Paget’s disease of bone

  • George Trovas Laboratory for Research of the Musculoskeletal System “Th. Garofalidis”, Medical School, University of Athens, KAT Hospital, 10 Athinas Str., Kifissia, 14561 Athens, Greece
Keywords: paget’s disease of bone, bone remodeling, bisphosphonates, alkaline phosphatase, treatment


Paget’s disease of bone is the most common metabolic bone disease after osteoporosis and affects 2-4% of adults over 55 years of age. Its etiology is only partly understood and includes both genetic and environmental factors. The disease may be asymptomatic and can be uncovered incidentally on x-ray or in biochemical tests performed for another condition. It can also manifest itself with bone pain, deformity, fracture or other complications. Paget’s disease is diagnosed by x-rays and in general has very typical radiological features, but nuclear bone scans define the extent of the disease. Plasma total alkaline phosphatase activity is the most clinically useful indicator of disease activity. It is elevated in most untreated patients, but may be within the normal range in patients with monostotic or limited disease. Bisphosphonate therapy is indicated for patients with symptoms and should also be considered in patients with disease sites that suggest a risk of complications, such as long bones, vertebrae or base of the skull. Orthopedic surgery in Paget’s disease patients includes almost the correction of fractures and arthroplasty.


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1. Paget, J. (1877). On a form of chronic inflammation of bones (osteitis deformans). Med. Chir. Trans. 60, 37–649. doi:10.1177/095952877706000105
2. Gianfrancesco F, Rendina D, Merlotti D, et al. Giant cell tumor occurring in familial Paget’s disease of bone: report of clinical characteristics and linkage analysis of a large pedigree. J Bone Miner Res. 2013; 28:341–50
3. van Staa TP, Selby P, Leufkens HG,et al. Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res. 2002; 17:465–71
4. Corral-Gudino L, Borao-Cengotita-Bengoa M, Del Pino-Montes J, Ralston SH. Epidemiology of Paget’s disease of bone: a systematic review and meta-analysis of secular changes. Bone.2013;55:347–52.
5. Cook,M. J., Pye, S. R., Lunt, al Incidence of Paget’s disease of bone in the UK: Evidence of a continuing decline. Rheumatol. Oxf. (2021) 60, 5668–5676. doi:10.1093/rheumatology/keab232
6. Gennari L,Merlotti D, Martini G,et al Paget’s disease of bone in Italy. J Bone Miner Res. 2006;21 Suppl 2: P14–21
7. Tiegs RD, LohseCM,Wollan PC,et al Long-term trends in the incidence of Paget’s disease of bone. Bone. 2000; 27:423–7.
8. Reddy SV, Menaa C, Singer FR, et al. Cell biology of Paget’s disease. J Bone Miner Res. 1999;14:3-8
9. Roodman GD, Windle JJ. Paget disease of bone. J Clin Invest.2005;115(2):200–8.
10. Ralston SH. Pathogenesis of Paget’s disease of bone. Bone 2008;43:819-25.
11. Gennari, L., Gianfrancesco, F., Di Stefano, M., et al. SQSTM1 gene analysis and gene-environment interaction in Paget’s disease of bone. J. Bone Min. Res.2010, 25, 1375–1384. doi:10.1002/jbmr.31
12. Navnit S. Makaram,Stuart H. Ralston Genetic Determinants of Paget’s Disease of Bone Current Osteoporosis Reports (2021) 19:327–337.
13. Mills, B. G., and Singer, F. R. Nuclear inclusions in Paget’s disease of bone. Science1976; 194, 201–202. doi:10.1126/science.959849
14. Mills, B. G., Singer, F. R., Weiner, L. P., et al Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget’s disease of bone. Clin. Orthop. Relat. Res. 1984 183,303–311. doi:10.1097/00003086-198403000-00044
15. Reddy, S. V., Singer, F. R., Mallette, L., at al. Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease. J. Bone Min. Res. 1996,11, 1602–1607. doi:10.1002/jbmr.5650111103
