Osteoporosis medication and reduced mortality risk in elderly women and men

Center, Jacqueline R.<sup>1,2,3</sup>; Bliuc, Dana<sup>1</sup>; Nguyen, Nguyen D.<sup>1</sup>; Nguyen, Tuan V.<sup>1,3,4</sup>; Eisman, John A.<sup>1,2,3</sup>

Affiliations

¹Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, 2010 Australia

²St. Vincent’s Hospital, Darlinghurst, Sydney, New South Wales, 2010 Australia

³Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia

⁴School of Public Health and Community Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia

Abstract

Context: Osteoporotic fractures are associated with premature mortality. Antiresorptive treatment reduces refracture but mortality reduction is unclear.

Objective: The objective of the study was to examine the effect of osteoporosis treatment [bisphosphonates (BP), hormone therapy (HT), and calcium ± vitamin D only (CaD)] on mortality risk.

Design: This was a prospective cohort study (April 1989 to May 2007).

Setting: The study was conducted with community-dwelling elderly (aged 60+ yr) subjects in Dubbo, a semiurban city, Australia.

Subjects: Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study.

Main Outcome Measure: Mortality according to treatment group was recorded.

Results: There were 325 (BP, n = 106; HT, n = 77; CaD, n = 142) women and 37 men (BP, n = 15; CaD, n = 22) on treatment. In women, mortality rates were lower with BP 0.8/100 person-years (0.4, 1.4) and HT 1.2/100 person-years (0.7, 2.1) but not CaD 3.2/100 person-years (2.5, 4.1) vs. no treatment 3.5/100 person-years (3.1, 3.8). Accounting for age, fracture occurrence, comorbidities, quadriceps strength, and bone mineral density, mortality risk remained lower for women on BP [hazard ratio (HR) 0.3 (0.2, 0.6)] but not HT [HR 0.8 (0.4, 1.8)]. For 429 women with fractures, mortality risk was still reduced in the BP group [adjusted HR 0.3 (0.2, 0.7)], not accounted for by a reduction in subsequent fractures. In men, lower mortality rates were observed with BP but not CaD [BP 1.0/100 person-years (0.3, 3.9) and CaD 3.1/100 person-years (1.5, 6.6) vs. no treatment 4.3/100 person-years (3.9, 4.8)]. After adjustment, mortality was similar, although not significant [HR 0.5 (0.1, 2.0)].

Conclusions: Osteoporosis therapy appears to reduce mortality risk in women and possibly men.

Links

DOI: 10.1210/jc.2010-2730

PubMed: 21289270

WoS: 000289242800042

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Year	Entry
2011	Russell RGG. Bisphosphonates: the first 40 years. Bone. July 2011;49(1):2-19.
2020	Pfeilschifter J, Steinebach I, Trampisch HJ, Rudolf H. Bisphosphonate drug holidays: risk of fractures and mortality in a prospective cohort study. Bone. September 2020;138:115431.
2020	Rogers MJ, Mönkkönen J, Munoz MA. Molecular mechanisms of action of bisphosphonates and new insights into their effects outside the skeleton. Bone. October 2020;139:115493.
2020	Center JR, Lyles KW, Bliuc D. Bisphosphonates and lifespan. Bone. December 2020;141:115566.
2013	Bliuc D, Nguyen ND, Nguyen TV, Eisman JA, Center JR. Compound risk of high mortality following osteoporotic fracture and refracture in elderly women and men. J Bone Miner Res. January 2013;28(11):2317-2324.
2012	Eisman JA, Bogoch ER, Dell R, Harrington JT, McKinney RE Jr, McLellan A, Mitchell PJ, Silverman S, Singleton R, Siris E; ASBMR Task Force on Secondary Fracture Prevention. Making the first fracture the last fracture: ASBMR task force report on secondary fracture prevention. J Bone Miner Res. October 2012;27(10):2039-2046.
2016	Adler RA, Fuleihan GE-H, Bauer DC, Camacho PM, Clarke BL, Clines GA, Compston JE, Drake MT, Edwards BJ, Favus MJ, Greenspan SL, McKinney R Jr, Pignolo RJ, Sellmeyer DE. 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.
2020	Leder BZ. What else do we need? a commentary on zoledronate effects on cancer and cardiac events. J Bone Miner Res. January 2020;35(1):18-19.
2020	Reid IR, Horne AM, Mihov B, Stewart A, Garratt E, Bastin S, Gamble GD. Effects of zoledronate on cancer, cardiac events, and mortality in osteopenic older women. J Bone Miner Res. January 2020;35(1):20-27.
2020	Alarkawi D, Ali MS, Bliuc D, Pallares N, Tebe C, Elhussein L, Caskey FJ, Arden NK, Ben‐Shlomo Y, Abrahamsen B, Diez‐Perez A, Pascual J, Pérez‐Sáez MJ, Center JR, Judge A, Cooper C, Javaid MK, Prieto‐Alhambra D. Oral bisphosphonate use and all‐cause mortality in patients with moderate–severe (grade 3B‐5D) chronic kidney disease: a population‐based cohort study. J Bone Miner Res. May 2020;35(5):894-900.
2020	Sing C, Kiel DP, Hubbard RB, Lau WCY, Li GHY, Kung AWC, Wong ICK, Cheung C. Nitrogen‐containing bisphosphonates are associated with reduced risk of pneumonia in patients with hip fracture. J Bone Miner Res. September 2020;35(9):1676-1684.
2021	Sato AY, Pellegrini GG, Cregor M, McAndrews K, Choi RB, Maiz M, Johnson O, McCabe LD, McCabe GP, Ferruzzi MG, Lila MA, Peacock M, Burr DB, Nakatsu CH, Weaver CM, Bellido T. Skeletal protection and promotion of microbiome diversity by dietary boosting of the endogenous antioxidant response. J Bone Miner Res. April 2021;36(4):768-778.
2022	Robertson CL, Ghosh G, Fitzgerald P, Hankey GJ, Levinger I, Golledge J, Almeida OP, Flicker L, Ebeling PR, Yeap BB. Bone turnover markers including undercarboxylated osteocalcin are associated with mortality risk in older men. J Bone Miner Res. August 2022;37(8):1464-1472.
2022	Chattaris T, Oh G, Gouskova NA, Kim DH, Kiel DP, Berry SD. Osteoporosis medications prevent subsequent fracture in frail older adults. J Bone Miner Res. November 2022;37(11):2103-2111.
2023	Alarkawi D, Tran T, Chen W, March LM, Blyth FM, Blank RD, Bliuc D, Center JR. Denosumab and mortality in a real-world setting: a comparative study. J Bone Miner Res. December 2023;38(12):1757-1770.
2020	Alarkawi D, Bliuc D, Tran T, Ahmed LA, Emaus N, Bjørnerem A, Jørgensen L, Christoffersen T, Eisman JA, Center JR. Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study. Osteoporos Int. January 2020;31(1):119-130.
2020	Sujic R, Luo J, Beaton DE, Bogoch ER, Sale JEM, Jaglal S, Jain R, Mamdani M; Ontario Osteoporosis Strategy Fracture Screening and Prevention Program Evaluation Team. Multiple simultaneous fractures are associated with higher all-cause mortality: results from a province-wide fracture liaison service. Osteoporos Int. February 2020;31(2):291-296.