Use and efficacy of bone morphogenetic proteins in fracture healing

Abstract

PurposeThis review evaluates the application of bone morphogenetic proteins (BMPs) in delayed bone repair, aiming at a broad audience from clinicians to scientists. Next to an overview of the role of the different BMPs, their antagonists and their current applications, special attention is focused on new scientific developments improving the effects of BMP-based therapy for bone repair.MethodsPublication searches in PubMed and Embase revealed 850 relevant articles on the criteria ‘BMP’ AND ‘bone repair’ (as of May 2011). The abstracts were carefully reviewed and papers were selected according to the content.ResultsThe resulting publications showed that BMP-2 and BMP-7 are clearly the most extensively evaluated BMPs, in general with positive results on bone healing, comparable to the use of unspecific preparations such as autologous bone grafts or platelet-rich plasma.ConclusionsAlthough the efficacy of BMPs as stimulators of bone repair has been demonstrated in model systems and clinical studies, the use of BMPs to enhance fracture healing in the clinical setting is still controversial. Issues such as when, where and how much of which BMP is the most effective and profitable to use still have to be elucidated. But optimisation of the BMP products used in combination with cheaper production methods will inevitably stimulate the clinical use of BMPs for bone fracture healing in the near future.

Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing

“…Also, the expressions of type IIB relative to type IIA procollagens and alpha 10 relative to alpha 11 integrin subunits were found to be good markers of chondrocytes differentiation state 16 . BMP-2 deficiency has been implicated in the delayed union or nonunion and recombinant BMP-2 and BMP-7 have been clinically used in the treatment of delayed union or nonunion 15,17,18 . In addition a possibility of involvement of a BMP-related genetic predisposition in impaired fracture healing has been reported 19 .…”

“…BMP-2 is a member of a subgroup of TGF-β superfamily and triggers various signaling events which in turn stimulate chondrogenesis, osteogenesis, angiogenesis and extracellular matrix remodeling leading to fracture healing 15 . BMP signaling appears to induce chondrocyte differentiation and maturation.…”

Peri-prosthetic tissue cells show osteogenic capacity to differentiate into the osteoblastic lineage

“…Moreover, since BMPs are known inducers of osteogenic differentiation, 24 and a local increase of synthesis of several BMPs in the peri‐prosthetic tissue has been reported,23 we also stimulated cells with OM supplemented with either BMP‐2 or BMP‐6. Several BMPs, including BMP‐2 and BMP‐6, have shown positive effects on bone formation, fracture healing, and implant osseointegration in several in vitro and in vivo animal models 30, 31, 32, 33. BMP‐2 is even used in clinical practice for accelerated healing of fractures and for spinal fusions 30, 34.…”

“…Several BMPs, including BMP‐2 and BMP‐6, have shown positive effects on bone formation, fracture healing, and implant osseointegration in several in vitro and in vivo animal models 30, 31, 32, 33. BMP‐2 is even used in clinical practice for accelerated healing of fractures and for spinal fusions 30, 34. In our recent study using the murine cell‐line KS483, a combination of BMP‐4 and GIN (a stimulator of Wnt‐signalling) was found to enhance mineralization and decrease the expression of Sclerostin (an inhibitor of bone formation) compared to BMP‐4 alone 35.…”

Could the use of bone morphogenetic proteins in fracture healing do more harm than good to our patients?

“…Dear Editor, Lissenberg-Thunnissen et al evaluated the application of bone morphogenetic proteins (BMPs) in delayed bone repair, aiming at a broad audience from clinicians to scientists [1]. Among the adverse effects of BMPs, stimulation of cancer cells, development of antibodies, ectopic bone formation in fracture healing and critical soft tissue swelling for cervical spine fusions were listed.…”