European Spine Journal

Spivak, Jeffrey; Hasharoni, Amir

doi: 10.1007/s005860100286pmid: 11716019

Hydroxyapatite- (HA-)based ceramics have been evaluated for a variety of applications in spinal surgery, utilizing in vivo animal models and human clinical series. In vivo animal studies have shown efficacy for these materials as a bone graft substitute in interbody fusions and as a bone graft extender or bioactive osteoinductive material carrier in posterolateral lumbar fusions. Clinically, HA ceramic has been shown to be effective as a bone graft extender in posterior spinal fusion surgery for childhood scoliosis, and as a structural bone graft substitute in anterior cervical spine fusions. As an osteoconductive material, it appears to function best as a bone graft extender or carrier for an osteoinductive bone growth factor rather than as a stand-alone bone graft substitute in nonstructural clinical applications. Injectable HA ceramics also hold promise as biocompatible and bioresorbable materials for use in spinal screw fixation strength augmentation and in minimally invasive vertebral body strength augmentation either following fracture or prophylactically in osteoporotic vertebrae.

Sommerfeldt, D.; Rubin, C.

doi: 10.1007/s005860100283pmid: 11716022

The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel – the local resorption and formation of bone – which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form–function relationship, beginning with extensive research in the musculoskeletal disciplines,and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

Steffen, Thomas; Stoll, Thierry; Arvinte, Tudor; Schenk, Robert

doi: 10.1007/s005860100325pmid: 11716010

Harvesting autologous bone graft from the iliac crest is associated with considerable secondary morbidity. Bone graft substitutes such as porous ceramics are increasingly used for spinal surgery. This paper presents the results of an animal study in which β-tricalcium phosphate (β-TCP) bone substitutes were used for anterior spinal surgery in sheep and baboons. The presented baboon study also investigated the effect of impregnating the ceramic material with transforming growth factor (TGF). In the first study, using the sheep model, a stand-alone instrumented anterior fusion was performed. The animals were randomized into three treatment groups: autologous bone, β-TCP granules, and sham group. The results were analyzed biomechanically and histologically at three survival intervals: 8, 16 and 32 weeks. An additional animal group was added later, with ceramic pre-filled implants. In the second study, a baboon model was used to assess the osteointegration of a 15-mm-diameter porous β-TCP block into the vertebral body. The experiment was partially motivated by a new surgical procedure proposed for local bone graft harvest. Three treatment groups were used: β-TCP plug, β-TCP plug impregnated with TGF-β3, and a sham group with empty defect. The evaluation for all animals included computer tomograms at 3 and 6 months, as well as histology at 6 months. In the sheep model, the mechanical evaluation failed to demonstrate differences between treatment groups. This was because massive anterior bone bridges formed in almost all the animals, masking the effects of individual treatments. Histologically, β-TCP was shown to be a good osteoconductor. While multiple signs of implant micromotion were documented, pre-filling the cages markedly improved the histological fusion outcomes. In the baboon study, the β-TCP plugs were completely osteointegrated at 6 months. For the group that used ceramic plugs impregnated with TGF-β3, no incremental advantage was seen as a result of this particular application. However, TGF-β3 is a potent growth factor at a very low dose. Not only does it speed up the ceramic material resorption, but it is also responsible for massive regional new bone formation. More experiments are required to better understand the biological effects of this growth factor in relation to bone formation, and to be able to take clinical advantage of them.

Delécrin, Joël; Deschamps, Cédric; Romih, Mostafa; Heymann, Dominique; Passuti, Norbert

doi: 10.1007/s005860100273pmid: 11716007

Quantitative experimental data showed differences in bone quality and ceramic incorporation between bone-rich and bone-poor implantation sites. Bone in-growth was significantly lower for ceramic implanted at a lumbar intertransverse than a laminar site. Bone-marrow enrichment of the lumbar intertransverse site (regarded as bone-poor) greatly facilitated ceramic osteointegration. The vertebral interbody site, despite theoretical richness in osteogenic precursor cells, might be bone-poor at the time of grafting as compared to the reference iliac crest site. These data have important clinical implications concerning the potential benefit of enriching both bone-poor and bone-rich sites.

Minamide, Akihito; Tamaki, Tetsuya; Yoshida, Munehito; Hashizume, Hiroshi; Nakagawa, Yukihiro

doi: 10.1007/s005860100274pmid: 11716017

The sintered bovine bone True Bone Ceramics (TBC) is one of the biomaterials based on calcium phosphate, an organized crystal of bone mineral and a biomaterial possessing a natural trabecular structure. We examined whether the sintered bovine bone can integrate with recipient bone and adjust to the strength of recipient bone for anterior spinal fusion in an animal model. Based on radiographic evaluation, manual palpation, biomechanical testing, and histological examination, spinal fusion with TBC resulted in a composition and structure similar to that of autograft (and to no implantation). TBC, with its moderate strength, tended to adjust to the bone stiffness of the host bone in the respective specimens as new bone growth developed. Our observations warrant further clinical investigation of the use of sintered bone as an effective spinal arthrodesis, especially in patients who have fragile vertebrae, as in osteoporosis.

