Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study

Abstract

Background: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. Aim: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. Methods: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. Results: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). Conclusions: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis.

Osteoprotegerin genetic polymorphisms and their influence on therapeutic response to ibandronate in postmenopausal osteoporotic females

“…The significant increase in OPG levels after 6 months of ibandronate medication in the osteoporotic group was seen in SNPs rs3134069 (A/C)T245G (AA genotype), SNPs rs3102735 (T/C) A163G, (TT and TC genotypes), and rs2073618 G1181C (GG and GC) genotypes, indicating that people with these genotype variants responded effectively to treatment in terms of increasing OPG levels. Villagómez et al (2023) showed that OPG SNPs rs2073618 and rs3102735 of the OPG gene responded to bisphosphonate (alendronate) treatment (68%), while 32% of postmenopausal osteoporotic females had a poor response to bisphosphonate (alendronate) due to gene variants [ 19 ]. Another study demonstrated that osteoporosis patients who did not respond to bisphosphonate treatment (40%) had a higher frequency of gene variations than patients who did respond to this medicine [ 20 ].…”

Gut microbes differ in postmenopausal women responding to prunes to maintain hip bone mineral density

“…This 1.0% definition was defined based on expected 12 month increase in hip BMD according to previous work on prunes and calcium and vitamin D interventions (25,26). However, this is less than the 3-5% cutoff recommended by the American Association of Clinical Endocrinologists and that defined by studies of responders to drug trials (15,16). This 1% cutoff allows for a larger sample size and accurate representation of responders to a dietary intervention.…”

“…Several studies have identified responders to pharmacological treatment for osteoporosis. In a retrospective cohort study of 82 Mexican postmenopausal women with osteoporosis, investigators identified an osteogenomic profile unique to responders after 12 months of anti-resorptive bisphosphonate alendronate treatment (15). Furthermore, in a larger cohort study of 145 French postmenopausal women with osteoporosis, after 18 months of anabolic teriparatide treatment, non-responders had low levels of bone remodeling biomarkers, as assessed by C-terminal fragment of type 1 collagen (CTX) (16).…”

Molecular and Cellular Mechanisms of Osteoporosis

“…Widely used bone resorption inhibitors, bisphosphonates, may not provide a therapeutic effect during the first 2 years of use in 20-40% of all patients. Patient genetic profiles are currently being studied in an attempt to generate predictive patterns for response to therapy and to personalize the treatment [187,188]. In therapy aimed at reducing bone resorption, the adjuvant use of antioxidants has been proposed as an alternative to the use of antiresorptive drugs to inhibit osteoclast activity, which could restore the balance between osteoclasts and osteoblasts and the process of physiological remodeling [189].…”