Association of Fat Body Mass With Vertebral Fractures in Postmenopausal Women With Early Breast Cancer Undergoing Adjuvant Aromatase Inhibitor Therapy

Pedersini, Rebecca; Amoroso, Vito; Maffezzoni, Filippo; Gallo, Fabio; Turla, Antonella; Monteverdi, Sara; Ardine, Mara; Ravanelli, Marco; Vassalli, Lucia; Rodella, Filippo; Formenti, Anna Maria; Volta, Alberto Dalla; Simoncini, Edda; Giustina, Andrea; Maroldi, Roberto; Berruti, Alfredo

doi:10.1001/jamanetworkopen.2019.11080

Cited by 26 publications

(42 citation statements)

References 58 publications

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“…Obese men on ADT may be at higher risk of bone fractures because of the loss of the protection associated with oestrogens and to the detrimental changes in bone quality associated with adiposity. In a large single institution cross-sectional study recently published,37 fat body mass assessed by DEXA scan had a protective effect on morphometric vertebral fractures in patients with breast cancer not undergoing AIs, whereas it was associated with an increased risk of fragility fractures in women on AIs. Evidence supports the obesity paradox even in advanced PCa,38 where early increase in fat body mass has recently been shown to predict a higher risk of SRE (HR 3.024, 95% CI 1.004 to 10.353, p<0.02), a higher risk of death (HR 2.373, 95% CI 1.012 to 5.567, p=0.04) and a non-significant higher risk of disease recurrence (HR 2.219, 95% CI 0.956 to 5.150, p=0.13) 39.…”

Section: Bone Health During Adtmentioning

confidence: 91%

Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

et al. 2020

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Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice. To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was to raise awareness on the importance of bone preservation in this complex setting, while providing an instrument to support physicians and facilitate the management of bone health. Current evidence regarding the effects on bone health of ADT, of novel hormone therapies (which improve progression delay, pain control and QoL while consistently carrying the risk of non-pathological fractures in both non-metastatic and metastatic PCa) and of bone turnover inhibitors (whose use is frequently suboptimal) is reviewed. Finally, the expert opinion to optimise bone health preservation is given.

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Section: Bone Health During Adtmentioning

confidence: 91%

Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

et al. 2020

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“…Screening for osteoporosis should include detailed patient's history aimed to identify other risk factors, including familiarity, age, lifestyle, concomitant medications, smoking habit, prior fractures, baseline body mass index (BMI) and measurement of BMD by dual-energy X-ray absorptiometry scan (DXA) at baseline [54,55]. However, some recent reports suggest that both BMD evaluation and low BMI were not accurate predictive factors for fracture risk in AIs-treated patients, since BMD data are associated with vertebral fractures in AI-naïve patients, but not in women receiving AIs [56,57]. This evidence induced to hypothesize that different pathophysiology mechanisms, as those affecting the bone geometry, bone microstructure, and other elements of bone quality, could contribute to the bone fragility in AIs-treated women [58].…”

Section: Etiopathophysiology Of Ais-induced Bone Lossmentioning

confidence: 99%

“…In the general population, obesity seems to be associated with a lower risk for osteoporotic fractures, when compared to low values of BMI, possibly due to a protective role of higher estrogen amounts. Conversely, in women undergoing AIs, fat body mass results positively associated with an increased risk for bone fractures, probably due to the loss of estrogen protection, and the oxidative stress and inflammation related to obesity [57].…”

Section: Etiopathophysiology Of Ais-induced Bone Lossmentioning

confidence: 99%

Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

Tenti

Correale

Cheleschi

et al. 2020

IJMS

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Aromatase inhibitors (AIs) have radically changed the prognosis of hormone receptor positive breast cancer (BC) in post-menopausal women, and are a mainstay of the adjuvant therapy for BC after surgery in place of, or following, Tamoxifen. However, AIs aren’t side effect-free; frequent adverse events involve the musculoskeletal system, in the form of bone loss, AI-associated arthralgia (AIA) syndrome and autoimmune rheumatic diseases. In this narrative review, we reported the main clinical features of these three detrimental conditions, their influence on therapy adherence, the possible underlying molecular mechanisms and the available pharmacological and non-pharmacological treatments. The best-known form is the AIs-induced osteoporosis, whose molecular pathway and therapeutic possibilities were extensively investigated in the last decade. AIA syndrome is a high prevalent joint pain disorder which often determines a premature discontinuation of the therapy. Several points still need to be clarified, as a universally accepted diagnostic definition, the pathogenetic mechanisms and satisfactory management strategies. The association of AIs therapy with autoimmune diseases is of the utmost interest. The related literature has been recently expanded, but many issues remain to be explored, the first being the molecular mechanisms.

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“…For this purpose, we used a prospectively collected dataset from a study approved and conducted at a single institution, whose preliminary results were previously reported. ( 4,8 )…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, postmenopausal women receiving AI therapy that had high‐fat body mass (FBM), as measured by dual‐energy X‐ray absorptiometry (DXA), had an increased prevalence of morphometric VFs as compared with women with low‐FBM. ( 8 ) Detrimental effects of adiposity on bone quality could be hypothesized through altered bone‐regulating hormones, including vitamin D, ( 9 ) increased oxidative stress, and inflammation, combined with bone effects induced by the low levels of estrogens with AI therapy. ( 8,10,11 )…”

Section: Introductionmentioning

confidence: 99%

The Interaction of Lean Body Mass With Fat Body Mass Is Associated With Vertebral Fracture Prevalence in Women With Early Breast Cancer Undergoing Aromatase Inhibitor Therapy

et al. 2020

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Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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Association of Fat Body Mass With Vertebral Fractures in Postmenopausal Women With Early Breast Cancer Undergoing Adjuvant Aromatase Inhibitor Therapy

Cited by 26 publications

References 58 publications

Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

The Interaction of Lean Body Mass With Fat Body Mass Is Associated With Vertebral Fracture Prevalence in Women With Early Breast Cancer Undergoing Aromatase Inhibitor Therapy

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