Cranial vault remodeling in microcephalic osteodysplastic primordial dwarfism type II and craniosynostosis.

This is a survey of the long-term result after various surgical treatments in a child with microcephalic osteodysplastic primordial dwarfism type II (MOPD II) and craniosynostosis. We report a 17-year-old patient with MOPD II but some unusual clinical signs including bilateral knee dislocation, a misplaced upper lobe bronchus, and hypoplasia of the anterior corpus callosum. Because of premature fusion of several cranial sutures, the child developed signs of increased intracranial pressure with somnolence and papilledema. Cranial vault remodeling with fronto-orbital advancement was performed twice at the age of 16 and 21 months to open the abnormally closed suture, increase the intracranial volume, and relieve the elevated intracranial pressure. Following this procedure, the child's neurologic situation recovered significantly. Surgical procedure of fronto-orbital advancement and the performed reoperation in our patient were safe with no major complications intraoperatively and postoperatively with good functional and satisfying aesthetic outcomes in the long-term follow-up, expressed by the patient, his parents, and the surgeons.

Pinealectomy affects bone mineral density and structure--an experimental study in sheep.

BACKGROUND: Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model. METHODS: Female sheep were arranged into four groups: Control, surgically ovariectomized (Ovx), surgically pinealectomized (Px) and Ovx+Px. Before and 6 months after surgery, iliac crest biopsies were harvested and structural parameters were measured using µCT. Markers of bone formation and resorption were determined. To evaluate long term changes after pinealectomy, bone mineral density (BMD) was analyzed at the distal radius at 0, 3, 9, 18 and 30 months. RESULTS: Cancellous bone volume (BV/TV) declined after 6 months by -13.3% Px and -21.5% OvxPx. The bone loss was due to increased trabecular separation as well as decreased thickness. The histomorphometric quantification and determination of collagen degradation products showed increased bone resorption following pinealectomy. Ovariectomy alone results in a transient bone loss at the distal radius followed by continuous increase to baseline levels. The bone resorption activity after pinealectomy causes a bone loss which was not transient, since a continuous decrease in BMD was observed until 30 months. CONCLUSIONS: The changes after pinealectomy in sheep are indicative of bone loss. Overall, these findings suggest that the pineal gland may influence bone metabolism and that pinealectomy can be used to induce bone loss in sheep.

Calcification or dedifferentiation: requirement to lock mesenchymal stem cells in a desired differentiation stage.

A current challenge in mesenchymal stem cell (MSC)-based cartilage repair is to solve donor and tissue-dependent variability of MSC cultures and to prevent chondrogenic cells from terminal differentiation like in the growth plate. The aim of this study was to select the best source for MSC which could promise stable cartilage formation in the absence of hypertrophy and ectopic in vivo mineralization. We hypothesized that MSC from synovium are superior to bone marrow- and adipose tissue-derived MSC since they are derived from a joint tissue. MSC were characterized by flow cytometry. MSC pellets were cultured under chondrogenic conditions and differentiation was evaluated by histology, gene expression analysis, and determination of alkaline phosphatase activity (ALP). After chondrogenic induction, pellets were transplanted subcutaneously into SCID mice. MSC from bone marrow, adipose tissue, and synovium revealed similar COL2A1/COL10A1 mRNA levels after chondrogenic induction and were positive for collagen-type-X. Bone marrow-derived and adipose tissue-derived MSC showed significantly higher ALP activity than MSC from synovium. Low ALP-activity before transplantation of pellets correlated with marginal calcification of explants. Surprisingly, non-mineralizing transplants specifically lost their collagen-type II, but not collagen-type I deposition in vivo, or were fully degraded. In conclusion, the lower donor-dependent ALP activation and reduced mineralization of synovium-derived heterotopic transplants did not lead to stable ectopic cartilage as known from articular chondrocytes, but correlated with fibrous dedifferentiation or complete degeneration of MSC pellets. This emphasizes that beside appropriate induction of differentiation, locking of MSC in the desired differentiation state is a major challenge for MSC-based repair strategies.

Myoelectric hand prostheses in very young children.

