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. 2021 May 5:35:100826.
doi: 10.1016/j.eclinm.2021.100826. eCollection 2021 May.

After the initial fracture in postmenopausal women, where do subsequent fractures occur?

Carolyn J Crandall  1 , Rebecca P Hunt  2 , Andrea Z LaCroix  3 , John A Robbins  4 , Jean Wactawski-Wende  5 , Karen C Johnson  6 , Maryam Sattari  7 , Katie L Stone  8 , Julie C Weitlauf  9 , Tanya R Gure  10 , Jane A Cauley  11
Affiliations

After the initial fracture in postmenopausal women, where do subsequent fractures occur?

Carolyn J Crandall et al. EClinicalMedicine. .

Abstract

Background: The locations of subsequent fractures after initial fracture in postmenopausal women are poorly characterized.

Methods: We conducted a prospective analysis of subsequent fractures after initial fracture in Women's Health Initiative (1993-2018) participants who provided follow-up (mean 15.4 years, SD 6.2 years) data (n = 157,282 participants; baseline age 50-79; 47,458 participants with incident fracture). Cox proportional hazards models were adjusted for age, race/ethnicity, body mass index, and other covariates.

Findings: The risk of each type of subsequent fracture was increased after each type of initial fracture. Incident lower arm/wrist fracture was associated with significantly elevated risks of subsequent fractures at the upper arm/shoulder, upper leg, knee, lower leg/ankle, hip/pelvis, and spine (adjusted hazard ratios [aHRs] ranging 2·63-5·68). The risk of hip fracture was increased after initial lower arm or wrist fracture (aHR 4·80, 95% CI 4·29-5·36), initial upper arm or shoulder fracture (aHR 5·06, 95% CI 4·39-5·82), initial upper leg fracture (aHR 5·11, 95% CI 3·91-6·67), initial knee fracture (aHR 5·03, 95% CI 4·20-6·03), initial lower leg/ankle fracture (aHR 4·10, 95% CI 3·58-4·68), and initial spine fracture (aHR 6·69, 95% CI 5·95-7·53). Associations were significant in all age groups, even women aged 50-59 years. Risks of subsequent fracture were more pronounced among non-Hispanic Black, Hispanic/Latina, and Asian/Pacific Islander than among non-Hispanic White women.

Interpretation: Increased risk of subsequent fracture is observed for all fracture types across all ages. Women who experience any of these fractures should be targeted for interventions to prevent subsequent fractures.

Funding: National Institutes of Health HHSN268201600018C,HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.

Keywords: Fracture; Osteoporosis.

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Conflict of interest statement

TG reports grants from National Heart, Lung, and Blood Institute, during the conduct of the study. RH reports grants from NHLBI, during the conduct of the study. KJ reports grants from NIH, during the conduct of the study. AL reports grants from National Institutes of Health, NHLBI, during the conduct of the study. KS reports grants from Merck & Co., outside the submitted work. JW-W reports grants from NHLBI, during the conduct of the study. MS reports grants from American Cancer Society, grants from The Centers for Disease Control and Prevention, grants from Florida Department of Health, outside the submitted work. The other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Analytic sample flow (STROBE algorithm).
Fig. 2
Fig. 2
Associations between initial fracture and subsequent fracture by site. Fx: fracture; Sub: subsequent; Ann: Annualized; HR: hazard ratio; CI: confidence interval Model 1 is adjusted for each of the clinical trial (Estrogen + Progestin, Estrogen-alone, Dietary Modification and Calcium + Vitamin D [time-dependent]) randomization arms, age, race/ethnicity, BMI and current hormone use at randomization (WHI Hormone Therapy (HT) trial active randomization arm or current hormone use for non-HT participants). Model 2 is adjusted for covariates in model 1 plus education, smoking status, total metabolic equivalent of task h/wk, total dietary + supplemental calcium intake, total dietary + supplemental vitamin D intake, number of falls, alcohol intake and physical function score. Fig. 2a. Associations between incident lower arm/wrist fracture and subsequent fracture by site. Figure 2b. Associations between incident upper arm or shoulder fracture and subsequent fracture by site. Fig. 2c. Associations between incident upper leg fracture and subsequent fracture by site. Fig. 2d Associations between incident knee fracture and subsequent fracture by site. Fig. 2e. Associations between incident lower leg/ankle fracture and subsequent fracture by site. Fig. 2f. Associations between incident hip/pelvis fracture and subsequent fracture by site. Fig. 2 g. Associations between incident vertebral fracture and subsequent fracture by site.
Fig. 3
Fig. 3
Associations between incident fracture and any subsequent clinical fracture by initial fracture site and age at screening. Fx: fracture; Sub: subsequent; Ann: Annualized; HR: hazard ratio; CI: confidence interval.
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