Deletion of the neurotrophin receptor p75NTR specifically in sensory neurons disrupted skeletal stem cell homeostasis and caused significant bone loss through reduced osteopontin (SPP1) expression. The p75NTR-SPP1 signaling pathway promotes both stem cell self-renewal and osteogenic differentiation, establishing sensory innervation as a critical component of the bone stem cell niche. This neural-skeletal connection represents a paradigm shift in understanding bone regulation beyond traditional mechanical and hormonal factors. The finding directly explains why Alzheimer's disease patients frequently develop osteopenia, as AD disrupts this same p75NTR-SPP1 pathway. This discovery opens therapeutic avenues targeting the nervous system for bone health, particularly relevant for aging populations where both neurodegeneration and osteoporosis converge. The sensory-specific nature of this mechanism suggests that preserving peripheral nerve function could be crucial for maintaining bone mass throughout life. While conducted in mouse models, the pathway's disruption in human AD cases suggests translational relevance. This research fundamentally reframes bone health as intimately connected to sensory nerve integrity.