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High fracture risk patients with glucocorticoid-induced osteoporosis should get an anabolic treatment first

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Abstract

Long-term glucocorticoid (GC) therapy induces glucocorticoid-induced osteoporosis (GIOP) and its associated fractures. Most specialty organizations recommend bisphosphonates as first-line therapies based only on bone mineral density efficacy data. Effective treatment of GIOP based on head-to-head trials with fracture endpoint has not yet been established. The pathophysiologic mechanisms of GIOP that lead to the detrimental effects on bone are not yet fully elucidated. Although GCs in an early and transitory period promote osteoclastic activity, in the current paper, we outline why GIOP is in fact a disease of the bone formation and then provide the rationale for the use of bone-forming agents as first-line therapy for patients with high fracture risk in GIOP.

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References

  1. Van Staa TP, Leufkens HG, Abenhaim L et al (2000) Use of oral corticosteroids in the United Kingdom. QJM Mon J Assoc Physicians 93:105–111

    Article  Google Scholar 

  2. Fardet L, Petersen I, Nazareth I (2015) Monitoring of patients on long-term glucocorticoid therapy: a population-based cohort study. Medicine (Baltimore) 94:e647. https://doi.org/10.1097/MD.0000000000000647

    Article  CAS  Google Scholar 

  3. Van Staa TP, Leufkens HGM, Abenhaim L et al (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000. https://doi.org/10.1359/jbmr.2000.15.6.993

    Article  PubMed  Google Scholar 

  4. Balasubramanian WSW, Adler RA et al (2016) Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis. Osteoporos Int 27:3239–3249. https://doi.org/10.1007/s00198-016-3646-z

    Article  PubMed  CAS  Google Scholar 

  5. Overman RA, Yeh J-Y, Deal CL (2013) Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res 65:294–298. https://doi.org/10.1002/acr.21796

    Article  Google Scholar 

  6. Seibel MJ, Cooper MS, Zhou H (2013) Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. Lancet Diabetes Endocrinol 1:59–70. https://doi.org/10.1016/S2213-8587(13)70045-7

    Article  PubMed  CAS  Google Scholar 

  7. Van Staa TP, Laan RF, Barton IP et al (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229. https://doi.org/10.1002/art.11283

    Article  PubMed  CAS  Google Scholar 

  8. Amiche MA, Albaum JM, Tadrous M, Pechlivanoglou P, Lévesque LE, Adachi JD, Cadarette SM (2016) Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials. Osteoporos Int 27:1709–1718. https://doi.org/10.1007/s00198-015-3455-9

    Article  PubMed  CAS  Google Scholar 

  9. O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841. https://doi.org/10.1210/en.2003-0990

    Article  PubMed  CAS  Google Scholar 

  10. Guañabens N, Gifre L, Peris P (2014) The role of Wnt signaling and sclerostin in the pathogenesis of glucocorticoid-induced osteoporosis. Curr Osteoporos Rep 12:90–97. https://doi.org/10.1007/s11914-014-0197-0

    Article  PubMed  Google Scholar 

  11. Sato AY, Cregor M, Delgado-Calle J, Condon KW, Allen MR, Peacock M, Plotkin LI, Bellido T (2016) Protection from glucocorticoid-induced osteoporosis by anti-catabolic signaling in the absence of sost/sclerostin. J Bone Miner Res 31:1791–1802. https://doi.org/10.1002/jbmr.2869

    Article  PubMed  CAS  Google Scholar 

  12. Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P (2007) A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 29:1548–1558. https://doi.org/10.1016/j.clinthera.2007.08.008

    Article  PubMed  CAS  Google Scholar 

  13. Adami G, Saag KG (2019) Glucocorticoid-induced osteoporosis: 2019 concise clinical review. Osteoporos Int 30:1145–1156. https://doi.org/10.1007/s00198-019-04906-x

    Article  PubMed  CAS  Google Scholar 

  14. Lane NE, Yao W (2011) New insights into the biology of glucocorticoid-induced osteoporosis. IBMS BoneKEy 8:229–236. https://doi.org/10.1138/20110511

