Biomarker Gene Discovery for Low Bone Mineral Density in Circulating Monocytes
9TH INTERNATIONAL CONFERENCE ON ENGINEERING AND APPLIED NATURAL SCIENCES ICEANS 2026, Konya, Türkiye, 25 - 26 Ekim 2026, ss.299-306, (Tam Metin Bildiri)
- Yayın Türü: Bildiri / Tam Metin Bildiri
- Basıldığı Şehir: Konya
- Basıldığı Ülke: Türkiye
- Sayfa Sayıları: ss.299-306
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Trakya Üniversitesi Adresli: Evet
Özet
Osteoporosis is defined by bone mineral density (BMD), which detects low bone mass only
after it develops, so blood-accessible markers remain of interest. Circulating monocytes, osteoclast
precursors, have been proposed as a source of such markers; it is examined how much of this signal
persists under nested validation. Three public microarray cohorts were re-analysed: 80 monocyte samples
from women with low or high hip BMD (discovery), 26 monocyte samples spanning the extremes of peak
bone mass, and 40 B-lymphocyte samples from postmenopausal women with low or high BMD. Linear
models with empirical Bayes moderation, adjusted for menopausal status, identified 457 differentially
expressed genes (FDR < 0.05) with modest effects (median |log2 fold change| 0.15), largely confined to
the postmenopausal stratum (282 genes versus none among premenopausal women). Over-represented
Reactome pathways related mainly to translation initiation and ribosome biogenesis rather than canonical
osteoclastogenic signalling. Classifiers with feature selection nested within cross-validation reached areas
under the ROC curve of 0.65–0.83, whereas a four-gene panel gave an apparent value of 0.93 that fell to
0.66 in independent monocytes and 0.61 in B cells, neither distinguishable from chance. Effect directions
replicated at chance level in premenopausal monocytes (49.0%) and modestly in postmenopausal B cells
(58.9%). The gene set included canonical bone effectors (RANKL, WNT1, BMP4, β-catenin) but showed
no enrichment for human genetic support for BMD (odds ratio 1.01). Monocyte transcriptomes therefore
support within-cohort discrimination but provide limited evidence for a transportable diagnostic panel;
omitting nested validation inflated apparent accuracy by approximately 0.28.
Keywords – bone mineral density, osteoporosis, circulating monocytes, transcriptomic biomarker, microarray