Skip to main content
Log in

Management of Paget’s disease of bone

  • Review
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Paget’s disease is a progressive focal bone condition which can result in pain, low quality of life, deformity and other complications. Disease progression can be halted with potent bisphosphonates, resulting in improvement in both quality of life and pain, and normalisation of scintigraphy, plain radiographs and bone histology. Zoledronate has transformed the treatment of Paget’s disease, producing sustained remissions in almost all patients. Thus, it is now possible to normalise bone cell activity and prevent disease progression at low cost, with one or two intravenous injections of zoledronate, greatly reducing follow-up costs. Patients with Paget’s disease who are symptomatic or at risk of complications should have the opportunity to reap these therapeutic benefits.

Summary

Potent bisphosphonates are highly effective in halting disease progression in Paget’s disease, but guidelines disagree about treatment indications. The efficacy, safety and low cost of zoledronate recommend its use in any patient who is symptomatic or judged to be at risk of complications from Paget’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Bijvoet OL, van der Sluys VJ, Jansen AP (1968) Effects of calcitonin on patients with Paget’s disease, thyrotoxicosis, or hypercalcaemia. Lancet 1:876–881

    CAS  PubMed  Google Scholar 

  2. Doyle FH, Greenberg PB, Joplin GF et al (1974) Radiological evidence of a dose-related response to long-term treatment of Paget’s disease with human calcitonin. Br J Radiol 47:1–8

    CAS  PubMed  Google Scholar 

  3. Smith R, Russell RGG, Bishop M (1971) Diphosphonates and Paget’s disease of bone. Lancet 297:945–947

    Google Scholar 

  4. Smith R, Russell RGG, Bishop MC, Woods CG, Bishop M (1973) Paget’s disease of bone: experience with a diphosphonate (disodium etidronate) in treatment. QJM 42:235–256

    CAS  PubMed  Google Scholar 

  5. Altman RD, Johnston CC, Khairi MR, Wellman H, Serafini AN, Sankey RR (1973) Influence of disodium etidronate on clinical and laboratory manifestations of Paget’s disease of bone (osteitis deformans). N Engl J Med 289:1379–1384

    CAS  PubMed  Google Scholar 

  6. Kantrowitz FG, Byrne MH, Schiller AL et al (1975) Clinical and biochemical effects of diphosphonate in Paget’s disease of bone. Arthritis Rheum 18:407

    Google Scholar 

  7. Khairi MRA, Altman RD, De Rosa GP et al (1977) Sodium etidronate in the treatment of Paget’s disease of bone: a study of long term results. Ann Intern Med 87:656–663

    CAS  PubMed  Google Scholar 

  8. Frijlink WB, te Velde J, Bijvoet OLM et al (1979) Treatment of Paget’s disease with (3-amino-1-hydoxypropylidene)-1,1-bisphosphonate (APD). Lancet i:799–803

    Google Scholar 

  9. Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, Mesenbrink P, Su G, Pak J, Zelenakas K, Luchi M, Richardson P, Hosking D (2005) Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 353:898–908

    CAS  PubMed  Google Scholar 

  10. Singer FR, Bone HG III, Hosking DJ et al (2014) Paget’s disease of bone: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 99:4408–4422

    CAS  PubMed  Google Scholar 

  11. Ralston SH, Corral-Gudino L, Cooper C et al (2019) Diagnosis and management of Paget’s disease of bone in adults: a clinical guideline. J Bone Miner Res 34:579–600

    PubMed  Google Scholar 

  12. Maldague BMD, Malghem JMD (1987) Dynamic radiologic patterns of Paget’s disease of Bone. Clin Orthop Relat Res 217:126–151

    Google Scholar 

  13. Siris ES, Feldman F (1997) Natural history of untreated Pagets disease of the tibia. J Bone Miner Res 12:691–692

    CAS  PubMed  Google Scholar 

  14. Renier JC, Audran M (1997) Progression in length and width of pagetic lesions, and estimation of age at disease onset. Rev Rhum 64:35–43

    CAS  Google Scholar 

  15. Vellenga CJ, Pauwels EK, Bijvoet OL, Frijlink WB, Mulder JD, Hermans J (1984) Untreated Paget disease of bone studied by scintigraphy. Radiology 153:799–805

    CAS  PubMed  Google Scholar 

  16. Davie M, Davies M, Francis R, Fraser W, Hosking D, Tansley R (1999) Paget’s disease of bone: a review of 889 patients. Bone 24:11S–12S

