Juvenile Paget disease is a disorder that affects bone growth. This disease causes bones to be abnormally large, misshapen, and easily broken (fractured).

The signs of juvenile Paget disease appear in infancy or early childhood. As bones grow, they become progressively weaker and more deformed. These abnormalities usually become more severe during the adolescent growth spurt, when bones grow very quickly.

Juvenile Paget disease affects the entire skeleton, resulting in widespread bone and joint pain. The bones of the skull tend to grow unusually large and thick, which can lead to hearing loss. The disease also affects bones of the spine (vertebrae). The deformed vertebrae can collapse, leading to abnormal curvature of the spine. Additionally, weight-bearing long bones in the legs tend to bow and fracture easily, which can interfere with standing and walking.

Juvenile Paget disease is rare; about 50 affected individuals have been identified worldwide.

Juvenile Paget disease is caused by mutations in the TNFRSF11B gene. This gene provides instructions for making a protein that is involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it.

Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Mutations in the TNFRSF11B gene lead to a much faster rate of bone remodeling starting early in life. Bone tissue is broken down more quickly than usual, and when new bone tissue grows it is larger, weaker, and less organized than normal bone. This abnormally fast bone remodeling underlies the problems with bone growth characteristic of juvenile Paget disease.

Genetic Testing Information

• Genetic Testing Registry: Hyperphosphatasemia with bone disease

Genetic and Rare Diseases Information Center

• Juvenile Paget disease

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• PAGET DISEASE OF BONE 5, JUVENILE-ONSET; PDB5

Scientific Articles on PubMed

• PubMed

• Chong B, Hegde M, Fawkner M, Simonet S, Cassinelli H, Coker M, Kanis J, Seidel J, Tau C, Tuysuz B, Yuksel B, Love D; International Hyperphosphatasia Collaborative Group. Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype. J Bone Miner Res. 2003 Dec;18(12):2095-104. doi: 10.1359/jbmr.2003.18.12.2095. Citation on PubMed
• Cundy T, Hegde M, Naot D, Chong B, King A, Wallace R, Mulley J, Love DR, Seidel J, Fawkner M, Banovic T, Callon KE, Grey AB, Reid IR, Middleton-Hardie CA, Cornish J. A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet. 2002 Sep 1;11(18):2119-27. doi: 10.1093/hmg/11.18.2119. Citation on PubMed
• Cundy T. Idiopathic hyperphosphatasia. Semin Musculoskelet Radiol. 2002 Dec;6(4):307-12. doi: 10.1055/s-2002-36729. Citation on PubMed
• Daroszewska A, Ralston SH. Mechanisms of disease: genetics of Paget's disease of bone and related disorders. Nat Clin Pract Rheumatol. 2006 May;2(5):270-7. doi: 10.1038/ncprheum0172. Citation on PubMed
• Janssens K, de Vernejoul MC, de Freitas F, Vanhoenacker F, Van Hul W. An intermediate form of juvenile Paget's disease caused by a truncating TNFRSF11B mutation. Bone. 2005 Mar;36(3):542-8. doi: 10.1016/j.bone.2004.12.004. Citation on PubMed
• Lucas GJ, Daroszewska A, Ralston SH. Contribution of genetic factors to the pathogenesis of Paget's disease of bone and related disorders. J Bone Miner Res. 2006 Dec;21 Suppl 2:P31-7. doi: 10.1359/jbmr.06s206. Citation on PubMed
• Ralston SH. Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):101-11. doi: 10.1016/j.berh.2007.11.005. Citation on PubMed
• 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. 2002 Jul 18;347(3):175-84. doi: 10.1056/NEJMoa013096. Citation on PubMed