Long-term glucocorticoid therapy, commonly used because of its potent anti-inflammatory effects, frequently leads to glucocorticoid-induced osteoporosis (GIOP), causing severe bone loss and increased fracture risk. Given the limited effectiveness of current therapies in addressing both bone structural deterioration and impaired bone innervation, we evaluated whether low-dose zoledronic acid (ZOL) could alleviate these detrimental effects on bone architecture and neural integrity in a rat model of GIOP. Thirty-six male Wistar rats were divided into three groups: control (saline), glucocorticoid-treated (methylprednisolone, 3 mg/kg every other day) and glucocorticoid-ZOL-treated (0.025 mg/kg monthly). After 8 and 16 weeks, comprehensive histological and immunohistochemical analyses were performed to assess bone morphology, the expression of osteocalcin (OC), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), as well as neural integrity using markers vasoactive intestinal polypeptide (VIP) and protein gene product 9.5 (PGP9.5). Glucocorticoid treatment significantly increased cytokine responses at trabecular bone surfaces, indicating accelerated remodelling and structural deterioration. It also adversely affected the neuronal morphology and distribution within the femoral bone. ZOL partially mitigated glucocorticoid-induced bone structural impairments, significantly reducing trabecular bone loss and remodelling disturbances. Importantly, ZOL did not exacerbate the glucocorticoid-induced neuronal alterations. We conclude that low-dose periodic administration of ZOL effectively reduces glucocorticoid-induced structural deterioration of the femoral bone without negatively influencing neuronal integrity. These findings support ZOL as a potential therapeutic strategy for simultaneously preserving bone health and neural function in glucocorticoid-induced osteoporosis.
Kostyshyn et al. (Wed,) studied this question.