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Osteoporotic patients treated with bisphosphonates do not show the increased mortality observed in those untreated

Abstract

Introduction

Osteoporosis has been said to be associated with increased mortality. On the other hand, it is debated whether treatment with bisphosphonates may reduce mortality in osteoporotic patients. To contribute to the clarification of these issues, we have studied in a prospective cohort the mortality in people without osteoporosis and in patients with osteoporosis, untreated or treated with bisphosphonates

Material and Methods

At their inclusion in the cohort, four groups of participants were identified: (a) people without osteoporosis (group 1); (b) osteoporotic patients treated with bisphosphonates (group 2); (c) osteoporotic patients who refused to be treated (group 3); and (d) patients who met osteoporosis diagnostic criteria but were not treated because their risk of fracture was considered to be low (group 4). To compare all four groups, unadjusted Kaplan–Meier estimates of survivorship were obtained and they were compared using log-rank test. Hazard ratios were then estimated via Cox regression adjusting for the main confounders. A comparison among the osteoporotic groups was made by means of a Cox regression analysis performed using only these three groups, adjusting for propensity scores.

Results

Two thousand six hundred and sixty-five people were included. In the unadjusted analysis, mortality in group 3 was higher than in the other groups (p < 0.001). Taking group 1 as a reference, Cox regression analysis showed the following mortality HRs for groups 2, 3, and 4 after adjusting for confounding factors: 0.82 (0.41–1.63), 1.37 (0.90–2.10), and 0.69 (0.46–1.02). In the analysis of the osteoporotic groups with the PS generated for them, and taking group 2 as a reference, the HRs were as follows: group 3, 2.38 (1.34–4.22); group 4, 1.45 (0.61–3.43).

Conclusion

Mortality in osteoporotic patients who refused treatment is higher than in osteoporotic patients treated with bisphosphonates. In unadjusted analysis, it was also higher than in non-osteoporotic people; however, this difference disappeared after adjustment for confounding factors.

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References

  1. 1.

    Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301:513–521

    CAS  Article  Google Scholar 

  2. 2.

    Huntjens KM, Kosar S, van Geel TACM, Geusens PP, Willems P, Kessels A, Winkens B, Brink P, van Helden S (2010) Risk of subsequent fracture and mortality within 5 years after a non-vertebral fracture. Osteoporos Int 21:2075–2082

    CAS  Article  Google Scholar 

  3. 3.

    Morin S, Lix LM, Azimaee M, Metge C, Caetano P, Leslie WD (2011) Mortality rates after incident non-traumatic fractures in older men and women. Osteoporos Int 22:2439–2448

    CAS  Article  Google Scholar 

  4. 4.

    Browner WS, Seeley DG, Vogt TM, Cummings SR (1991) Non-trauma mortality in elderly women with low bone mineral density. Study of Osteoporotic Fractures Research Group. Lancet 338:355–358

    CAS  Article  Google Scholar 

  5. 5.

    Johansson C, Black D, Johnell O, Odén A, Mellström D (1998) Bone mineral density is a predictor of survival. Calcif Tissue Int 63:190–196

    CAS  Article  Google Scholar 

  6. 6.

    Trivedi DP, Khaw KT (2001) Bone mineral density at the hip predicts mortality in elderly men. Osteoporos Int 12:259–265

    CAS  Article  Google Scholar 

  7. 7.

    Suzuki T, Yoshida H (2010) Low bone mineral density at femoral neck is a predictor of increased mortality in elderly Japanese women. Osteoporos Int 21:71–79

    CAS  Article  Google Scholar 

  8. 8.

    Hauger AV, Bergland A, Holvik K, Ståhle A, Emaus N, Strand BH (2018) Osteoporosis and osteopenia in the distal forearm predict all-cause mortality independent of grip strength: 22-year follow-up in the population-based Tromsø study. Osteoporos Int 29:2447–2456

    CAS  Article  Google Scholar 

  9. 9.

    Pasco JA, Mohebbi M, Holloway KL, Brennan-Olsen SL, Hyde NK, Kotowicz MAJ (2017) Musculoskeletal decline and mortality: prospective data from the Geelong osteoporosis study. J Cachexia Sarcopenia Muscle 8:482–489

    Article  Google Scholar 

  10. 10.

    Qu X, Huang X, Jin F, Wang H, Hao Y, Tang T, Dai K (2013) Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 166:385–393

    Article  Google Scholar 

  11. 11.

    Lyles KW, Colon-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809

    CAS  Article  Google Scholar 

  12. 12.

    Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Wong S, Wiessing KR, Bolland MJ, Bastin S, Gamble GD (2018) Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med 379:2407–2416

    CAS  Article  Google Scholar 

  13. 13.

    Beaupre LA, Morrish DW, Hanley DA, Maksymowych WP, Bell NR, Juby AG, Majumdar SR (2011) Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos Int 22:983–991

    CAS  Article  Google Scholar 

  14. 14.