    CAS  PubMed  Google Scholar 

  17. Van Staa TP, Selby P, Leufkens HGM et al (2002) Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res 17:465–471

    PubMed  Google Scholar 

  18. Langston AL, Campbell MK, Fraser WD, Maclennan G, Selby P, Ralston SH (2007) Clinical determinants of quality of life in Paget’s disease of bone. Calcif Tissue Int 80:1–9

    CAS  PubMed  Google Scholar 

  19. Dimitriadis PA, Bamiou DE, Bibas AG (2012) Hearing loss in Paget’s disease: a temporal bone histopathology study. Otol Neurotol 33:142–146

    PubMed  Google Scholar 

  20. Deep NL, Besch-Stokes JG, Lane JI, Driscoll CLW, Carlson ML (2017) Paget’s disease of the temporal bone: a single-institution contemporary review of 27 patients. Otol Neurotol 38:907–915

    PubMed  Google Scholar 

  21. Harinck HIJ, Papapoulos SE, Blanksma HJ, Moolenaar AJ, Vermeij P, Bijvoet OL (1987) Paget’s disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). BMJ 295:1301–1305

    CAS  PubMed  Google Scholar 

  22. Harinck HIJ, Bijvoet OLM, Blanksma HJ et al (1987) Efficacious management with aminobisphosphonate (APD) in Paget’s disease of bone. Clin Orthop 217:79–98

    Google Scholar 

  23. Dodd GW, Ibbertson HK, Fraser TRC, Holdaway IM, Wattie D (1987) Radiological assessment of Paget’s disease of bone after treatment with the bisphosphonates EHDP and APD. Br J Radiol 60:849–860

    CAS  PubMed  Google Scholar 

  24. Fenton AJ, Gutteridge DH, Kent GN, Price RI, Retallack RW, Bhagat CI, Worth GK, Thompson RI, Watson IG, Barry-Walsh C (1991) Intravenous aminobisphosphonate in Paget’s disease: clinical, biochemical, histomorphometric and radiological responses. Clin Endocrinol 34:197–204

    CAS  Google Scholar 

  25. Gutteridge DH, Retallack RW, Ward LC, Stuckey BG, Stewart GO, Prince RL, Kent GN, Bhagat CI, Price RI, Thompson RI, Nicholson GC (1996) Clinical, biochemical, hematologic, and radiographic responses in Pagets disease following intravenous pamidronate disodium - a 2-year study. Bone 19:387–394

    CAS  PubMed  Google Scholar 

  26. Bijvoet OLM, Frijlink WB, Jie K, van der Linden H, Meijer CJ, Mulder H, van Paassen H, Reitsma PH, te Velde J, de Vries E, van der Wey J (1980) APD in Paget’s disease of bone. Arthritis Rheum 23:1193–1204

    CAS  PubMed  Google Scholar 

  27. Vellenga CJLR, Pauwels EKJ, Bijvoet OLM, Harinck HI, Frijlink WB (1985) Quantitative bone scintigraphy in Paget’s disease treated with APD. Br J Radiol 58:1165–1172

    CAS  PubMed  Google Scholar 

  28. Siris E, Weinstein RS, Altman R, Conte JM, Favus M, Lombardi A, Lyles K, McIlwain H, Murphy WA Jr, Reda C, Rude R, Seton M, Tiegs R, Thompson D, Tucci JR, Yates AJ, Zimering M (1996) Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab 81:961–967

    CAS  PubMed  Google Scholar 

  29. Reid IR, Nicholson GC, Weinstein RS, Hosking DJ, Cundy T, Kotowicz MA, Murphy WA Jr, Yeap S, Dufresne S, Lombardi A, Musliner TA, Thompson DE, Yates AJ (1996) Biochemical and radiologic improvement in Paget’s disease of bone treated with alendronate - a randomized, placebo-controlled trial. Am J Med 101:341–348

    CAS  PubMed  Google Scholar 

  30. Miller PD, Brown JP, Siris ES, Hoseyni MS, Axelrod DW, Bekker PJ (1999) A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget’s disease of bone. Am J Med 106:513–520

    CAS  PubMed  Google Scholar 

  31. Hosking DJ, Eusebio RA, Chines AA (1998) Pagets-disease of bone - reduction of disease activity with oral risedronate. Bone 22:51–55

