Del Real Álvaro, Valero Carmen, Olmos José M, Hernández Jose L, Riancho José A
Departamento de Medicina y Psiquiatría, Universidad de Cantabria, 39008 Santander, Spain.
Servicio de Medicina Interna, Hospital U.M. Valdecilla, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), 39008 Santander, Spain.
Pharmaceutics. 2022 Apr 2;14(4):776. doi: 10.3390/pharmaceutics14040776.
Osteoporosis is a skeletal disorder defined by a decreased bone mineral density (BMD) and an increased susceptibility to fractures. Bisphosphonates and selective oestrogen receptor modulators (SERM) are among the most widely used drugs. They inhibit bone resorption by targeting the mevalonate and oestrogen pathways, respectively. The aim of this study was to determine if common variants of genes in those pathways influence drug responses. We studied 192 women treated with oral aminobisphosphonates and 51 with SERMs. Genotypes at 154 SNPs of the mevalonate pathway and 806 in the oestrogen pathway were analyzed. Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, = 0.0003). These results suggest that genotyping genes in these pathways may help predict the response to antiresorptive drugs and hence make personalized therapeutic choices.
骨质疏松症是一种骨骼疾病，其定义为骨矿物质密度（BMD）降低以及骨折易感性增加。双膦酸盐和选择性雌激素受体调节剂（SERM）是使用最广泛的药物之一。它们分别通过靶向甲羟戊酸途径和雌激素途径来抑制骨吸收。本研究的目的是确定这些途径中基因的常见变异是否会影响药物反应。我们研究了192名接受口服氨基双膦酸盐治疗的女性和51名接受SERM治疗的女性。分析了甲羟戊酸途径154个单核苷酸多态性（SNP）以及雌激素途径806个SNP的基因型。位于FDPS和FNTA基因中的几个SNP与双膦酸盐诱导的髋部骨矿物质密度（BMD）变化相关，而PDSS1、CYP19A1、CYP1A1和CYP1A2基因的多态性与SERM诱导的脊柱BMD变化相关。经过多变量分析后，FDPS和FNTA基因组合的基因型与双膦酸盐反应的关联性更强（r = 0.34；P = 0.00009），而CYP19A1和PDSS1基因型的组合与SERM反应相关（r = 0.62，P = 0.0003）。这些结果表明，对这些途径中的基因进行基因分型可能有助于预测对抗吸收药物的反应，从而做出个性化的治疗选择。
