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Osteoporosis: Treat-to-Target

A Correction to this article was published on 14 August 2019

This article has been updated

Abstract

Purpose of Review

Treat-to-target (goal-directed therapy) has been proposed as a strategy to assist clinicians in selecting the most appropriate initial treatment for osteoporosis and guiding subsequent decisions to continue, change, or stop treatment. This is a review of the current medical evidence regarding treatment targets and potential clinical applications in managing patients with osteoporosis.

Recent Findings

Analyses of randomized placebo-controlled trials of approved agents to treat osteoporosis have generally shown that larger increases in bone mineral density are associated with greater reduction in fracture risk. Achievement of T-scores > −2.5 to −2.0 with treatment appears to provide little additional fracture protection.

Summary

The paradigm of treat-to-target is aimed at enhancing and individualizing the care of patients with osteoporosis. Based on the best available data, the most promising target is T-score > −2.5. More data are needed to validate the clinical utility of treat-to-target for osteoporosis.

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Change history

  • 14 August 2019

    The author Edward Michael Lewiecki is listed incorrectly in indexing sources as ���Michael Lewiecki E.���

  • 14 August 2019

    The author Edward Michael Lewiecki is listed incorrectly in indexing sources as ���Michael Lewiecki E.���

  • 14 August 2019

    The author Edward Michael Lewiecki is listed incorrectly in indexing sources as ���Michael Lewiecki E.���

  • 14 August 2019

    The author Edward Michael Lewiecki is listed incorrectly in indexing sources as ���Michael Lewiecki E.���

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359–81.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Kanis JA, Harvey NC, Cooper C, Johansson H, Oden A, McCloskey EV, et al. A systematic review of intervention thresholds based on FRAX: a report prepared for the National Osteoporosis Guideline Group and the international osteoporosis foundation. Arch Osteoporos. 2016;11(1):25.

    Article  PubMed  Google Scholar 

  3. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010;182(17):1864–73.

    Article  PubMed  PubMed Central  Google Scholar 

  4. • Lewiecki EM, Cummings SR, Cosman F. Treat-to-target for osteoporosis: is now the time? J Clin Endocrinol Metab. 2013;98(3):946–53. This is a detailed description of the rationale supporting the development of treat-to-target for osteoporosis

    CAS  Article  PubMed  Google Scholar 

  5. • Cummings SR, Cosman F, Eastell R, Reid IR, Mehta M, Lewiecki EM. Goal-directed treatment of osteoporosis. J Bone Miner Res. 2013;28(3):433–8. Additional information is provided here on the benefits and limitations of osteoporosis treatment targets

    Article  PubMed  Google Scholar 

  6. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.

    CAS  Article  PubMed  Google Scholar 

  7. Chamberlain JJ, Rhinehart AS, Shaefer Jr CF, Neuman A. Diagnosis and Management of Diabetes: synopsis of the 2016 American Diabetes Association standards of medical Care in Diabetes. Ann Intern Med. 2016;164(8):542–52.

    Article  PubMed  Google Scholar 

  8. Singh JA, Saag KG, Bridges Jr SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1–26.

    Article  PubMed  Google Scholar 

  9. Miller PD. Underdiagnosis and Undertreatment of osteoporosis: the battle to Be won. J Clin Endocrinol Metab. 2016;101(3):852–9.

    CAS  Article  PubMed  Google Scholar 

  10. Solomon DH, Johnston SS, Boytsov NN, McMorrow D, Lane JM, Krohn KD. Osteoporosis medication use after hip fracture in U.S. patients between 2002 and 2011. J Bone Miner Res. 2014;29(9):1929–37.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Khosla S, Shane E. A crisis in the treatment of osteoporosis. J Bone Miner Res. 2016;31(8):1485–7.

    Article  PubMed  Google Scholar 

  12. Lewiecki EM, Watts NB. Assessing response to osteoporosis therapy. Osteoporos Int. 2008;19(10):1363–8.

    CAS  Article  PubMed  Google Scholar 

  13. Diez-Perez A, Adachi JD, Agnusdei D, Bilezikian JP, Compston JE, Cummings SR, et al. Treatment failure in osteoporosis. Osteoporos Int. 2012;23:2769–74.

