Advertisement

Journal of Bone and Mineral Metabolism

, Volume 26, Issue 6, pp 635–641 | Cite as

Scintigraphic, biochemical, and clinical response to zoledronic acid treatment in patients with Paget’s disease of bone

  • Avraam Avramidis
  • Stergios A. Polyzos
  • Efstratios Moralidis
  • Georgios Arsos
  • Zoe Efstathiadou
  • Konstantinos Karakatsanis
  • Georgios Grollios
  • Marina Kita
Original Article

Abstract

Bisphosphonates have long been used with success in the treatment of Paget’s disease of bone (PDB). The aim of this study was to evaluate the early (up to 3 months) and late (at 12 months) scintigraphic, biochemical, and clinical response to a single intravenous infusion of zoledronic acid (ZOL) in patients with PDB serially assessed for 1 year. Nine patients with 30 bone lesions caused by PDB were prospectively evaluated. Total serum alkaline phosphatase (SAP) was serially measured. Scintigraphy was performed before and at 3 and 12 months after ZOL administration, and bone lesions were assessed quantitatively. After treatment, pain was alleviated in five of six patients starting from the first month. At 3 months, a significant decrease of SAP levels compared to baseline values was found (322 ± 211 IU/l before vs. 101 ± 36 IU/l 3 months after; P < 0.05), with normal values attained in all except one patient. The scintigraphic index of involvement (SII), a marker for the perpatient activity of the disease, was reduced from 14.4 ± 7.6 to 7.2 ± 1.8 (P = 0.01). The scintigraphic ratio (SR), a marker for the per-lesion activity of the disease, was reduced from 12.8 ± 7.7 to 7.0 ± 2.9 (P < 0.001). The values of markers of disease activity remained unchanged up to 12 months. A single intravenous administration of ZOL leads to a favorable clinical, biochemical, and scintigraphic response in patients with PDB starting as early as 3 months after treatment and lasting no less than 12 months (i.e., considerably longer than the other existing therapies).

