Context: There are few data on long-term mortality following osteoporotic fracture and fewer following subsequent fracture.
Objectives: To examine long-term mortality risk in women and men following all osteoporotic fractures and to assess the association of subsequent fracture with that risk.
Design, Setting, and Participants: Prospective cohort from the Dubbo Osteoporosis Epidemiology Study of community-dwelling women and men aged 60 years and older from Dubbo, Australia, who sustained a fracture between April 1989 and May 2007.
Main Outcome Measures: Age- and sex-specific standardized mortality ratios (SMRs) compared with the overall Dubbo population for hip, vertebral, major, and minor fractures.
Results: In women, there were 952 low-trauma fractures followed by 461 deaths, and in men, 343 fractures were followed by 197 deaths. Age-adjusted SMRs were increased following hip fractures (SMRs, 2.43 [95% confidence interval [CI], 2.02-2.93] and 3.51 [95% CI, 2.65-4.66]), vertebral fractures (SMRs, 1.82 [95% CI, 1.52-2.17] and 2.12 [95% CI, 1.66-2.72]), major fractures (SMRs, 1.65 [95% CI, 1.31-2.08] and 1.70 [95% CI, 1.23-2.36]), and minor fractures (SMRs, 1.42 [95% CI, 1.19-1.70] and 1.33 [95% CI, 0.99-1.80]) for both women and men, respectively. Mortality was increased for all ages for all fractures except minor fractures for which increased mortality was only apparent for those older than 75 years. Increased mortality risk persisted for 5 years for all fractures and up to 10 years for hip fractures. Increases in absolute mortality that were above expected, for 5 years after fracture, ranged from 1.3 to 13.2 per 100 person-years in women and from 2.7 to 22.3 per 100 person-years in men, depending on fracture type. Subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men. Mortality risk following a subsequent fracture then declined but beyond 5 years still remained higher than in the general population (SMR, 1.41 [95% CI, 1.01-1.97] and SMR, 1.78 [95% CI, 0.96-3.31] for women and men, respectively). Predictors of mortality after any fragility fracture for both men and women included age, quadriceps weakness, and subsequent fracture but not comorbidities. Low bone mineral density, having smoked, and sway were also predictors for women and less physical activity for men.
Conclusions: In a sample of older women and men, all low-trauma fractures were associated with increased mortality risk for 5 to 10 years. Subsequent fracture was associated with increased mortality risk for an additional 5 years.
|2007||Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S; HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. NEJM. November 1, 2007;357(18):1799-1809.|
|2000||Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. April 2000;15(4):721-739.|
|1999||Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. March 13, 1999;353(9156):878-882.|
|2003||Kanis JA, Oden A, Johnell O, Laet CD, Jonsson B, Oglesby AK. The components of excess mortality after hip fracture. Bone. May 2003;32(5):468-473.|
|2002||Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.|
|2004||Johnell O, Kanis JA, Odén A, Sernbo I, Redlund-Johnell I, Petterson C, De Laet C, Jönsson B. Mortality after osteoporotic fractures. Osteoporos Int. January 2004;15(1):38-42.|
|2019||Torres GHF, Guzman LFE, Alvarenga JC, Lopes NHM, Pereira RMR. Association of moderate/severe vertebral fractures with reduced trabecular volumetric bone density in older women and reduced areal femoral neck bone density in older men from the community: a cross-sectional study (SPAH). Maturitas. February 2019;120:61-67.|
