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http://hdl.handle.net/1942/29119
Title: | Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis | Authors: | Bliuc, Dana Tran, Thach van Geel, Tineke Adachi, Jonathan D. Berger, Claudie VAN DEN BERGH, Joop Eisman, John A. GEUSENS, Piet Goltzman, David Hanley, David A. Josse, Robert Kaiser, Stephanie Kovacs, Christopher S. Langsetmo, Lisa Prior, Jerilynn C. Nguyen, Tuan, V Center, Jacqueline R. |
Issue Date: | 2019 | Publisher: | WILEY | Source: | JOURNAL OF BONE AND MINERAL RESEARCH,, p. 1-11 | Abstract: | Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. (c) 2019 American Society for Bone and Mineral Research. | Notes: | [Bliuc, Dana; Tran, Thach; Eisman, John A.; Nguyen, Tuan, V] Garvan Inst Med Res, Osteoporosis & Bone Biol, Sydney, NSW, Australia. [van Geel, Tineke; Eisman, John A.] Maxima Med Ctr, Dept Data & Analyt, Mb Veldhoven, Netherlands. [Adachi, Jonathan D.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Berger, Claudie] McGill Univ, CaMos Natl Coordinating Ctr, Montreal, PQ, Canada. [van den Bergh, Joop] Maastricht Univ, Res Sch Nutr, Dept Internal Med, Subdiv Rheumatol,Med Ctr, Maastricht, Netherlands. [van den Bergh, Joop] VieCuri Med Ctr Noord Limburg, Dept Internal Med, Venlo, Netherlands. [Eisman, John A.; Nguyen, Tuan, V] UNSW Australia, Fac Med, Clin Sch, St Vincents Hosp, Sydney, NSW, Australia. [Eisman, John A.; Nguyen, Tuan, V] Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW, Australia. [Geusens, Piet] Univ Hasselt, Biomed Res Inst, Hasselt, Belgium. [Goltzman, David] McGill Univ, Dept Med, Montreal, PQ, Canada. [Hanley, David A.] Univ Calgary, Dept Med, Calgary, AB, Canada. [Josse, Robert] Univ Toronto, Dept Med, Toronto, ON, Canada. [Kaiser, Stephanie] Dalhousie Univ, Dept Med, Halifax, NS, Canada. [Kovacs, Christopher S.] Mem Univ, Fac Med, St John, NF, Canada. [Langsetmo, Lisa] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Prior, Jerilynn C.] Univ British Columbia, Dept Med & Endocrinol, Vancouver, BC, Canada. [Nguyen, Tuan, V; Center, Jacqueline R.] Univ Technol, Sch Biomed Engn, Sydney UTS, Sydney, NSW, Australia. [Bliuc, Dana; Tran, Thach; Eisman, John A.; Nguyen, Tuan, V; Center, Jacqueline R.] UNSW Sydney, St Vincents Clin Sch, Sydney, NSW, Australia. | Keywords: | FRACTURE; MORTALITY RISK; BISPHOSPHONATE; BONE LOSS; PROSPECTIVE STUDY;FRACTURE; MORTALITY RISK; BISPHOSPHONATE; BONE LOSS; PROSPECTIVE STUDY | Document URI: | http://hdl.handle.net/1942/29119 | ISSN: | 0884-0431 | e-ISSN: | 1523-4681 | DOI: | 10.1002/jbmr.3816 | ISI #: | 000480479400001 | Rights: | 2019 American Society for Bone and Mineral Research | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
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