PB1986 BLOOD CELL PRODUCTION IS NOT INFLUENCED BY BONE HEALTH STATUS IN HOMOEOSTASIS - THE COLAUS/OSTEOLAUS COHORT

Background: The hematopoietic stem cell (HSC) niche constitutes a complex bone marrow (BM) microenvironment critical to tightly control HSC proliferation. Several stromal components have been associated to the HSC niche, including osteoblasts, mesenchymal stromal and progenitor cells, perivascular cells and adipocytes. Perturbation of the BM stromal compartment is capable of driving hematopoietic dysplasia and even leukemic transformation. Recently, the effect of reduced bone mineral density (BMD) on hematopoiesis was investigated in several cohorts, with conflicting results. Osteoporosis is characterized by both reduced BMD and microarchitectural deterioration, which constitute the most frequent alteration of the BM microenvironment. It still remains unclear to which extent modification of the BM microenvironment, in particular in the context of osteoporosis, influences blood cell production. Aims: To describe the association between lumbar spine BMD and microarchitecture (measured by the trabecular bone score - TBS), and complete blood counts. Methods: We analyzed the complete peripheral blood counts and bone parameters of 1475 postmenopausal women taking part of the CoLaus/OsteoLaus cohort, a Caucasian population-based sample in Lausanne, Switzerland. BMD and TBS were measured by two different Dual X-rays Absorptiometry (DXA) machines (Hologic and GE Lunar) at 5-year interval. For this study, we focused on patients with homeostatic hematopoiesis. Exclusion criteria were thus any active treatment or disease that could influence haematopoiesis and any active treatment for osteoporosis (excepted vitamin D, calcium and menopausal hormone replacement therapy - HRT -). Bivariate and multivariate associations between each peripheral blood cell count and BMD or TBS were performed. Multivariable analyses were adjusted for age, body mass index (BMI), C-reactive protein and HRT. Results: Our study included 803 (16.9% osteoporotic) and 901 (13.2% osteoporotic) women, respectively for the two timepoints. At the first timepoint of analysis, participants were on average 63-year-old, with a BMI of 25.6 kg/m^2; 15 (1.9%) had anemia, 29 (3.6%) leukopenia, and 5 (0.6%) thrombocytopenia. No consistent significant associations between blood counts and BMD or TBS were found across bone markers or timepoints. In order to investigate an effect of extreme values reflecting the highest and the lowest bone quality, we compared participants in the highest BMD and TBS tertiles and participants in the lowest BMD and TBS tertiles. Neutrophils were significantly different in the lowest BMD and TBS tertile (3.18 ± 0.09 vs. 3.47 ± 0.08 G/l, p = 0.028) at the first assessment. At the second assessment, significant differences were found for leucocytes (5.90 ± 0.11 vs. 5.56 ± 0.10 G/l, p = 0.033), lymphocytes (1.87 ± 0.04 vs. 1.72 ± 0.04 G/l p = 0.033) and monocytes (0.49 ± 0.01 vs. 0.46 ± 0.1 G/l, p = 0.033). No significant association was therefore reproducible between timepoints. Summary/Conclusion: In this cohort of postmenopausal women assessed at two separate timepoints and with two different DXA instruments, BM microenvironment changes related to bone condition did not have a reproductible impact on blood cell production in homeostasis. This study underlines the complexity of understanding the clinical relevance of changes in the BM, and prompt further research given disparate results obtained in other clinical scenarios, namely in the context of stress hematopoiesis.