4. Discussion
bone loss, osteopenia, fracture, osteoporosis
OSTEOPOROTIC FRACTURE, BONE LOSS, OSTEOPENIA, SECONDARY, OSTEOPOROSIS
To the best of our knowledge, this is the first randomized controlled trial (RCT) conducted to examine the effect of a hop extract on bone health in postmenopausal women with osteopenia. In this population, we demonstrated that a daily supplementation with 100 µg of 8-PN from a standardized hop extract for 48 weeks increased total body BMD compared to placebo. An improvement of the SF-36 physical functioning score was also observed in the HE group suggesting a higher perceived ability to perform daily activities. However, no significant effect was found in BMD at specific sites (lumbar spine, femoral neck, and total hip), plasma bone biomarkers, and other secondary outcomes, notably blood lipids and glucose homeostasis parameters.This beneficial impact on BMD is consistent with previous studies performed in the ovariectomized rat with standardized hop extract, which showed an increase in BMD following 8 to 12 weeks of supplementation while using a daily dose of 8-PN from 6 to 27 times higher in a human dose equivalent [Bone turnover biochemical markers help clinicians to identify patients at high risk for fracture and to monitor the efficacy of osteoporosis treatments. However, no significant difference between the HE and placebo groups was observed regarding the bone biochemical markers concentrations after 48 weeks of supplementation. Among the available biochemical markers, pro-collagen type I The magnitude of HE effects on bone density is not comparable to those of osteoporosis medications, but it could be of interest as a preventive measure for women with low bone mass that cannot be prescribed medication at this stage. Dawson-Hughes et al. have reported that after 3 years of vitamin D (700 IU) and calcium (500 mg) supplementation, a 1.1% net increase in total body BMD compared to placebo was associated with a relative risk reduction of 0.4 of first osteoporotic fracture in men and women [Dawnson Hugues et al. have reported in older women without intervention an annual bone loss of about 1% in the total body and 0.8% in the lumbar spine region [The main mechanism of action of HE is the estrogenic activity of 8-PN, which has been demonstrated in vitro and in vivo and which has been recently extensively reviewed [Despite the fact that volunteers were asked to maintain a similar diet throughout the study, significantly higher changes from baseline at week 48 were observed for fat, vitamin KAnother hypothesis for the important variability in response observed in this trial could be the inter-individual variation in prenylflavonoids metabolism that was reported previously [A novel aspect of this trial was the analysis of the participants’ gut microbiome and its relationship to the responsiveness of treatment. No difference between HE and placebo was observed for overall association parameters, alpha-diversity indices, and SCFA levels throughout the study, hence indicating no major shift in the gut microbiome composition and function. However, the explorative multivariate analysis indicated that after 48 weeks among the taxa identified as the most relevant to discriminate the two groups, there was notably a higher abundance of the genera Strengths of this study include the sample size calculation, the robust design (randomized, placebo-controlled, double-blind), the good adherence rate, the low drop-out rate, and the integrated analysis, including the impact of treatment on the microbiome and HE metabolites. The main limitation is the relatively short duration considering bone loss, as a duration of at least 2 years would incorporate more complete bone remodeling cycles and further strengthen the evidence provided by DXA in this trial. However, the bone remodelling cycle is known to last 120–200 days [To conclude, in postmenopausal women with osteopenia, daily consumption of a standardized hop extract with 100 µg of 8-PN during 48 weeks was found to have a beneficial increase of 1% of the total body BMD compared to placebo, above and beyond an increase associated with a calcium and vitamin D supplementation. Furthermore, even if no major shift of the gut microbiota composition was observed, modulation of some taxa previously identified as associated with bone loss was noted in the HE group and deserves further investigation. New clinical trials with notably a longer duration are needed to confirm the beneficial effect of standardized hop extract on bone health.