle.Autophagy. 2019 Jun;15(6):1082-1099. doi: 10.1080/15548627.2019.1569933. Epub 2019 Jan 29.
• [20] Paget's disease of the nipple in a Her2-positive breast cancer xenograft model.Breast Cancer Res Treat. 2020 Feb;179(3):577-584. doi: 10.1007/s10549-019-05490-8. Epub 2019 Nov 13.
• [21] Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.Nat Genet. 2010 Jun;42(6):520-4. doi: 10.1038/ng.562. Epub 2010 May 2.
• [22] A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.Sci Rep. 2017 Mar 17;7:44751. doi: 10.1038/srep44751.
• [23] Role of ATF7-TAF12 interactions in the vitamin D response hypersensitivity of osteoclast precursors in Paget's disease.J Bone Miner Res. 2013 Jun;28(6):1489-500. doi: 10.1002/jbmr.1884.
• [24] NFAM1 signaling enhances osteoclast formation and bone resorption activity in Paget's disease of bone.Bone. 2017 Aug;101:236-244. doi: 10.1016/j.bone.2017.05.013. Epub 2017 May 12.
• [25] Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions in a case of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia with a novel mutation in the valosin-containing protein gene.Neuromuscul Disord. 2016 Jul;26(7):436-40. doi: 10.1016/j.nmd.2016.05.001. Epub 2016 May 5.
• [26] Genetic Variation in RIN3 in the Belgian Population Supports Its Involvement in the Pathogenesis of Paget's Disease of Bone and Modifies the Age of Onset.Calcif Tissue Int. 2019 Jun;104(6):613-621. doi: 10.1007/s00223-019-00530-3. Epub 2019 Feb 6.
• [27] Osteoclast inhibitory peptide-1 (OIP-1) inhibits measles virus nucleocapsid protein stimulated osteoclast formation/activity.J Cell Biochem. 2008 Jul 1;104(4):1500-8. doi: 10.1002/jcb.21723.