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Wiener Medizinische Wochenschrift

, Volume 167, Issue 1–2, pp 18–24 | Cite as

Diagnosis and treatment of Paget’s disease of bone

A clinical practice guideline
  • Christian MuschitzEmail author
  • Xaver Feichtinger
  • Judith Haschka
  • Roland Kocijan
main topic
  • 755 Downloads

Summary

Paget’s disease of bone (osteitis deformans) is a benign focal disorder of accelerated skeletal remodeling. Either a single bone (monostotic) or multiple bones (polyostotic) can be affected. In patients with suspected Paget’s disease plain radiographs of the suspicious regions of the skeleton are recommended. The initial biochemical evaluation of a patient should be done using serum total ALP (alkaline phosphatase) or with the use of a more specific marker of bone formation: PINP (intact N-terminal type 1 procollagen propeptide) or CTX (cross-linked C‑telopeptide). Treatment with a bisphosphonate is recommended for most patients with active Paget’s disease who are at risk for further skeletal and extraskeletal complications. A single dose of 5 mg i.v. zoledronate as the treatment of choice in patients without contraindications is suggested. Oral bisphosphonates are less potent when compared to zoledronate. Treatment with an antiresorptive agent induces a more rapid decrease in resorption markers compared to formation marker. Measurement of total ALP or other baseline disease activity markers (e. g. CTX) at 6 to 12 weeks, when bone turnover will have shown a substantial decline, is an acceptable and cost-effective option. Maximum suppression of high bone turnover may require measurement at 6 months after administration. In patients with increased bone turnover, biochemical follow-up is recommended to be used as a more objective indicator of relapse rather than symptoms. The prolonged response after zoledronate treatment should be assessed every 1–2 years after normal bone turnover. With less potent drugs, every 6 to 12 months is appropriate.

Keywords

Paget’s disease Diagnosis Imaging Biochemistry Bisphosphonates 

Diagnose und Behandlung der Knochenerkrankung Morbus Paget

Eine klinische Praxisstudie

Zusammenfassung

Morbus Paget (Osteitis deformans) ist eine fokale benigne Erkrankung des Knochens mit beschleunigtem Knochenumsatz. Betroffen sind entweder einzelne (monostotische Form) oder mehrere Knochen (polyostotische Form). Diagnostisch werden Röntgenaufnahmen der suszipierten Skelettregionen empfohlen. Zur weiteren serologischen Untersuchung wird die alkalische Phosphatase (AP) empfohlen. Zusätzlich können spezifische Serummarker der Knochenformation (PINP Prokollagen Typ 1 N-terminales Propeptid) oder der Knochenresorption (CTX Cross-linked C‑Telopeptid) bestimmt werden. Zur Behandlung von Patienten mit einem aktiven M. Paget und einem erhöhten Risiko für weitere skeletale oder extraskeletale Manifestationen werden Bisphosphonate empfohlen. Eine einmalige i.v.-Dosis von 5 mg Zoledronat ist Mittel der Wahl bei Patienten ohne Kontraindikationen. Orale Bisphosphonate sind im Vergleich zu i.v.-Applikationen weniger potent. Die Behandlung mit einem antiresorptiven Medikament induziert eine schnellere Reduktion der Resorptionsmarker im Vergleich zu den Formationsmarkern. Die Bestimmung der AP oder anderer Marker (z. B. CTX) 6 bis 12 Wochen nach der Applikation eines Bisphosphonats ist eine kostengünstige Methode zur Überprüfung des therapeutischen Erfolgs. Die maximale Suppression wird erst nach 6 Monaten erreicht. Bei Patienten mit erhöhtem Knochenumsatz ist die Bestimmung der biochemischen Marker ein objektiverer Indikator im Vergleich zur Symptomkontrolle. Das Ansprechen auf eine Therapie mit Zoledronat sollte 1 bis 2 Jahre nach Applikation serologisch kontrolliert werden; mit weniger potenten antiresorptiven Medikamenten alle 6 bis 12 Monate.

Schlüsselwörter

Morbus Paget Diagnose Bildgebung Biochemie Bisphosphonate 

Notes

Conflict of interest

C. Muschitz has received speaker and/or consultancy honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed Pharma/Takeda, Kwizda Pharma, Boehringer Ingelheim, Actavis, Alexion, and Daiichi-Sankyo. C. Muschitz has received educational grants/research support from the Austrian Society for Bone and Mineral Research, Roche Austria, Eli Lilly Austria, Eli Lilly International, and Amgen Austria. He has nothing to disclose concerning this manuscript. R. Kocijan has received speaker honoraria from Eli Lilly. He has nothing to disclose concerning this manuscript. X. Feichtinger and J. Haschka declare that they have no competing interests.

