Skip to main content

Advertisement

Log in

Changes in Osteoprotegerin/RANKL System, Bone Mineral Density, and Bone Biochemicals Markers in Patients with Recent Spinal Cord Injury

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 ± 9.5 years) and 12 able-bodied (AB) men (26.9 ± 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (−4.3%), pelvis (−15.7%) and lower limbs (−15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. F Biering-Sørensen H Bohr O Schaadt (1988) ArticleTitleBone mineral content of the lumbar spine and lower extremities years after spinal cord lesion Paraplegia 26 293–301 Occurrence Handle3205570

    PubMed  Google Scholar 

  2. F Biering-Sørensen H Bohr O Schaadt (1990) ArticleTitleLongitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury Eur J Clin Invest 20 330–335 Occurrence Handle2114994

    PubMed  Google Scholar 

  3. M Dauty B Perrouin-Verbe Y Maugars C Dubois JF Mathie (2000) ArticleTitleSupralesional and sublesional bone mineral density in spinal cord-injured patients Bone 27 305–309 Occurrence Handle10.1016/S8756-3282(00)00326-4 Occurrence Handle10913927

    Article  PubMed  Google Scholar 

  4. DE Garland CA Stewart RH Adkins SS Hu C Rosen FJ Liotta DA Weinstein (1992) ArticleTitleOsteoporosis after spinal cord injury J Orthop Res 10 371–378 Occurrence Handle10.1002/jor.1100100309 Occurrence Handle1569500

    Article  PubMed  Google Scholar 

  5. WD Leslie PW Nance (1993) ArticleTitleDissociated hip and spine demineralization: a specific finding in spinal cord injury Arch Phys Med Rehabil 74 960–964 Occurrence Handle8379843

    PubMed  Google Scholar 

  6. SM Szollar EME Martin JG Parthemore DJ Sartoris LJ Deftos (1997) ArticleTitleDensitometric patterns of spinal cord injury associated bone loss Spinal Cord 35 374–382 Occurrence Handle10.1038/sj.sc.3100394 Occurrence Handle9194260

    Article  PubMed  Google Scholar 

  7. A Chantraine B Nusgens CM Lapiere (1986) ArticleTitleBone remodelling during the development of osteoporosis in paraplegia Calcif Tissue Int 38 323–327 Occurrence Handle3089553

    PubMed  Google Scholar 

  8. P Pietschmann P Pils W Woloszczuk R Maerk D Lessan J Stipicic (1992) ArticleTitleIncreased serum osteocalcin levels in patients with paraplegia Paraplegia 30 204–209 Occurrence Handle1630849

    PubMed  Google Scholar 

  9. D Roberts W Lee RC Cuneo J Wittmann G Ward R Flatman B McWhinney PE Hickman (1998) ArticleTitleLongitudinal study of bone turnover after acute spinal cord injury J Clin Endocrinol Metab 83 415–422 Occurrence Handle10.1210/jc.83.2.415 Occurrence Handle9467550

    Article  PubMed  Google Scholar 

  10. E Wilmet AA Ismail A Heilporn D Welraeds P Bergmann (1995) ArticleTitleLongitudinal study of the bone mineral content and of soft tissue composition after spinal cord section Paraplegia 33 674–677 Occurrence Handle8584304

    PubMed  Google Scholar 

  11. JF Keating M Kerr M Delargy (1992) ArticleTitleMinimal trauma causing fractures in patients with spinal cord injury Disabil Rehabil 14 108–109 Occurrence Handle1600181

    PubMed  Google Scholar 

  12. H Inoue H Tanaka T Moriwake M Oka C Sekiguchi Y Seino (2000) ArticleTitleAltered biochemical markers of bone turnover in humans during 120 days of bed rest Bone 26 281–286 Occurrence Handle10.1016/S8756-3282(99)00282-3 Occurrence Handle10710002

    Article  PubMed  Google Scholar 

  13. SA Lueken SB Arnaud AK Taylor D Baylink (1993) ArticleTitleChanges in markers of bone formation and resorption in a bed rest model of weightlessness J Bone Miner Res 8 1433–1437 Occurrence Handle8304043

    PubMed  Google Scholar 

  14. D Uebelhart B Demiaux-Domenech M Roth A Chantraine (1995) ArticleTitleBone metabolism in spinal cord injured individuals and in others who have prolonged immobilisation. A review Paraplegia 33 669–673 Occurrence Handle8584303

