- 829 Downloads
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.
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.
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.
KeywordsOsteoporosis Treatment Target Goal Goal-directed
Compliance with Ethical Standards
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.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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 CrossRefPubMedGoogle 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 CrossRefPubMedPubMedCentralGoogle 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.
- 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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
- 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.CrossRefPubMedPubMedCentralGoogle 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.Google Scholar