Funding source

This review article was not supported by any grant or pharmaceutical company.

References

  1. 1.
    Ringe JD, Jend HH, Becker H. Epidemiologie der Osteitis deformans Paget. Munch Med Wschr. 1984;126:683–6.Google Scholar
  2. 2.
    Mikosch P, Trifina E, Roschger P, Haller J, Klaushofer K. Klinik und Diagnose des Morbus Paget. J Mineralstoffwechsel Muskuloskelet Erkrank. 2012;19:68–73.Google Scholar
  3. 3.
    Lyles KW, Siris ES, Singer FR, Meunier PJ. A clinical approach to diagnosis and management of Paget’s disease of bone. J Bone Miner Res. 2001;16:1379–87.CrossRefPubMedGoogle Scholar
  4. 4.
    Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490.CrossRefPubMedGoogle Scholar
  5. 5.
    Swiglo BA, Murad MH, Schünemann HJ, Kunz R, Vigersky RA, Guyatt GH, et al. A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. J Clin Endocrinol Metab. 2008;93:666–73.CrossRefPubMedGoogle Scholar
  6. 6.
    Singer FR, Bone HG, Hosking DJ, Lyles KW, Murad MH, Reid IR, et al. Paget‘s disease of bone: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:4408–22.CrossRefPubMedGoogle Scholar
  7. 7.
    Ralston SH, Langston AL, Reid IR. Pathogenesis and management of Paget’s disease of bone. Lancet. 2008;372:155–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics. 2002;22:1191–216.CrossRefPubMedGoogle Scholar
  9. 9.
    Maldague B, Malghem J. Dynamic radiologic patterns of Paget’s disease of bone. Clin Orthop Relat Res. 1987;(217):126–51. doi: 10.1097/00003086-198704000-00012.PubMedGoogle Scholar
  10. 10.
    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(Suppl 4):L151–63.CrossRefPubMedGoogle Scholar
  11. 11.
    Shirazi PH, Ryan WG, Fordham EW. Bone scanning in evaluation of Paget’s disease of bone. CRC Crit Rev Clin Radiol Nucl Med. 1974;5:523–58.PubMedGoogle Scholar
  12. 12.
    Fogelman I, Carr D. A comparison of bone scanning and radiology in the assessment of patients with symptomatic Paget’s disease. Eur J Nucl Med. 1980;5:417–21.PubMedGoogle Scholar
  13. 13.
    Eekhoff MEMW, Zwinderman AH, Haverkort DMAD, Cremers SCLM, Hamdy NAT, Papapoulos SE. Determinants of induction and duration of remission of Paget’s disease of bone after bisphosphonate (olpadronate) therapy. Bone. 2003;33:831–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Alvarez L, Peris P, Pons F, Guañabens N, Herranz R, Monegal A, et al. Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget’s disease activity. Arthritis Rheum. 1997;40:461–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Blumsohn A, Naylor KE, Assiri AM, Eastell R. Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease. Clin Chem. 1995;41:1592–8.PubMedGoogle Scholar
  16. 16.
    Withold W, Schulte U, Reinauer H. Method for determination of bone alkaline phosphatase activity: analytical performance and clinical usefulness in patients with metabolic and malignant bone diseases. Clin Chem. 1996;42:210–7.PubMedGoogle Scholar
  17. 17.
    Alvarez L, Guañabens N, Peris P, Monegal A, Bedini JL, Deulofeu R, et al. Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget’s disease. J Bone Miner Res. 1995;10:458–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Reid IR, Miller P, Lyles K, Fraser W, Brown JP, Saidi Y, et al. Comparison of a single infusion of zoledronic acid with risedronate for Paget‘s disease. N Engl J Med. 2005;353:898–908.CrossRefPubMedGoogle Scholar
  19. 19.
    Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001;296:235–42.PubMedGoogle Scholar
  20. 20.
    Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799–809.CrossRefPubMedGoogle Scholar
  21. 21.
    Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD, et al. Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res. 2007;22:142–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Reid IR, Lyles K, Su G, Brown JP, Walsh JP, del Pino-Montes J, et al. A single infusion of zoledronic acid produces sustained remissions in Paget disease: data to 6.5 years. J Bone Miner Res. 2011;26:2261–70.CrossRefPubMedGoogle Scholar
  23. 23.
