Bone selective effect of an estradiol conjugate with a novel tetracycline-derived bone-targeting agent

In this study a novel bone-targeting agent containing elements of the tricarbonylmethane system of ring A of tetracycline was developed and was shown to bind to the mineral constituent of bone, hydroxyapatite. Conjugation of this bone-targeting agent to estradiol resulted in a bone-targeted estrogen (BTE2-A1) with an enhanced ability to bind to hydroxyapatite. In an ovariectomized rat model of osteoporosis a partial separation of the skeletal effects of estradiol from the uterine effects was observed following subcutaneous administration of BTE2-A1. This novel bone-targeting estradiol delivery system has the potential to improve the safety profile of estradiol in the treatment of osteoporosis.

Graphical abstractA novel bone-targeting agent containing elements of the tricarbonylmethane system of ring A of tetracycline was developed and conjugated to estradiol, resulting in a bone-targeted estrogen.Figure optionsDownload full-size imageDownload as PowerPoint slide