Low bone mass is frequently observed in Alzheimer's disease (AD), yet the underlying mechanisms remain poorly understood. In this study, we demonstrate that sensory nerves constitute a critical component of the skeletal stem cell (SSC) niche. Deletion of the neurotrophin receptor p75NTR in neurons or sensory-specific cells, but not in osteogenic or sympathetic cells, resulted in reduced sensory innervation, disrupted SSC homeostasis, and significant bone loss. Although a cell-intrinsic role of p75NTR in SSCs cannot be ruled out, further experiments involving sensory denervation or transplantation into hosts with sensory-neuron-specific p75NTR deficiency confirmed impaired SSC osteogenesis. Mechanistically, p75NTR controls the expression of neuronal osteopontin (SPP1), which in turn promotes SSC self-renewal and osteogenic differentiation. Notably, this p75NTR-SPP1 signaling axis was found to be disrupted in AD mouse models, offering a direct mechanistic explanation for AD-associated osteopenia and highlighting the therapeutic potential of targeting neural control of SSCs.