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The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality

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Abstract

Summary

Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.

Introduction

The aim of the present study was to evaluate the effect of oral calcitonin on bone collagen maturation measured as the ratio between the degradation products of newly synthesized C-telopeptides of type I collagen (ααCTX) and mature isomerized ββCTX in postmenopausal women.

Methods

Participants were from a phase II study. A total of 168 postmenopausal women were included and treated with placebo, 0.15, 0.4, 1, or 2.5 mg calcitonin daily. The non-isomerized ααCTX and isomerized ββCTX were measured in 24-hour urine samples obtained at baseline, and after 1 day, 1 month and 3 months of therapy.

Results

Calcitonin, significantly and dose-dependently inhibited bone resorption by up to 50% as measured by ααCTX and isomerized ββCTX. Bone collagen maturation measured as the ratio between ααCTX and ββCTX remained unchanged during treatment with calcitonin.

Conclusions

Calcitonin dose-dependently and significantly reduced both ααCTX to ββCTX levels in urine without affecting the ααCTX to ββCTX ratio. This is in direct contrast to other anti-resorptive therapies, in which strong treatment-dependent effect on the endogenous age profile of bone has been observed. These data highlight that even though the treatments may have comparable effects on BMD, endogenous bone composition, which may be associated to bone quality, is strongly affected by the type of intervention, in which calcitonin display highly divergent effects from that of other anti-resorptives.

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References

  1. Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K (2007) Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res 22:487–494

    Article  PubMed  CAS  Google Scholar 

  2. Takahashi H, Epker B, Frost HM (1964) Resorption precedes formative activity. Surg Forum 15:437–438

    PubMed  CAS  Google Scholar 

  3. Hattner R, Epker BN, Frost HM (1965) Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature 206:489–490

    Article  PubMed  CAS  Google Scholar 

  4. Parfitt AM (1982) The coupling of bone formation to bone resorption: a critical analysis of the concept and of its relevance to the pathogenesis of osteoporosis. Metab Bone Dis Relat Res 4:1–6

    Article  PubMed  CAS  Google Scholar 

  5. Rodan GA (1991) Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption. J Bone Miner Res 6:527–530

    PubMed  CAS  Google Scholar 

  6. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536

    Article  PubMed  CAS  Google Scholar 

  7. Ravn P, Hosking D, Thompson D, Cizza G, Wasnich RD, McClung M, Yates AJ, Bjarnason NH, Christiansen C (1999) Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study. J Clin Endocrinol Metab 84:2363–2368

    Article  PubMed  CAS  Google Scholar 

  8. Ravn P, Clemmesen B, Christiansen C (1999) Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group. Bone 24:237–244

    Article  PubMed  CAS  Google Scholar 

  9. Ravn P, Thompson DE, Ross PD, Christiansen C (2003) Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis. Bone 33:150–158

    Article  PubMed  CAS  Google Scholar 

  10. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301

    Article  PubMed  CAS  Google Scholar 

  11. Cloos PA, Lyubimova N, Solberg H, Qvist P, Christiansen C, Byrjalsen I, Christgau S (2004) An immunoassay for measuring fragments of newly synthesized collagen type I produced during metastatic invasion of bone. Clin Lab 50:279–289

    PubMed  CAS  Google Scholar 

  12. Fledelius C, Johnsen AH, Cloos PA, Bonde M, Qvist P (1997) Characterization of urinary degradation products derived from type I collagen. Identification of a beta-isomerized Asp-Gly sequence within the C-terminal telopeptide (alpha1) region. J Biol Chem 272:9755–9763

    Article  PubMed  CAS  Google Scholar 

  13. Schaller S, Henriksen K, Hoegh-Andersen P, Sondergaard BC, Sumer EU, Tanko LB, Qvist P, Karsdal MA (2005) In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist? Assay Drug Dev Technol 3:553–580

    Article  PubMed  CAS  Google Scholar 

  14. Ravn P, Hosking D, Thompson D, Cizza G, Wasnich RD, McClung M, Yates AJ, Bjarnason NH, Christiansen C (1999) Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study. J Clin Endocrinol Metab 84:2363–2368

    Article  PubMed  CAS  Google Scholar 

  15. Ravn P, Clemmesen B, Christiansen C (1999) Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group. Bone 24:237–244

    Article  PubMed  CAS  Google Scholar 

  16. Greenspan SL, Parker RA, Ferguson L, Rosen HN, Maitland-Ramsey L, Karpf DB (1998) Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: a randomized clinical trial. J Bone Miner Res 13:1431–1438

    Article  PubMed  CAS  Google Scholar 

  17. Grados F, Brazier M, Kamel S, Mathieu M, Hurtebize N, Maamer M, Garabedian M, Sebert JL, Fardellone P (2003) Prediction of bone mass density variation by bone remodeling markers in postmenopausal women with vitamin D insufficiency treated with calcium and vitamin D supplementation. J Clin Endocrinol Metab 88:5175–5179

    Article  PubMed  CAS  Google Scholar 

  18. Schaller S, Henriksen K, Sveigaard C, Heegaard AM, Helix N, Stahlhut M, Ovejero MC, Johansen JV, Solberg H, Andersen TL et al (2004) The chloride channel inhibitor n53736 prevents bone resorption in ovariectomized rats without changing bone formation. J Bone Miner Res 19:1144–1153

    Article  PubMed  CAS  Google Scholar 

  19. Cloos PA, Fledelius C (2000) Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: a biological clock of protein aging with clinical potential. Biochem J 345(Pt 3):473–480

    Article  PubMed  CAS  Google Scholar 

  20. Alexandersen P, Peris P, Guanabens N, Byrjalsen I, Alvarez L, Solberg H, Cloos PA (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 

