Skip to main content

Advertisement

SpringerLink
Log in

Biochemical Response to Bisphosphonate Therapy in Pagetic Patients with Skull Involvement

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget’s disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, α-α CTX, and β-β CTX) were measured at baseline and 6 months after therapy. The extent of the disease was evaluated using the Coutris’ index. Pagetic patients were classified into three groups: patients with skull involvement (G-I, n = 12), patients without skull involvement (G-II, n = 28), and a subgroup of patients from G-II without skull involvement but with similar disease extent to G-I (G-III, n = 10). At baseline, patients from G-I showed significantly higher values in most markers compared to G-II. α-α CTX was the marker with the highest values in all groups. Moreover, monostotic patients with skull involvement showed higher serum baseline values of TAP per unit of affected area than monostotic patients without skull involvement. After therapy, the percentage of patients with markers within the normal range was lower in G-I than in G-II and G-III. In conclusion, pagetic patients with skull involvement showed a marked increase in bone turnover and a lower response to therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Selby PL, Davie MWJ, Ralston SH, Stone MD (2002) Guidelines on the management of Paget’s disease of bone. Bone 31:10–19

    Article  Google Scholar 

  2. Siris E, Roodman G (2003) Paget’s disease of bone. In: Favus MJ (ed), Primer on the Metabolic Bone Disease and Disorders of Mineral Metabolism, 5th ed. American Society for Bone and Mineral Research, Washington DC, pp 495–506

    Google Scholar 

  3. Alvarez L, Peris P, Guañabens N, Vidal S, Quintó L, Monegal A, Pons F, Ballesta AM, Muñoz-Gómez J (2004) Long-term biochemical response after bisphosphonate therapy in Paget’s disease of bone. Proposed intervals for monitoring treatment. Rheumatology 43:869–874

    Article  PubMed  CAS  Google Scholar 

  4. Papapoulos SE, Frolich M (1996) Prediction of the outcome of treatment of Paget’s disease of bone with bisphosphonates from short-term changes in the rate of bone resorption. J Clin Endocrinol Metab 81:3993–3997

    Article  PubMed  CAS  Google Scholar 

  5. Patel S, Stone MD, Coupland C, Hosking DJ (1993) Determinants of remission of Paget’s disease of bone. J Bone Miner Res 8:1467–1473

    Article  PubMed  CAS  Google Scholar 

  6. Khan SA, Mc Closkey EV, Nakatsuka K, Orgee J, Coombes GM, Kanis JA (1996) Duration of response with oral clodronate in Paget’s disease of bone. Bone 18:185–190

    Article  PubMed  CAS  Google Scholar 

  7. Meunier PJ, Salson C, Mathieu L, Chapuy MC, Delmas P, Alexandre C, Charhon S (1987) Skeletal distribution and biochemical parameters of Paget’s disease. Clin Orthop Relat Res 217:37–44

    PubMed  Google Scholar 

  8. Harnick HIJ, Bijvoet OLM, Vellenga CJLR, Blanksma HJ, Frijlink WB (1986) Relation between signs and symptoms in Paget’s disease of bone. QJM 58:133–151

    Google Scholar 

  9. Alvarez L, Peris P, Pons F, Guañabens N, Herranz R, Monegal A, Bedini JL, Deulofeu R, Martínez de Osaba MJ, Muñoz-Gómez J, Ballesta AM (1997) Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget’s disease activity. Arthritis Rheum 40:461–468

    PubMed  CAS  Google Scholar 

  10. Smith SE, Murphey MD, Motamedi K, Mulligan ME, Resnik CS, Gannon FH (2002) Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. Radiographics 22:1191–1216

    PubMed  Google Scholar 

  11. Alvarez L, Guañabens N, Peris P, Vidal S, Ros I, Monegal A, Bedini JL, Deulofeu R, Pons F, Muñoz-Gómez J, Ballesta AM (2001) Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget’s disease. Bone 29:447–452

    Article  PubMed  CAS  Google Scholar 

  12. Alexandersen P, Peris P, Guañabens N, Byrjalsen I, Alvarez L, Solberg H, Cloos PAC (2005) Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget’s disease of bone. J Bone Miner Res 20:588–595

