Mineral Composition is Altered by Osteoblast Expression of an Engineered Gs-Coupled Receptor

Activation of the Gs G protein–coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive Gs signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive Gs activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive Gs signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm3 (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous Gs activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients

Bone regeneration: current concepts and future directions

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis

Correlation of pQCT bone strength index with mechanical testing in distraction osteogenesis

Distraction osteogenesis is an established method of treatment of non-unions and limb length discrepancies. Despite improvements in surgical techniques and fixation devices there is still a considerable possibility of failure of the regenerate bone after frame removal. The hypothesis of the present experimental study was that a noninvasive bone strength marker, the strength-strain index (SSI) measured by peripheral quantitative computerized tomography (pQCT), could be significantly correlated with a biomechanical bone strength index, the maximum load at bone failure (Fmax), assessed in a three-point bending test. The right tibias of fifteen male New Zealand White rabbits were subjected to gradual lengthening using an external fixator. At the end of the consolidation phase (55th day) the animals were sacrificed and the lengthened tibiae were collected free of soft tissue, after removal of the lengthener, for immediate scanning and mechanical testing. The values of cortical bone mineral density, cortical bone area, and the corresponding SSIy, as measured by pQCT, were assessed for statistically significant correlation relative to the values of the Fmax and stiffness as evaluated by the three-point bending test were assessed. SSIy showed a statistically significant positive correlation with the maximum load (Fmax) with a correlation value R = 0.846 (p < 0.001), and it was a good predictor of Fmax since it was able to describe the 71.6% of variability of Fmax(R2 = 0.716). Furthermore, cortical bone area appeared to be highly correlated with Fmax (p < 0.005), but it was a less efficient predictor of Fmax (R2 = 0.471). There was, also, a statistically significant correlation between SSIy and bone stiffness as assessed in the 3-point bending test (p < 0.005). In conclusion, the present study reveals that the SSI can be used as a sensitive index of adequate consolidation of the regenerate bone, possibly able to reduce mechanical failure due to premature frame removal. In clinical relevance, the aforementioned hypothesis should be applied in studies of human populations and possible confirmation of its validity would establish pQCT as a valuable diagnostic tool not only in distraction osteogenesis but also in other techniques of bone healing. © 2009 Elsevier Inc. All rights reserved

Unusual insidious spinal accessory nerve palsy: A case report

Introduction. Isolated spinal accessory nerve dysfunction has a major detrimental impact on the functional performance of the shoulder girdle, and is a well-documented complication of surgical procedures in the posterior triangle of the neck. To the best of our knowledge, the natural course and the most effective way of handling spontaneous spinal accessory nerve palsy has been described in only a few instances in the literature. Case presentation. We report the case of a 36-year-old Caucasian, Greek man with spontaneous unilateral trapezius palsy with an insidious course. To the best of our knowledge, few such cases have been documented in the literature. The unusual clinical presentation and functional performance mismatch with the imaging findings were also observed. Our patient showed a deterioration that was different from the usual course of this pathology, with an early onset of irreversible trapezius muscle dysfunction two months after the first clinical signs started to manifest. A surgical reconstruction was proposed as the most efficient treatment, but our patient declined this. Although he failed to recover fully after conservative treatment for eight months, he regained moderate function and is currently virtually pain-free. Conclusion. Clinicians have to be aware that due to anatomical variation and the potential for compensation by the levator scapulae, the clinical consequences of any injury to the spinal accessory nerve may vary. © 2010 Charopoulos et al; licensee BioMed Central Ltd

Effect of primary hyperparathyroidism on volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in postmenopausal women

Context: Primary hyperparathyroidism (PH) is characterized by inappropriate PTH elevation with or without hypercalcemia. Bone disease involves catabolic action at cortical sites, whereas cancellous sites and geometry might be relatively preserved. Objective: Our objective was to examine the effect of PH on quantitative and qualitative bone characteristics using peripheral quantitative computed tomography at the tibia in postmenopausal women with PH and healthy controls. Design and Setting: We conducted a cross-sectional study at a tertiary referral center. Patients: Fifty-two postmenopausal women with PH and 56 healthy controls, comparable for age and anthropometric measures, participated. Intervention: There was no intervention. Main Outcome Measure: We assessed volumetric bone mineral density (vBMD), bone mineral content (BMC), cortical thickness, cortical and trabecular area, peri- and endosteal circumference, and polar stress strength index assessed by peripheral quantitative computed tomography of the left tibia at 4% (cancellous), 14% (transition zone), and 38% (cortical) from the distal end. Results: At 4%, there was a significant decrease of trabecular BMC and vBMD (P < 0.001), effect particularly evident in hypercalcemic patients, whereas trabecular area was comparable. At 38%, cortical BMC(P < 0.01), vBMD (P < 0.01), area (P < 0.05), and thickness (P < 0.001) were reduced in the PH group, particularly in hypercalcemic patients. Endosteal circumference increased (P < 0.001), whereas periosteal circumference was comparable, indicating cancellization of cortical bone. At 14%, polar stress strength index was significantly decreased (P < 0.01) in hypercalcemic patients, indicating impairment of bone mechanical properties. Conclusions: Normocalcemic PH is characterized by catabolic actions at both cortical and cancellous sites (38 and 4%, respectively), an effect accentuated in hypercalcemic patients. Cortical geometric properties are adversely affected even in normocalcemic patients, whereas trabecular properties are generally preserved. Copyright © 2006 by The Endocrine Society