Injectable bone-graft substitutes: Current products, their characteristics and indications, and new developments

Abstract

More than a decade has passed since the first injectable bone substitutes were introduced for use in orthopaedic trauma, and over recent years the number of commercial products has increased dramatically. Despite the fact that these bone substitutes have been on the market for many years, knowledge amongst potential users on how and when they might be useful is still fairly limited. Most injectable bone substitutes belong to one of two major groups: by far the largest group contains products based on various calcium phosphate (CP) mixtures, whilst the smaller group consists of calcium sulphate (CS) compounds. Following mixing, the CP or CS paste can be injected into – for instance – a fracture space for augmentation as an alternative to bone graft, or around a screw for augmentation if the bone is weak. Within minutes an in situ process makes the substitute hard; the mechanical strength in compression resembles that of cancellous bone, whereas the strength in bending and shear is lower. Over time, CP products undergo remodelling through a cell-mediated process that seems to mimic the normal bone remodelling, whilst CS products are dissolved through a faster process that is not cell-mediated. For CP, a number of clinical studies have shown that it can be useful for augmentation of metaphyseal fractures when a space is present. Randomised studies have verified that CP works especially well in tibial plateau fractures when compared with conventional bone grafting. So far the number of clinical studies on CS products is very low.

Development at present seems to be heading towards premixed or directly mixed products as well as new compounds that contain fibres or other components to enhance bending and shear strength. Products that are based on combinations of CP and CS are also being developed to combine the fast-dissolving CS with the stronger and more slowly remodelling CP. Injectable bone substitutes, and especially CS, have also been targeted as potentially good carriers for antibiotics and growth factors.

Introduction

Injectable bone substitutes that are self-setting in situ can bring significant benefits in several clinical situations, such as augmentation of osteoporotic fractures, treatment of maxillofacial defects and deformities, and for certain indications in the spine. Even though the first injectable bone substitutes were introduced more than a decade ago, they still in many ways represent a new treatment option where currently the proper indications for many products have yet to be defined. In fact, it might be reasonable to state that the orthopaedic community is still within the learning curve in many aspects of many of these products. The rapid development – including the frequent introduction of new products – makes it very difficult for most potential users to be aware of differences and similarities between the products and when and how to use them.

The purposes of this paper are to describe the basic aspects of the most common of the injectable bone substitutes that are currently available, to present relevant clinical data to increase awareness of how these products can be used and what to expect when using them, and finally to provide some future perspectives.