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However, serious side\u2010effects can occur during the therapy. To search for novel potent BPs with lower side\u2010effects, a series of imidazole\u2010containing BPs (zoledronic acid [ZOL]; ZOL derivatives by substitution of the hydrogen at the 2\u2010position on the imidazole ring with a methyl [MIDP], ethyl [EIDP], <jats:italic>n<\/jats:italic>\u2010propyl [PIDP], or <jats:italic>n<\/jats:italic>\u2010butyl group [BIDP]) were developed and the effects on receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\u2010induced osteoclast differentiation were investigated using the murine macrophage RAW 264.7 cells at the protein, gene, and morphological and functional levels. Influences of these BPs on the cell growth and proliferation of RAW 264.7 were also studied in order to determine cytotoxicity. The results showed that PIDP significantly inhibited the RANKL\u2010induced osteoclast formation in a dose\u2010dependent fashion without inducing cytotoxicity under the concentration of 12.5\u00a0\u03bcM. It exerted remarkable suppressive effects on the development of actin rings, the bone resorption, and the expressions of osteoclastogenesis\u2010related gene and protein markers. The down\u2010regulation of c\u2010Jun N\u2010terminal kinase (JNK), protein kinase B (Akt), and inhibitor of nuclear factor kappa\u2010B (I\u03baB) phosphorylation in the early signaling event and subsequent inhibition of the expression of c\u2010Fos and nuclear factor of activated T cells (NFATc1) might be involved in these effects. All these results indicated that PIDP might be a promising drug to treat bone\u2010related disorders.<\/jats:p>","DOI":"10.1111\/cbdd.13767","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T18:59:51Z","timestamp":1596221991000},"page":"121-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacological evaluation of imidazole\u2010derived bisphosphonates on receptor activator of nuclear factor\u2010\u03baB ligand\u2010induced osteoclast differentiation and function"],"prefix":"10.1111","volume":"97","author":[{"given":"Jianguo","family":"Lin","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Nuclear Medicine Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine Wuxi China"},{"name":"Department of Radiopharmaceuticals School of Pharmacy Nanjing Medical University Nanjing 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