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Postmenopausal Fracture History and Survival After Reproductive Cancer Diagnosis.

ABSTRACT: Background:Postmenopausal bone fracture's have been proposed as a marker of lifetime estrogen exposure and have been associated with decreased risk of breast and endometrial cancer. It is plausible that prediagnostic fractures may be related to survival of estrogen-sensitive cancers. Methods:We evaluated a cohort of breast (n = 6411), endometrial (n = 1127), and ovarian (n = 658) cancer cases diagnosed between 1992 and 2010 while participating in the Women's Health Initiative. Postmenopausal fracture history was assessed from baseline reports of fractures after age 55 years and incident fractures that occurred at least one year prior to cancer diagnosis during study follow-up. Using Cox regression, we compared women with and without a history of fractures with respect to overall and cancer-specific survival. Estimates were adjusted for participant factors, including hormone therapy use; hormone receptor status was not included in our analysis. Results:Among women with breast cancer, a history of prediagnostic fractures at any site was associated with poorer overall survival (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.05 to 1.43). A history of hip, forearm, or spine fractures, or hip fracture alone, was associated with increased risk of mortality (HR = 1.26, 95% CI = 1.01 to 1.58, and HR = 2.05, 95% CI = 1.27 to 3.32, respectively). Fracture history was associated neither with cancer-specific survival among breast cancer survivors, nor with overall or disease-specific mortality among endometrial and ovarian cancer survivors. Conclusions:Postmenopausal breast cancer patients with a history of fractures, especially of the hip, are more likely to die of any cause than breast cancer survivors without a fracture history. Identifying and intervening in fracture risk factors should be standard of care for all women diagnosed with breast cancer.

SUBMITTER: Newcomb PA

PROVIDER: S-EPMC6643753 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Postmenopausal Fracture History and Survival After Reproductive Cancer Diagnosis.

Newcomb Polly A PA Adams Scott V SV Mayer Sophie S Passarelli Michael N MN Tinker Lesley L Lane Dorothy D Chlebowski Rowan T RT Crandall Carolyn J CJ

JNCI cancer spectrum 20180101 1

<h4>Background</h4>Postmenopausal bone fracture's have been proposed as a marker of lifetime estrogen exposure and have been associated with decreased risk of breast and endometrial cancer. It is plausible that prediagnostic fractures may be related to survival of estrogen-sensitive cancers.<h4>Methods</h4>We evaluated a cohort of breast (n = 6411), endometrial (n = 1127), and ovarian (n = 658) cancer cases diagnosed between 1992 and 2010 while participating in the Women's Health Initiative. Pos ...[more]

PMID: 31355356

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Project description:ImportanceAlthough estrogen level is positively associated with bone mineral density, there are limited data on the risk of fractures after menopause.ObjectiveTo investigate whether female reproductive factors are associated with fractures among postmenopausal women.Design, setting, and participantsThis population-based retrospective cohort study used data from the Korean National Health Insurance Service database on 1 272 115 postmenopausal women without previous fracture who underwent both cardiovascular and breast and/or cervical cancer screening from January 1 to December 31, 2009. Outcome data were obtained through December 31, 2018.ExposuresInformation was obtained about reproductive factors (age at menarche, age at menopause, parity, breastfeeding, and exogenous hormone use) by self-administered questionnaire.Main outcomes and measuresIncidence of any fractures and site-specific fractures (vertebral, hip, and others).ResultsAmong the 1 272 115 participants, mean (SD) age was 61.0 (8.1) years. Compared with earlier age at menarche (≤12 years), later age at menarche (≥17 years) was associated with a higher risk of any fracture (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.17-1.31) and vertebral fracture (aHR, 1.42; 95% CI, 1.28-1.58). Compared with earlier age at menopause (<40 years), later age at menopause (≥55 years) was associated with a lower risk of any fracture (aHR, 0.89; 95% CI, 0.86-0.93), vertebral fracture (aHR, 0.77; 95% CI, 0.73-0.81), and hip fracture (aHR, 0.88; 95% CI, 0.78-1.00). Longer reproductive span (≥40 years) was associated with lower risk of fractures compared with shorter reproductive span (<30 years) (any fracture: aHR, 0.86; 95% CI, 0.84-0.88; vertebral fracture: aHR, 0.73; 95% CI, 0.71-0.76; and hip fracture: aHR, 0.87; 95% CI, 0.80-0.95). Parous women had a lower risk of any fracture than nulliparous women (aHR, 0.96; 95% CI, 0.92-0.99). Although breastfeeding for 12 months or longer was associated with a higher risk of any fractures (aHR, 1.05; 95% CI, 1.03-1.08) and vertebral fractures (aHR, 1.22; 95% CI, 1.17-1.27), it was associated with a lower risk of hip fracture (aHR, 0.84; 95% CI, 0.76-0.93). Hormone therapy for 5 years or longer was associated with lower risk of any factures (aHR, 0.85; 95% CI, 0.83-0.88), while use of oral contraceptives for 1 year or longer was associated with a higher risk of any fractures (aHR, 1.03; 95% CI, 1.01-1.05).Conclusions and relevanceThe findings of this cohort study suggest that female reproductive factors are independent risk factors for fracture, with a higher risk associated with shorter lifetime endogenous estrogen exposure. Interventions to reduce fracture risk may be needed for women at high risk, including those without osteoporosis.

