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Bisphosphonates bind strongly to bone and reduce bone resorption through effects on both osteoclasts and osteoblasts.^1,2 Clodronate is a non-nitrogenous bisphosphonate that has been used in the treatment of osteoporosis and other metabolic bone diseases. It binds to hydroxyapatite crystals with an affinity constant of 0.72 µM, inhibiting their growth (IC₅₀ = 1.34 µM) and bone resorption.³ Clondronate is metabolized intracellularly to a β-γ-methylene analog of ATP that is cytotoxic to both osteoclasts and macrophages, which belong to the same cell lineage as osteoclasts.⁴ Liposome-encapsulated bisphosphonates such as clodronate have been used in biological research to selectively deplete macrophage-like cells and cancer cells.⁵