    PubMed  Google Scholar 

  15. WS Simonet DL Lacey CR Dunstan M Kelley MS Chang R Luthy HG Nguyen S Wooden L Bennett T Boone G Shimamota M DeRose R Elliot A Colombero HL Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gregg TM Hughes D Hill W Pattison P Cambell S Sanders G Van J Tarpley P Derby R Lee WJ Boyle InstitutionalAuthorNamefor the Amgem EST program (1997) ArticleTitleOsteoprotegerin: a novel secreted protein involved in the regulation of bone density Cell 89 309–319 Occurrence Handle10.1016/S0092-8674(00)80209-3 Occurrence Handle9108485

    Article  PubMed  Google Scholar 

  16. DL Lacey E Timms HL Tan MJ Kelley CR Dunstan T Burgess R Elliott A Colombero G Elliott S Scully H Hsu J Sullivan N Hawkins E Davy C Capparelli A Eli YX Qian S Kaufman I Sarosi V Shalhoub G Senaldi J Guo J Delaney WJ Boyle (1998) ArticleTitleOsteoprotegerin (OPG) ligand is a cytokine that regulates osteoclast differentiation and activation Cell 93 165–176 Occurrence Handle10.1016/S0092-8674(00)81569-X Occurrence Handle9568710

    Article  PubMed  Google Scholar 

  17. SL Teitelbaum (2000) ArticleTitleBone resorption by osteoclasts Science 289 1504–1508 Occurrence Handle10.1126/science.289.5484.1504 Occurrence Handle10968780

    Article  PubMed  Google Scholar 

  18. N Bucay I Sorosi CR Dunstan S Morony J Tarrley C Capparelli S Scully HL Tan W Xu DL Lacey WJ Boyle WS Simonet (1998) ArticleTitleOsteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification Genes Dev 12 1260–1268 Occurrence Handle9573043

    PubMed  Google Scholar 

  19. S Mochizuki N Fujise K Higashio E Tsuda (2002) ArticleTitleOsteoclastogeneis inhibitory factor/osteprotegerin ameliorates the decrease in both bone mineral density and bone strength in immobilized rats J Bone Miner Metab 20 14–20 Occurrence Handle10.1007/s774-002-8441-x Occurrence Handle11810411

    Article  PubMed  Google Scholar 

  20. TA Bateman CR Dunstan VL Ferguson DL Lacey RA Ayers SJ Simske (2000) ArticleTitleOsteoprotegerin mitigates tail suspension-induced osteopenia Bone 26 443–449 Occurrence Handle10.1016/S8756-3282(00)00256-8 Occurrence Handle10773583

    Article  PubMed  Google Scholar 

  21. L Maïmoun I Couret JP Micallef E Peruchon D Mariano-Goulart M Rossi JL Leroux F Ohanna (2002) ArticleTitleUse of bone biochemical markers with dual-energy X-ray absorptiometriy for early determination of bone loss in persons with spinal cord injury Metabolism 8 958–963

    Google Scholar 

  22. P Bergmann A Heilporn A Schoutens J Paternot Tricot (1977–78) ArticleTitleA longitudinal study of calcium and bone metabolism in paraplegic patients Paraplegia 15 147–159

    Google Scholar 

  23. AF Stewart MD Adler CM Byers GV Segre AE Broadus (1982) ArticleTitleCalcium homeostasis in immobilization: an example of resorptive hypercalciuria N Engl J Med 306 1136–1140 Occurrence Handle6280047

    PubMed  Google Scholar 

  24. D Uebelhart D Hartmann H Vuagnat M Castagnier HJ Hachen A Chantraine (1994) ArticleTitleEarly modifications of biochemical markers of bone metabolism in spinal cord injury patients. A preliminary study Scand J Rehabil Med 26 197–202 Occurrence Handle7878394

    PubMed  Google Scholar 

  25. WA Bauman AM Spungen J Wang RN Pierson E Schwartz (1999) ArticleTitleContinuous loss of bone during chronic immobilization: a monozygotic twin study Osteoporos Int 10 123–127 Occurrence Handle10.1007/s001980050206 Occurrence Handle10501792

    Article  PubMed  Google Scholar 

  26. P Minaire P Meunier C Edouart J Bernard P Courpron J Bourret (1974) ArticleTitleQuantitative histogical data on disuse osteoporosis: comparison with biological data Calcif Tissue Res 17 57–73 Occurrence Handle4451877

