Metabolite Profiling of Osteoporosis and Atherosclerosis in Postmenopausal Women: A Cross-Sectional Study

Miika Värri,1 Leo Niskanen,2 Tomi-Pekka Tuomainen,3 Risto Honkanen,1,4 Heikki Kröger,1,5 Marjo T Tuppurainen1,6 1Kuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 2Department of Endocrinology and Metabolism, Abdominal Centre, Helsinki University Hospital, Universities of Helsinki and Eastern Finland, Helsinki, Finland; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 4Lapland Hospital District, Rovaniemi, Finland; 5Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland; 6Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, FinlandCorrespondence: Miika VärriKuopio Musculoskeletal Research Unit (KMRU), Surgery, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, FinlandTel +358503655083Fax +358 17 172 611Email mvarri@uef.fiPurpose: Atherosclerosis (AS) and osteoporosis (OP) are common causes of morbidity and mortality in postmenopausal women and are connected via an unknown mechanistic link. Metabolite profiling of blood samples may allow the identification of new biomarkers and pathways for this enigmatic association.Patients and Methods: We studied the difference in 148 metabolite levels from serum samples in postmenopausal women with AS and OP compared with those in healthy participants in this cross-sectional study. Quantitative AS was assessed by carotid artery intima-media thickness (cIMT) and carotid artery calcifications (CACs) by ultrasound, as well as OP by femoral neck (FN) bone mineral density (BMD) and 148 metabolic measures with high-throughput proton (1H) nuclear magnetic resonance (NMR) in serum samples from 280 postmenopausal (PM) women. Subjects were a randomly selected subsample from the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The final study population included the following groups: OP with CAC (n=16, group I), non-OP with no CAC (n=59, group II), high cIMT tertile with OP (n=11, group III) and low cIMT tertile without OP (n=48, group IV).Results: There were differences in several metabolite levels between groups I and II. The acetate level was lower in group I compared to that in group II (group I mean ± SD: 0.033 ± 0.0070; group II: 0.041 ± 0.014, CI95%: 0.018‒0.15, p=0.014). The result was similar with diacylglycerol (p=0.002), leucine (p=0.031), valine (p=0.022) and several very low-density lipoprotein (VLDL) metabolite levels, which were lower in group I compared to those in group II. However, no associations were found in adjusted analyses with total body (TB) fat mass (FM), age and statin use (p> 0.05).Conclusion: Our novel study found differences in the metabolite profiling of altered amino acid and lipoprotein metabolism in participants with OP and AS compared with those in healthy women. The causative mechanisms remain unknown and further studies are needed.Keywords: metabolomics, carotid artery calcification, postmenopausal women, osteoporosis, carotid intima-media thickness, acetate