    Article  Google Scholar 

  15. Ton FN, Gunawardene SC, Lee H, Neer RM (2004) Effects of low-dose prednisone on bone metabolism. J Bone Miner Res 20:464–470. https://doi.org/10.1359/JBMR.041125

    Article  PubMed  CAS  Google Scholar 

  16. Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 17:144–149. https://doi.org/10.1016/j.tem.2006.03.009

    Article  PubMed  CAS  Google Scholar 

  17. Lespessailles E (2013) Bisphosphonates and glucocorticoid-induced osteoporosis: efficacy and tolerability. Jt Bone Spine Rev Rhum 80:258–264. https://doi.org/10.1016/j.jbspin.2012.08.005

    Article  CAS  Google Scholar 

  18. Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, Humphrey MB, Lane NE, Magrey M, Miller M, Morrison L, Rao M, Robinson AB, Saha S, Wolver S, Bannuru RR, Vaysbrot E, Osani M, Turgunbaev M, Miller AS, McAlindon T (2017) 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis: ACR guideline for glucocorticoid-induced osteoporosis prevention and treatment. Arthritis Rheumatol 69:1521–1537. https://doi.org/10.1002/art.40137

  19. Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, Giannini S, Giusti A, Malavolta N, Minisola S, Osella G, Pedrazzoni M, Sinigaglia L, Viapiana O, Isaia GC (2016) Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo 68:1–39. https://doi.org/10.4081/reumatismo.2016.870

    Article  PubMed  CAS  Google Scholar 

  20. Lekamwasam S, Agnusdei D, Bilezikian J et al (2012) A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 23:2257–2276. https://doi.org/10.1007/s00198-012-1958-1

  21. Briot K, Cortet B, Roux C, Fardet L, Abitbol V, Bacchetta J, Buchon D, Debiais F, Guggenbuhl P, Laroche M, Legrand E, Lespessailles E, Marcelli C, Weryha G, Thomas T, Bone Section of the French Society for Rheumatology (SFR) and Osteoporosis Research and Information Group (GRIO) (2014) 2014 update of recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis. Jt Bone Spine Rev Rhum 81:493–501. https://doi.org/10.1016/j.jbspin.2014.10.001

  22. Reid DM, Devogelaer J-P, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, Mesenbrink P, Sambrook PN (2009) Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. The Lancet 373:1253–1263. https://doi.org/10.1016/S0140-6736(09)60250-6

    Article  CAS  Google Scholar 

  23. Saag KG, Pannacciulli N, Geusens P, Adachi JD, Messina OD, Morales-Torres J, Emkey R, Butler PW, Yin X, Lems WF (2019) Denosumab versus risedronate in glucocorticoid-induced osteoporosis: final results of a twenty-four–month randomized, double-blind, double-dummy trial. Arthritis Rheumatol 71:1174–1184. https://doi.org/10.1002/art.40874

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Saag KG, Zanchetta JR, Devogelaer J-P, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial: Teriparatide Versus Alendronate in Glucocorticoid-Induced OP. Arthritis Rheum 60:3346–3355. https://doi.org/10.1002/art.24879

    Article  PubMed  CAS  Google Scholar 

  25. Dempster DW, Roschger P, Misof BM, Zhou H, Paschalis EP, Alam J, Ruff VA, Klaushofer K, Taylor KA (2016) Differential effects of teriparatide and zoledronic acid on bone mineralization density distribution at 6 and 24 months in the SHOTZ study: mineralization density with TPTD vs ZOL. J Bone Miner Res 31:1527–1535. https://doi.org/10.1002/jbmr.2825

