Bone morphogenetic proteins in a rabbit posterolateral spinal fusion model: an overview

Bol u slabinskom dijelu kralježnice je važan javnozdravstveni problem u cijelom svijetu. Kirurško liječenje uključuje spinalnu fuziju kao operativnu tehniku kojoj je cilj izazvati sraštavanje dva susjedna kralježka i postići njihovu imobilizaciju, u cilju sprječavanja pojave boli. Kako bi se postiglo sraštavanje, u spinalnim fuzijama se koristi nekoliko osteoinduktivnih materijala koji potiču stvaranje nove kosti između kralježaka. Najčešće korišteni materijal je autograft. Uporaba autografta sa sobom nosi i razne komplikacije te je postotak neuspjelih spinalnih fuzija relativno visok. Kako bi se postigao manji morbiditet i veća uspješnost spinalnih fuzija, na animalnim modelima su testirani razni materijali i molekule koji bi mogli zamijeniti trenutno korištene materijale i unaprijediti standardnu tehniku spinalne fuzije. Jedan od najperspektivnijih kandidata uključuje koštane morfogenetske proteine (BMP). Od svih koštanih morfogenetskih proteina, BMP2 i BMP7 su najčešće korišteni u animalnim modelima spinalne fuzije. Poslijednjih godina, u prektliničkim i kliničkim ispitivanjima se počeo koristiti i BMP6. U sklopu istraživanja potencijala koštanih morfogenetskih proteina kao alternative autograftu, provedena su mnoga istraživanja koja uključuju „proof of concept“ korak, pokuse učinkovitosti i sigurnosti, testiranje raznih nosača za BMP molekule te pokuse koji uključuju najčešće komplikacije. Ovaj rad donosi pregled dosadašnje uporabe koštanih morfogenetskih proteina u modelu posterolateralne spinalne fuzije kunića.Lower back pain is an important public health issue worldwide. In recent decades, interventional spine procedures, including spinal fusion surgeries have become common lower back pain therapy, with a 40% increase in the number of spinal fusions performed between 1998 and 2004. Spinal fusion is the surgical technique of joining two vertebrae so that they heal into a single, solid bone. This is done to prevent movement and occurrence of the pain. In order to achieve solid spinal fusion, various osteoinductive materials that stimulate the formation of the new bone are used in the spinal fusion procedure. Autograft is the most preferred osteoinductive material for spine fusion surgeries. However, the use of autografts is often associated with certain limitations and morbidity. Despite all efforts to improve the spinal fusion technique, the reported non-union rate remains high. All these shortcomings of the standard techniques have urged the development of alternative materials and/or supplements for bone grafting, to enhance new bone formation and facilitate more rapid and robust fusion, with lower morbidity and higher success. Recent efforts in the field have been focused on bone morphogenic proteins (BMP). Of all the bone morphogenetic proteins, BMP2 and BMP7 are most commonly used in animal models of spinal fusion. Both BMP2 and BMP7 have strong osteoinductive properties and their effect on the formation of new bone has been proven in many animal models. In recent years, pre-clinical and clinical trials have also begun for the use of BMP6. As part of enhancing the potential of bone morphogenetic proteins as an alternative for bone grafting, many studies have been carried out involving a “proof of concept” step, feasibility and efficacy trials, testing of various BMP carriers, and complication experiments. This paper provides an overview of the current use of bone morphogenetic proteins in a rabbit model of posterolateral spinal fusion

Bone morphogenetic proteins in a rabbit posterolateral spinal fusion model: an overview

