Recent advances in bone-targeted therapy.

The coordination between bone resorption and bone formation plays an essential role in keeping the mass and microstructure integrity of the bone in a steady state. However, this balance can be disturbed in many pathological conditions of the bone. Nowadays, the classical modalities for treating bone-related disorders are being challenged by severe obstacles owing to low tissue selectivity and considerable safety concerns. Moreover, as a highly mineralized tissue, the bone shows innate rigidity, low permeability, and reduced blood flow, features that further hinder the effective treatment of bone diseases. With the development of bone biology and precision medicine, one novel concept of bone-targeted therapy appears to be promising, with improved therapeutic efficacy and minimized systematic toxicity. Here we focus on the recent advances in bone-targeted treatment based on the unique biology of bone tissues. We summarize commonly used bone-targeting moieties, with an emphasis on bisphosphonates, tetracyclines, and biomimetic bone-targeting moieties. We also introduce potential bone-targeting strategies aimed at the bone matrix and major cell types in the bone. Based on these bone-targeting moieties and strategies, we discuss the potential applications of targeted therapy to treat bone diseases. We expect that this review will put together useful insights to help with the search for therapeutic efficacy in bone-related conditions.