Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study

D. Bliuc; T. Tran; T. van Geel; J. D. Adachi; C. Berger; J. van den Bergh; J. A. Eisman; P. Geusens; D. Goltzman; D. A. Hanley; R. G. Josse; S. Kaiser; C. S. Kovacs; L. Langsetmo; J. C. Prior; T. Nguyen; J. R. Center; CaMos Research Group

doi:10.1007/s00198-018-4806-0

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study

D. Bliuc^*, T. Tran, T. van Geel, J. D. Adachi, C. Berger, J. van den Bergh, J. A. Eisman, P. Geusens, D. Goltzman, D. A. Hanley, R. G. Josse, S. Kaiser, C. S. Kovacs, L. Langsetmo, J. C. Prior, T. Nguyen, J. R. Center, CaMos Research Group

^*Corresponding author for this work

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Abstract

A Summary In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways.

Introduction Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture.

Methods A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models.

Results There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate].

Conclusion Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Original language	English
Pages (from-to)	817-828
Number of pages	12
Journal	Osteoporosis International
Volume	30
Issue number	4
DOIs	https://doi.org/10.1007/s00198-018-4806-0
Publication status	Published - Apr 2019

Keywords

Bisphosphonate
Fracture
Mortality risk
Osteoporosis
Prospective study
DELTA T-CELLS
SUBSEQUENT FRACTURE
BONE LOSS
OSTEOPOROTIC FRACTURE
ZOLEDRONIC ACID
HIP FRACTURE
WOMEN
MEN
PAMIDRONATE
EFFICACY

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Bliuc, D., Tran, T., van Geel, T., Adachi, J. D., Berger, C., van den Bergh, J., Eisman, J. A., Geusens, P., Goltzman, D., Hanley, D. A., Josse, R. G., Kaiser, S., Kovacs, C. S., Langsetmo, L., Prior, J. C., Nguyen, T., Center, J. R., & CaMos Research Group (2019). Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study. Osteoporosis International, 30(4), 817-828. https://doi.org/10.1007/s00198-018-4806-0

@article{f4b18ff3fa6946ed8b2382261a87d8c1,

title = "Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study",

abstract = "A Summary In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways.Introduction Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture.Methods A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models.Results There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate].Conclusion Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.",

keywords = "Bisphosphonate, Fracture, Mortality risk, Osteoporosis, Prospective study, DELTA T-CELLS, SUBSEQUENT FRACTURE, BONE LOSS, OSTEOPOROTIC FRACTURE, ZOLEDRONIC ACID, HIP FRACTURE, WOMEN, MEN, PAMIDRONATE, EFFICACY",

author = "D. Bliuc and T. Tran and {van Geel}, T. and Adachi, {J. D.} and C. Berger and {van den Bergh}, J. and Eisman, {J. A.} and P. Geusens and D. Goltzman and Hanley, {D. A.} and Josse, {R. G.} and S. Kaiser and Kovacs, {C. S.} and L. Langsetmo and Prior, {J. C.} and T. Nguyen and Center, {J. R.} and {CaMos Research Group}",

note = "Funding Information: Funding information The Canadian Multicentre Osteoporosis Study was funded by the Canadian Institutes of Health Research (CIHR); Merck Frosst Canada Ltd.; Eli Lilly Canada Inc.; Novartis Pharmaceuticals Inc.; The Alliance: Sanofi-Aventis & Procter and Gamble Pharmaceuticals Canada Inc.; Servier Canada Inc.; Amgen Canada Inc.; The Dairy Farmers of Canada and The Arthritis Society. Funding Information: DB, TT, TvG, JAE and JRC designed the study. DB, TT, JAE and JRC analysed the data. DB, TT and JRC drafted the manuscript. All authors contributed to the interpretation of the data and revision of the manuscript. JRC had primary responsibility for final content and acts as guarantor. All authors read and approved the final manuscript. The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; nor did they have a role in preparation, review, or approval of the manuscript and the decision to submit for publication. Publisher Copyright: {\textcopyright} 2019, International Osteoporosis Foundation and National Osteoporosis Foundation.",

year = "2019",

month = apr,

doi = "10.1007/s00198-018-4806-0",

language = "English",

volume = "30",

pages = "817--828",

journal = "Osteoporosis International",

issn = "0937-941X",

publisher = "Springer-Verlag London Ltd.",

number = "4",

}

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, T, Center, JR & CaMos Research Group 2019, 'Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study', Osteoporosis International, vol. 30, no. 4, pp. 817-828. https://doi.org/10.1007/s00198-018-4806-0

TY - JOUR

T1 - Mortality risk reduction differs according to bisphosphonate class

T2 - a 15-year observational study

AU - Bliuc, D.

AU - Tran, T.

AU - van Geel, T.

AU - Adachi, J. D.

AU - Berger, C.

AU - van den Bergh, J.

AU - Eisman, J. A.

AU - Geusens, P.

AU - Goltzman, D.

AU - Hanley, D. A.

AU - Josse, R. G.

AU - Kaiser, S.

AU - Kovacs, C. S.

AU - Langsetmo, L.

AU - Prior, J. C.

AU - Nguyen, T.

AU - Center, J. R.

AU - CaMos Research Group

N1 - Funding Information: Funding information The Canadian Multicentre Osteoporosis Study was funded by the Canadian Institutes of Health Research (CIHR); Merck Frosst Canada Ltd.; Eli Lilly Canada Inc.; Novartis Pharmaceuticals Inc.; The Alliance: Sanofi-Aventis & Procter and Gamble Pharmaceuticals Canada Inc.; Servier Canada Inc.; Amgen Canada Inc.; The Dairy Farmers of Canada and The Arthritis Society. Funding Information: DB, TT, TvG, JAE and JRC designed the study. DB, TT, JAE and JRC analysed the data. DB, TT and JRC drafted the manuscript. All authors contributed to the interpretation of the data and revision of the manuscript. JRC had primary responsibility for final content and acts as guarantor. All authors read and approved the final manuscript. The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; nor did they have a role in preparation, review, or approval of the manuscript and the decision to submit for publication. Publisher Copyright: © 2019, International Osteoporosis Foundation and National Osteoporosis Foundation.

PY - 2019/4

Y1 - 2019/4

N2 - A Summary In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways.Introduction Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture.Methods A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models.Results There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate].Conclusion Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

AB - A Summary In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways.Introduction Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture.Methods A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models.Results There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate].Conclusion Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

KW - Bisphosphonate

KW - Fracture

KW - Mortality risk

KW - Osteoporosis

KW - Prospective study

KW - DELTA T-CELLS

KW - SUBSEQUENT FRACTURE

KW - BONE LOSS

KW - OSTEOPOROTIC FRACTURE

KW - ZOLEDRONIC ACID

KW - HIP FRACTURE

KW - WOMEN

KW - MEN

KW - PAMIDRONATE

KW - EFFICACY

U2 - 10.1007/s00198-018-4806-0

DO - 10.1007/s00198-018-4806-0

M3 - Article

C2 - 30607457

SN - 0937-941X

VL - 30

SP - 817

EP - 828

JO - Osteoporosis International

JF - Osteoporosis International

IS - 4

ER -