Tartronates: a new generation of drugs affecting bone metabolism

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
G CaselliA Teti

Abstract

In the search for a new class of bone-sparing agents for treating osteopenic disorders, we hypothesized that tartronic acid derivatives, sharing the chemical characteristics both of bisphosphonates and of Gla residues contained in matrix proteins such as osteocalcin, could positively affect bone metabolism. A series of tartronates was therefore tested for their ability to affect bone metabolism. In vitro resorption tests were performed examining pit formation by freshly isolated rat and rabbit osteoclasts plated onto bone slices and exposed to the drugs for 48 h. Tartronates bearing a linear side-chain (DF 1222 and DF 1363A) were the most effective in inhibiting pit excavation in the pM-nM range. Tartronates did not affect osteoclast viability, number, adhesion, or tartrate resistant acid phosphatase activity. Transient cell retraction was observed in osteoclasts plated onto glass and exposed to DF 1222. The maximal effect was seen in cells treated for 4 h at a concentration of 1 pM. DF 1222 accelerated mineralization in cultures of periosteal cells without affecting other osteoblast-like functions. This product was therefore tested in vivo in ovariectomized mice. Bone mass in femur was evaluated, by ash gravimetry, 21 days aft...Continue Reading

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Citations

Jan 27, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A TetiK A Hruska
Jan 5, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A TetiP Bianco
Nov 26, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·I VillanovaA Teti
Jul 12, 2002·Journal of Pharmaceutical and Biomedical Analysis·R FicarraP Ficarra
Sep 21, 2016·Scientific Reports·Daniela M SousaMeriem Lamghari
Mar 13, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mattia CapulliAnna Teti
Jun 5, 2004·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Anna TarantaMaria Luisa Bianchi
Nov 14, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Andrea Del FattoreAnna Teti
Jan 19, 2012·Nature Communications·Barbara PeruzziAnna Teti
Sep 18, 2014·BoneKEy Reports·Silvia MarinoMattia Capulli
Jul 7, 2020·Biochemical Society Transactions·Zi ZouCijun Shuai
Jan 22, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Alfredo CapparielloAnna Teti
Dec 18, 2019·The Science of the Total Environment·Siti Aqilah Nadhirah Md RahimYolande Pérès
Jul 27, 2007·Journal of Cell Science·Lise Sofie Haug Nissen-MeyerKaare M Gautvik

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