|2020||Smith C, Voisin S, Al Saedi A, Phu S, Brennan-Speranza T, Parker L, Eynon N, Hiam D, Yan X, Scott D, Blekkenhorst LC, Lewis JR, Seeman E, Byrnes E, Flicker L, Duque G, Yeap BB, Levinger I. Osteocalcin and its forms across the lifespan in adult men. Bone. January 2020;130:115085.|
|2020||Mandai S, Sato H, Iimori S, Naito S, Tanaka H, Ando F, Susa K, Isobe K, Mori T, Nomura N, Sohara E, Okado T, Uchida S, Fushimi K, Rai T. Nationwide in-hospital mortality following major fractures among hemodialysis patients and the general population: an observational cohort study. Bone. January 2020;130:115122.|
|2020||Ma Y, Wu X, Xiao X, Ma Y, Feng L, Yan W, Chen J, Yang D. Effects of teriparatide versus percutaneous vertebroplasty on pain relief, quality of life and cost-effectiveness in postmenopausal females with acute osteoporotic vertebral compression fracture: a prospective cohort study. Bone. February 2020;131:115154.|
|2020||Yang J, Mao Y, Nieves JW. Identification of prevalent vertebral fractures using vertebral fracture assessment (VFA) in asymptomatic postmenopausal women: a systematic review and meta-analysis. Bone. July 2020;136:115358.|
|2020||Whitney DG, Bell S, Etter JP, Prisby RD. The cardiovascular disease burden of non-traumatic fractures for adults with and without cerebral palsy. Bone. July 2020;136:115376.|
|2020||Cai S, Fan J, Zhu L, Ye J, Rao X, Fan C, Zhong Y, Li Y. Bone mineral density and osteoporosis in relation to all-cause and cause-specific mortality in NHANES: a population-based cohort study. Bone. December 2020;141:115597.|
|2020||Center JR, Lyles KW, Bliuc D. Bisphosphonates and lifespan. Bone. December 2020;141:115566.|
|2021||Cappelle S, Moreau M, Karmali R, Iconaru L, Baleanu F, Kinnard V, Paesmans M, Rozenberg S, Rubinstein M, Surquin M, Blard P-H, Chapurlat R, Body JJ, Bergmann P. Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: a substudy of the FRISBEE cohort. Bone. February 2021;143:115613.|
|2021||Talevski J, Sanders KM, Busija L, Beauchamp A, Duque G, Borgström F, Kanis JA, Svedbom A, Stuart AL, Brennan-Olsen S. Health service use pathways associated with recovery of quality of life at 12-months for individual fracture sites: analyses of the International Costs and Utilities Related to Osteoporotic fractures study (ICUROS). Bone. March 2021;144:115805.|
|2021||Delbar A, Pflimlin A, Delabrière I, Ternynck C, Chantelot C, Puisieux F, Cortet B, Paccou J. Persistence with osteoporosis treatment in patients from the Lille University Hospital Fracture Liaison Service. Bone. March 2021;144:115838.|
|2014||Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson‐Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. November 2014;29(11):2520-2526.|
|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||Harding AT, Weeks BK, Lambert C, Watson SL, Weis LJ, Beck BR. A comparison of bone‐targeted exercise strategies to reduce fracture risk in middle‐aged and older men with osteopenia and osteoporosis: LIFTMOR‐M semi‐randomized controlled trial. J Bone Miner Res. August 2020;35(8):1404-1414.|
|2020||Wu G-J, Chen J-T, Lin P-I, Cherng Y-G, Yang S-T, Chen R-M. Inhibition of the estrogen receptor alpha signaling delays bone regeneration and alters osteoblast maturation, energy metabolism, and angiogenesis. Life Sci. October 1, 2020;258:118195.|
|2020||González-Quevedo D, Bautista-Enrique D, Pérez-del-Río V, Bravo-Bardají M, García-de-Quevedo D, Tamimi I. Fracture liaison service and mortality in elderly hip fracture patients: a prospective cohort study. Osteoporos Int. January 2020;31(1):77-84.|
|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.|
|2020||Cui L, He T, Jiang Y, Li M, Wang O, Jiajue R, Chi Y, Xu Q, Xing X, Xia W. Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data. Osteoporos Int. February 2020;31(2):307-316.|