16. O’Driscoll, J. B., Buckler, H. M., Jeacock, J.,et all, Dogs, distemper and osteitis deformans: A further epidemiological study. Bone Min.1990 11,209–216. doi:10.1016/0169-6009(90)90060-s
17. Helfrich MH, Hobson RP, Grabowski PS, et al. A negative search for a paramyxoviral etiology of Paget’s disease of bone: molecular, immunological, and ultrastructural studies in UK patients. J Bone Miner Res.2000;15(12):2315–29.
18. Ralston, S. H., Afzal, M. A., Helfrich, M. H., et al. Multicenter blinded analysis of RT-PCR detection methods for paramyxoviruses in relation to Paget’s disease of bone. J. Bone Min. Res. 22,2007,569–577. doi:10.1359/jbmr.070103
19. Hocking LJ, Mellis DJ, McCabe PS, et al. Functional interaction between sequestosome-1/p62 andautophagy-linked FYVE-containing protein WDFY3 in humanosteoclasts. Biochem Biophys Res Commun. 2010;402(3):543–8.
20. Teramachi J, Nagata Y, Mohammad K, et al. Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease. J Clin Invest. 2016;126(3):1012–22.
21. Kurihara N, Hiruma Y, Yamana K, et al. Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget’s disease. Cell Metab. 2011;13(1):23–34.
22. Piga AM, Lopez-Abente G, Ibanez AE, et al. Risk factors for Paget’s disease: a new hypothesis. Int J Epidemiol. 1988;17(1):198–201.
23. Holdaway IM, Ibbertson HK, Wattie D, et al. Previous pet ownership and Paget’s disease. Bone Miner.1990;8(1):53–8.
24. Lever JH. Paget’s disease of bone in Lancashire and arsenic pesticide in cotton mill wastewater: a speculative hypothesis. Bone. 2002;31(3):434–6.
25. Diboun, I., Wani, S., Ralston, S. H.,et al. Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status. Elife 10; 2021 e65715. doi:10.7554/eLife.65715
26. Nguyen, H. D., Bisson,M., Scott, M., et al. miRprofile in pagetic osteoclasts: from large-scale sequencing to gene expression study. J. Mol. Med.2021; 99, 1771–1781. doi:10.1007/s00109-021-02128-5
27. Singer F, Bone HG, Hosking DJ et al. Paget’s Disease of Bone: an Endocrine Society Clinical Practice Guideline.J Clin Endocrinol Metab 2014;99:4408_22.
28. Merchant SN, Rosowski JJ. Conductive hearing loss caused by third-window lesions of the inner ear. Otol Neurotol. 2008; 29:282–289
29. Guma M, Rotes D, Holgado S, et al. Paget’s disease of bone: study of 314 patients. Med Clin (Barc). 2002;119(14):537–40.
30. Eekhoff ME, van der Klift M, KroonHM, et al. Paget’s disease of bone in the Netherlands: a population-based radiological and biochemical survey — theRotterdam Study. J Bone Miner Res 2004; 19:566-70.
31. Reid IR, Davidson JS, Wattie D, et al.Comparative responses of bone turnover markers to bisphosphonate therapy in Paget’s disease of bone. Bone 2004;35:224-30.
32. Shirazi PH, Ryan WG, Fordham EW. Bone scanning in evaluation of Paget’s disease of bone. CRC Crit Rev Clin Radiol Nucl Med. 1974; 5:523–558.
33. López C, Thomas DV, Davies AM. Neoplastic transformation and tumour-like lesions in Paget’s disease of bone: a pictorial review. Eur Radiol. 2003;13: L151–L163.
34. Ralston SH. Paget’s Disease of Bone. N Engl J Med 2013; 368:644-50. DOI: 10.1056/NEJMcp1204713.
35. Langston AL, Campbell MK, Fraser WD, et al. Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget’s disease of bone. J Bone Miner Res. 2010; 25:20-31.
36. Tan A, Goodman K, Walker A, et al. Long-Term Randomized Trial of Intensive Versus Symptomatic Management in Paget’s Disease of Bone: The PRISM-EZ Study. J Bone Miner Res. 2017; 32:1165-1173.
37. Ralston SH, Corral-Gudino L, Cooper C, et al. Diagnosis and management of Paget’s disease of bone in adults: A clinical guideline. J Bone Miner Res 2019;34(4):579–604. doi: 10.1002/jbmr.3657
38. Cundy T, Maslowski K, Grey A, et al. Durability of Response to Zoledronate Treatment and Competing Mortality in Paget’s Disease of Bone. J Bone Miner Res. 2017;32:753–756.
39. 39 126. Reid IR, Miller P, Lyles K, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med. 2005; 353:898-908.