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We recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (cSe-Bu) consisting of osteogenic compounds mitigated methylprednisone (Mp)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. to this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100-180 nm of diluted emulsion and the zeta potential was −28 mV. CSE-BuF enhanced the circulating levels of five osteogenic compounds compared to CSE-Bu. CSE-BuF (50 mg/kg) promoted bone regeneration at the osteotomy site and completely prevented Mp-induced loss of bone mass and strength by concomitant osteogenic and anti-resorptive mechanisms. The MP-induced downregulations of miR29a (the positive regulator of the osteoblast transcription factor, Runx2) and miR17 and miR20a (the negative regulators of the osteoclastogenic cytokine RAnKL) in bone was prevented by cSe-Buf. in addition, cSe-Buf protected rats from the MP-induced sarcopenia and/or muscle atrophy by downregulating the skeletal muscle atrogenes, adverse changes in body weight and composition. cSe-Buf did not impact the antiinflammatory effect of MP. Our preclinical study established CSE-BuF as a prophylactic agent against Mp-induced osteopenia and muscle atrophy. Worldwide nearly 60% of patients of rheumatoid arthritis (RA) are treated with glucocorticoids (GC) 1. Prednisone/methylprednisolone, the most frequently used GC is given in combination with disease modifying anti-rheumatic drugs (DMARDs) to provide better clinical benefit. However, long-term use of GC has several metabolic adverse effects and the most prominent among those being osteoporosis and sarcopenia 2,3. The clinically used drugs for GC-induced osteoporosis (GIO) are anti-resorptives (bisphosphonates and denosumab)

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