    Sambrook PN, Cameron ID, Chen JS, March LM, Simpson JM, Cumming RG, Seibel MJ (2011) Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study. Osteoporos Int 22:2551–2556

    CAS  Article  Google Scholar 

  15. 15.

    Center JR, Bliuc D, Nguyen ND, Nguyen TV, Eisman JA (2011) Osteoporosis medication and reduced mortality risk in elderly women and men. J Clin Endocrinol Metab 96:1006–1014

    CAS  Article  Google Scholar 

  16. 16.

    Bliuc D, Tran T, van Geel T, Adachi JD, Berger C, van den Bergh J, Eisman JA, Geusens P, Goltzman D, Hanley DA, Josse RG, Kaiser S, Kovacs CS, Langsetmo L, Prior JC, Nguyen TV, Center JR, CaMOS Research Group (2019) Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study. Osteoporos Int 30:817–828

    CAS  Article  Google Scholar 

  17. 17.

    Cummings SR, Lui LY, Eastell R, Allen IE (2019) Association between drug treatments for patients with osteoporosis and overall mortality rates. A meta-analysis. JAMA Intern Med 179:1491–1500

    Article  Google Scholar 

  18. 18.

    Hernández JL, Olmos JM, Pariente E, Martínez J, Valero C, García-Velasco P, Nan D, Llorca J, González-Macías J (2010) Metabolic syndrome and bone metabolism. Menopause 17:955–961

    Article  Google Scholar 

  19. 19.

    Olmos JM, Hernández JL, García-BVelasco P, Martínez J, Llorca J, González-Macías J (2016) Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults. Osteoporos Int 27:105–113

    CAS  Article  Google Scholar 

  20. 20.

    Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, National LR, Foundation O (2014) Clinician´s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381

    CAS  Article  Google Scholar 

  21. 21.

    Briot K, Roux C, Thomas T, Bolain H, Buchon D, Chapurlat R, Debiais F, Feron JM, Gauvain JB, Guggenbuhl P, Legrand E, Lehr-Drylewicz AM, Lespessailles E, Tremollieres F, Weryha G, Cortet B (2018) Update of French recommendations on the management of postmenopausal osteoporosis. Joint Bone Spine 85:519–530

    Article  Google Scholar 

  22. 22.

    González-Macías J, Del Pino-Montes J, Olmos JM, Nogués X, en nombre de la Comisión de Redacción de las Guías de Osteoporosis de la SEIOMM (2015) Clinical practice guidelines for postmenopausal, glucocorticoid-induced and male osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd updated version 2014). Rev Clin Esp 215:515–526

    Article  Google Scholar 

  23. 23.

    González-Macías J, Marín F, Vila J, Díez-Pérez A, Abizanda M, Alvarez R, Gimeno A, Pegenaute E, en representación de los investigadores del Proyecto ECOSAP (2004) Prevalencia de factores de riesgo de osteoporosis y fracturas osteoporóticas en una serie de 5.195 mujeres mayores de 65 años. Med Clin 123:85–89 (Barc)

    Article  Google Scholar 

  24. 24.

    Bolland MJ, Grey AB, Gamble GD, Reid IR (2010) Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab 95:1174–1181

    CAS  Article  Google Scholar 

  25. 25.

    Kranenburg G, Bartstra JW, Weijmans M, de Jong PA, Mali WP, Verhaar HJ, Visseren FLJ, Spiering W (2016) Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis 252:106–115

    CAS  Article  Google Scholar 

  26. 26.

    Shrank WH, Patrick AR, Brookhart MA (2011) Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med 26:546–550

    Article  Google Scholar 

  27. 27.

    Williams B, Diehr P, LoGerfo J (2010) Evaluating a preventive services index to adjust for healthy behaviors in observational studies of older adults. Prev Chronic Dis 7:A110

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Bastin S, Gamble GD (2020) Effects of zoledronate on cancer, cardiac events, and mortality in osteopenic older women. J Bone Miner Res 35:20–27

    CAS  Article  Google Scholar 

  29. 29.

    Sing CW, Kiel DP, Hubbard RB, Lau WC, Li GH, Kung AW, Wong IC, Cheung CL (2020) Nitrogen-containing bisphosphonates are associated with reduced risk of pneumonia in patients with hip fracture. J Bone Miner Res 35:1676–1684

    CAS  Article  Google Scholar 

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Funding

Funded by grants from the Instituto de Salud Carlos III (PI18/00762), that included FEDER funds from the EU. Ministerio de Economía y Competitividad, Spain.

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Correspondence to C. Valero.

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C. Valero, JM Olmos, J. Llorca, JL. Hernández-Hernández, J. Castillo, J. Martínez, and J. González-Macías declare that they have no conflict of interest.

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Valero, C., Olmos, J.M., Llorca, J. et al. Osteoporotic patients treated with bisphosphonates do not show the increased mortality observed in those untreated. J Bone Miner Metab 39, 876–882 (2021). https://doi.org/10.1007/s00774-021-01228-z

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Keywords

  • Mortality
  • Osteoporosis
  • Bisphosphonates
  • Bone mineral density
  • Vitamin D