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Paget disease of bone 3(PDB3)

MedGen UID:
895927
Concept ID:
C4085252
Disease or Syndrome
Synonym: Paget disease of bone, familial
 
Gene (location): SQSTM1 (5q35.3)
 
Monarch Initiative: MONDO:0008176
OMIM®: 167250

Definition

Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). Genetic Heterogeneity of Paget Disease of Bone Also see PDB2 (602080), caused by mutation in the TNFRSF11A gene (603499) on chromosome 18q21; PDB4 (606263), mapped to chromosome 5q31; PDB5 (239000), caused by mutation in the TNFRSF11B gene (602643) on chromosome 8q24; and PDB6 (616833), caused by mutation in the ZNF687 gene (610568) on chromosome 1q21. Suggestive linkage of a form of PDB to chromosome 6p (PDB1) was reported by Fotino et al. (1977); however, further studies did not confirm linkage to this site (Moore and Hoffman, 1988; Nance et al., 2000; Good et al., 2001). [from OMIM]

Additional description

From MedlinePlus Genetics
Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).

The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.

Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.

Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.

Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.

A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.  https://medlineplus.gov/genetics/condition/paget-disease-of-bone

Clinical features

From HPO
Bone pain
MedGen UID:
57489
Concept ID:
C0151825
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
Osteosarcoma
MedGen UID:
10501
Concept ID:
C0029463
Neoplastic Process
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Recurrent long bone fractures
MedGen UID:
66802
Concept ID:
C0240231
Finding
An increased tendency to fractures of the long bones (Mainly, the femur, tibia, fibula, humerus, radius, and ulna).
Patchy osteosclerosis
MedGen UID:
383784
Concept ID:
C1855845
Finding
Patchy (irregular) increase in bone density. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Osteolysis
MedGen UID:
1648424
Concept ID:
C4721411
Pathologic Function
Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee
Br J Haematol 2024 Mar;204(3):784-804. Epub 2024 Jan 21 doi: 10.1111/bjh.19236. PMID: 38247114
Singer FR
Best Pract Res Clin Rheumatol 2020 Jun;34(3):101506. Epub 2020 Apr 11 doi: 10.1016/j.berh.2020.101506. PMID: 32291204
Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, Guañabens N, Javaid MK, Layfield R, O'Neill TW, Russell RGG, Stone MD, Simpson K, Wilkinson D, Wills R, Zillikens MC, Tuck SP
J Bone Miner Res 2019 Apr;34(4):579-604. Epub 2019 Feb 25 doi: 10.1002/jbmr.3657. PMID: 30803025Free PMC Article

Recent clinical studies

Etiology

Seemann LL, Hanos CT, Pujalte GGA
Prim Care 2024 Sep;51(3):445-454. Epub 2024 May 23 doi: 10.1016/j.pop.2024.04.005. PMID: 39067970
Reid IR, Green JR, Lyles KW, Reid DM, Trechsel U, Hosking DJ, Black DM, Cummings SR, Russell RGG, Eriksen EF
Bone 2020 Aug;137:115390. Epub 2020 Apr 27 doi: 10.1016/j.bone.2020.115390. PMID: 32353565
Pianou NK, Stavrou PZ, Vlontzou E, Rondogianni P, Exarhos DN, Datseris IE
Hell J Nucl Med 2019 Jan-Apr;22(1):6-9. Epub 2019 Mar 7 doi: 10.1967/s002449910952. PMID: 30843003
Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, Guañabens N, Javaid MK, Layfield R, O'Neill TW, Russell RGG, Stone MD, Simpson K, Wilkinson D, Wills R, Zillikens MC, Tuck SP
J Bone Miner Res 2019 Apr;34(4):579-604. Epub 2019 Feb 25 doi: 10.1002/jbmr.3657. PMID: 30803025Free PMC Article
Ottaviani G, Jaffe N
Cancer Treat Res 2009;152:3-13. doi: 10.1007/978-1-4419-0284-9_1. PMID: 20213383

Diagnosis

Seemann LL, Hanos CT, Pujalte GGA
Prim Care 2024 Sep;51(3):445-454. Epub 2024 May 23 doi: 10.1016/j.pop.2024.04.005. PMID: 39067970
Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee
Br J Haematol 2024 Mar;204(3):784-804. Epub 2024 Jan 21 doi: 10.1111/bjh.19236. PMID: 38247114
Schini M, Vilaca T, Gossiel F, Salam S, Eastell R
Endocr Rev 2023 May 8;44(3):417-473. doi: 10.1210/endrev/bnac031. PMID: 36510335Free PMC Article
Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, Guañabens N, Javaid MK, Layfield R, O'Neill TW, Russell RGG, Stone MD, Simpson K, Wilkinson D, Wills R, Zillikens MC, Tuck SP
J Bone Miner Res 2019 Apr;34(4):579-604. Epub 2019 Feb 25 doi: 10.1002/jbmr.3657. PMID: 30803025Free PMC Article
Lalam RK, Cassar-Pullicino VN, Winn N
Semin Musculoskelet Radiol 2016 Jul;20(3):287-299. Epub 2016 Oct 14 doi: 10.1055/s-0036-1592368. PMID: 27741544