|2020||Luo Y. Age-related periosteal expansion at femoral neck among elderly women may maintain bending stiffness, but not femoral strength. Osteoporos Int. February 2020;31(2):371-377.|
|2020||Peng K, Yang M, Tian M, Chen M, Zhang J, Wu X, Ivers R, Si L. Cost-effectiveness of a multidisciplinary co-management program for the older hip fracture patients in Beijing. Osteoporos Int. August 2020;31(8):1545-1553.|
|2020||Christensen DL, Nappo KE, Wolfe JA, Tropf JG, Berge MJ, Wheatley BM, Saxena S, Yow BG, Tintle SM. Ten-year fracture risk predicted by proximal femur Hounsfield units. Osteoporos Int. November 2020;31(11):2123-2130.|
|2020||Thomas T, Casado E, Geusens P, Lems WF, Timoshanko J, Taylor D, Hofbauer LC. Is a treat-to-target strategy in osteoporosis applicable in clinical practice? consensus among a panel of European experts. Osteoporos Int. December 2020;31(12):2303-2311.|
|2020||Hopkins TJ, Eggington S, Quinn M, Nichols-Ricker CI. Cost-effectiveness of balloon kyphoplasty and vertebroplasty versus conservative medical management in the USA. Osteoporos Int. December 2020;31(12):2461-2471.|
|2021||Chandran M, Ganesan G, Tan KB, Reginster J-Y, Hiligsmann M. Cost-effectiveness of FRAX®-based intervention thresholds for management of osteoporosis in Singaporean women. Osteoporos Int. January 2021;32(1):133-144.|
|2021||Kanis JA, Harvey NC, Lorentzon M, Liu E, Vandenput L, McCloskey EV, Johansson H. Combining fracture outcomes in phase 3 trials of osteoporosis: an analysis of the effects of denosumab in postmenopausal women. Osteoporos Int. January 2021;32(1):165-171.|
|2021||Lee S-B, Park Y, Kim D-W, Kwon J-W, Ha J-W, Yang J-H, Lee BH, Suk K-S, Moon S-H, Kim H-S, Lee H-M. Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly. Osteoporos Int. February 2021;32(2):233-241.|
|2021||Lems WF, Paccou J, Zhang J, Fuggle NR, Chandran M, Harvey NC, Cooper C, Javaid K, Ferrari S, Akesson KE; International Osteoporosis Foundation Fracture Working Group. Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services. Osteoporos Int. March 2021;32(3):399-411.|
|2021||Swanson CM, Blatchford PJ, Stone KL, Cauley JA, Lane NE, Rogers-Soeder TS, Redline S, Bauer DC, Wright KP, Wierman ME, Kohrt WM, Orwoll ES; The Osteoporotic Fractures in Men (MrOS) Study. Sleep duration and bone health measures in older men. Osteoporos Int. March 2021;32(3):515-527.|
|2019||Yeh P-S, Lee Y-W, Chang W-H, Wang W, Wang J-L, Liu S-H, Chen R-M. Biomechanical and tomographic differences in the microarchitecture and strength of trabecular and cortical bone in the early stage of male osteoporosis. PLoS One. 2019;14(8):e0219718.|
|2019||Priddy C. Mechanotransduction in Living Bone: Effects of the Keap1-Nrf2 Pathway [Master's thesis]. Indianapolis, IN: Purdue University; August 2019.|
|2019||Maynard RD. Establishing the Functional Role of Cped1 in the Genetic Regulation of the Osteoblast Rochester, NY: University of Rochester; 2019.|
|2010||Reyes MJ. Age-Related Influence of Bone Remodeling on Local Tissue Properties of Human Cortical Bone [PhD thesis]. San Antionio, TX: University of Texas at San Antonio; December 2010.|
|2011||Burkhart TA. Biomechanics of the Upper Extremity in Response to Dynamic Impact Loading Indicative of a Forward Fall: An Experimental and Numerical Investigation [PhD thesis]. University of Windsor; 2011.|
|2016||Collins CJ. A Comprehensive Evaluation of Methods to Determine Mechanical Properties of Long Bone [PhD thesis]. University of Wisconsin – Madison; 2016.|
|2016||Meyer LA. Testing and Modeling Mechanical Properties of Ex Vivo Trabecular Bone [PhD thesis]. Madison, WI: University of Wisconsin; 2016.|