Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

López-Delgado, Laura; Riancho‐Zarrabeitia, Leyre; Riancho, José A.

doi:10.1517/17425255.2016.1154533

Cited by 17 publications

(13 citation statements)

References 107 publications

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“…Variability in side effects due to bisphosphonate in patients; It may be caused by the interpersonal difference of genes related to osteoclasts and bone cycle affected by bisphosphonates. [ 6 ] Although the family history in our case supports this view, many recent studies have illustrated variability in target genes and their relationship with bone mass and other determinants of fracture risk such as bone characteristics, skeletal geometry, and bone turnover markers. The importance of genetic factors in bone quality, treatment response to osteoporosis, and bone turnover has been also proven.…”

Section: Discussionsupporting

confidence: 64%

“…In addition, the risk for exposure to adverse effects due to bisphosphonate use has been shown to have a polygenic basis. [ 4 - 6 ] In this report, we present two cases (mother and daughter) of the same family who developed bilateral multiple atypical femoral fractures (AFFs) after three and four years of bisphosphonate use, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Is there a familial predisposition to bisphosphonate-induced atypical femoral fractures?

Okçu¹,

Koçak²,

Kaya³

et al. 2021

Turk J Phys Med Rehab

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Bisphosphonates are commonly used in the treatment of osteoporosis. Atypical femoral fracture (AFF) is a well-known adverse effect of bisphosphonate use. The importance of genetic factors has been demonstrated in bone quality, bone turnover, and in the response to osteoporosis treatment. Herein, we present two cases of bilateral AFFs after bisphosphonate use for a short period of time in members of the same family (mother and her daughter) and discuss genetic predisposition to bisphosphonate-induced AFFs in the light of literature data.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Is there a familial predisposition to bisphosphonate-induced atypical femoral fractures?

Okçu¹,

Koçak²,

Kaya³

et al. 2021

Turk J Phys Med Rehab

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show abstract

“…At the current stage of genetics research, there are few instances where genetic association findings are directly used clinically. However, because hip geometry contributes to hip fracture risk, discovery of genetic determinants of hip geometry may have utility in predicting fracture as methods to derive polygenic risk scores mature further . Because hip geometry still evolves in early life and even beyond, the identification of genetic determinants of hip architecture could be used as potential diagnostic tools and drug targets to improve bone strength.…”

Section: Discussionmentioning

confidence: 99%

“…They are associated with a more than twofold increase in the likelihood of mortality, a fourfold increase in the probability of requiring institutional care, and a twofold increase in entering low-income status 1 year postfracture as compared to patients who do not sustain hip fractures. (2) Hip fractures may be preventable in as many as 50% of cases through the use of the available pharmacotherapies, (3) but improvements in the identification of high-risk patients are necessary. (4,5) The most often studied phenotype for genetic studies of osteoporosis is bone mineral density (BMD) as assessed by dualenergy X-ray absorptiometry (DXA) of the hip.…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry

Hsu

Estrada

Εvangelou

et al. 2019

Journal of Bone and Mineral Research

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Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with ~2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p ≤ 2.6 × 10−8) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 × 10−5). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility.

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“…To date, we have only limited knowledge about Vγ9Vδ2 T cell activation in vivo , with or without stimulatory compounds and cytokines. We also know that some tumors may upregulate expression of FDPS, the enzyme responsible for converting IPP to farnesol ( 78 ). Such tumors may have smaller pools of IPP hence lesser capacity for directly activating Vγ9Vδ2 T cells.…”

Section: Tumor Mechanisms For Immune Evasionmentioning

confidence: 99%

Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local

Pauza¹,

Liou²,

Lahusen³

et al. 2018

Front. Immunol.

101

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Human gamma delta T cells have extraordinary properties including the capacity for tumor cell killing. The major gamma delta T cell subset in human beings is designated Vγ9Vδ2 and is activated by intermediates of isoprenoid biosynthesis or aminobisphosphonate inhibitors of farnesyldiphosphate synthase. Activated cells are potent for killing a broad range of tumor cells and demonstrated the capacity for tumor reduction in murine xenotransplant tumor models. Translating these findings to the clinic produced promising initial results but greater potency is needed. Here, we review the literature on gamma delta T cells in cancer therapy with emphasis on the Vγ9Vδ2 T cell subset. Our goal was to examine obstacles preventing effective Vγ9Vδ2 T cell therapy and strategies for overcoming them. We focus on the potential for local activation of Vγ9Vδ2 T cells within the tumor environment to increase potency and achieve objective responses during cancer therapy. The gamma delta T cells and especially the Vγ9Vδ2 T cell subset, have the potential to overcome many problems in cancer therapy especially for tumors with no known treatment, lacking tumor-specific antigens for targeting by antibodies and CAR-T, or unresponsive to immune checkpoint inhibitors. Translation of amazing work from many laboratories studying gamma delta T cells is needed to fulfill the promise of effective and safe cancer immunotherapy.

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Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Cited by 17 publications

References 107 publications

Is there a familial predisposition to bisphosphonate-induced atypical femoral fractures?

Is there a familial predisposition to bisphosphonate-induced atypical femoral fractures?

Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry

Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local

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