Pharmacogenetics of osteoporosis

Marini, Francesca; Brandi, Maria Luisa

doi:10.1016/j.beem.2014.07.004

Cited by 14 publications

(10 citation statements)

References 58 publications

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“…In any case, all the mechanisms may also be the cause of different impacts of individual polymorphisms on the analysed parameters. Other limitations can involve gene-gene and gene-environment interactions, or epigenetic factors which could influence the pharmacodynamics and pharmacokinetics of individual drug response [ 18 ]. Nevertheless, the pharmacogenetic research is promising, especially for osteoporosis, that require long-term treatments and where different therapy types exist to be alternatively chosen.…”

Section: Discussionmentioning

confidence: 99%

“…SERMs are used for prevention and treatment of postmenopausal osteoporosis and breast cancer prevention in high-risk postmenopausal women with osteoporosis [ 17 ]. Raloxifene, a member of SERMs, simulates estrogen action on the skeletal system through agonistic binding to estrogen receptors without the negative effects on breast and endometrium [ 18 ]. As in the case of association studies, the results of pharmacogenetic ones have not always been consistent.…”

Section: Introductionmentioning

confidence: 99%

“…The individual variation of response to anti-osteoporotic treatments ranges from good to little response or nonresponse (estimated proportion from 5 to 10%), and it may be due to individual genetic factors or environmental influences that could interfere with drug dynamics and kinetics [ 23 ]. Common variations in the human genome are today considered as the most important cause of variable drug responses [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

et al. 2018

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BackgroundThe study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.MethodsWe analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements.ResultsWomen with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (− 0.26 ± 0.10 of BMD-FN T-score; − 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (− 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (− 0.22 ± 0.08 of T-score) and CC (− 0.35 ± 0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a − 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed − 0.39 ± 0.11 and − 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively.ConclusionsThe rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0684-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

et al. 2018

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“…Note, however, that most data on post-menopausal women available in the literature has been obtained from Caucasian populations aged 65 or over, and that information from other ethnic groups is limited. 39 Finally, we considered whether unmeasured confounders may have introduced spurious associations between BMD and incident fracture. Indeed, the assumption of sequential ignorability was probably not met in this study because BMD slopes were observed after participants were randomly allocated to placebo and BZA groups.…”

Section: Discussionmentioning

confidence: 99%

A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on incidence of vertebral fractures, either directly or through non-linear changes in bone mass density

Detilleux

Reginster

Chines

et al. 2012

Stat Methods Med Res

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“…By binding to calcitonin receptors in bone and the brain, osteoclastic activity is diminished and analgesic effects are mediated. Salmon calcitonin is currently marketed and has been shown to be significantly more potent than human calcitonin [24, 25]. Gastrointestinal symptoms have been observed, but these effects can be minimized with different modes of administration.…”

Section: Osteoporosis Treatmentsmentioning

confidence: 99%

Advances in Controlled Drug Delivery for Treatment of Osteoporosis

Asafo-Adjei

Chen

Najarzadeh

et al. 2016

Curr Osteoporos Rep

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Osteoporosis, which is characterized by resorption of bone exceeding formation, remains a significant human health concern, and the impact of this condition will only increase with the “greying” of the worldwide population. This review focuses on current and emerging approaches for delivering therapeutic agents to restore bone remodeling homeostasis. Well-known antiresorptive and anabolic agents such as estrogen, estrogen analogs, bisphosphonates, calcitonin, and parathyroid hormone, along with newer modulators and antibodies, are primarily administered orally, intravenously, or subcutaneously. Although these treatments can be effective, continuing problems include patient non-compliance and adverse systemic or remote-site effects. Controlled drug delivery via polymeric, targeted, and active release systems extends drug half-life by shielding against premature degradation and improves bioavailability, while also providing prolonged, sustained, or intermittent release at therapeutic doses to more effectively treat osteoporosis and associated fracture risk.

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Pharmacogenetics of osteoporosis

Cited by 14 publications

References 58 publications

The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

A Bayesian path analysis to estimate causal effects of bazedoxifene acetate on incidence of vertebral fractures, either directly or through non-linear changes in bone mass density

Advances in Controlled Drug Delivery for Treatment of Osteoporosis

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