LAUSR

OBJECTIVE Haematopoiesis was shown to regulate bone metabolism in in vivo studies. However, whether haematopoiesis has causal effects on bone health has never been investigated in human. We aimed to evaluate the causal relationships of blood traits with bone mineral density (BMD) and fracture. DESIGN AND METHODS Using two-sample Mendelian randomization, causal relationship of 29 blood traits with estimated BMD (eBMD), total body BMD (TBBMD), lumbar spine BMD (LSBMD), femoral neck BMD (FNBMD) and fracture were evaluated by inverse-variance weighted (IVW) method and multiple sensitivity analyses. Relevant genetic data were obtained from largest possible publicly available genome-wide association studies. RESULTS Eight genetically determined red blood cell traits showed positive causal effects on eBMD, with beta estimates ranging from 0.009 (mean corpuscular haemoglobin) to 0.057 (haemoglobin concentration), while three white blood cell traits, including lymphocyte count (beta:-0.020; 95% CI: -0.033 to -0.007), neutrophil count (beta:-0.020; 95% CI:-0.035 to -0.006) and white blood cell count (beta:-0.027; 95% CI:-0.039 to -0.014), were inversely associated with eBMD. Causal effects for six of these blood traits were validated on TBBMD, LSBMD, FNBMD and/or fracture. The association of reticulocyte count (beta:0.040; 95% CI:0.016 to 0.063), haemoglobin (beta:0.058; 95% CI:0.021 to 0.094) and mean corpuscular haemoglobin concentration (beta:0.030; 95% CI:0.007 to 0.054) with eBMD remained significant in multivariable IVW analyses adjusted for other blood traits. CONCLUSION This study provided evidence that haematopoietic system might regulate skeletal system in human and suggested the possible pathophysiology of bone diseases among people with haematological diseases.