Myoelectric prostheses have generally been provided for adolescent or adult patients. The availability of smaller-sized electric hands has enabled the introduction of myoelectric prostheses to preschool children, mainly in the Scandinavian countries. This study evaluates the acceptance of myoelectric prostheses in 41 children with unilateral upper limb deficiency between the ages of two and five years. The prosthesis was used for an average time of 5.8 hours per day. The level of amputation was found to influence the acceptance rate. Furthermore, prosthetic use training by an occupational therapist is related to successful use of the prosthesis. The general drop-out rate in preschool children is very low compared to adults. Therefore, infants can profit from myoelectric hand prostheses. Since a correct indication and an intense training program significantly influence the acceptance rate, introduction of myoelectric prostheses to preschool children should take place at specialised centres with an interdisciplinary team.

Reducing Blood Loss in Revision Total Hip and Knee Arthroplasty: Tranexamic Acid Is Effective in Aseptic Revisions and in Second-Stage Reimplantations for Periprosthetic Infection.

INTRODUCTION: The aim of the study was to determine the usefulness of tranexamic acid (TXA) in revision total hip arthroplasty (rTHA) and revision total knee arthroplasty (rTKA). We analyzed the perioperative blood loss with and without TXA in aseptic rTHA and rTKA as well as in second-stage reimplantation for hip and knee periprosthetic infection. MATERIALS AND METHODS: In this prospective cohort study, 147 patients receiving TXA (96 rTHA, 51 rTKA) were compared to a retrospective cohort of 155 patients without TXA (103 rTHA, 52 rTKA). The TXA regimen consisted of a preoperative bolus of 10 mg/kg bodyweight (BW) TXA plus 1 mg/kgBW/h perioperatively. Given blood products were documented and the perioperative blood loss was calculated. Thromboembolic events were registered until three months postoperatively. In subgroups, the effects of TXA were separately analyzed in 215 aseptic revisions as well as in 87 reimplantations in two-stage revisions for periprosthetic infection. RESULTS: Both TXA groups showed a significantly reduced mean blood loss compared to the respective control groups. The TXA group of rTHA patients had a mean blood loss of 2916 ml ± 1226 ml versus 3611 ml ± 1474 ml in the control group (p<.001). For the TXA group of rTKA patients, mean calculated blood loss was 2756 ml ± 975 ml compared to 3441 ml ± 1100 ml in the control group (p=.0012). A significantly reduced blood loss was also found in the TXA subgroups for aseptic and septic revision procedures. No thromboembolic events were recorded among the TXA groups. CONCLUSIONS: There is a significant reduction of perioperative blood loss under TXA influence without an increased incidence of adverse events. The standard use of TXA can be recommended in aseptic hip and knee revision arthroplasties as well as in second-stage reimplantations for periprosthetic infection.

Seasonal changes in bone metabolism in sheep.

There is a great need for animal models of osteoporosis and sheep are a suitable large animal that meets most requirements. Since it is known that bone mass in humans responds to seasonal changes, this study investigated natural bone metabolism in sheep in order to better define the sheep as a model for osteoporosis. Bone mineral density (BMD), trabecular structure, biochemical markers of bone formation and resorption and estrogen were analysed over a period of 18 months. The lowest BMDs, measured by peripheral quantitative computed tomography (pQCT), were observed during winter. Thereafter, a 5.1% increase in BMD was observed during spring and summer (P<0.05). Bone resorption markers showed a variable pattern, with higher values in spring compared to autumn (P<0.001). The physiological estrus phase during autumn was detected by serum estrogen levels. The findings show that it is necessary to take seasonal variations into account if sheep are used to establish an animal model for osteoporosis.

Leptin inhibits bone formation not only in rodents, but also in sheep.