Project description:The ability of bone mineral density (BMD) and other risk factors to predict fracture risk is well-established for as long as 5 to 10 years. However, their value to predict risk over a longer term has not been directly studied. We investigated whether a single assessment of femoral neck BMD and fracture history can predict fracture risk over 20 to 25 years. We used data from the Study of Osteoporotic Fractures (SOF) that assessed BMD and risk factors in 7959 women age ≥67 (mean = 73.4) in 1988-1990. Follow-up for fractures continued for 25 years for hip fracture, and for 20 years for any nonvertebral fracture. Using age-adjusted proportional hazards models, we analyzed the relationships between a single baseline assessment of femoral neck BMD, fracture history and age, and 20-25-year fracture incidence. The 25-year cumulative incidence of hip fracture was 17.9%; 20-year incidence of any nonvertebral fracture was 46.2%. The 25-year hip fracture incidence was highest in those ≥80 years old (22.6%) compared to 13.9% in women aged <70 years. A single femoral neck BMD measurement strongly predicted long-term hip fracture risk to 25 years: 29.6% risk in the lowest BMD quartile versus 7.6% with the highest relative hazard (RH) = 4.9 (95% CI, 4.1 to 6.0). Femoral neck BMD predicted hip fracture with little degradation over time from RH/SD = 2.6 (2.2 to 3.0) for 0 to 5 years to RH/SD = 1.8 (1.4 to 2.4) for 20 to 25 years. Lifetime hip fracture risk was similar (∼30%) regardless of age from 67 to >80 years. History of hip fracture predicted hip fractures only slightly better than history of nonvertebral fracture (RH = 1.6 [95% CI, 1.1 to 2.2] versus RH = 1.4 [95% CI, 1.2 to 1.5], respectively). Fracture history remained strongly predictive up to 25 years. We conclude that a single BMD and fracture history assessment can predict fracture risk over 20 to 25 years. Long-term risk of hip fracture remains extremely high in the oldest age groups, supporting risk assessment and consideration of treatment even in the oldest, highest-risk women.© 2017 American Society for Bone and Mineral Research.

Project description:Study questionWhat is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women?Summary answerHigher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity.What is known alreadyPostmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI.Study design, size, durationThis study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis.Participants/materials, setting, methodsData were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI.Main results and the role of chanceWomen who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies.Limitations, reasons for cautionThe WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics.Wider implications of the findingsThis study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention.Study funding/competing interest(s)HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare.Trial registration numberN/A.

