The effect of bisphosphonates on bone microstructure and strength

Abstract

Osteoporosis (OP) is a common disease, especially among postmenopausal women. OP is regarded as the main cause of fragility fractures. Bisphosphonate (BP) medications, approved by the FDA in 1995, have been adopted as the most common and frontline treatment to OP. The most obvious positive effect of BP is their ability to improve bone mineral density (BMD). However, lots of concerns have been raised after BP medications coming into market for about ten years. A new type of hip fractures (atypical fractures) has been reported and linked with long-term BP treatment. It is still debatable on the effect of BP on bone health. Previous studies have evaluated BP’s effect either by measuring BMD quantitatively or following up fracture cases. There are very limit studies from an engineering background investigating BP’s effect on bone strength and microstructure, especially on those bones sustaining fractures despite BP treatment. The femoral heads from trauma patients’ hip replacement operations were collected and worked as a BP study group (10 femoral heads) and fracture control group (13 femoral heads) depending on whether or not the patient had been treated with BP before fractures. Cadaver samples were collected from an elderly control group (5 femoral heads). Five cylindrical sub-samples were cored from the same location of each femoral head. All the five cylinder sub-samples were micro-CT scanned for microstructure measurements. Two of the five cylinder sub-samples were selected randomly and compressively mechanically tested for apparent strength. Another two sub-samples were further synchrotron radiation scanned for a sub-micro features study, especially focusing on the trabecular microcracks and fully broken trabeculae. The apparent strength for BP treated samples is 29% and 48% lower than that of non-treated fracture controls and elderly controls, respectively. The density and microstructure parameters for the BP study group are slightly higher than or at a similar level as those of non-treated fracture controls. However, there are 24% and 55% more microcracks existing in BP treated samples than that of non-treated fracture controls and elderly controls, respectively. There are a sub-group of patients with whom BP treatment does not work very well, as they still fractured even with BP treatment for years. The bone mass density and trabecular microstructure may not be the cause of lower apparent strength. Microcracks and fully broken trabeculae can partly explain the lower strength, but further studies at the sub-micro and fibrillar levels are highly suggested.