Bol u slabinskom dijelu kralježnice je važan javnozdravstveni problem u cijelom svijetu. Kirurško liječenje uključuje spinalnu fuziju kao operativnu tehniku kojoj je cilj izazvati sraštavanje dva susjedna kralježka i postići njihovu imobilizaciju, u cilju sprječavanja pojave boli. Kako bi se postiglo sraštavanje, u spinalnim fuzijama se koristi nekoliko osteoinduktivnih materijala koji potiču stvaranje nove kosti između kralježaka. Najčešće korišteni materijal je autograft. Uporaba autografta sa sobom nosi i razne komplikacije te je postotak neuspjelih spinalnih fuzija relativno visok. Kako bi se postigao manji morbiditet i veća uspješnost spinalnih fuzija, na animalnim modelima su testirani razni materijali i molekule koji bi mogli zamijeniti trenutno korištene materijale i unaprijediti standardnu tehniku spinalne fuzije. Jedan od najperspektivnijih kandidata uključuje koštane morfogenetske proteine (BMP). Od svih koštanih morfogenetskih proteina, BMP2 i BMP7 su najčešće korišteni u animalnim modelima spinalne fuzije. Poslijednjih godina, u prektliničkim i kliničkim ispitivanjima se počeo koristiti i BMP6. U sklopu istraživanja potencijala koštanih morfogenetskih proteina kao alternative autograftu, provedena su mnoga istraživanja koja uključuju „proof of concept“ korak, pokuse učinkovitosti i sigurnosti, testiranje raznih nosača za BMP molekule te pokuse koji uključuju najčešće komplikacije. Ovaj rad donosi pregled dosadašnje uporabe koštanih morfogenetskih proteina u modelu posterolateralne spinalne fuzije kunića.Lower back pain is an important public health issue worldwide. In recent decades, interventional spine procedures, including spinal fusion surgeries have become common lower back pain therapy, with a 40% increase in the number of spinal fusions performed between 1998 and 2004. Spinal fusion is the surgical technique of joining two vertebrae so that they heal into a single, solid bone. This is done to prevent movement and occurrence of the pain. In order to achieve solid spinal fusion, various osteoinductive materials that stimulate the formation of the new bone are used in the spinal fusion procedure. Autograft is the most preferred osteoinductive material for spine fusion surgeries. However, the use of autografts is often associated with certain limitations and morbidity. Despite all efforts to improve the spinal fusion technique, the reported non-union rate remains high. All these shortcomings of the standard techniques have urged the development of alternative materials and/or supplements for bone grafting, to enhance new bone formation and facilitate more rapid and robust fusion, with lower morbidity and higher success. Recent efforts in the field have been focused on bone morphogenic proteins (BMP). Of all the bone morphogenetic proteins, BMP2 and BMP7 are most commonly used in animal models of spinal fusion. Both BMP2 and BMP7 have strong osteoinductive properties and their effect on the formation of new bone has been proven in many animal models. In recent years, pre-clinical and clinical trials have also begun for the use of BMP6. As part of enhancing the potential of bone morphogenetic proteins as an alternative for bone grafting, many studies have been carried out involving a “proof of concept” step, feasibility and efficacy trials, testing of various BMP carriers, and complication experiments. This paper provides an overview of the current use of bone morphogenetic proteins in a rabbit model of posterolateral spinal fusion

OSTEOGROW – novi lijek za koštanu regeneraciju

Molecular processes required for bone repair are a prerequisite for the development of new biological procedures for stimulation of bone healing. Currently, there is no adequate therapy available that can accelerate long bone fractures healing. Specifically there is a need for the development of a new osteogenic device that will offer safe healing in particular of the trabecular bone. The Osteogrow project has developed a new therapy that promises to be safe and cost-effective and might decrease the need for secondary interventions. The Osteogrow device contains an autologous blood coagulum (ABC) made from the peripheral blood and recombinant bone morphogenetic protein 6 (BMP6). BMP6 has been selected as compared to BMP2 or BMP7/OP1 as it does not bind avidly to the BMP antagonist Noggin. ABC was chosen as a substrate for the delivery since BMP6 binds tightly to the number of plasma proteins resulting in the sustained and linear release over seven to ten days without provoking inflammation and immune responses. With support of the EU FP7 grant we have completed the preclinical development of Osteogrow and started Osteogrow first in humans (FIH) clinical studies. Osteogrow is tested clinically in two indications: the distal radial fracture and high tibial osteotomy to establish the safety and potential efficacy for Osteogrow for regeneration of the metaphyseal bone. Beyond currently tested clinical indications, this therapy would also be employed for posterolateral spinal fusion to treat degenerative spine disorders.Molekularni procesi potrebni za regeneraciju kosti su preduvjet za razvoj novih bioloških postupaka neophodnih za stimulaciju koštanog cijeljenja. U ovome trenutku na tržištu ne postoji adekvatna terapija koja može ubrzati cijeljenje prijeloma dugih kostiju. Postoji potreba za razvojem nove koštane naprave koji će ponuditi sigurno i ekonomično liječenje. Projekt Osteogrow razvio je potpuno novu terapiju koja obećava da će biti sigurna i isplativa te će smanjiti potrebu za sekundarnim intervencijama. Osteogrow sadrži autologni krvni ugrušak (ABC) kao nosač koji se sastoji od periferne krvi u koji se dodaje rekombinantni protein BMP6 (engl. Bone Morphogenetic Protein). BMP6 je odabran kao poželjni koštani morfogentski protein u usporedbi s BMP2 ili BMP7 / OP1 jer se ne veže na BMP antagonist, Noggin. Autologni krvni ugrušak odabran je kao nosač BMP6 molekule, jer se veliki broj proteina plazme čvrsto veže na BMP6. Uz potporu EU FP7 programa završena su pretklinička testiranja Osteogrow-a i započela je prva primjena Osteogrow lijeka u ljudi (FIH) unutar odobrene kliničke studije. Osteogrow se testira unutar dvije indikacije: distalna radijalna fraktura i visoka osteotomija goljenične kosti koje su odabrane kako bi se utvrdila sigurnost i potencijalna učinkovitost Osteogrow lijeka u regeneraciji metafizalne kosti. Osim trenutno testiranih kliničkih indikacija, ova terapija će se koristiti za liječenje degenerativnih bolesti kralježnice