UNLABELLED: This study examines the effect of long-term ICV administration of leptin in ewes. We found that central application significantly decreased osteoblast activity as measured by serum analysis as well as by histomorphometry, resulting in decreased trabecular bone volume. These data provide additional evidence that bone formation and therefore bone remodeling is at least in part centrally controlled. INTRODUCTION: Genetic studies in mice have identified leptin as a potent inhibitor of bone formation acting through the central nervous system and unraveled the central nature of bone mass control and its disorders. Although these studies have radically enhanced our understanding of skeletal physiology because they have established a hypothalamic regulation of bone remodeling through the sympathetic nervous system, controversy remains about the physiological relevance of these observations because leptin's effect on bone after intracerebroventricular (ICV) application has only been shown in mice. To address whether leptin has a role in regulating bone mass beyond rodents, we treated ewes with long-term ICV application of leptin and analyzed the bone phenotype after a treatment period of 3 months. MATERIALS AND METHODS: Three groups of corriedale sheep were compared: (1) control entire (control), (2) ovariectomy (OVX) and ICV application of cerebrospinal fluid (CSF); and (iii) OVX and ICV application of leptin (leptin). Analysis included histomorphometric characterization of iliac crest, spine and femur by histology and biomechanical testing and measurement of bone turnover parameters in serum and urine. RESULTS: Central application of leptin decreased bone formation by 70% and mineralizing surface (MS/BS, 39.4 +/- 3.3% versus 16.1 +/- 2.1%) significantly (p < 0.01). Whereas OVX increased osteoclast indices and urinary cross-lap excretion by two and three times, respectively, serum parameters of osteoblast activity were significantly reduced by ICV application of leptin (p < 0.01). Consequently, ewes treated with leptin were osteopenic (iliac crest BV/TV entire, 22.7 +/- 1.3%; CSF, 18.9 +/- 2.4%; leptin, 12.4 +/- 2.6%), whereas bone torsional failure load reflecting the cortex of the tibia was not yet changed after 3 months of treatment (p < 0.01). CONCLUSIONS: Taken together, these data suggest that leptin controls bone formation after ICV application, leading to reduction of trabecular bone mass in sheep. Most importantly, however, they show that the central regulation of bone formation is not limited to rodents, but is also found in large animals, providing further evidence that bone remodeling in vertebrates is centrally controlled.

Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro.

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.

Core Decompression and Autologous Bone Marrow Concentrate for Treatment of Femoral Head Osteonecrosis: A Randomized Prospective Study.

The aim of this study was to investigate the safety of injection of bone marrow aspirate concentrate during core decompression and to study its clinical (visual analogue scale; Harris-Hip-score) and radiological outcomes (magnetic resonance imaging). In this prospective and randomized clinical trial we evaluated 24 consecutive patients with non-traumatic femoral head necrosis (FHN) during a period of two years after intervention. In vitro analysis of mesenchymal stem cells was performed by evaluating the fibroblast colony forming units (CFU-Fs). Postoperatively, significant decrease in pain associated with a functional benefit lasting was observed. However, there was no difference in the clinical outcome between the two study groups. Over the period of two years there was no significant difference between the head survival rate between both groups. In contrast to that, we could not perceive any significant change in the volume of FHN in both treatment groups related to the longitudinal course after treating. The number of CFU showed a significant increase after centrifugation. This trial could not detect a benefit from the additional injection of bone marrow concentrate with regard to bone regeneration and clinical outcome in the short term.

Haematogenous infection of a total knee arthroplasty with Klebsiella pneumoniae.

This case report describes a prosthetic joint infection due to the haematogenous spread of Klebsiella pneumoniae from a genitourinary focus. Prior to the infection, the patient was diagnosed with early stage prostatic carcinoma, which had been successfully treated with surgery. However, in the time period following surgical treatment, the patient suffered recurring urinary tract infections. During the course of these recurring infections, he developed a concurrent bacterial infection of his total knee arthroplasty. Two sequential joint aspirates revealed K pneumoniae to be the cause. Therefore, two-stage revision total knee arthroplasty was performed. This case reiterates the fact that invasive therapeutic procedures can cause bacteraemia resulting in infection of a joint replacement. We would therefore like to emphasise the importance of prophylactic antibiotic treatment prior to invasive therapies, particularly in organs with potentially large counts of bacteria.

The collagen component of biological bone graft substitutes promotes ectopic bone formation by human mesenchymal stem cells.

