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Eriksen, Erik Fink; Glerup, Henning

doi:10.1023/a:1015263514765

Cited by 63 publications

(16 citation statements)

References 22 publications

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“…Vitamin D 3 deficiency is prevalent in the elderly population and has been linked to an increased risk for breast cancer [23]. To assess the potential impact of vitamin D 3 signaling in aging mammary glands, we used real time PCR to assess VDR gene expression in mammary glands harvested from 12, 14 and 16 month old virgin mice.…”

Section: Resultsmentioning

confidence: 99%

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

et al. 2011

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The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment.

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Section: Resultsmentioning

confidence: 99%

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

et al. 2011

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“…Vitamin D is associated with muscular health 7 and contributes to the maintenance of muscle strength during ageing 5,8. Higher serum vitamin D concentrations have also been associated with greater muscle strength in healthy older individuals 4,5 who have suffered falls 9 and in those who have osteoporosis 6.…”

Section: Introductionmentioning

confidence: 99%

Serum 25-hydroxyvitamin D levels are associated with functional capacity but not with postural balance in osteoporotic postmenopausal women

Brech¹,

Ciolac²,

Peterson³

et al. 2017

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OBJECTIVES:In post-menopausal women with osteoporosis, insufficient vitamin D levels decrease calcium fixation in the bones and calcium transport in the sarcoplasmic reticulum, which impairs muscle strength, possibly leading to detrimental consequences for the preservation of functional capacity and postural balance, fall prevention, and fracture risk. The aim of this study was to evaluate the association between vitamin D levels and knee muscle strength, postural balance and functional mobility among postmenopausal women with osteoporosis.METHODS:This cross-sectional study included 63 osteoporotic older women (aged 60.6±3.1 years). The subjects completed the Timed Up and Go Test to measure functional mobility, and postural balance was assessed on the AccuSway Plus portable force platform. Maximal strength was tested using an isokinetic dynamometer for knee flexion and extension. The subjects were assessed as a group and were divided into quartiles according to their vitamin D levels. Clinicaltrials.gov: NCT02771834.RESULTS:Vitamin D status was independently associated with the normalized peak torque of the knee extensors (β=0.59; p=0.04) and Timed Up and Go Test (β=-0.07; p<0.001). No between-group differences were observed in the demographic and clinical variables or postural balance; however, significant differences were observed in the Timed Up and Go Test, and the group with the highest vitamin D levels exhibited better performance than the group with the lowest vitamin D levels (p<0.001).CONCLUSION:The serum vitamin D levels were independently associated with normalized knee extension strength and functional mobility in postmenopausal women with osteoporosis.

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“…Depletion of any of these hormones leads to a bone mass reduction, which in some cases is very severe (Eriksen & Glerup 2002). In postmenopausal women, the only sources of estrogens are through the aromatase function in peripheral tissues and through steroid sulfatase activity (Reed et al 2005), which is also active in bone (Muir et al 2004).…”

Section: Introductionmentioning

confidence: 99%

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Rodríguez-Sanz

Garcia-Giralt

Prieto-Alhambra

et al. 2015

Journal of Molecular Endocrinology

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Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P!0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss. Journal of Molecular EndocrinologyResearch M RODRI´GUEZ-SANZ and others CYP11A1 is associated with AI-related bone loss 55:1 69-79http://jme.endocrinology-journals.org Ñ 2015 Society for Endocrinology DOI: 10.1530/JME-15-0079Printed in Great BritainPublished by Bioscientifica Ltd. IntroductionAromatase inhibitors (AIs) are commonly used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Although AIs are generally well tolerated with few serious adverse events, a number of musculoskeletal side effects affecting quality of life have been noted and often lead to discontinuation of therapy (Eastell et al. 2006, Henry et al. 2008.The most common side effects reported with AIs are exacerbation of menopausal symptoms as a result of low estrogen levels; these include pain syndromes, bone loss and associated fracture , Laroche et al. 2014. Several prospective studies and clinical trials have noted the need for assessment and treatment of these musculoskeletal adverse events (Reid et al. 2008, Brufsky et al. 2009, Servitja et al. 2012. In particular, bone mineral density (BMD) reduction and fracture incidence associated with AI therapy can be significantly reduced by oral bisphosphonates (BP) treatment (Bouvard et al. 2014).We are currently conducting a prospective, nonselected, observational, clinical cohort study (BarcelonaAromatase induced bone loss in early breast cancer (B-ABLE...

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Cited by 63 publications

References 22 publications

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

Serum 25-hydroxyvitamin D levels are associated with functional capacity but not with postural balance in osteoporotic postmenopausal women

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

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