    CAS  PubMed  Google Scholar 

  32. Siris ES, Chines AA, Altman RD, Brown JP, Johnston CC Jr, Lang R, McClung M, Mallette LE, Miller PD, Ryan WG, Singer FR, Tucci JR, Eusebio RA, Bekker PJ (1998) Risedronate in the treatment of Pagets-disease of bone - an open label, multicenter study. J Bone Miner Res 13:1032–1038

    CAS  PubMed  Google Scholar 

  33. Singer FR, Clemens TL, Eusebio RA, Bekker PJ (1998) Risedronate, a highly effective oral agent in the treatment of patients with severe Pagets-disease. J Clin Endocrinol Metab 83:1906–1910

    CAS  PubMed  Google Scholar 

  34. Brown JP, Chines AA, Myers WR, Eusebio RA, Ritter-Hrncirik C, Hayes CW (2000) Improvement of pagetic bone lesions with risedronate treatment: a radiologic study. Bone 26:263–267

    CAS  PubMed  Google Scholar 

  35. Reid IR, Wattie D, Gamble GD et al (2017) Long-term effects of intravenous ibandronate in Paget’s disease of bone. Calcif Tissue Int 100:250–254

    CAS  PubMed  Google Scholar 

  36. Reid IR, Davidson JS, Wattie D, Wu F, Lucas J, Gamble GD, Rutland MD, Cundy T (2004) Comparative responses of bone turnover markers to bisphosphonate therapy in Paget's disease of bone. Bone 35:224–230

    CAS  PubMed  Google Scholar 

  37. Reid IR, Lyles K, Su GQ, Brown JP, Walsh JP, del Pino-Montes J, Miller PD, Fraser WD, Cafoncelli S, Bucci-Rechtweg C, Hosking DJ (2011) A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res 26:2261–2270

    CAS  PubMed  Google Scholar 

  38. Cundy T, Maslowski K, Grey A, Reid IR (2017) Durability of response to zoledronate treatment and competing mortality in Paget’s disease of bone. J Bone Miner Res 32:753–756

    CAS  PubMed  Google Scholar 

  39. Devogelaer JP, Geusens P, Daci E, Gielen E, Denhaerynck K, Macdonald K, Hermans C, Vancayzeele S, Abraham I, Boonen S (2014) Remission over 3 years in patients with Paget disease of bone treated with a single intravenous infusion of 5 mg zoledronic acid. Calcif Tissue Int 94:311–318

    CAS  PubMed  Google Scholar 

  40. de Castro GRW, Heiden GI, Zimmermann AF et al (2012) Paget’s disease of bone: analysis of 134 cases from an island in southern Brazil: another cluster of Paget’s disease of bone in South America. Rheumatol Int 32:627–631

    Google Scholar 

  41. Reid IR, Maslowski K (2017) Long-term bone scintigraphy results after intravenous zoledronate in Paget’s disease of Bone. Calcif Tissue Int 101:43–49

    CAS  PubMed  Google Scholar 

  42. Durgia H, Sahoo J, Kamalanathan S, Palui R, Kumar R, Halanaik D, Ananthakrishnan R, Sankar G, Sridharan K, Raj H (2019) Response to zoledronic acid in patients with active Paget’s disease of bone: a retrospective study. Indian J Endocrinol Metab 23:117–121

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Avramidis A, Polyzos SA, Moralidis E et al (2008) Scintigraphic, biochemical, and clinical response to zoledronic acid treatment in patients with Paget’s disease of bone. J Bone Miner Metab 26:635–641

    CAS  PubMed  Google Scholar 

  44. Reid IR, Brown JP, Levitt N et al (2013) Re-treatment of relapsed Paget’s disease of bone with zoledronic acid - results from an open-label study. Bonekey Rep 2:442. https://doi.org/10.1038/bonekey.2013.1176

    Article  PubMed  PubMed Central  Google Scholar 

  45. Langston AL, Campbell MK, Fraser WD, MacLennan G, Selby PL, Ralston SH, PRISM Trial Group (2010) Randomized trial of intensive bisphosphonate treatment versus symptomatic management in Paget's disease of bone. J Bone Miner Res 25:20–31

    CAS  PubMed  Google Scholar 

  46. Corral-Gudino L, Borao-Cengotita-Bengoa M, Del Pino-Montes J et al (2013) Epidemiology of Paget’s disease of bone: a systematic review and meta-analysis of secular changes. Bone 55:347–352

    PubMed  Google Scholar 

  47. Wallace E, Wong JC, Reid IR (1995) Pamidronate treatment of the neurologic sequelae of pagetic spinal stenosis. Arch Int Med 155:1813–1815

