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Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

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An Erratum to this article was published on 31 October 2016

Abstract

Summary

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention.

Introduction

The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period.

Methods

This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups.

Results

Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged.

Conclusions

This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

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References

  1. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J 281:21–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wallimann T, Tokarska-Schlattner U (2011) The creatine kinase system and pleiotropic effects of creatine. Amino Acids 40:1271–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sakai D, Tong HS, Minkin C (1995) Osteoclast molecular phenotyping by random cDNA sequencing. Bone 17:111–119

    Article  CAS  PubMed  Google Scholar 

  4. Chen J, Sun Y, Mao X, Liu Q, Wu H, Chen Y (2010) RANKL up-regulates brain-type creatine kinase via poly (ADP-ribose) polymerase-1 during osteoclastogenesis. J Biol Chem 285:36315–36321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chang EJ, Ha J, Oerlemans F, Lee YL, Lee SW, Ryu J, Hj K, et al. (2008) Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption. Nat Med 14:966–972

    Article  CAS  PubMed  Google Scholar 

  6. Yoneyama T, Fowler HL, Pendleton JW, et al. (1989) Elevated levels of creatine kinase BB isoenzyme in three patients with adult osteopetrosis. N Engl J Med 320:1284–1285

    CAS  PubMed  Google Scholar 

  7. Gram J, Antonsen S, Hørder M, et al. (1991) Elevated serum level of creatine kinase BB in autosomal dominant osteopetrosis type II. Calcif Tissue Int 48:438–439

    Article  CAS  PubMed  Google Scholar 

  8. Yoneyama T, Fowler HL, Pendleton JW, et al. (1992) Elevated serum levels of creatine kinase bb in autosomal dominant osteopetrosis type II—a family study. Clin Genet 42:39–42

    Article  CAS  PubMed  Google Scholar 

  9. Whyte MP, Chines A, Silva DP Jr, et al. (1996) Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetrosis among the sclerosing bone disorder. J Bone Miner Res 11:1438–1443

    Article  CAS  PubMed  Google Scholar 

  10. Waguespack SG, Hui SL, White KE, et al. (2002) Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers. J Clin Endocrinol Metab 87(5):2212–2217

    Article  CAS  PubMed  Google Scholar 

  11. Whyte MP, Wenkert D, Clements KL, et al. (2003) Bisphosphonate-induced osteopetrosis. N Engl J Med 349:457–463

    Article  CAS  PubMed  Google Scholar 

  12. Whyte MP, McAlister WH, Novack DV, et al. (2008) Bisphosphonate-induced osteopetrosis: novel bone modelling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases. J Bone Miner Res 23:1698–1707

    Article  PubMed  Google Scholar 

  13. Glorieux FH (2001) A disease of osteoblast. Lancet 358:S45

    Article  PubMed  Google Scholar 

  14. Sillence DO (1981) Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop 159:11–25

    Google Scholar 

  15. Valadares ER, Carneiro TB, Santos PM, et al. (2014) What is new in genetics and osteogenesis imperfecta classification? J Pediatr 90:536–541

    Article  Google Scholar 

  16. Rauch F, Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363:1377–1385

    Article  CAS  PubMed  Google Scholar 

  17. Glorieux FH (2001) The use of bisphosphonates in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 2001 14(Suppl 6):1491–1495

    Google Scholar 

  18. Gatti D, Antoniazzi F, Prizzi R, et al. (2005) Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 20:758–763

    Article  CAS  PubMed  Google Scholar 

  19. Maruotti N, Corrado A, Neve A, Cantatore FP (2012) Bisphosphonates effects on osteoblast. Eur J Clin Pharmacol 68:1013–1018

    Article  CAS  PubMed  Google Scholar 

  20. D’Eufemia P, Finocchiaro R, Villani C, Zambrano A, Lodato V, Palombaro M, Properzi E, Celli M (2014) Serum brain-type creatine kinase increases in children with osteogenesis imperfecta during neridronate treatment. Pediatr Res 75:626–630

    Article  PubMed  Google Scholar 

  21. Tanaka M, Mori H, Kayasuga R, Kawabata K (2015) Induction of creatine kinase release from cultured osteoclasts via the pharmacological action aminobisphosphonates 3:4–59.

  22. Schumann G, Bonora R, Ceriotti F, Clerc-Renaud P, Ferrero CA, Férard G, Franck PF, Gella FJ, et al. (2002) IFCC primary reference procedures for the measurements of catalytic activity concentration of enzymes at 37°C. Part 2: references procedures for the measurements of catalytic concentration of creatine kinase. Clin Chem Lab Med 40:635–642

    CAS  PubMed  Google Scholar 

  23. Trainer TD, Gruenig D (1968) A rapid method for the analysis of creatine phosphokinase isoenzymes. Clin Chim Acta 21:151–154

    Article  CAS  PubMed  Google Scholar 

  24. Zemel BS, Kalkwarf HJ, Gilsanz V, et al. (2011) Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab 96:3160–3169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Russell RG, Watts NB, Ebetino FH, et al. (2008) Mechanism of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 19:733–759

    Article  CAS  PubMed  Google Scholar 

  26. Matsumoto T, Nagase Y, Iwasawa M, Yasui T, Masuda H, Kadono Y, Nakamuratetsuro Y, et al. (2011) Distinguishing the proapoptotic and antiresorptive function of riseidronate in murine osteoclast. Arthritis & Rheumatism 63:3908–3917

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, “Sapienza”, University of Rome, Rome, Italy

    P. D’Eufemia, R. Finocchiaro, A. Zambrano, V. Lodato, L. Celli, S. Finocchiaro, A. Turchetti & M. Celli

  2. Department of Anatomic Histologic Forensic and Locomotor Apparatus Sciences, “Sapienza” University of Rome, Rome, Italy

    P. Persiani

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  1. P. D’Eufemia
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  2. R. Finocchiaro
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  3. A. Zambrano
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  4. V. Lodato
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  5. L. Celli
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  6. S. Finocchiaro
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  8. A. Turchetti
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  9. M. Celli
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Correspondence to P. D’Eufemia.

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Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00198-016-3815-0.

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D’Eufemia, P., Finocchiaro, R., Zambrano, A. et al. Serum creatine kinase isoenzymes in children with osteogenesis imperfecta. Osteoporos Int 28, 339–346 (2017). https://doi.org/10.1007/s00198-016-3729-x

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  • DOI: https://doi.org/10.1007/s00198-016-3729-x

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