Effect of Surgical Fit on Integration of Cancellous Bone and Implant Cortical Bone Shear Strength for a Porous Titanium

Authors

Nicky Bertollo, Masaaki Matsubara, Tsuyoshi Shinoda, Dong Chen, Mukesh Kumar, William R. Walsh

Abstract

Porous scaffold dowels of Ti6Al4V were prepared and implanted into cancellous and cortical bone sites in adult sheep. Cancellous implants were examined under gap, line-to-line, and press-fit conditions, whereas line-to-line implantation was used in cortical sites. Cortical shear strength increased significantly with time and reached 26.1 ± 8.6 MPa at 12 weeks, accompanied by a concomitant increase in bone integration and remodeling. In cancellous sites, bone integration was well established at 4 and 12 weeks under conditions of press-fit and line-to-line match between implant and surgical defect. New bone growth was also found in the gap conditions, although to a lesser extent. These findings suggest that the porous Ti6Al4V could prove an effective scaffold material for uncemented fixation in cortical and cancellous sites.

Link to Article

http://dx.doi.org/10.1016/j.arth.2010.12.007

Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout

Authors

Ashika Chhana, Karen E Callon, Bregina Pool, Dorit Naot, Maureen Watson, Greg D Gamble, Fiona M McQueen, Jillian Cornish, Nicola Dalbeth

Abstract

Bone erosion is a common manifestation of chronic tophaceous gout. [This study sought] to investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function. The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals. Quantitative real-time PCR and von Kossa stained mineralised bone formation assays were used to assess the effects of MSU crystals on osteoblast differentiation using MC3T3-E1 cells. The numbers of osteoblasts and bone lining cells were quantified in bone samples from patients with gout. MSU crystals rapidly reduced viability in all cell types in a dose-dependent manner. The inhibitory effect on cell viability was independent of crystal phagocytosis and was not influenced by differing crystal length or addition of serum. Long-term culture of MC3T3-E1 cells with MSU crystals showed a reduction in mineralisation and decreased mRNA expression of genes related to osteoblast differentiation such as Runx2, Sp7 (osterix), Ibsp (bone sialoprotein), and Bglap (osteocalcin). Fewer osteoblast and lining cells were present on bone directly adjacent to gouty tophus than bone unaffected by tophus in patients with gout. MSU crystals have profound inhibitory effects on osteoblast viability and differentiation. These data suggest that bone erosion in gout occurs at the tophus–bone interface through alteration of physiological bone turnover, with both excessive osteoclast formation, and reduced osteoblast differentiation from mesenchymal stem cells.

Link to Article

http://dx.doi.org/10.1136/ard.2010.144774

Conditional inactivation of CXCR4 in osteoprecursors reduces postnatal bone formation due to impaired osteoblast development

Authors

Wei Zhu, Gang Liang, Zhiping Huang, Stephen B. Doty and Adele L. Boskey

Abstract

Cystine (C)-X-C motif chemokine receptor 4 (CXCR4), the primary receptor for stromal derived factor-1 (SDF-1), is involved in bone morphogenic protein 2 (BMP2)-induced osteogenic differentiation of mesenchymal progenitors. To target the in vivo function of CXCR4 in bone and explore the underlying mechanisms, we conditionally inactivated CXCR4 in osteoprecursors by crossing osterix (Osx)-Cre mice with floxed CXCR4 mice (CXCR4fl/fl) to generate knockouts with CXCR4 deletion driven by the Osx promoter (Osx::CXCR4fl/fl). The Cre-mediated excision of CXCR4 occurred exclusively in bone of Osx::CXCR4fl/fl mice. When compared to littermate controls, Osx::CXCR4fl/fl mice developed smaller osteopenic skeletons, evidenced by reduced trabecular and cortical bone mass, lower bone mineral density, and a slower mineral apposition rate. In addition, Osx::CXCR4fl/fl mice displayed chondrocyte disorganization in the epiphyseal growth plate, associated with decreased proliferation and collagen matrix syntheses. Moreover, mature osteoblast-related expression of type I collagen α1 (Col1α1) and osteocalcin (OCN) was reduced in bone of Osx::CXCR4fl/fl mice versus controls, suggesting that CXCR4-deficiency results in arrested osteoblast progression. Primary cultures for osteoblastic cells derived from Osx::CXCR4fl/fl mice also showed decreased proliferation and impaired osteoblast differentiation in response to BMP2 or BMP6 stimulation, and suppressed activation of intracellular BMP receptor-regulated Smads (R-Smads) and Erk1/2 was identified in CXCR4-deficient cells and bone tissues. These findings provide the first in vivo evidence that CXCR4 functions in postnatal bone development via regulating osteoblast development in cooperation with BMP signaling. Thus, CXCR4 acts as an endogenous signaling component necessary for bone formation.

