Background: Osteopenia and osteoporosis are both common bone diseases in
postmenopausal women, but their clinical manifestations tend to be
unnoticeable until bone loss-induced fractures occur which could endanger
personal safety and lead to other injuries. This phenomenon makes it
difficult to identify the population with osteoporosis, leading to failure
to receive treatment timely. As a significant public health concern, the
early diagnosis of osteopenia and osteoporosis has become an urgent
clinical topic. Methods: We conducted metabolomic analysis on plasma
samples and 16S sequencing on fecal samples from humans. While 142 women
participated in metabolomic analysis, only 118 of them joined the
transcriptomics cohort. By statistical methods, we managed to identify
relevant biomarkers of osteopenia and osteoporosis consisting of
metabolites and genera and establish early diagnosis models, including
clinical features, classical indexes and selected biomarkers. The
efficiency of these models was also validated. Results: Metabolites
included homo-L-arginine, 3-methylglutarylcarnitine, linoleyl carnitine,
and estrone glucuronide, and gut microbes included Coprococcus, Dialister,
Erysipelatoclostridium, Marvinbryantia and Stenotrophomonas were
identified as biomarkers of osteoporosis while the metabolite
dihomo-gamma-linolenoylethanolamide and genera including
Lachnospiraceae_NC2004_group, Lachnospiraceae_NK4A136_group and Roseburia
were identified as as biomarkers of osteopenia. The area under the curve
(AUC) of early diagnosis models for distinguishing osteoporosis from
normal, osteopenia from normal and osteoporosis from osteopenia were 0.95,
0.77, and 0.92 respectively. Conclusion: We identified biomarkers of both
osteopenia and osteoporosis consisting of metabolites and gut microbes and
investigated the mechanisms underlying their influence on the reduction of
BMD. High-reliability prediction models were built through artificial
neural networks and random forest and these models can help early
diagnosis of osteopenia and osteoporosis to realize early intervention and
early treatment.