Synthetic bone substitutes are attractive materials for repairing a variety of bone defects. They are readily available in unlimited quantities, have a defined composition without batch variability and bear no risk of disease transmission. When combined with mesenchymal stem cells (MSCs), bone healing can be further enhanced due to the osteogenic potential of these cells. However, human MSCs showed considerable donor variability in ectopic bone formation assays on synthetic bone substitutes, which may limit clinical success. This study addresses whether bone formation variability of MSCs is cell-intrinsic or biomaterial-dependent and may be improved using biological bone substitutes with and without collagen. Ectopic bone formation of MSCs from nine donors was tested in immune-deficient mice on biological bone substitutes of bovine and equine origin, containing collagen (bHA-C; eHA-C) or not (bHA; eHA). Synthetic ß-TCP was used for comparison. Histology of 8-week explants demonstrated a significant influence of the bone graft substitute (BGS) on donor variability of ectopic bone formation with best results seen for eHA-C (15/17) and ß-TCP (16/18). Bone was of human origin in all groups according to species-specific in situ hybridization, but MSCs from one donor formed no bone with any bone substitute. According to histomorphometry, most neo-bone was formed on eHA-C with significant differences to bHA, eHA and ß-TCP (p<0.001). Collagen-free biological BGSs were inferior to biological BGSs with collagen (p<0.001), while species-origin was of little influence. In conclusion, BGS composition had a strong influence on ectopic bone formation ability of MSCs, and biological BGSs with a collagen component seem most promising to display the strong osteogenic potential of MSCs.

Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis.

BACKGROUND: Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone. METHODS: Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed. RESULTS: Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group. CONCLUSIONS: ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.

Mechanical stability in a human radius fracture treated with a novel tissue-engineered bone substitute: a non-invasive, longitudinal assessment using high-resolution pQCT in combination with finite element analysis.

The clinical gold standard in orthopaedics for treating fractures with large bone defects is still the use of autologous, cancellous bone autografts. While this material provides a strong healing response, the use of autografts is often associated with additional morbidity. Therefore, there is a demand for off-the-shelf biomaterials that perform similar to autografts. Biomechanical assessment of such a biomaterial in vivo has so far been limited. Recently, the development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure bone structure in humans in great detail. Finite element analysis (FEA) has been used to accurately estimate bone mechanical function from three-dimensional CT images. The aim of this study was therefore to determine the feasibility of these two methods in combination, to quantify bone healing in a clinical case with a fracture at the distal radius which was treated with a new bone graft substitute. Validation was sought through a conceptional ovine model. The bones were scanned using HR-pQCT and subsequently biomechanically tested. FEA-derived stiffness was validated relative to the experimental data. The developed processing methods were then adapted and applied to in vivo follow-up data of the patient. Our analyses indicated an 18% increase of bone stiffness within 2 months. To our knowledge, this was the first time that microstructural finite element analyses have been performed on bone-implant constructs in a clinical setting. From this clinical case study, we conclude that HR-pQCT-based micro-finite element analyses show high potential to quantify bone healing in patients.

Interobserver reliability of radiographic measurements of contralateral feet of pediatric patients with unilateral clubfoot.

BACKGROUND: Radiographs have traditionally been used to describe and quantify foot deformities in infants and children. We hypothesized that the interobserver reliability of measurements obtained from radiographs of pediatric feet would be low, especially with regard to the infant foot, and that normal ranges and standard deviations would decrease in association with increasing patient age. METHODS: We retrospectively reviewed 494 radiographs of 121 patients treated for unilateral clubfoot at our institution and studied the contralateral normal foot. All anteroposterior radiographs, lateral radiographs, and lateral radiographs made with the foot in maximum dorsiflexion were analyzed by three observers, and the values were recorded. The databases created by the three observers were statistically analyzed according to five predefined age groups (birth to less than three months, three months to less than twelve months, twelve months to less than three years, three years to less than seven years, and seven years to less than fourteen years). RESULTS: The anteroposterior talocalcaneal angle was rated as having good interobserver reliability (i.e., an intraclass correlation coefficient of 0.61 to 0.80) for all patients in each age group. Other angles that were associated with good interobserver reliability were the anteroposterior calcaneus-fifth metatarsal angle in the twelve months to less than three-year age group, the three-year to less than seven-year age group, and the seven-year to less than fourteen-year age group; the lateral talocalcaneal angle in the three-year to less than seven-year age group; the lateral tibiotalar angle in the three-year to less than seven-year age group; and the lateral talus-first metatarsal angle in the seven-year to less than fourteen-year age group. All other angles were rated as having very good interobserver reliability (i.e., an intraclass correlation coefficient of 0.81 to 1). The mean difference and the maximum difference among the observers decreased for all angles in nearly all age groups. CONCLUSIONS: Interobserver reliability with regard to the radiographic measurement of pediatric feet was higher than expected, although measurement discrepancies can be as great as 30° with the infant foot. Interobserver reliability tended to improve with increasing patient age. The standard deviation showed a trend toward a decrease as patient age increased, although the trend was less notable than expected.