Therapy

Seemann LL, Hanos CT, Pujalte GGA
Prim Care 2024 Sep;51(3):445-454. Epub 2024 May 23 doi: 10.1016/j.pop.2024.04.005. PMID: 39067970
Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee
Br J Haematol 2024 Mar;204(3):784-804. Epub 2024 Jan 21 doi: 10.1111/bjh.19236. PMID: 38247114
McClung MR, Ebetino FH
Bone 2020 Aug;137:115407. Epub 2020 May 6 doi: 10.1016/j.bone.2020.115407. PMID: 32387834
Reid IR, Green JR, Lyles KW, Reid DM, Trechsel U, Hosking DJ, Black DM, Cummings SR, Russell RGG, Eriksen EF
Bone 2020 Aug;137:115390. Epub 2020 Apr 27 doi: 10.1016/j.bone.2020.115390. PMID: 32353565
Ralston SH, Corral-Gudino L, Cooper C, Francis RM, Fraser WD, Gennari L, Guañabens N, Javaid MK, Layfield R, O'Neill TW, Russell RGG, Stone MD, Simpson K, Wilkinson D, Wills R, Zillikens MC, Tuck SP
J Bone Miner Res 2019 Apr;34(4):579-604. Epub 2019 Feb 25 doi: 10.1002/jbmr.3657. PMID: 30803025Free PMC Article

Prognosis

Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee
Br J Haematol 2024 Mar;204(3):784-804. Epub 2024 Jan 21 doi: 10.1111/bjh.19236. PMID: 38247114
Trojani MC, Santucci-Darmanin S, Breuil V, Carle GF, Pierrefite-Carle V
Joint Bone Spine 2022 May;89(3):105301. Epub 2021 Oct 18 doi: 10.1016/j.jbspin.2021.105301. PMID: 34673234
Pianou NK, Stavrou PZ, Vlontzou E, Rondogianni P, Exarhos DN, Datseris IE
Hell J Nucl Med 2019 Jan-Apr;22(1):6-9. Epub 2019 Mar 7 doi: 10.1967/s002449910952. PMID: 30843003
Ottaviani G, Jaffe N
Cancer Treat Res 2009;152:3-13. doi: 10.1007/978-1-4419-0284-9_1. PMID: 20213383
Nemzek WR
Top Magn Reson Imaging 1996 Jun;8(3):132-54. PMID: 8840469

Clinical prediction guides

Wang J, Zhang Y, Cao J, Wang Y, Anwar N, Zhang Z, Zhang D, Ma Y, Xiao Y, Xiao L, Wang X
Autophagy 2023 Sep;19(9):2409-2427. Epub 2023 Mar 8 doi: 10.1080/15548627.2023.2186112. PMID: 36858962Free PMC Article
Langdahl BL, Uitterlinden AG, Ralston SH
Best Pract Res Clin Rheumatol 2022 Sep;36(3):101791. Epub 2022 Nov 3 doi: 10.1016/j.berh.2022.101791. PMID: 36336607
Reid IR, Green JR, Lyles KW, Reid DM, Trechsel U, Hosking DJ, Black DM, Cummings SR, Russell RGG, Eriksen EF
Bone 2020 Aug;137:115390. Epub 2020 Apr 27 doi: 10.1016/j.bone.2020.115390. PMID: 32353565
Pianou NK, Stavrou PZ, Vlontzou E, Rondogianni P, Exarhos DN, Datseris IE
Hell J Nucl Med 2019 Jan-Apr;22(1):6-9. Epub 2019 Mar 7 doi: 10.1967/s002449910952. PMID: 30843003
Corral-Gudino L, Tan AJ, Del Pino-Montes J, Ralston SH
Cochrane Database Syst Rev 2017 Dec 1;12(12):CD004956. doi: 10.1002/14651858.CD004956.pub3. PMID: 29192423Free PMC Article

Recent systematic reviews

Leccese D, Rodolico GR, Sperti M, Cassandrini D, Bartolini M, Ingannato A, Nacmias B, Bracco L, Malandrini A, Santorelli FM, Bessi V, Matà S
Clin Neurol Neurosurg 2023 Sep;232:107875. Epub 2023 Jul 5 doi: 10.1016/j.clineuro.2023.107875. PMID: 37441929
Corral-Gudino L, Tan AJ, Del Pino-Montes J, Ralston SH
Cochrane Database Syst Rev 2017 Dec 1;12(12):CD004956. doi: 10.1002/14651858.CD004956.pub3. PMID: 29192423Free PMC Article
Tan A, Ralston SH
Calcif Tissue Int 2014 Nov;95(5):385-92. Epub 2014 Aug 27 doi: 10.1007/s00223-014-9904-1. PMID: 25160936
Hess LM, Jeter JM, Benham-Hutchins M, Alberts DS
Am J Med 2008 Jun;121(6):475-483.e3. doi: 10.1016/j.amjmed.2008.01.047. PMID: 18501224Free PMC Article

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