Link to Article

http://dx.doi.org/10.1074/jbc.M111.250985

Validation of noninvasive quantification of bone marrow fat volume with microCT in aging rats

Authors

Oddom Demontiero, Wei Li, Emma Thembani and Gustavo Duque

Abstract

Marrow fat infiltration is one of the hallmarks of age-related bone loss. This fat infiltration has been quantified by invasive and noninvasive methods. However, the validity of the noninvasive methods has not been correlated with a gold standard. In this study we aim to validate the usefulness of marrow fat quantification by correlating microCT (μCT) images with histology analysis. Fat volume (FV) and bone volume (BV) of distal femora of young (4 months) and old (27 months) Louvain/c (LOU) rats (n = 22) were quantified by histology and compared with μCT images analyzed by an image analysis software (SliceOMatic). We found that for SliceOMatic/μCT the intra-rater reliability for duplicate measurements was 0.94 (p < 0.001) and the inter-rater reliability for FV/BV ratio in young and old rats was 98% and 99% respectively. Both methods showed a significant increase (~ 2 fold) in the FV/BV ratio in the old rats as compared with their young counterparts (p < 0.001). A significantly higher correlation (r2 = 0.85) in the old rats was found between our noninvasive method and histology. Furthermore, our noninvasive method showed good agreement with histology. In conclusion, noninvasive quantification of FV/BV ratio using an image analysis software is as reliable as histology for identifying age related marrow fat changes with high inter and intra-rater reliability. These findings provide a new noninvasive method for quantifying marrow fat, which is useful and can be tested not only in animals but also in human studies.

Link to Article

http://dx.doi.org/10.1016/j.exger.2011.01.001

Chlorthalidone improves vertebral bone quality in genetic hypercalciuric stone-forming rats

Authors

David A. Bushinsky, Thomas Willett, John R. Asplin, Christopher Culbertson, Sara P.Y. Che, Marc Grynpas Ph.D

Abstract

We have bred a strain of rats to maximize urine (U) calcium (Ca) excretion and model hypercalciuric nephrolithiasis. These genetic hypercalciuric stone-forming (GHS) rats excrete more UCa than control Sprague-Dawley rats, uniformly form kidney stones and, similar to patients, demonstrate lower bone mineral density. Clinically thiazide diuretics reduce UCa and prevent stone formation; however, whether they benefit bone is not clear. We used GHS rats to test the hypothesis that the thiazide diuretic chlorthalidone (CTD) would have a favorable effect on bone density and quality. Twenty GHS rats received a fixed amount of a 1.2% Ca diet and half were also fed CTD (4-5 mg/kg/day). Rats fed CTD had a marked reduction in UCa. The axial and appendicular skeletons were studied. An increase in trabecular mineralization was observed with CTD compared to controls. CTD also improved the architecture of trabecular bone. Using µCT, trabecular bone volume (BV/TV), trabecular thickness and trabecular number were increased with CTD. A significant increase in trabecular thickness with CTD was confirmed by static histomorphometry. CTD also improved the connectivity of trabecular bone. Significant improvements in vertebral strength and stiffness were measured by vertebral compression. Conversely, a slight loss of bending strength was detected in the femoral diaphysis with CTD. Thus, results obtained in hypercalciuric rats suggest that CTD can favorably influence vertebral fracture risk. CTD did not alter formation parameters suggesting that the improved vertebral bone strength was due to decreased bone resorption and retention of bone structure.

Link to Article

http://dx.doi.org/10.1002/jbmr.374

Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

Authors

Daniel Schwarz, Krikor Arman, Mehreen Kakwan, Ameen Jamali, Ayman Elmeligy, Steven Buchman

Abstract

The authors' goal was to ascertain regenerate bone-healing metrics using quantitative histomorphometry at a single consolidation period. Rats underwent either mandibular distraction osteogenesis (n = 7) or partially reduced fractures (n = 7); their contralateral mandibles were used as controls (n = 11). External fixators were secured and unilateral osteotomies performed, followed by either mandibular distraction osteogenesis (4 days' latency, then 0.3 mm every 12 hours for 8 days; 5.1 mm) or partially reduced fractures (fixed immediately postoperatively; 2.1 mm); both groups underwent 4 weeks of consolidation. After tissue processing, bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, and osteocyte count per high-power field were analyzed by means of quantitative histomorphometry. Contralateral mandibles had statistically greater bone volume/tissue volume ratio and osteocyte count per high-power field compared with both mandibular distraction osteogenesis and partially reduced fractures by almost 50 percent, whereas osteoid volume/tissue volume ratio was statistically greater in both mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles. No statistical difference in bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, or osteocyte count per high-power field was found between mandibular distraction osteogenesis specimens and partially reduced fractures. The authors' findings demonstrate significantly decreased bone quantity and maturity in mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles using the clinically analogous protocols. If these results are extrapolated clinically, treatment strategies may require modification to ensure reliable, predictable, and improved outcomes.

Link to Article

http://dx.doi.org/10.1097/PRS.0b013e3181e3b351