Influence of defective bone marrow osteogenesis on fracture repair in an experimental model of senile osteoporosis.

Bone marrow osteogenesis in senile osteoporotic bone is impaired and, as such, may have significant implications on the successful outcome of fracture repair. Here we utilize a well-established murine model of senile osteoporosis, the P6 strain of senescence-accelerated mice (SAMP6), to investigate fracture healing in aged osteoporotic bone. A femoral osteotomy was created in SAMP6 and in non-osteoporotic age-matched control R1 senescence-resistant mice (SAMR1). The course of fracture healing was evaluated over a period of 42 days using quantitative microCT and histological analysis. The differentiation capabilities of bone mesenchymal progenitor cells derived from SAMP6 and SAMR1 mice was examined, and their osteogenic potential determined. Although preliminary in vitro analysis confirmed that bone marrow-derived stem cells (BMSC) isolated from SAMP6 mice had a reduced osteogenic capacity, no significant deficit in fracture repair as determined by quantitative microCT could be detected. This was supported by histology assessment, where complete bridging of the fracture gap was evident by day 28 and was fully healed day 42 in both SAMP6 and SAMR1 mice. Further in vitro studies revealed that periosteal-derived progenitor cells (PDPC) isolated from SAMP6 mice had an osteogenic potential comparable to that observed in SAMR1 mice. In conclusion, fracture healing in SAMP6 mice is not detrimentally affected by impairment of BMSC osteogenesis, suggesting that bone marrow-mediated repair processes are dispensable for normal bone healing in this senile osteoporotic fracture model. Furthermore, the influence of PDPC in the repair process may partly explain the absence of any detectable deficits in fracture repair in SAMP6 mice.

Ectopic expression of delta FBJ murine osteosarcoma viral oncogene homolog B mediates transdifferentiation of adipose-like spheroids into osteo-like microtissues.

Differentiation and transdifferentiation strategies have a large role in the manipulation of cells in replacing dysfunctional cells and tissues. We developed adipose-like microtissues using gravity-enforced self-assembly of monodispersed human primary preadipocytes to determine their transdifferentiation capacity to form bone-like tissues. Using lentivirus-derived particles to induce ectopic bone morphogenetic protein (BMP)-2 and delta FBJ murine osteosarcoma viral oncogene homolog B (DeltaFosB) gene expression, we demonstrated a time-dependent induction of osteoblast-specific genes and properties such as calcium deposits, bone-like extracellular matrix (ECM), and matrix mineralization. DeltaFosB was able to trigger partial Pref-1-mediated de-differentiation of adipocytes, which also retained their adipocytic cell phenotype. Osteoblast-specific structures could be co-localized in the ECM of lipid-containing cells analyzed using immunofluorescence and transmission electron microscopy when BMP-2 and DeltaFosB were co-expressed, suggesting that differentiated adipocytes are able to transdifferentiate into osteoblasts via a transient hybrid adipocyte-preadipocyte-osteoblast cell phenotype. Microtissues transgenic for BMP-2 and DeltaFosB expression were able to reproduce bone matrix, which occurs to a lesser extent in conventional two-dimensional (2D) cultures but is known to play a decisive role in the development and function of bone in vivo. This demonstrates that ECM-inclusive studies are essential for future characterization assays. Therefore, 3D cultures provide a superior ex vivo system for the improved characterization of phenotypical and functional alterations resulting from interventions directed toward differentiation processes. Precise control of transdifferentiation of adipocytes into osteoblasts in a 3D culture mimicking in vivo tissue conditions as closely as possible will foster important advances in regenerative medicine and tissue engineering.

