Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy

Neuner, Joan; Shi, Yushu; Kong, Amanda L.; Kamaraju, Sailaja; Smith, Elizabeth C.; Smallwood, Alicia; Laud, Purushottam W.; Charlson, John A.

doi:10.1007/s11764-017-0666-4

Cited by 10 publications

(10 citation statements)

References 28 publications

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“…(10) Although one report suggested a threefold increased fracture incidence, (23) a large nationwide population-based cohort study using US Medicare data identified minimal excess risk from AI use compared with tamoxifen (11% higher for nonvertebral fractures, not significantly increased for hip fractures). (24) Our findings are therefore in agreement with the latter study. Our observation that fracture risk was relatively low in women initiating AI therapy may indicate that higher baseline BMI, BMD, and lower prevalence of prior fracture may offset the adverse effects of AI exposure.…”

Section: Discussionsupporting

confidence: 93%

“…Although one report suggested a threefold increased fracture incidence, a large nationwide population‐based cohort study using US Medicare data identified minimal excess risk from AI use compared with tamoxifen (11% higher for nonvertebral fractures, not significantly increased for hip fractures) . Our findings are therefore in agreement with the latter study.…”

Section: Discussionsupporting

confidence: 91%

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Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Leslie

Morin

Lix

et al. 2019

Journal of Bone and Mineral Research

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FRAX was developed to predict 10‐year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under “secondary osteoporosis”. To inform use of FRAX in women treated with AI, we used a population‐based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months’ AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10‐year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45–0.68; 10‐year hip fracture observed/predicted ratio 0.33, 95% CI 0.18–0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p‐interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64–0.95), hip fracture (HR = 0.46, 95% CI 0.29–0.73) and any fracture (HR = 0.75, 95% CI 0.63–0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non‐users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Leslie

Morin

Lix

et al. 2019

Journal of Bone and Mineral Research

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“…If this were a frequent occurrence, then mean BMD among women with breast cancer not receiving AIs (and particularly among those selected to receive tamoxifen rather than AIs) should be lower than in the general population, but this was not the case. Regardless of the mechanism, our findings suggest that fracture risk in women encountered in routine clinical practice receiving AI therapy may not be as elevated as has previously been suggested and is consistent with the U.S. Medicare data suggesting little excess risk . A smaller observational real‐life cohort found that 3 years of AI treatment was not associated with a major increase in fracture risk in 267 postmenopausal nonosteoporotic women with breast cancer .…”

Section: Discussionsupporting

confidence: 86%

“…The use of aromatase inhibitors (AIs) increases bone turnover and induces bone loss at trabecular‐rich bone sites at an average rate of 1% to 3% per year, with reports of up to threefold increased fracture incidence . In contrast, a large nationwide population‐based cohort study using U.S. Medicare data identified minimal excess fracture risk from AI use compared with tamoxifen (11% higher for nonvertebral fractures, not significantly increased for hip fractures) .…”

Section: Introductionmentioning

confidence: 99%

Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

et al. 2019

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Background Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Materials and Methods Using a population‐based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). Results At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93–1.42), hip fracture (HR, 0.90; 95% CI, 0.56–1.43), or any fracture (HR, 1.06; 95% CI, 0.88–1.28) compared with the general population. Conclusion Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. Implications for Practice In a population‐based observational registry that included 1,775 patients initiating long‐term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.

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“…A Danish cohort study reported a higher risk of fracture occurrence related to AIs, compared to endocrine‐untreated patients, whereas TAM had a protective effect on bone mass in postmenopausal women with breast cancer . In a 2018 report on a population‐based, retrospective cohort study, Neuner and colleagues further corroborate this finding. They describe an increased risk for nonvertebral fractures in patients treated with AI, compared to TAM.…”

Section: Introductionmentioning

confidence: 87%

Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates

Pineda-Moncusí

Garcia-Giralt

Díez-Pérez

et al. 2019

Journal of Bone and Mineral Research

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Aromatase inhibitors have been associated with accelerated bone loss and an increased risk of osteoporotic fractures. Currently, bisphosphonates are recommended to reduce fracture risk in these patients. The aim of this study is to evaluate the fracture risk in breast cancer patients receiving aromatase inhibitors, compared to tamoxifen users, and to assess the effectiveness of oral bisphosphonates in reducing fracture risk. We performed an observational cohort study up to 10 years of follow-up. Data were extracted from primary care records in a population database. Women diagnosed with breast cancer between 2006 and 2015 and treated with tamoxifen or aromatase inhibitors (n = 36,472) were stratified according to low (without osteoporosis diagnosis nor bisphosphonates exposure) or high (with osteoporosis and/or treated with bisphosphonates) fracture risk. Cox models were used to calculate hazard ratios (HR [95% CI]) of fracture from the propensity score-matched patients. Sensitivity analyses account for competing risk of death were performed (subdistribution hazard ratio [SHR] [95% CI]). In postmenopausal women, fracture risk in aromatase inhibitor users showed an HR 1.40 [95% CI,1.05 to 1.87] and SHR 1.48 [95% CI, 1.11 to 1.98], compared to tamoxifen. Observing aromatase inhibitors patients at high risk of fracture, bisphosphonate-treated patients had an HR 0.73 [95% CI, 0.51 to 1.04] and SHR 0.69 [95% CI, 0.48 to 0.98] compared to nontreated. In conclusion, fracture risk in postmenopausal women during aromatase inhibitor treatment, in reallife conditions, was >40% compared to tamoxifen, corroborating previous randomized controlled trials results. In high-risk patients, bisphosphonate users had lower significant fracture incidence during aromatase inhibitor therapy than nonbisphosphonate users. Monitoring fracture risk and related risk factors in aromatase inhibitor patients is advisable. n 292 PINEDA-MONCUSÍ ET AL. 215 (1.43) 62 (0.82) Rheumatoid arthritis, n (%) 117 (0.78) 43 (0.57) Chronic kidney disease, n (%) 513 (3.41) 75 (0.99) Osteoporosis, n (%) 1859 (12.40) 371 (4.92) Hypnotics/sedative, n (%) 8843 (58.70) 3621 (48.00) AI = aromatase inhibitor; BMI = body mass index; TAM = tamoxifen. Journal of Bone and Mineral Research n 294 PINEDA-MONCUSÍ ET AL.

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Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy

Abstract: Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.

Cited by 10 publications

References 28 publications

Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Performance of FRAX in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Increased Fracture Risk in Women Treated With Aromatase Inhibitors Versus Tamoxifen: Beneficial Effect of Bisphosphonates

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