    PubMed  Google Scholar 

  27. KJ Obrant B Merle J Bejui PD Delmas (1990) ArticleTitleSerum bone-gla protein after fracture Clin Orthop 258 300–303 Occurrence Handle2394055

    PubMed  Google Scholar 

  28. S Jaovisidha DJ Sartoris EME Martin M Maeseneer ParticleDe SM Szollar LJ Deftos (1997) ArticleTitleInfluence of spondylopathy on bone densitometry using dual energy X-Ray absorptiometry Calcif Tissue Int 60 424–429 Occurrence Handle10.1007/s002239900257 Occurrence Handle9115159

    Article  PubMed  Google Scholar 

  29. P Szulc LC Hofbauer AE Heufelder S Roth PD Delmas (2001) ArticleTitleOsteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status J Clin Endocrinol Metab 86 3162–3165 Occurrence Handle10.1210/jc.86.7.3162 Occurrence Handle11443182

    Article  PubMed  Google Scholar 

  30. PJ Kostenuik V Shalhoud (2001) ArticleTitleOsteoprotegerin: a physiological and pharmacological inhibitor of bone resorption Curr Pharm Des 7 613–635 Occurrence Handle10.2174/1381612013397807 Occurrence Handle11375772

    Article  PubMed  Google Scholar 

  31. WS Browner LY Lui SR Cummings (2001) ArticleTitleAssociations of serum Osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women J Clin Endocrinol Metab 86 631–637 Occurrence Handle10.1210/jc.86.2.631 Occurrence Handle11158021

    Article  PubMed  Google Scholar 

  32. H Yasuda N Shima N Nakagawa S Mochizuki K Yano N Fujise Y Sato M Goto K Yamaguchi M Kuriyama T Kano A Murakami E Tsuda T Morinaga K Higashio (1998) ArticleTitleIdentity of osteoclastogenesis-inhibitonary factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro Endocrinology 139 1329–1337 Occurrence Handle10.1210/en.139.3.1329 Occurrence Handle9492069

    Article  PubMed  Google Scholar 

  33. YL Ma RL Cain DL Halladay X Yang Q Zeng RR Miles S Chandrasekhar TJ Martin JE Onyia (2001) ArticleTitleCatabolic effects of continuous human PTH (1-38) in vivo is associated with sustained stimulation of RANKL and inhibition of Osteoprotegerin and gene-associated bone formation Endocrinology 142 4047–4054 Occurrence Handle10.1210/en.142.9.4047 Occurrence Handle11517184

    Article  PubMed  Google Scholar 

  34. J Rubbin CL Ackert-Bicknell L Zhu X Fan TC Murphy MS Nanes R Marcus L Holloway WG Beamer CJ Rosen (2002) ArticleTitleIGF-1 regulates Osteoprotegerin (OPG) and receptor activator of nucleor-kB ligand in vitro and OPG in vivo J Clin Endocrinol Metab 87 4273–4279 Occurrence Handle10.1210/jc.2002-020656 Occurrence Handle12213884

    Article  PubMed  Google Scholar 

  35. S Khosla EJ Atkinson CR Dunstan WM O’Fallon (2002) ArticleTitleEffect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men J Clin Endocrinol Metab 87 1550–1554 Occurrence Handle10.1210/jc.87.4.1550 Occurrence Handle11932280

    Article  PubMed  Google Scholar 

  36. KR Shetty CH Sutton DA Mattson D Rudman (1993) ArticleTitleHyposomatomedinemia in quadraplegic men Am J Med Sci 305 95–100 Occurrence Handle8427299

    PubMed  Google Scholar 

  37. PD Tsitouras YG Zhong AM Spungen WA Bauman (1995) ArticleTitleSerum testosterone and growth hormone/insulin-like growth factor-I in adults with spinal cord injury Horm Metab Res 27 287–292 Occurrence Handle7557841

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Maïmoun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maïmoun, L., Couret, I., Mariano-Goulart, D. et al. Changes in Osteoprotegerin/RANKL System, Bone Mineral Density, and Bone Biochemicals Markers in Patients with Recent Spinal Cord Injury. Calcif Tissue Int 76, 404–411 (2005). https://doi.org/10.1007/s00223-004-0048-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-004-0048-6

Keywords

Navigation