Effects of Drugs and Trace Elements in Bone

The long term effect of drugs and growth factors on bone quality

We are studying the long term effect of drugs like bisphosphonates, which are specific to bone due to their binding to bone crystals and which inhibit bone resorption and therefore decrease bone turnover, on bone mineralization, architecture and quality because the lack of resorption caused by these drugs, coupled with their extremely long half-life, may lead in the long term to fatigue damages. We have shown that second generation bisphosphonates such as pamidronate protect the skeleton and increase mechanical strength in certain conditions. We are now studying third generation bisphosphonates such as zoledronate which is the most potent of the existing bisphosphonates. We have also explored the use of insulin-like growth factor 1(IGF-1) as an anabolic agent for bone and have shown a differential effect on mechanical properties in cancellous versus cortical bone. We are also investigating the interactions between bone, metallic implants, inflammation, and bisphosphonates to help prevent the loosening of hip and knee prosthesis.

Effects of trace elements on bone

It is possible to alter the mineralization and chemistry of the mineral of bone by the use of trace elements such as fluoride and strontium and therefore change their solubilities and other material properties. In the case of fluoride, we have shown that a biphasic effect can be observed where at low dose, bone mass and bone strength are increased, while at high doses, further increases in bone mass induce bone disorganization and a decrease in bone strength. This may be due to excessive shifts towards higher mineralization which prevents normal bone turnover leading to tissue disorganization. Similar effects are seen with strontium which increases bone mass at low doses but can induces a mineralization defect similar to osteomalacia at high doses. Other trace elements which affect mineralization such as aluminium and vanadium are also under investigation.