Effects of two novel bisphosphonates on bone cells in vitro
Abstract
Bisphosphonates are now widely used in the treatment of bone diseases, particularly where there is uncontrolled bone resorption, as they are known to be potent inhibitors of osteoclasis. It is still unclear whether the bisphosphonates act by inhibiting osteoclast maturation or by blocking the mechanism of bone resorption, and little is known of their effects on osteoblasts. Recent studies with 3-amino-1, hydroxypropylidene-1,1-bisphosphonic acid (APD) in the treatment of osteolytic metastases in breast cancer have suggested that APD may affect osteoblasts directly. We have now investigated the effects of two novel bisphosphonates, CGP 47072 and CGP 42446A on osteoclastogenesis in fetal rat calvariae cultured on collagen gels and on human osteoblasts (hOB) cultured as explants from bone taken from patients at surgery. We also compared the action of these new bisphosphonates with that of APD, which at concentrations of 2.5 x 10(-6) M to 2.5 x 10(-10) M inhibited osteoclast recruitment, even when this was stimulated by conditioned medium from MCF7 breast cancer cells. This bisphosphonate was particularly potent if cultured with calvaria taken at 19 days gestation, when more immature osteoclast precursors are present. If calvariae from 20 days gestation were used, which contain more mature cells, it produced less inhibition. In contrast, CGP 42446A (2.5 x 10(-6) M to 2.5 x 10(-8) M) was more effective in inhibiting osteoclast maturation in calvariae from 20 days gestation than…
Read the paper
Related studies
- Development of a crushable foam model for human trabecular bone
- Data-driven motion compensation in HR-pQCT.
- Modeling of structure, quality, and function in the orthodontic patient
- Exploring the mechanism of Heidihuang Pill in the treatment of osteoporosis based on network pharmacology, molecular docking, and experimental validation
- Effect of fabric on the accuracy of computed tomography-based finite element analyses of the vertebra
- Use of interventions involving virtual reality tasks during the climacteric: a systematic review
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.