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Abstract
Osteoporosis is a skeletal disease associated with excessive bone turnover. Among the compounds with antiresorptive activity, nitrogen-containing bisphosphonates play the most important role in antiosteoporotic treatment. In previous studies, we obtained two aminomethylidenebisphosphonates—benzene-1,4-bis[aminomethylidene(bisphosphonic)] (WG12399C) acid and naphthalene-1,5-bis[aminomethylidene(bisphosphonic)] (WG12592A) acid—which showed a significant antiproliferative activity toward J774E macrophages, a model of osteoclast precursors. The aim of these studies was to evaluate the antiresorptive activity of these aminobisphosphonates in ovariectomized (OVX) Balb/c mice. The influence of WG12399C and WG12592A administration on bone microstructure and bone strength was studied. Intravenous injections of WG12399C and WG12592A bisphosphonates remarkably prevented OVX-induced bone loss; for example, they sustained bone mineral density at control levels and restored other bone parameters such as trabecular separation. This was accompanied by a remarkable reduction in the number of TRAP-positive cells in bone tissue. However, a significant improvement in the quality of bone structure did not correlate with a parallel increase in bone strength. In ex vivo studies, WG12399C and WG12592A remarkably bisphosphonates reduced osteoclastogenesis and partially inhibited the resorptive activity of mature osteoclasts. Our results show interesting biological activity of two aminobisphosphonates, which may be of interest in the context of antiresorptive therapy.
Highlights
We examined the effect of BPs on osteoclastogenesis in vitro
We have shown that WG12399C and WG12592A significantly restrain the proliferation rate of J774E cells, which are a convenient model of osteoclast precursors for in vitro studies [13]
All reagents and solvents used in the synthesis were of commercial quality and purchased from
Summary
Osteoporosis is a skeletal disorder characterized by the imbalance between bone formation and resorption, which leads to a decrease in bone mass and density and to progressive changes in bone structure [1]. This, in turn, results in a higher risk of bone fracture, most commonly in the vertebrae, wrist, or hip [2]. Osteoporosis is a global health problem affecting an estimated 200 million people [3]. Aging and chronic estrogen deficiency are the most important risk factors for osteoporosis [4,5]. Numerous therapeutic agents have been developed to treat osteoporosis. These include either boneanabolic or antiresorptive drugs [6]. Among these drugs, the most active compounds
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