Bone graft substitutes and bone morphogenetic proteins for osteoporotic fractures: what is the evidence?

Abstract

Despite improvements in implants and surgical techniques, osteoporotic fractures remain challenging to treat. Among other major risk factors, decreased expression of morphogenetic proteins has been identified for impaired fracture healing in osteoporosis. Bone grafts or bone graft substitutes are often used for stabilizing the implant and for providing a scaffold for ingrowth of new bone. Both synthetic and naturally occurring biomaterials are available. Products generally contain hydroxyapatite, tricalcium phosphate, dicalcium phosphate, calcium phosphate cement, calcium sulfate (plaster of Paris), or combinations of the above. Products have been used for the treatment of osteoporotic fractures of the proximal humerus, distal radius, vertebra, hip, and tibia plateau. Although there is generally consensus that screw augmentation increased the biomechanical properties and implant stability, the results of using these products for void filling are not unequivocal. In osteoporotic patients, Bone Morphogenetic Proteins (BMPs) have the potential impact to improve fracture healing by augmenting the impaired molecular and cellular mechanisms. However, the clinical evidence on the use of BMPs in patients with osteoporotic fractures is poor as there are no published clinical trials, case series or case studies. Even pre-clinical literature on in vitro and in vivo data is weak as most articles focus on the beneficial role for BMPs for restoration of the underlying pathophysiological factors of osteoporosis but do not look at the specific effects on osteoporotic fracture healing. Limited data on animal experiments suggest stimulation of fracture healing in ovariectomized rats by the use of BMPs. In conclusion, there is only limited data on the clinical relevance and optimal indications for the use of bone graft substitute materials and BMPs on the treatment of osteoporotic fractures despite the clinical benefits of these materials in other clinical indications. Given the general compromised outcome in osteoporotic fractures and limited alternatives for enhancement of fracture healing, clinicians and researchers should focus on this important topic and provide more data in this field in order to enable a sound clinical use of these materials in osteoporotic fractures.

Combination therapy with BMP‑2 and psoralen enhances fracture healing in ovariectomized mice

“…There is a great requirement for additional and affordable anabolic treatments to remedy impaired fracture healing. The evidence supporting the close association of BMPs with bone metabolism and the identification of the role of BMPs in the process of fracture healing and the pathogenesis of osteoporosis makes them attractive target molecules for the development of anabolic therapies for the prevention as well as for the treatment of osteoporotic fractures (29,30). Consistent with other studies, which have reported enhanced fracture repair and stimulated early new bone formation with rhBMP-2 treatment in ovariectomized rats (7,8), the present study indicated that rhBMP-2 has a positive effect on fracture healing in estrogen-deficient mice.…”

Management of complex proximal humerus fractures in the elderly: what is the role of open reduction and internal fixation?

“…60 Bone morphogenic proteins and biomaterials may become useful adjuncts as BMPs are thought to be involved in the development of osteoporosis, but at this stage the literature is limited to preclinical trials. 61 It seems that current opinion will concur that it does not matter what technique of fixation is employed, or which augmentation method utilised. Good outcomes will still rely on anatomic reduction of the tuberosities and the humeral head.…”

Sustitutivos óseos

“…Entre sus propiedades destacan su fácil obtención, capacidad de osteoconducción, rápida absorción y fácil modelado. Sin embargo, diferencias en la morfología y estructura de sus cristales, en la porosidad, en las propiedades mecánicas y en la constitución química del SC pueden alterar significativamente sus propiedades biológicas (2,5,16) . Además, se han descubierto muchos efectos adversos y ausencia de efectos, en parte debidos a su rápida resorción.…”

“…El potencial osteogénico y osteoinductivo de las BMP ha sido ampliamente validado, con tasas de fusión similares al hueso autólogo. Solo se ha aprobado el uso de BMP-2 para fusión lumbar y fracturas abiertas de tibia, y BMP-7 para pseudoartrosis de tibia (2,10,16) . Se consideran las moléculas más potentes en la inducción de la consolidación ósea, pero a pesar de la evidencia de las BMP, no dominan las estrategias para la regeneración ósea debido a diferentes cuestiones como el limitado conocimiento de sus mecanismos funcionales, la poca claridad en relación con la dosis ideal, los prerrequisitos necesarios para su éxito (disponibilidad de las células osteoprogenitoras en la fractura o pseudoartrosis o la necesidad de un adecuado aporte sanguíneo) (10) o los altos costes.…”

“…Los hidrogeles de ingeniería tisular, los compuestos poliméricos sintéticos y la terapia génica vírica también tendrían potencial de uso en fusión vertebral, pero se necesita una mayor investigación para poder utilizarlos en la práctica clínica (26) . En otra revisión de fracturas osteoporóticas, Lieshout y Alt (16) concluyen que es decepcionante observar que existen muy pocos datos en relación con los sustitutivos óseos y BMP, que no permiten realizar un algoritmo basado en la evidencia en esta patología, por lo que animan a los investigadores a centrarse en estos materiales y su uso en fracturas osteoporóticas.…”