    CAS  Article  PubMed  Google Scholar 

  14. McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med. 2013;126(1):13–20.

    CAS  Article  PubMed  Google Scholar 

  15. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22(10):1479–89.

    Article  PubMed  Google Scholar 

  16. Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29(1):1–23.

    Article  PubMed  Google Scholar 

  17. McClung MR. Cancel the denosumab holiday. Osteoporos Int. 2016;27(5):1677–82.

    CAS  Article  PubMed  Google Scholar 

  18. •• Cummings SR, Cosman F, Lewiecki EM, Schousboe JT, Bauer DC, Black DM, et al. Goal-directed treatment for osteoporosis: a progress report from the ASBMR-NOF working group on goal-directed treatment for osteoporosis. J Bone Miner Res. 2017;32(1):3–10. This report summarizes the best available medical evidence regarding the potential use of treatment targets for osteoporosis and proposes further studies to evaluate the clinical utility of treatment targets

    CAS  Article  PubMed  Google Scholar 

  19. •• Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16–35. This report from the ASBMR Task Force suggests consideration of a bisphosphonate holiday when the T-score is > -2.5 and fracture risk is low, consistent with consideration of the same T-score value as a treatment target

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Lee J, Vasikaran S. Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann Lab Med. 2012;32(2):105–12.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. World Health Organization. FRAX WHO Fracture Risk Assessment Tool. World Health Organization [Internet]. http://www.shef.ac.uk/FRAX/ (2016). Accessed 9/10/2016.

  22. Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA. Does osteoporosis therapy invalidate FRAX for fracture prediction? J Bone Miner Res. 2012;27(6):1243–51.

    CAS  Article  PubMed  Google Scholar 

  23. Leslie WD, Majumdar SR, Lix LM, Morin SN, Johansson H, Oden A, et al. Can change in FRAX score be used to "treat to target"? A population-based cohort study. J Bone Miner Res. 2014;29(5):1074–80.

    Article  PubMed  Google Scholar 

  24. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312(7041):1254–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Hochberg MC, Ross PD, Black D, Cummings SR, Genant HK, Nevitt MC, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis Rheum. 1999;42(6):1246–54.

    CAS  Article  PubMed  Google Scholar 

  26. Jacques RM, Boonen S, Cosman F, Reid IR, Bauer DC, Black DM, et al. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-pivotal fracture trial (PFT). J Bone Miner Res. 2012;27(8):1627–34.

    CAS  Article  PubMed  Google Scholar 

  27. Austin M, Yang YC, Vittinghoff E, Adami S, Boonen S, Bauer DC, et al. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res. 2012;27(3):687–93.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD. Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab. 2002;87(4):1586–92.

    CAS  Article  PubMed  Google Scholar 

  29. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab. 2000;85(1):231–6.

    CAS  Article  PubMed  Google Scholar 

  30. •• Black DM, Vittinghoff E, Eastell R, Bouxsein M, McCulloch C, Cawthon PM, et al. Hip BMD by DXA can reliably estimate reduction in hip risk in osteoporosis trials: a meta-regression. J Bone Miner Res. 2015;30(S1):S49. This analysis of multiple clinical trials shows a robust correlation between increases in BMD with treatment and reduction of fracture risk

    Google Scholar 

  31. •• Ferrari S, Libanati C, Lin CJF, Adami S, Brown JP, Cosman F, et al. Relationship between total hip BMD T-score and incidence of nonvertebral fracture with up to 8 years of denosumab treatment. J Bone Miner Res. 2015;30(Suppl. 1):S49. This is a report that larger increases in BMD with denosumab are associated with a greater reduction in fracture risk

    Google Scholar 

  32. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the fracture intervention trial long-term extension (FLEX): a randomized trial. JAMA. 2006;296(24):2927–38.

