Bone and bone marrow (BM) are interdependent organs with reciprocal regulatory functions throughout life. Bone and BM contain multiple functionally distinct resident macrophage subsets, including haematopoietic stem cell (HSC) niche macrophages and osteal tissue macrophages (osteomacs). Using multiple in vivo and ex vivo strategies we have demonstrated that osteomacs and HSC niche macrophages express the mature resident macrophage marker CD169 (encoded by Siglec1). Both HSC niche macrophages and osteomacs are resilient to lethal total body irradiation, persisting long-term post-autologous haematopoietic stem and progenitor cell (HSPC) transplantation, achieving self-renewal via proliferation in situ. Depletion of CD169⁺ recipient macrophages post-HSPC transplantation compromised donor HSC engraftment, supporting a key role for these cells in re-establishing the BM environment following lethal irradiation to facilitate donor engraftment. We have also demonstrated that CD169⁺ osteomacs are critical for optimal bone healing; with a strong correlation between the magnitude of fracture callus formation and the number of osteomacs within the callus (r²=0.8; p<0.0001). Exogenous delivery of the macrophage growth factor, colony stimulating factor 1 (CSF1), significantly increased CD169⁺ resident BM macrophage number, increased the number of BM HSC and enhanced bone repair in multiple models. We now have novel evidence supporting a role for CD169⁺ bone/BM macrophage cross-talk with bone-forming osteoblasts in maintaining skeletal homeostasis at steady state. Importantly, CD169 was not expressed by osteoclasts, specialized bone-resorbing cells of the myeloid lineage, permitting clear segregation between osteoclast and macrophage contributions to bone physiology. Siglec1 haploinsufficiency and deficiency reduced BM macrophage and osteomac number, which was associated with reduced osteoblast number and activity, and a significant reduction in bone volume in Siglec1-knockout mice. This is the first demonstration of a macrophage-restricted deficiency resulting in systemic osteopenia/osteoporosis. Overall, CD169⁺ bone/BM-resident macrophages play important roles in maintaining both haematopoietic and skeletal health and regeneration.