Project description:SummaryOdanacatib is a cathepsin K inhibitor investigated for the treatment of postmenopausal osteoporosis. Phase 2 data indicate that 50 mg once weekly inhibits bone resorption and increases bone mineral density, with only a transient decrease in bone formation. We describe the background, design and participant characteristics for the phase 3 registration trial.IntroductionOdanacatib (ODN) is a selective cathepsin K inhibitor being evaluated for the treatment of osteoporosis. In a phase 2 trial, ODN 50 mg once weekly reduced bone resorption while preserving bone formation and progressively increased BMD over 5 years. We describe the phase III Long-Term ODN Fracture Trial (LOFT), an event-driven, randomized, blinded placebo-controlled trial, with preplanned interim analyses to permit early termination if significant fracture risk reduction was demonstrated. An extension was planned, with participants remaining on their randomized treatment for up to 5 years, then transitioning to open-label ODN.MethodsThe three primary outcomes were radiologically determined vertebral, hip, and clinical non-vertebral fractures. Secondary end points included clinical vertebral fractures, BMD, bone turnover markers, and safety and tolerability, including bone histology. Participants were women, 65 years or older, with a BMD T-score≤-2.5 at the total hip (TH) or femoral neck (FN) or with a prior radiographic vertebral fracture and a T-score≤-1.5 at the TH or FN. They were randomized to ODN or placebo tablets. All received weekly vitamin D3 (5600 international units (IU)) and daily calcium supplements as needed to ensure a daily intake of approximately 1200 mg.ResultsAltogether, 16,713 participants were randomized at 387 centers. After a planned interim analysis, an independent data monitoring committee recommended that the study be stopped early due to robust efficacy and a favorable benefit/risk profile. Following the base study closeout, 8256 participants entered the study extension.ConclusionsThis report details the background and study design of this fracture end point trial and describes the baseline characteristics of its participants.

Project description:ImportanceThe number of cancer survivors living in the US is projected to be 26.1 million by 2040. Cancer survivors may be at increased risk of bone fractures, but research is limited in several important ways.ObjectiveTo investigate the associations of cancer diagnoses, including time since diagnosis and stage at diagnosis, with risks of pelvic, radial, and vertebral fractures (separately and combined) among older cancer survivors and compared with fracture risk among older adults without a history of cancer. Secondarily, to examine differences in risk of fracture stratified by modifiable behaviors, treatment, and cancer type.Design, setting, and participantsThis longitudinal cohort study used data from 92 431 older adults in the US Cancer Prevention Study II Nutrition Cohort linked with 1999 to 2017 Medicare claims. Data were analyzed from July 15, 2021, to May 3, 2022.ExposuresCancer history, time since cancer diagnosis, and stage at cancer diagnosis.Main outcomes and measuresHazard ratios (HRs) and 95% CIs for the risk of pelvic, radial, vertebral, and total frailty-related fractures were estimated using multivariate Cox proportional hazards regression. Stratification was used for secondary aims.ResultsAmong 92 431 participants (mean [SD] age, was 69.4 [6.0] years, 51 820 [56%] women, and 90 458 [97.9%] White], 12 943 participants experienced a frailty-related bone fracture. Compared with participants without a history of cancer, cancer survivors who were diagnosed 1 to less than 5 years earlier with advanced stage cancer had higher risk of fracture (HR, 2.12; 95% CI, 1.75-2.58). The higher fracture risk in cancer survivors with recent advanced stage diagnosis (vs no cancer) was driven largely by vertebral (HR, 2.46; 95% CI, 1.93-3.13) and pelvic (HR, 2.46; 95% CI, 1.84-3.29) fracture sites. Compared with cancer survivors who did not receive chemotherapy, survivors who received chemotherapy were more likely to have a fracture; this association was stronger within 5 years of diagnosis (HR, 1.31; 95% CI, 1.09-1.57) than 5 or more years after diagnosis (HR, 1.22; 95% CI, 0.99-1.51). Although the HR for risk of fracture was lower among physically active cancer survivors 5 or more years after diagnosis (HR, 0.76; 95% CI, 0.54-1.07), this result was not statistically significant, whereas current smoking was significantly associated with higher risk of fracture (HR, 2.27; 95% CI, 1.55-3.33).Conclusions and relevanceFindings from this cohort study suggest that older adults with a history of cancer may benefit from clinical guidance on prevention of frailty-related fractures. If study findings are replicated, fracture prevention programs for survivors might include referrals for physical activity with cancer exercise professionals and smoking cessation programs.

Dataset Information

Postmenopausal Fracture History and Survival After Reproductive Cancer Diagnosis.

Publications

Postmenopausal Fracture History and Survival After Reproductive Cancer Diagnosis.

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