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      Radiotherapy-related insufficiency fractures and bone mineral density: what is the connection?


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          Radiotherapy-related insufficiency fractures (RRIFs) represent a common, burdensome consequence of pelvic radiotherapy. Their underlying mechanisms remain unclear, and data on the effect of osteoporosis are contradictory, with limited studies assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA).


          BMD by DXA (Hologic) scan and fracture risk following pelvic RRIF were retrospectively assessed in 39 patients (median age 68 years) at a tertiary cancer centre. Patient characteristics and treatment history are presented narratively; correlations were explored using univariate regression analyses.


          Additional cancer treatments included chemotherapy ( n = 31), surgery ( n = 20) and brachytherapy ( n = 19). Median interval between initiation of radiotherapy and RRIF was 11 (7.5–20.8) and that between RRIF and DXA 3 was (1–6) months. Three patients had normal BMD, 16 had osteopenia and 16 osteoporosis, following World Health Organization classification. Four patients were <40 years at the time of DXA (all Z-scores > –2). Median 10-year risk for hip and major osteoporotic fracture was 3.1% (1.5–5.7) and 11.5% (7.1–13.8), respectively. Only 33.3% of patients had high fracture risk (hip fracture >4% and/or major osteoporotic >20%), and 31% fell above the intervention threshold per National Osteoporosis Guidelines Group (NOGG) guidance (2017). Higher BMD was predicted by lower pelvic radiotherapy dose (only in L3 and L4), concomitant chemotherapy and higher body mass index.


          At the time of RRIF, most patients did not have osteoporosis, some had normal BMD and overall had low fracture risk. Whilst low BMD is a probable risk factor, it is unlikely to be the main mechanism underlying RRIFs, and further studies are required to understand the predictive value of BMD.

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          European guidance for the diagnosis and management of osteoporosis in postmenopausal women

          Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. Methods Systematic reviews were updated. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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            Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.

            In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.
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              Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study.

              The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm(2)/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = -0.50; P < .01) and bone formation rate (r = -0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI. At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                25 April 2023
                25 April 2023
                01 July 2023
                : 12
                : 7
                : e220328
                [1 ]Department of Endocrinology , Christie Hospital NHS Foundation Trust, Manchester, UK
                [2 ]Department of Endocrinology , University of Manchester, School of Medical Sciences, Manchester, UK
                [3 ]Department of Radiology , Christie Hospital NHS Foundation Trust, Manchester, UK
                [4 ]Department of Radiotherapy , Christie Hospital NHS Foundation Trust, Manchester, UK
                [5 ]Department of Clinical Oncology , Christie Hospital NHS Foundation Trust, Manchester, UK
                [6 ]Department of Endocrinology , University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
                Author notes
                Correspondence should be addressed to V Chatzimavridou-Grigoriadou or C E Higham: viktoria.chatzimavridou@ 123456nhs.net or claire.higham2@ 123456nhs.net
                Author information
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                : 31 March 2023
                : 25 April 2023

                radiotherapy-related insufficiency fractures,insufficiency fracture,radiotherapy,bone mineral density,clinical predictors,late effects of cancer therapy


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