Bone metabolism has recently been revealed to be under nerve regulation. In this study, the integrity of the sensory innervation contributing to bone metabolism was examined by capsaicin-induced sensory neuron lesions. Eight-week-old male Wistar strain rats in a modeling phase of skeletal growth were divided into four groups (8 rats per group) and treated with capsaicin at one of three different doses (37.5, 75, 150 mg/kg) or vehicle, subcutaneously. Five weeks later, high-dose (150 mg/kg) capsaicin treatment had reduced trabecular bone volume (BV/TV) due to increased trabecular separation (Tb.Sp) in the proximal tibia and the modification of mechanical properties such as strength, ductility, and toughness toward increasing bone fragility in the trunk of the sixth lumbar vertebrae (L6). Moderate-dose (75 mg/kg) capsaicin treatment had no significant effect on trabecular BV/TV or bone mechanical properties but increased Tb.Sp as seen high-dose capsaicin treatment. Bone histomorphometry showed osteoclast number (Oc.N/BS) and surface (Oc.S/BS) were increased in both the moderate-dose and high-dose capsaicin treatment groups. High-dose capsaicin significantly increased the level of tartrate-resistant acid phosphatase form 5b (TRAP 5b) in plasma, a systemic bone resorption marker, but had no influence on plasma osteocalcin concentration, a bone formation marker, suggesting that capsaicin-induced sensory nerve denervation increased bone resorption but had no influence on bone formation. Low-dose (37.5mg/kg) capsaicin had no influence on bone remodeling. These results suggest that sensory nerve innervation contributes to the maintenance of trabecular bone mass and its mechanical properties by inhibiting bone resorption.
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