The long-term effects of ovariectomy on bone metabolism in sheep.

Osteoporosis and associated fractures are major public health concerns, and as such require appropriate large animal models to further our understanding of this disease. Although sheep appear to be an ideal model with which to study bone loss caused by estrogen depletion, limited data are available concerning the long-term effect of ovariectomy on bone in sheep. The goal of the present study was to observe the ovariectomy-induced changes in bone mass, structure, and metabolism in sheep over a period of 18 months. Six ewes were ovariectomized (OVX) and compared to an age-matched control group by analyzing bone mineral density, trabecular structure, biochemical markers of bone formation and resorption, and plasma estrogen levels. Bone loss (13%, P < 0.01) occurred during the first 4 months after surgery, then stabilized and returned to pre-OVX levels for the remainder of the study. Trabecular architecture was also altered and tended toward osteopenia with recovery to baseline values. Markers of bone formation and resorption were elevated up to 6 months postovariectomy, after which time levels returned to baseline values. Although estradiol measurements demonstrated a clear decline following surgical ovariectomy, levels returned to normal after 6 months. Therefore, the detrimental effect of ovariectomy on sheep bone metabolism seems to be reversible, with normal bone parameters being reestablished within 6 months after surgery. These data seem to indicate that the sheep is not an appropriate model for human postmenopausal osteoporosis.

A comparative analysis of phenotype expression in human osteoblasts from heterotopic ossification and normal bone.

BACKGROUND AND AIMS: Heterotopic ossification (HO) is a pathological bone formation process in which ectopic bone is formed in soft tissue. The formation of bone depends on the expression of the osteoblast phenotype. Earlier studies have shown conflicting results on the expression of phenotype markers of cells originating from HO and normal bone. The hypothesis of the present study is that cells from HO show an altered expression of osteoblast-specific phenotype markers compared to normal osteoblasts. The aims of the study were to further characterize the expression of osteoblast phenotypemarkers and to provide a comparison with other study results. PATIENTS AND METHODS: Using an in vitro technique, reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemistry, we compared the phenotype gene expression (type I collagen, alkaline phosphatase, Cbfa-1, osteocalcin) of osteoblasts from resected HO and normal bone (iliac crest). RESULTS: Cells from HO expressed the osteoblast phenotype (type I collagen, alkaline phosphatase) but were characterized by a depleted osteocalcin expression. The expression of Cbfa-1 (osteocalcin transcription gene) showed a large variety in our study. Preoperative radiotherapy had no effect on phenotype expression in cells from HO. CONCLUSION: Our results provide a characterization of cells originating from HO and support the thesis of an impaired osteoblast differentiation underlying the formation of HO. The transcription axis from Cbfa-1 to osteocalcin could be involved in the pathogenesis of HO.

Animal models for fracture treatment in osteoporosis.

Demographic changes in the age structure of occidental populations are giving rise to osteoporosis and associated fractures, which are becoming a major public health burden. Various animal models have been established and used to investigate the pathogenesis of osteoporosis and to facilitate the preclinical testing of new treatment options such as antiresorptive drugs. Although osteoporosis can be induced in animals, spontaneous fractures without adequate trauma were only found in nonhuman primates. An animal model designed to investigate new ways to treat fractures of osteoporotic bone has to fulfill requirements that are very different from those of pharmacological testing. The aspects of major interest in orthopedic applications are bone fragility, efficacy of implant fixation and bone healing. Existing animal models for osteoporosis were critically reviewed focusing on these aspects. The advantages and disadvantages of the models with regard to their application in the testing of new fracture-fixation devices or biological approaches to stimulate bone healing are discussed. Ovariectomy alone does not cause the bone loss seen in osteoporotic human patients. New models to simulate fracture of osteoporotic bone need to be explored and used to address the specific aims of an experiment.