Muschik, Michael; Ludwig, Ralph; Halbhübner, Silke; Bursche, Kathrin; Stoll, Thierry

doi: 10.1007/s005860100271pmid: 11716016

The aim of this study is to evaluate the ability of β-tricalcium phosphate (TCP) in granular form to achieve dorsal spondylodesis in adolescent idiopathic scoliosis (AIS). Twenty-eight patients underwent surgical correction and were followed up for 13±8 (range 6–33) months. Posterolateral grafting was performed, using either autograft bone mixed with allograft bone ( n =19; "bone group") or autograft bone mixed with 25 g TCP ( n =9; "TCP group"). Patients were followed by clinical examination, X-rays and computed tomographic (CT) scans to measure bone mineral density. Fusion involved 12±1 (range 10–14) vertebrae. The segments were fused after 6±1 months in both groups according to the radiographs. No pseudarthrosis was observed. Bone mineral density was 430±111 (range 273–629) mg/cm 3 in the TCP group versus 337±134 (range 130–669) mg/cm 3 in the bone group. Resorption of TCP was complete on the radiographs after 8±2 (range 6–10) months. Based upon the results of this small preliminary study, the use of TCP appears to be a valuable alternative to allografts for application in the spine, even when large amounts of bone are needed.

Janssen, M.; Lam, C.; Beckham, R.

doi: 10.1007/s005860100292pmid: 11716014

Interbody lumbar fusions provide a proven logical solution to diseases of the intervertebral discs by eliminating motion of the segment. Historically, there are many techniques to achieve spinal fusion in the lumbar spine. These include anterior, posterior, and foramenal approaches, often in combination with various internal fixation devices. The surgeon's choice of the approach and mechanical or biological implant is dependent on the patient's specific pathology and anatomy, in addition to the experience and training of the surgeon in similar conditions. In the past decade, new mechanical spine implants/spacers have been designed to provide restoration of disc height and improve stabilization of the spine. The ability to radiographically assess the "biology" of bone incorporation in these mechanical (metal) spacers has become a significant limitation. The femoral ring allograft (FRA) and the posterior lumbar interbody fusion (PLIF) spacers have been developed as "biological cages" that permit restoration of the anterior column with machined allograft bone biological cages. Test results demonstrate that the FRA and PLIF spacers have a compressive strength of over 25,000 N. The pyramid-shaped teeth on the surfaces and the geometry of the implant increase the resistance to expulsion at clinically relevant loads (1053 and 1236 N). The technique of anterior column reconstruction with both the FRA and the PLIF biological cages have been previously reported. Clinical outcomes and experience with the FRA spacer (137 patients) and the PLIF spacer (13 patients) were reported on and did not reveal any evidence of bone cage resorption or infectious inflammatory process. There was clinical migration with one PLIF spacer, which was later revised with an anterior approach and a FRA spacer. The radiographic outcomes demonstrated that 94% arthrodesis was achieved with the biological spacer and additional posterior instrumentation. The clinical success of every spine fusion procedure is dependent on many factors such as the extent of the instability, the pathology, type of graft used, the patient's pathology/anatomy and lifestyle.

Hadjipavlou, Alexander; Simmons, James; Tzermiadianos, Michael; Katonis, Pavlos; Simmons, David

doi: 10.1007/s005860100275pmid: 11716018

In order to assess the effectiveness of calcium sulphate (plaster of Paris; POP) as a substitute for autologous bone graft, we performed lumbar intervertebral fusion in mature sheep using POP and a variety of other graft materials, and reviewed the literature. The osteoconductivity of the POP grafts was compared to that of grafts carried out with autogenous iliac crest, frozen allogeneic bone, and ProOsteon 500 coralline bone. We also compared the osteogenicity of POP to admixtures of autogenous iliac crest bone with POP and coralline bone, and to an osteoinductive demineralized sheep bone preparation (DBM). The substrates were loaded into tubular titanium mesh, implanted into excavated disc spaces and recovered after a period of 4 months. Fusion mass segments tested in flexion and tension showed that POP was equal to autogenous bone and most other substrates. The POP fusions were significantly tougher than the DBM fusions, even though histomorphometry failed to reveal differences in the amount of trabecular bone. We conclude that POP can be used to achieve a biomechanically stable interbody lumbar vertebral fusion. In addition, our literature review indicated that POP can be used as a vehicle for local delivery of antibiotics in bone infections.

Sandhu, H.; Khan, S.; Suh, D.; Boden, S.

doi: 10.1007/s005860100303pmid: 11716009

Preclinical investigations on the use of bone morphogenetic proteins (BMP) in the spine have yielded promising results. This has led to the preliminary introduction of these growth factors in controlled clinical trials. Initial data made available suggest that these differentiating factors will play a major role in the treatment of spinal disorders in the future. This article reviews key preclinical studies and their results that formed the basis for introduction into clinical trials. Non-primate and non-human primate models of spine fusion with BMP are reviewed objectively, and important issues regarding carrier, dose, and site of implantation are discussed. Finally, exciting new gene therapy research is discussed, with comments made on its applicability for the future.

Bohner, M.

doi: 10.1007/s005860100276pmid: 11716008

In 1983, Brown and Chow (10) discovered the first calcium phosphate cement (CPC). This discovery opened a new era in the use of calcium phosphates (CaP) as bone substitute. The first commercial CPC have now been introduced, and porous CaP with totally new properties should follow soon. In this article, the CaP traditionally used in spinal surgery are compared with these new CaP. Particular emphasis is placed on the use of CPC for bone augmentation.