    Article  PubMed  CAS  Google Scholar 

  26. Ferrari S (2009) Remodelage osseux : nouvelles approches thérapeutiques. Rev Méd Suisse 5:1325–1328

    PubMed  CAS  Google Scholar 

  27. Glüer C-C, Marin F, Ringe JD, Hawkins F, Möricke R, Papaioannu N, Farahmand P, Minisola S, Martínez G, Nolla JM, Niedhart C, Guañabens N, Nuti R, Martín-Mola E, Thomasius F, Kapetanos G, Peña J, Graeff C, Petto H, Sanz B, Reisinger A, Zysset PK (2013) Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial: Teriparatide and Risedronate in Gio in men in the EuroGIOPs trial. J Bone Miner Res 28:1355–1368. https://doi.org/10.1002/jbmr.1870

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Takahata M, Maher JR, Juneja SC, Inzana J, Xing L, Schwarz EM, Berger AJ, Awad HA (2012) Mechanisms of bone fragility in a mouse model of glucocorticoid-treated rheumatoid arthritis: implications for insufficiency fracture risk. Arthritis Rheum 64:3649–3659. https://doi.org/10.1002/art.34639

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mellibovsky L, Prieto-Alhambra D, Mellibovsky F, Güerri-Fernández R, Nogués X, Randall C, Hansma PK, Díez-Perez A (2015) Bone tissue properties measurement by reference point indentation in glucocorticoid-induced osteoporosis. J Bone Miner Res 30:1651–1656. https://doi.org/10.1002/jbmr.2497

    Article  CAS  Google Scholar 

  30. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439–446. https://doi.org/10.1172/JCI6610

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD (1998) Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest 102:1627–1633. https://doi.org/10.1172/JCI3914

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Goltzman D (2008) Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone. Arch Biochem Biophys 473:218–224. https://doi.org/10.1016/j.abb.2008.03.003

    Article  PubMed  CAS  Google Scholar 

  33. Saag KG, Shane E, Boonen S, Marín F, Donley DW, Taylor KA, Dalsky GP, Marcus R (2007) Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 357:2028–2039. https://doi.org/10.1056/NEJMoa071408

    Article  PubMed  CAS  Google Scholar 

  34. Geusens P, Marin F, Kendler DL, Russo LA, Zerbini CAF, Minisola S, Body JJ, Lespessailles E, Greenspan SL, Bagur A, Stepan JJ, Lakatos P, Casado E, Moericke R, López-Romero P, Fahrleitner-Pammer A (2018) Effects of teriparatide compared with risedronate on the risk of fractures in subgroups of postmenopausal women with severe osteoporosis: the VERO trial: Cdc42 in osteoarthritis. J Bone Miner Res. 33:783–794. https://doi.org/10.1002/jbmr.3384

    Article  PubMed  CAS  Google Scholar 

  35. Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM (2003) The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med 349:1216–1226. https://doi.org/10.1056/NEJMoa035725

    Article  PubMed  CAS  Google Scholar 

  36. Ettinger B, Martin SJ, Crans G, Pavo I (2004) Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res 19:745–751. https://doi.org/10.1359/jbmr.040117

    Article  PubMed  CAS  Google Scholar 

  37. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan J, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ, PaTH Study Investigators (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207–1215. https://doi.org/10.1056/NEJMoa031975

    Article  PubMed  CAS  Google Scholar 

  38. Cosman F, Eriksen EF, Recknor C, Miller PD, Guañabens N, Kasperk C, Papanastasiou P, Readie A, Rao H, Gasser JA, Bucci-Rechtweg C, Boonen S (2011) Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] in postmenopausal osteoporosis. J Bone Miner Res 26:503–511. https://doi.org/10.1002/jbmr.238

    Article  PubMed  CAS  Google Scholar 

  39. Achiou Z, Toumi H, Touvier J, Boudenot A, Uzbekov R, Ominsky MS, Pallu S, Lespessailles E (2015) Sclerostin antibody and interval treadmill training effects in a rodent model of glucocorticoid-induced osteopenia. Bone 81:691–701. https://doi.org/10.1016/j.bone.2015.09.010

