Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 5/2020

01-05-2020 | Bisphosphonate | Review

Management of Paget’s disease of bone

Author: I.R. Reid

Published in: Osteoporosis International | Issue 5/2020

Login to get access

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.
Literature
1.
Bijvoet OL, van der Sluys VJ, Jansen AP (1968) Effects of calcitonin on patients with Paget’s disease, thyrotoxicosis, or hypercalcaemia. Lancet 1:876–881PubMed
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 47:1–8PubMed
3.
Smith R, Russell RGG, Bishop M (1971) Diphosphonates and Paget’s disease of bone. Lancet 297:945–947
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 42:235–256PubMed
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 289:1379–1384PubMed
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
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 87:656–663PubMed
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
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 353:898–908PubMed
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 99:4408–4422PubMed
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 34:579–600PubMed
12.
Maldague BMD, Malghem JMD (1987) Dynamic radiologic patterns of Paget’s disease of Bone. Clin Orthop Relat Res 217:126–151
13.
Siris ES, Feldman F (1997) Natural history of untreated Pagets disease of the tibia. J Bone Miner Res 12:691–692PubMed
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
15.
Vellenga CJ, Pauwels EK, Bijvoet OL, Frijlink WB, Mulder JD, Hermans J (1984) Untreated Paget disease of bone studied by scintigraphy. Radiology 153:799–805PubMed
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–12SPubMed
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 17:465–471PubMed
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 80:1–9PubMed
19.
Dimitriadis PA, Bamiou DE, Bibas AG (2012) Hearing loss in Paget’s disease: a temporal bone histopathology study. Otol Neurotol 33:142–146PubMed
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 38:907–915PubMed
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 295:1301–1305PubMed
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
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 60:849–860PubMed
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
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 19:387–394PubMed
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 23:1193–1204PubMed
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 58:1165–1172PubMed
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 81:961–967PubMed
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 101:341–348PubMed
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 106:513–520PubMed
31.
Hosking DJ, Eusebio RA, Chines AA (1998) Pagets-disease of bone - reduction of disease activity with oral risedronate. Bone 22:51–55PubMed
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 13:1032–1038PubMed
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 83:1906–1910PubMed
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 26:263–267PubMed
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 100:250–254PubMed
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 35:224–230PubMed
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 26:2261–2270PubMed
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 32:753–756PubMed
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 94:311–318PubMed
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
41.
Reid IR, Maslowski K (2017) Long-term bone scintigraphy results after intravenous zoledronate in Paget’s disease of Bone. Calcif Tissue Int 101:43–49PubMed
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 23:117–121PubMedPubMedCentral
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 26:635–641PubMed
44.
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 25:20–31PubMed
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 55:347–352PubMed
47.
Wallace E, Wong JC, Reid IR (1995) Pamidronate treatment of the neurologic sequelae of pagetic spinal stenosis. Arch Int Med 155:1813–1815
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
49.
Charhon S, Chapuy MC, Valentin-Opran A, Meunier PJ (1982) Intravenous etidronate for spinal cord dysfunction due to Paget’s disease. Lancet 1:391–392PubMed
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
51.
Walpin LA, Singer FR (1979) Paget’s disease. Reversal of severe paraparesis using calcitonin. Spine 4:213–219PubMed
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 23:715–724PubMed
53.
Sadar ES, Walton RJ, Gossman HH (1972) Neurological dysfunction in Paget’s disease of the vertebral column. J Neurosurg 37:661–665PubMed
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 26:27–30PubMed
55.
Hadjipavlou AG, Gaitanis IN, Katonis PG et al (2001) Paget’s disease of the spine and its management. Eur Spine J 10:370–384PubMedPubMedCentral
56.
Merkow RL, Pellicci PM, Hely DP et al (1984) Total hip replacement for Paget’s disease of the hip. J Bone Joint Surg 66:752–758PubMed
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
60.
Marr DS, Rosenthal DI, Cohen GL et al (1994) Rapid postoperative osteolysis in Paget disease. A case report. J Bone Joint Surg 76:274–277PubMed
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
62.
el Sammaa M, Linthicum FHJ, House HP et al (1986) Calcitonin as treatment for hearing loss in Paget’s disease. Am J Otol 7:241–243PubMed
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 10:458–465PubMed
64.
Djulbegovic B, Guyatt G (2019) Evidence vs consensus in clinical practice guidelines. JAMA 322:725–726
65.
Delmas PD, Meunier PJ (1997) The management of Paget’s disease of bone. N Engl J Med 336:558–566PubMed
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 16:1379–1387PubMed
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 99:322–325PubMed
Metadata
Title
Management of Paget’s disease of bone
Author
I.R. Reid
Publication date
01-05-2020
Publisher
Springer London
Published in
Osteoporosis International / Issue 5/2020
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-019-05259-1

Other articles of this Issue 5/2020

Osteoporosis International 5/2020 Go to the issue

Original Article

Risk for hip fracture before and after total knee replacement in Sweden

Original Article

Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data

Original Article

Postmenopausal women with osteoporosis consume high amounts of vegetables but insufficient dairy products and calcium to benefit from their virtues: the CoLaus/OsteoLaus cohort

Letter to the Editor

Comments on Kanis et al.: Algorithm for the management of patients at low, high, and very high risk of osteoporotic fractures

Original Article

Treatment of bone loss in proximal femurs of postmenopausal osteoporotic women with AGN1 local osteo-enhancement procedure (LOEP) increases hip bone mineral density and hip strength: a long-term prospective cohort study

Original Article

Comparison of multimedia and printed patient education tools for patients with osteoporosis: a 6-month randomized controlled trial