    Reid IR, Gamble GD, Mesenbrink P, Lakatos P, Black DM. Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab. 2010;95:4380–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Siris ES, Chines AA, Altman RD, Brown JP, Johnston CC, Lang R, et al. Risedronate in the treatment of Paget’s disease of bone: an open label, multicenter study. J Bone Miner Res. 1998;13:1032–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Hosking DJ, Eusebio RA, Chines AA. Paget’s disease of bone: reduction of disease activity with oral risedronate. Bone. 1998;22:51–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Singer FR, Clemens TL, Eusebio RA, Bekker Risedronate PJ. A highly effective oral agent in the treatment of patients with severe Paget’s disease. J Clin Endocrinol Metab. 1998;83:1906–10.PubMedGoogle Scholar
  27. 27.
    Reid IR, Davidson JS, Wattie D, Wu F, Lucas J, Gamble GD, et al. Comparative responses of bone turnover markers to bisphosphonate therapy in Paget’s disease of bone. Bone. 2004;35:224–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Dodd GW, Ibbertson HK, Fraser TR, Holdaway IM, Wattie D. Radiological assessment of Paget’s disease of bone after treatment with the bisphosphonates EHDP and APD. Br J Radiol. 1987;60:849–60.CrossRefPubMedGoogle Scholar
  29. 29.
    Siris E, Weinstein RS, Altman R, Conte JM, Favus M, Lombardi A, et al. Comparative study of alendronate versus etidronate for the treatment of Paget’s disease of bone. J Clin Endocrinol Metab. 1996;81:961–7.PubMedGoogle Scholar
  30. 30.
    Frijlink WB, Bijvoet OL, te Velde J, Heynen G. Treatment of Paget’s disease with (3-amino-1-hydroxypropylidene)-1, 1‑bisphosphonate (A.P.D.). Lancet. 1979;1:799–803.CrossRefPubMedGoogle Scholar
  31. 31.
    Reid IR, Sharma S, Kalluru R, Eagleton C. Treatment of Paget’s disease of bone with denosumab: case report and literature review. Calcif Tissue Int. 2016; doi: 10.1007/s00223-016-0150-6.Google Scholar
  32. 32.
    Polyzos SA, Singhellakis PN, Naot D, Adamidou F, Malandrinou FC, Anastasilakis AD, et al. Denosumab treatment for juvenile Paget’s disease: results from two adult patients with osteoprotegerin deficiency (“Balkan” mutation in the TNFRSF11B gene). J Clin Endocrinol Metab. 2014;99:703–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Grasemann C, Schündeln MM, Hövel M, Schweiger B, Bergmann C, Herrmann R, et al. Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease. J Clin Endocrinol Metab. 2013;98:3121–6.CrossRefPubMedGoogle Scholar
  34. 34.
    Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, et al. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006;38:617–27.CrossRefPubMedGoogle Scholar
  35. 35.
    Wallace E, Wong J, Reid IR. Pamidronate treatment of the neurologic sequelae of pagetic spinal stenosis. Arch Intern Med. 1995;155:1813–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Patel S, Stone MD, Coupland C, Hosking DJ. Determinants of remission of Paget’s disease of bone. J Bone Miner Res. 1993;8:1467–73.CrossRefPubMedGoogle Scholar
  37. 37.
    el Sammaa M, Linthicum FH, House HP, House JW. Calcitonin as treatment for hearing loss in Paget’s disease. Am J Otol. 1986;7:241–3.PubMedGoogle Scholar
  38. 38.
    Iorio R, Healy WL. Heterotopic ossification after hip and knee arthroplasty: risk factors, prevention, and treatment. J Am Acad Orthop Surg. 2002;10:409–16.CrossRefPubMedGoogle Scholar
  39. 39.
    Finerman GA, Gonick HC, Smith RK, Mayfield JM. Diphosphonate treatment of Paget’s disease. Clin Orthop Relat Res. 1976;:115–24. doi: 10.1097/00003086-197610000-00018.PubMedGoogle Scholar
  40. 40.
    Meyers MH, Singer FR. Osteotomy for tibia vara in Paget’s disease under cover of calcitonin. J Bone Joint Surg Am. 1978;60:810–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Chen JR, Rhee RS, Wallach S, Avramides A, Flores A. Neurologic disturbances in Paget disease of bone: response to calcitonin. Neurology. 1979;29:448–57.CrossRefPubMedGoogle Scholar
  42. 42.
    Chawla S, Henshaw R, Seeger L, Choy E, Blay J‑Y, Ferrari S, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14:901–8.CrossRefPubMedGoogle Scholar
  43. 43.
    van Staa TP, Selby P, Leufkens HGM, Lyles K, Sprafka JM, Cooper C. Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res. 2002;17:465–71.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Christian Muschitz
    • 1
    Email author
  • Xaver Feichtinger
    • 1
  • Judith Haschka
    • 1
  • Roland Kocijan
    • 1
  1. 1.Metabolic Bone Diseases UnitSt. Vincent HospitalViennaAustria

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