Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

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The incorporation of magnesium ions (in the range 5-10 mol% in respect to Ca) into the hydroxyapatite structure, which is of great interest for the developing of artificial bone, was performed using magnesium chloride, calcium hydroxide and phosphoric acid, as reactants. Among the synthesized powders, the synthetic HA powder containing 5.7% Mg substituting for calcium was selected, due to its better chemico-physical features, and transformed into granules of 400-600 microm, for biocompatibility tests (genotoxicity, carcinogenicity, toxicity, in vitro cytotoxicity and in vivo skin irritation-sensitization tests). In vivo tests were carried out on New Zealand White rabbits using the granulate as filling for a femoral bone defect: osteoconductivity and resorption were found to be enhanced compared to commercial stoichiometric HA granulate, taken as control.

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Pre-operative physiotherapy in patients undergoing hip arthroplasty does not improve impairment and health-related quality of life after intervention. Physiotherapy and educational therapy may be useful for end-stage osteoarthritis.

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Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.

This article is a review of spondylolysis and spondylolisthesis in younger age groups. Since Herbinaux first described the pathology (1782), many classifications and theories of etiopathogenesis have been proposed. The congenital and isthmic types, as classified by Wiltse, are the most frequent in younger age groups, but the postsurgical progressive forms (3-5%) have been described as increasing in frequency secondary to neoplastic surgery in children. The general incidence is 4-5% at the age of 6 years, and in 30-50% of cases these types do not progress to spondylolisthesis. Most cases are asymptomatic (80%). Standard radiographic examinations (A-P, L, Oblique) are helpful in diagnosis and can suggest what the prognosis will be in terms of the evolution, and also what treatment is indicated (degree of slippage, slip angle, lumbar and lumbosacral index, SPTI). A bone scan (PBS and SPECT) is useful in the early stages of spondylolysis (pre-spondylosis). Although the CT scan is the most accurate examination, MRI is becoming important for diagnosis because of the frequency with which it is used as a primary investigation method. Depending on patient age, progression, degree of slippage, and symptoms, different therapeutic approaches have been proposed and are described in this paper.