    CAS  Article  PubMed  Google Scholar 

  33. Schwartz AV, Bauer DC, Cummings SR, Cauley JA, Ensrud KE, Palermo L, et al. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res. 2010;25(5):976–82.

    CAS  Article  PubMed  Google Scholar 

  34. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-pivotal fracture trial (PFT). J Bone Miner Res. 2012;27(2):243–54.

    CAS  Article  PubMed  Google Scholar 

  35. Cosman F, Cauley JA, Eastell R, Boonen S, Palermo L, Reid IR, et al. Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab. 2014;99(12):4546–54.

    CAS  Article  PubMed  Google Scholar 

  36. Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis- for whom and for how long? N Engl J Med. 2012;366(22):2051–3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis-where do We go from here? N Engl J Med. 2012;366(22):2048–51.

    CAS  Article  PubMed  Google Scholar 

  38. Ferrari S, Adachi JD, Lippuner K, Zapalowski C, Miller PD, Reginster JY, et al. Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. Osteoporos Int. 2015;26(12):2763–71.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Kim TY, Schafer AL. Variability in DXA reporting and other challenges in osteoporosis evaluation. JAMA Intern Med. 2016;176(3):393–5.

    Article  PubMed  Google Scholar 

  40. Lewiecki EM, Binkley N, Petak SM. DXA quality matters. J Clin Densitom. 2006;9(4):388–92.

    Article  PubMed  Google Scholar 

  41. Watts NB. Fundamentals and pitfalls of bone densitometry using dual-energy X-ray absorptiometry (DXA). Osteoporos Int. 2004;15(11):847–54.

    Article  PubMed  Google Scholar 

  42. Lewiecki EM, Lane NE. Common mistakes in the clinical use of bone mineral density testing. Nat Clin Pract Rheumatol. 2008;4(12):667–74.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Shepherd JA, Schousboe JT, Broy SB, Engelke K, Leslie WD. Executive summary of the 2015 ISCD position development conference on advanced measures from DXA and QCT: fracture prediction beyond BMD. J Clin Densitom. 2015;18(3):274–86.

    Article  PubMed  Google Scholar 

  44. Lewiecki EM, Binkley N, Morgan SL, Shuhart CR, Camargos BM, Carey JJ, et al. Best practices for dual-energy X-ray absorptiometry measurement and reporting: International Society for Clinical Densitometry Guidance. J Clin Densitom. 2016;19(2):127–40.

    Article  PubMed  Google Scholar 

  45. Kanis JA, McCloskey E, Branco J, Brandi ML, Dennison E, Devogelaer JP, et al. Goal-directed treatment of osteoporosis in Europe. Osteoporos Int. 2014;25(11):2533–43.

    CAS  Article  PubMed  Google Scholar 

  46. McCloskey E, Leslie WD. Goal-directed therapy in osteoporosis. J Bone Miner Res. 2013;28(3):439–41.

    Article  PubMed  Google Scholar 

  47. Chesnut III CH, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group Am J Med. 2000;109(4):267–76.

    CAS  Google Scholar 

  48. Lewiecki EM, Binkley N. What we don't know about osteoporosis. J Endocrinol Investig. 2016;39(5):491–3.

    CAS  Article  Google Scholar 

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Correspondence to E. Michael Lewiecki.

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Conflict of Interest

E. Michael Lewiecki reports grants and personal fees from Amgen, grants and personal fees from Merck, grants and personal fees from Lilly, personal fees from Radius, during the conduct of the study.

Consulting/advisory board fees from Amgen, Eli Lilly, Merck, Alexion, Shire; grant/research support from Amgen, Merck, Eli Lilly; speaking fees from Shire, Alexion.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Therapeutics and Medical Management

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Michael Lewiecki, E. Osteoporosis: Treat-to-Target. Curr Osteoporos Rep 15, 103–109 (2017). https://doi.org/10.1007/s11914-017-0350-7

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  • DOI: https://doi.org/10.1007/s11914-017-0350-7

Keywords

  • Osteoporosis
  • Treatment
  • Target
  • Goal
  • Goal-directed