Evaluation of composition and mineral structure of callus tissue in rat femoral fracture.

ABSTRACT. Callus formation is a critical step for successful fracture healing. Little is known about the molecular composition and mineral structure of the newly formed tissue in the callus. The aim was to evaluate the feasibility of small angle x-ray scattering (SAXS) to assess mineral structure of callus and cortical bone and if it could provide complementary information with the compositional analyses from Fourier transform infrared (FTIR) microspectroscopy. Femurs of 12 male Sprague-Dawley rats at 9 weeks of age were fractured and fixed with an intramedullary 1.1 mm K-wire. Fractures were treated with the combinations of bone morphogenetic protein-7 and/or zoledronate. Rats were sacrificed after 6 weeks and both femurs were prepared for FTIR and SAXS analysis. Significant differences were found in the molecular composition and mineral structure between the fracture callus, fracture cortex, and control cortex. The degree of mineralization, collagen maturity, and degree of orientation of the mineral plates were lower in the callus tissue than in the cortices. The results indicate the feasibility of SAXS in the investigation of mineral structure of bone fracture callus and provide complementary information with the composition analyzed with FTIR. Moreover, this study contributes to the limited FTIR and SAXS data in the field

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density: A bone chamber study in rats

Background and purpose The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft. Methods Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry. Results Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls. Interpretation An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete

Adherence of hip and knee arthroplasty studies to RSA standardization guidelines

Peer reviewe

No positive effects of OP-1 device on the incorporation of impacted graft materials after 8 weeks: a bone chamber study in goats.

Contains fulltext : 52973.pdf (publisher's version ) (Open Access)BACKGROUND: Bone morphogenetic proteins (BMPs) have the potential to improve clinical outcome after hip revision surgery by improving graft incorporation and implant fixation. However, impaction of cancellous bone grafts and TCP/HA bone substitute mixed with OP-1 device in a bone chamber in goats in a previous study led to reduced fibrous tissue ingrowth after 4 weeks. New bone formation was not promoted by OP-1. In the current study we examined whether this reduction represented a final loss of ingrowth or was just a delay, and whether the reduction can be overcome and ultimately results in a better late ingrowth. METHODS: Bone chambers with impacted allografts and impacted TCP/HA granules mixed with 2 doses of OP-1 device were implanted in proximal medial goat tibias. Impacted allografts and TCP/HA not treated with OP-1 served as controls. After 8 weeks, the incorporation was evaluated using histology and histomorphometry. RESULTS: Histology revealed evidence of bone graft incorporation, which proceeded in a similar way in both allografts and TCP/HA, with and without the addition of OP-1. After 8 weeks, no difference in bone ingrowth was found between the OP-1 groups and their controls. It was only in the allografts that the addition of OP-1 resulted in more fibrous tissue ingrowth. INTERPRETATION: We conclude that the previously observed delay in fibrous tissue ingrowth can be only partially overcome

Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation

Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage

The effect of a biphasic injectable bone substitute on the interface strength in a rabbit knee prosthesis model

10.1186/1749-799x-8-25Journal of Orthopaedic Surgery and Research812