RECENT FINDINGS: A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.
OBJECTIVE: This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.
DISCUSSION: Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.
CONCLUSION: Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.