    Article  PubMed  CAS  Google Scholar 

  40. Chandler H, Brooks DJ, Hattersley G, Bouxsein ML, Lanske B (2019) Abaloparatide increases bone mineral density and bone strength in ovariectomized rabbits with glucocorticoid-induced osteopenia. Osteoporos Int 30:1607–1616. https://doi.org/10.1007/s00198-019-04999-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons (2009) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw – 2009 Update. Aust Endod J 35:119–130. https://doi.org/10.1111/j.1747-4477.2009.00213.x

    Article  PubMed  Google Scholar 

  42. Albert SG, Reddy S (2017) Clinical evaluation of cost efficacy of drugs for treatment of osteoporosis: a meta-analysis. Endocr Pract 23:841–856. https://doi.org/10.4158/EP161678.RA

    Article  PubMed  Google Scholar 

  43. Murphy DR, Smolen LJ, Klein TM, Klein RW (2012) The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden. BMC Musculoskelet Disord 13:213. https://doi.org/10.1186/1471-2474-13-213

    Article  PubMed  PubMed Central  Google Scholar 

  44. Subbiah V, Madsen VS, Raymond AK, Benjamin RS, Ludwig JA (2010) Of mice and men: divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int 21:1041–1045. https://doi.org/10.1007/s00198-009-1004-0

    Article  PubMed  CAS  Google Scholar 

  45. Cipriani C, Irani D, Bilezikian JP (2013) Erratum: safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res 28:431–431. https://doi.org/10.1002/jbmr.1837

    Article  Google Scholar 

  46. Capriani C, Irani D, Bilezikian JP (2012) Safety of osteoanabolic therapy: a decade of experience. J Bone Miner Res 27:2419–2428. https://doi.org/10.1002/jbmr.1800

    Article  PubMed  CAS  Google Scholar 

  47. Gilsenan A, Harding A, Kellier-Steele N, Harris D, Midkiff K, Andrews E (2018) The Forteo Patient Registry linkage to multiple state cancer registries: study design and results from the first 8 years. Osteoporos Int 29:2335–2343. https://doi.org/10.1007/s00198-018-4604-8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Hagino H, Narita R, Yokoyama Y, Watanabe M, Tomomitsu M (2019) A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis. Osteoporos Int 30:2027–2037. https://doi.org/10.1007/s00198-019-05038-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Sato D, Takahata M, Ota M et al (2020) Siglec-15-targeting therapy protects against glucocorticoid-induced osteoporosis of growing skeleton in juvenile rats. Bone:115331. https://doi.org/10.1016/j.bone.2020.115331

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Acknowledgements

The authors wish to acknowledge Kenneth G. Saag and Marie Beth Humphrey who conducted a debate on the current subject at the ACR/ARP 2019 annual meeting that inspired the writing of this position paper.

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Authors and Affiliations

  1. EA 4708 - I3MTO Laboratory, University of Orleans, 45067, Orleans, France

    E. Lespessailles

  2. Department of Rheumatology, Translational Medicine Research Platform, Regional Hospital of Orleans, 14 avenue de l’hopital, 45067, Orleans Cedex 2, France

    E. Lespessailles

  3. INSERM UMR 1033, University of Lyon, Hôpital E Herriot, Lyon, France

    R. Chapurlat

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E. Lespessailles received speaker and consultant fees from Abbvie, Amgen, Expanscience, Lilly, Sublimed, and UCB and research grants from Abbvie, Amgen, Lilly, MSD, and UCB. R. Chapurlat received occasional fees for interventions as an expert or speaker from Amgen, UCB, Abbvie, Pfizer, BMS, Lilly, Arrow, Medac, Mylan, Fresenius Kabi, PKMed, Biocon, Regeneron, MSD, Chugai, Sanofi, Janssen, and Kyowa Kirin

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Lespessailles, E., Chapurlat, R. High fracture risk patients with glucocorticoid-induced osteoporosis should get an anabolic treatment first. Osteoporos Int 31, 1829–1834 (2020). https://doi.org/10.1007/s00198-020-05568-w

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