    CAS  Google Scholar 

  48. Douglas DL, Duckworth T, Kanis JA et al (1981) Spinal cord dysfunction in Paget’s disease of bone. J Bone Joint Surg 63-B:495–502

    Google Scholar 

  49. Charhon S, Chapuy MC, Valentin-Opran A, Meunier PJ (1982) Intravenous etidronate for spinal cord dysfunction due to Paget’s disease. Lancet 1:391–392

    CAS  PubMed  Google Scholar 

  50. Chen J-R, Rhee RSC, Wallach S et al (1979) Neurologic disturbances in Paget disease of bone: response to calcitonin. J Neurol 29:448–457

    CAS  Google Scholar 

  51. Walpin LA, Singer FR (1979) Paget’s disease. Reversal of severe paraparesis using calcitonin. Spine 4:213–219

    CAS  PubMed  Google Scholar 

  52. Smidt WR, Hadjipavlou AG, Lander P, Dzioba RB (1994) An algorithmic approach to the treatment of Paget’s disease of the spine. Orthop Rev 23:715–724

    CAS  PubMed  Google Scholar 

  53. Sadar ES, Walton RJ, Gossman HH (1972) Neurological dysfunction in Paget’s disease of the vertebral column. J Neurosurg 37:661–665

    CAS  PubMed  Google Scholar 

  54. Jorge-Mora A, Amhaz-Escanlar S, Lois-Iglesias A, Leborans-Eiris S, Pino-Minguez J (2016) Surgical treatment in spine Paget’s disease: a systematic review. Eur J Orthop Surg Traumatol 26:27–30

    PubMed  Google Scholar 

  55. Hadjipavlou AG, Gaitanis IN, Katonis PG et al (2001) Paget’s disease of the spine and its management. Eur Spine J 10:370–384

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Merkow RL, Pellicci PM, Hely DP et al (1984) Total hip replacement for Paget’s disease of the hip. J Bone Joint Surg 66:752–758

    CAS  PubMed  Google Scholar 

  57. Parvizi J, Schall DM, Lewallen DG et al (2002) Outcome of uncemented hip arthroplasty components in patients with Paget’s disease. Clin Orthop Relat Res:127–134

  58. Lewallen DG (1999) Hip arthroplasty in patients with Paget’s disease. Clin Orthop Relat Res:243–250

  59. Parvizi J, Klein GR, Sim FHAFNPJ et al (2006) Surgical management of Paget’s disease of bone. J Bone Mineral Res 21(suppl 2):75–82

    Google Scholar 

  60. Marr DS, Rosenthal DI, Cohen GL et al (1994) Rapid postoperative osteolysis in Paget disease. A case report. J Bone Joint Surg 76:274–277

    CAS  PubMed  Google Scholar 

  61. Tsang WK, Yuen MK (2015) Post-traumatic postoperative osteolysis: an under-recognised cause of recrudescence of osteolysis in quiescent osteoblastic pagetic bone. Hong Kong J Radiol 18:41–45

    Google Scholar 

  62. el Sammaa M, Linthicum FHJ, House HP et al (1986) Calcitonin as treatment for hearing loss in Paget’s disease. Am J Otol 7:241–243

    PubMed  Google Scholar 

  63. Alvarez L, Guanabens N, Peris P et al (1995) Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease. J Bone Miner Res 10:458–465

    CAS  PubMed  Google Scholar 

  64. Djulbegovic B, Guyatt G (2019) Evidence vs consensus in clinical practice guidelines. JAMA 322:725–726

    Google Scholar 

  65. Delmas PD, Meunier PJ (1997) The management of Paget’s disease of bone. N Engl J Med 336:558–566

    CAS  PubMed  Google Scholar 

  66. Lyles KW, Siris ES, Singer FR, Meunier PJ (2001) A clinical approach to diagnosis and management of Paget’s disease of bone. J Bone Miner Res 16:1379–1387

    CAS  PubMed  Google Scholar 

  67. Reid IR, Sharma S, Kalluru R, Eagleton C (2016) Treatment of Paget’s disease of bone with denosumab: case report and literature review. Calcif Tissue Int 99:322–325

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to I.R. Reid.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reid, I. Management of Paget’s disease of bone. Osteoporos Int 31, 827–837 (2020). https://doi.org/10.1007/s00198-019-05259-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-019-05259-1

Keywords

Navigation