Key words

alkaline phosphatase bisphosphonate Paget’s disease scintigraphy zoledronic acid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Selby PL, Davie MW, Ralston SH, Stone MD (2002) Guidelines on the management of Paget’s disease of bone. Bone (NY) 31:366–373Google Scholar
  2. 2.
    Takata S, Hashimoto J, Nakatsuka K, Yoshimura N, Yoh K, Ohno I, Yabe H, Abe S, Fukunaga M, Terada M, Zamma M, Ralston SH, Morii H, Yoshikawa H (2006) Guidelines for diagnosis and management of Paget’s disease of bone in Japan. J Bone Miner Metab 24:359–367PubMedCrossRefGoogle Scholar
  3. 3.
    Cooper C, Harvey NC, Dennison EM, van Staa TP (2006) Update on the epidemiology of Paget’s disease of bone. J Bone Miner Res 21(suppl 2):3–8CrossRefGoogle Scholar
  4. 4.
    Gennari L, Merlotti D, Martini G, Nuti R (2006) Paget’s disease of bone in Italy. J Bone Miner Res 21(suppl 2):14–21CrossRefGoogle Scholar
  5. 5.
    Selby PL (2006) Guidelines for the diagnosis and management of Paget’s disease: a UK perspective. J Bone Miner Res 21(suppl 2):92–93CrossRefGoogle Scholar
  6. 6.
    Hosking D, Lyles K, Brown JP, Fraser WD, Miller P, Curiel MD, Devogelaer JP, Hooper M, Su G, Zelenakas K, Pak J, Fashola T, Saidi Y, Eriksen EF, Reid IR (2007) Long-term control of bone turnover in Paget’s disease with zoledronic acid and risedronate. J Bone Miner Res 22:142–148PubMedCrossRefGoogle Scholar
  7. 7.
    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: 898–908PubMedCrossRefGoogle Scholar
  8. 8.
    Reid IR (2006) Zoledronate: efficacy and safety. J Bone Miner Res 21(suppl 2):83–87CrossRefGoogle Scholar
  9. 9.
    Siris ES, Lyles KW, Singer FR, Meunier PJ (2006) Medical management of Paget’s disease of bone: indications for treatment and review of current therapies. J Bone Miner Res 21(suppl 2):94–98CrossRefGoogle Scholar
  10. 10.
    Keating GM, Scott LJ (2007) Zoledronic acid: a review of its use in the treatment of Paget’s disease of bone. Drugs 67:793–804PubMedCrossRefGoogle Scholar
  11. 11.
    Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH (2006) Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone (NY) 38:617–627Google Scholar
  12. 12.
    Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) 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 296:235–242PubMedGoogle Scholar
  13. 13.
    Shapiro J, Smith B, Beck T, Ballard P, Dapthary M, BrintzenhofeSzoc K, Caminis J (2007) Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury. Calcif Tissue Int 80:316–322PubMedCrossRefGoogle Scholar
  14. 14.
    Tziomalos K, Florentin M, Krikis N, Perifanis V, Karagiannis A, Harsoulis F (2007) Persistent effect of zoledronic acid in Paget’s disease. Clin Exp Rheumatol 25:464–466PubMedGoogle Scholar
  15. 15.
    Carrasquillo JA, Whatley M, Dyer V, Figg WD, Dahut W (2001) Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning. J Nucl Med 42:1359–1363PubMedGoogle Scholar
  16. 16.
    Patel U, Gallacher SJ, Boyle IT, McKillop JH (1990) Serial bone scans in Paget’s disease: development of new lesions, natural variation in lesion intensity and nature of changes seen after treatment. Nucl Med Commun 11:747–760PubMedCrossRefGoogle Scholar
  17. 17.
    Vellenga CJ, Pauwels EK, Bijvoet OL, Harinck HI, Frijlink WB (1985) Quantitative bone scintigraphy in Paget’s disease treated with APD. Br J Radiol 58:1165–1172PubMedGoogle Scholar
  18. 18.
    Pons F, Alvarez L, Peris P, Guanabens N, Vidal-Sicart S, Monegal A, Pavia J, Ballesta AM, Munos-Gomez J, Herranz R (1999) Quantitative evaluation of bone scintigraphy in the assessment of Paget’s disease activity. Nucl Med Commun 20:525–528PubMedCrossRefGoogle Scholar
  19. 19.
    Lavender JP, Evans IM, Arnot R, Bowring S, Doyle FH, Joplin GF, MacIntyre I (1977) A comparison of radiography and radioisotope scanning in the detection of Paget’s disease and in the assessment of response to human calcitonin. Br J Radiol 50: 243–250PubMedGoogle Scholar
  20. 20.
    Waxman AD, Ducker S, McKee D, Siemsen JK, Singer FR (1977) Evaluation of 99mTc diphosphonate kinetics and bone scans in patients with Paget’s disease before and after calcitonin treatment. Radiology 125:761–764PubMedGoogle Scholar
  21. 21.
    Lentle BC, Russell AS, Heslip PG, Percy JS (1976) The scintigraphic findings in Paget’s disease of bone. Clin Radiol 27: 129–135PubMedCrossRefGoogle Scholar
  22. 22.
    Rashid M, Khairi A, Johnston C Jr (1977) Treatment of Paget’s disease of bone (osteitis deformans) with sodium etidronate (EHDP). Clin Orthop Relat Res 127:94–105PubMedGoogle Scholar
  23. 23.
    Ang G, Feiglin D, Moses AM (2003) Symptomatic and scintigraphic improvement after intravenous pamidronate treatment of Paget’s disease of bone in patients with normal serum alkaline phosphatase levels. Endocr Pract 9:280–283PubMedGoogle Scholar
  24. 24.
    Ryan PJ, Gibson T, Fogelman I (1992) Bone scintigraphy following intravenous pamidronate for Paget’s disease of bone. J Nucl Med 33:1589–1593PubMedGoogle Scholar
  25. 25.
    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 (NY) 35:224–230Google Scholar
  26. 26.
    Fogelman I, Carr D, Boyle IT (1981) The role of bone scanning in Paget’s disease. Metab Bone Dis Relat Res 3:243–254PubMedCrossRefGoogle Scholar
  27. 27.
    Vellenga CJ, Bijvoet OL, Pauwels EK (1988) Bone scintigraphy and radiology in Paget’s disease of bone: a review. Am J Physiol Imaging 3:154–168PubMedGoogle Scholar
  28. 28.
    Avramides A, Flores A, DeRose J, Wallach S (1976) Paget’s disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment. J Clin Endocrinol Metab 42:459–463PubMedCrossRefGoogle Scholar
  29. 29.
    Papapoulos SE, Eekhoff EM, Zwinderman AH (2006) Acquired resistance to bisphosphonates in Paget’s disease of bone. J Bone Miner Res 21(suppl 2):88–91CrossRefGoogle Scholar
  30. 30.
    Merlotti D, Gennari L, Martini G, Valleggi F, De PV, Avanzati A, Nuti R (2007) Comparison of different intravenous bisphosphonate regimens for Paget’s disease of bone. J Bone Miner Res 22:1510–1517PubMedCrossRefGoogle Scholar
  31. 31.
    Cremers SC, Eekhoff ME, Den HJ, Hamdy NA, Vermeij P, Papapoulos SE (2003) Relationships between pharmacokinetics and rate of bone turnover after intravenous bisphosphonate (olpadronate) in patients with Paget’s disease of bone. J Bone Miner Res 18:868–875PubMedCrossRefGoogle Scholar
  32. 32.
    Stone MD, Marshall DH, Hosking DJ, Perkins AC, Evans AJ, Wastie ML (1992) Bisphosphonate space measurement in Paget’s disease of bone treated with APD. J Bone Miner Res 7:295–301PubMedCrossRefGoogle Scholar
  33. 33.
    Fleisch H (1998) Bisphosphonates: mechanisms of action. Endocr Rev 19:80–100PubMedCrossRefGoogle Scholar
  34. 34.
    Kavanagh KL, Guo K, Dunford JE, Wu X, Knapp S, Ebetino FH, Rogers MJ, Russell RG, Oppermann U (2006) The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A 103:7829–7834PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Avraam Avramidis
    • 1
  • Stergios A. Polyzos
    • 1
  • Efstratios Moralidis
    • 2
  • Georgios Arsos
    • 2
  • Zoe Efstathiadou
    • 1
  • Konstantinos Karakatsanis
    • 2
  • Georgios Grollios
    • 3
  • Marina Kita
    • 1
  1. 1.Department of EndocrinologyHippokratio General HospitalThessalonikiGreece
  2. 2.Department of Nuclear MedicineAristotle University, Hippokratio General HospitalThessalonikiGreece
  3. 3.Department of RadiologyHippokratio General HospitalThessalonikiGreece

Personalised recommendations