    Article  PubMed  CAS  Google Scholar 

  13. Coutris G, Cayla J, Rondier J, Talbot JN, Bonvarlet JP, Milhaud G (1975) Analyse des perturbations des voies principales du metabolism calcique dans la maladie de Paget: effets de l’administration de calcitonine. Rev Rhum Mal Osteoartic 42:759–767

    PubMed  CAS  Google Scholar 

  14. Allen MR, Hock JM, Burr DB (2004) Periosteum: biology, regulation, and response to osteoporosis therapies. Bone 35:1003–1012

    Article  PubMed  CAS  Google Scholar 

  15. Solchaga LA, Cassieda P, Caplan AI (1998) Different response to osteo-inductive agents in bone marrow- and periosteum-derived cell preparations. Acta Orthop Scand 69:426–432

    Article  PubMed  CAS  Google Scholar 

  16. Everts V, Korper W, Jansen C, Steinfort J, Lammerse I, Heera S, Docherty AJ, Beertsen W (1999) Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone. FASEB J 13:1219–1230

    PubMed  CAS  Google Scholar 

  17. Alvarez L, Ricos C, Peris P, Guañabens N, Monegal A, Pons F, Ballesta AM (2000) Components of biological variation of biochemical markers of bone turnover in Paget’s bone disease. Bone 26:571–576

    Article  PubMed  CAS  Google Scholar 

  18. Fledelius C, Johnsen AH, Cloos PAC, Bonde M, Qvist P (1997) Characterisation of urinary degradation products derived from type I collagen. J Biol Chem 272:9755–9763

    Article  PubMed  CAS  Google Scholar 

  19. Cloos PAC, Fledelius C (2000) Collagen fragments in urine derived from bone resorption are highly racemized and isomerized. A biological clock of protein ageing with clinical potential. Biochem J 345:473–480

    Article  PubMed  CAS  Google Scholar 

  20. Garnero P, Fledelius C, Gineyts E, Serre CM, Vignot E, Delmas PD (1997) Decreased beta-isomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget’s disease of bone. J Bone Miner Res 12:1407–1415

    Article  PubMed  CAS  Google Scholar 

  21. Garnero P, Gineyts E, Schaffer AV, Seamen J, Delmas PD (1998) Measurement of urinary excretion of nonisomerized and b-isomerized forms of type I collagen breakdown products to monitor the effects of the bisphosphonate zoledronate in Paget’s disease. Arthritis Rheum 41:354–360

    Article  PubMed  CAS  Google Scholar 

  22. Langton AL, Ralston SH (2004) Management of Paget’s disease of bone. Rheumatology 43:955–959

    Article  Google Scholar 

  23. Guañabens N, Alvarez L, Cerdá D, Vidal S, Monegal A, Peris P, Ros I, Ballesta A, Pons F (2003) Similar effects of tiludronate and risedronate on Paget’s disease activity assessed by bone markers. J Bone Miner Res 18(suppl 2):S388–S389

    Google Scholar 

  24. 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

    Article  PubMed  CAS  Google Scholar 

  25. Donáth J, Krasznai M, Fornet B, Gergely P Jr, Poór G (2004) Effect of bisphosphonates treatment in patients with Paget’s disease of the skull. Rheumatology 43:89–94

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported in part by a grant from the Instituto de Salud Carlos III C03/08. We are grateful to Llorenç Quintó for revising the statistical analysis.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Hospital Clinic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain

    P. Peris, A. Monegal, M. Angeles Martínez & N. Guañabens

  2. Department of Clinical Biochemistry, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain

    L. Alvarez

  3. Department of Nuclear Medicine, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain

    S. Vidal & F. Pons

  4. Nordic Bioscience, Osteopark, Herlev Hovedgade 207, DK-2730, Herlev, Denmark

    D. Kasper & D. J. Leeming

Authors
  1. P. Peris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Vidal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. J. Leeming
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Monegal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Angeles Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F. Pons
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. Guañabens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Peris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peris, P., Alvarez, L., Vidal, S. et al. Biochemical Response to Bisphosphonate Therapy in Pagetic Patients with Skull Involvement. Calcif Tissue Int 79, 22–26 (2006). https://doi.org/10.1007/s00223-005-0247-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-005-0247-9

Keywords

Search

Navigation