Abstract :
[en] Osteoporosis is a disease characterized by a loss of bone mass and deterioration of the
microarchitecture of bone tissue. This pathology primarily affecting elderly, in the context of an
increasingly aging population, represents real public health problem. Nowadays, to monitor patients
affected by osteoporosis, bone remodeling biomarkers are used in clinic, such as CTX, PINP, and b-ALP.
However, these markers present some limitations like in the case of CTX, which is influenced by the
circadian rhythm and the fasting condition. In addition, patient compliance with currently available
anti-osteoporotic drugs is quite low, which increases the risk of fractures. This is why, in our Clinical
Metabolomics Group of the University of Liège, we decided to focus on a longitudinal osteoporotic
cohort by identify new markers linked to the pathology, to investigate the impact of different
treatments, and to study patient compliance, by applying a 1H-NMR-based metabolomics approach
study.
This study was conducted on 53 osteoporotic patients for which plasma samples was collected
at three different time points (0 months, 3 months, and 12 months). 42 metabolites were identified
per sample in order to statistically analyze the entire dataset. The obtained samples were classified
into 4 groups according to the absence or the type of treatment used at the time of the visit: no
treatment, dietary supplements, bisphosphonates, denosumab, and teriparatide.
Various PLS-DA analyses were realised to compare the different treatments; no significant
models were obtained, except for the separation between the "no treatment" and "teriparatide"
groups which highlighted ornithine and histidine, both increased in the "no treatment" group.
Subsequently, for each treatment group, a PLS model aiming to correlate individual's
metabolome with the markers value (CTX, PINP, and b-ALP) was performed. Firstly, correlations were
found in the "no treatment" group and the "denosumab" group for the three biomarkers. In addition,
a correlation between the metabolome of individuals treated with teriparatide and CTX was
demonstrated. Finally, the "dietary supplements" and "bisphosphonates" groups did not show any
significant correlations.
Despite these promising results, this work contains several limitations that need to be
improved if a new metabolomics study is undertaken. Indeed, among these limitations, the patient
groups are not homogeneous/too restricted, or the samples are not standardized (different times and
impact of food). This is why it would be interesting in the future to conduct a new well-standardized
metabolomics study in order to go into more detail in the analysis, especially by studying the individual
changes in the metabolome over the three visits, and to consolidate the results obtained.