  21. Leeming DJ, Koizumi M, Byrjalsen I, Li B, Qvist P, Tanko LB (2006) The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients. Cancer Epidemiol.Biomarkers Prev 15:32–38

    Article  PubMed  CAS  Google Scholar 

  22. Viguet-Carrin S, Roux JP, Arlot ME, Merabet Z, Leeming DJ, Byrjalsen I, Delmas PD, Bouxsein ML (2006) Contribution of the advanced glycation end product pentosidine and of maturation of type I collagen to compressive biomechanical properties of human lumbar vertebrae. Bone 39:1073–1079

    Article  PubMed  CAS  Google Scholar 

  23. Byrjalsen I, Leeming DJ, Qvist P, Christiansen C, Karsdal MA (2007) Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies. Osteoporos Int

  24. Tanko LB, Bagger YZ, Alexandersen P, Devogelaer JP, Reginster JY, Chick R, Olson M, Benmammar H, Mindeholm L, Azria M et al (2004) Safety and efficacy of a novel salmon calcitonin (sCT) technology-based oral formulation in healthy postmenopausal women: acute and 3-month effects on biomarkers of bone turnover. J Bone Miner Res 19:1531–1538

    Article  PubMed  CAS  Google Scholar 

  25. Leeming DJ, Delling G, Koizumi M, Henriksen K, Karsdal MA, Li B, Qvist P, Tanko LB, Byrjalsen I (2006) Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion. Cancer Epidemiol Biomarkers Prev 15:1392–1395

    Article  PubMed  CAS  Google Scholar 

  26. Mori S, Harruff R, Ambrosius W, Burr DB (1997) Trabecular bone volume and microdamage accumulation in the femoral heads of women with and without femoral neck fractures. Bone 21:521–526

    Article  PubMed  CAS  Google Scholar 

  27. Stepan JJ, Burr DB, Pavo I, Sipos A, Michalska D, Li J, Fahrleitner-Pammer A, Petto H, Westmore M, Michalsky D et al (2007) Low bone mineral density is associated with bone microdamage accumulation in postmenopausal women with osteoporosis. Bone 41:378–385

    Article  PubMed  Google Scholar 

  28. Diab T, Vashishth D (2007) Morphology, localization and accumulation of in vivo microdamage in human cortical bone. Bone 40:612–618

    Article  PubMed  Google Scholar 

  29. Rogers MJ (2003) New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des 9:2643–2658

    Article  PubMed  CAS  Google Scholar 

  30. Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Berger ML, Santora AC, Sherwood LM (2001) Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 286:2815–2822

    Article  PubMed  CAS  Google Scholar 

  31. Miller PD, Siris ES, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Chen YT, Berger ML, Santora AC, Sherwood LM (2002) Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the National Osteoporosis Risk Assessment. J Bone Miner Res 17:2222–2230

    Article  PubMed  Google Scholar 

  32. Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34:195–202

    Article  PubMed  CAS  Google Scholar 

  33. Hui SL, Slemenda CW, Johnston CC Jr (1988) Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 81:1804–1809

    Article  PubMed  CAS  Google Scholar 

  34. Faulkner KG (2000) Bone matters: are density increases necessary to reduce fracture risk? J Bone Miner Res 15:183–187

    Article  PubMed  CAS  Google Scholar 

  35. Esser RE, Angelo RA, Murphey MD, Watts LM, Thornburg LP, Palmer JT, Talhouk JW, Smith RE (1994) Cysteine proteinase inhibitors decrease articular cartilage and bone destruction in chronic inflammatory arthritis. Arthritis Rheum 37:236–247

    Article  PubMed  CAS  Google Scholar 

  36. Sarkar S, Reginster JY, Crans GG, Diez-Perez A, Pinette KV, Delmas PD (2004) Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res 19:394–401

    Article  PubMed  Google Scholar 

  37. Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289

    Article  PubMed  CAS  Google Scholar 

  38. Garnero P, Cloos P, Sornay-Rendu E, Qvist P, Delmas PD (2002) Type I collagen racemization and isomerization and the risk of fracture in postmenopausal women: the OFELY prospective study. J Bone Miner Res 17:826–833

    Article  PubMed  CAS  Google Scholar 

  39. Seeman E, Delmas PD (2006) Bone quality-the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261

    Article  PubMed  CAS  Google Scholar 

  40. Civitelli R, Gonnelli S, Zacchei F, Bigazzi S, Vattimo A, Avioli LV, Gennari C (1988) Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment. J Clin Invest 82:1268–1274

    Article  PubMed  CAS  Google Scholar 

  41. Chambers TJ, Moore A (1983) The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab 57:819–824

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

MA Karsdal, I Byrjalsen, DJ Leeming and Christiansen C are full-time employees of Nordic Bioscience involved in the development of biochemical markers for bone and cartilage diseases. Nordic Bioscience is involved in the development of oral calcitonin.

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Authors and Affiliations

  1. Nordic Bioscience A/S, Herlev Hovedgade 207, Herlev, 2730, Denmark

    M. A. Karsdal, I. Byrjalsen, D. J. Leeming & C. Christiansen

  2. INSERM Research Unit 403 and Claude Bernard University, Lyon, France

    P. D. Delmas

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  1. M. A. Karsdal
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  2. I. Byrjalsen
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  3. D. J. Leeming
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  4. P. D. Delmas
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  5. C. Christiansen
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Correspondence to M. A. Karsdal.

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Karsdal, M.A., Byrjalsen, I., Leeming, D.J. et al. The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality. Osteoporos Int 19, 1355–1361 (2008). https://doi.org/10.1007/s00198-008-0603-5

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  • DOI: https://doi.org/10.1007/s00198-008-0603-5

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