Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta

Authors

J.A. Meganck, D.L. Begun, J.D. McElderry, A. Swick, K.M. Kozloff, S.A. Goldstein, M.D. Morris, J.C. Marini, M.S. Caird

Abstract

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (μCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture.

Link to Article

http://dx.doi.org/10.1016/j.bone.2013.06.003

Immunohistochemical characterization of axonal sprouting in mice

Authors

Erin J. Feeney, Diane Stephenson, Robin Kleiman, Susan Bove, Courtney Cron, Lara Moody, Mercedes Robinson, Julio J. Ramirez

Abstract

Purpose: Transgenic manipulation of mouse physiology facilitates the preclinical study of genetic risk factors, neural plasticity, and reactive processes accompanying Alzheimer's disease. Alternatively, entorhinal cortex lesions (ECLs) model pathophysiological denervation and axonal sprouting in rat. Given reports of anatomical differences between the mouse and rat hippocampus, application of the ECL paradigm to transgenic mice first requires comprehensive characterization of axonal sprouting in the wild-type. Methods: Adult male C57BL/6 mice sustained unilateral transections of the perforant pathway. Subjects were sacrificed at 1, 4, 10, 18, and 28 days postlesion, and hippocampal sections were stained for AChE, the postsynaptic terminal marker drebrin, and the presynaptic terminal proteins SNAP-25, GAP-43, synapsin, and synaptophysin. To examine synaptic turnover and reinnervation, ipsilateral-to-contralateral staining densities were determined within the dentate molecular layer, and shrinkage-corrected ratios were compared to 28 day-yoked sham cases. Results: At 28 days postlesion, ipsilateral terminal marker densities exhibited significant depression. In contrast, qualitative analyses at earlier time points suggested altered AChE staining patterns and increased SNAP-25 and synapsin immunoreactivity in the inner molecular layer (IML) of the dentate gyrus. Conclusions: C57BL/6 mice exhibit synaptic reorganization following perforant path transections. The IML may provide a key target for evaluation and intervention in ECL mouse models.

Link to Article

http://dx.doi.org/10.3233/RNN-130311

Porous Tantalum Coatings Prepared by Vacuum Plasma Spraying Enhance BMSCs Osteogenic Differentiation and Bone Regeneration In Vitro and In Vivo

Authors

Ze Tang, Youtao Xie, Fei Yang, Yan Huang, Chuandong Wang, Kerong Dai, Xuebin Zheng, Xiaoling Zhang

Abstract

Tantalum, as a potential metallic implant biomaterial, is attracting more and more attention because of its excellent anticorrosion and biocompatibility. However, its significantly high elastic modulus and large mechanical incompatibility with bone tissue make it unsuitable for load-bearing implants. In this study, porous tantalum coatings were first successfully fabricated on titanium substrates by vacuum plasma spraying (VPS), which would exert the excellent biocompatibility of tantalum and alleviate the elastic modulus of tantalum for bone tissue. We evaluated cytocompatibility and osteogenesis activity of the porous tantalum coatings using human bone marrow stromal cells (hBMSCs) and its ability to repair rabbit femur bone defects. The morphology and actin cytoskeletons of hBMSCs were observed via electron microscopy and confocal, and the cell viability, proliferation and osteogenic differentiation potential of hBMSCs were examined quantitatively by PrestoBlue assay, Ki67 immunofluorescence assay, real-time PCR technology and ALP staining. For in vivo detection, the repaired femur were evaluated by histomorphology and double fluorescence labeling 3 months postoperation. Porous tantalum coating surfaces promoted hBMSCs adhesion, proliferation, osteogenesis activity and had better osseointegration and faster new bone formation rate than titanium coating control. Our observation suggested that the porous tantalum coatings had good biocompatibility and could enhance osseoinductivity in vitro and promote new bone formation in vivo. The porous tantalum coatings prepared by VPS is a promising strategy for bone regeneration.

Link to Article

http://dx.doi.org/10.1371/journal.pone.0066263

Returning to overuse activity following a supraspinatus and infraspinatus tear leads to joint damage in a rat model

Authors

Katherine E. Reuther, Stephen J. Thomas, Elisabeth F. Evans, Jennica J. Tucker, Joseph J. Sarver, Sarah Ilkhani-Pour, Chancellor F. Gray, Pramod B. Voleti, David L. Glaser, Louis J. Soslowsky

Abstract

Large rotator cuff tears (supraspinatus and infraspinatus) are common in patients who perform overhead activities (laborers, athletes). In addition, following large cuff tears, these patients commonly attempt to return to pre-injury activity levels. However, there is a limited understanding of the damaging effects on the uninjured joint tissues when doing so. Therefore, the objective of this study was to investigate the effect of returning to overuse activity following a supraspinatus and infraspinatus tear on shoulder function and the structural and biological properties of the intact tendons and glenoid cartilage. Forty rats underwent 4 weeks of overuse followed by detachment of the supraspinatus and infraspinatus tendons and were then randomized into two groups: return to overuse or cage activity. Ambulatory measurements were performed over time and structural and biological properties of the adjacent tendons and cartilage were evaluated. Results demonstrated that animals returning to overuse activity did not have altered shoulder function but despite this, did have altered cartilage and tendon properties. These mechanical changes corresponded to altered transcriptional regulation of chondrogenic genes within cartilage and tendon. This study helps define the mechanical and biological mechanisms leading to joint damage and provides a framework for treating active cuff tear patients.

Link to Article

http://dx.doi.org/10.1016/j.jbiomech.2013.05.007

Eldecalcitol, a vitamin D analog, reduces bone turnover and increases trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys

Authors

Susan Y. Smith, Nancy Doyle, Marilyne Boyer, Luc Chouinard, Hitoshi Saito

Abstract

Vitamin D insufficiency is common in elderly people worldwide, and intake of supplementary calcium and vitamin D is recommended to those with a high risk of fracture. Several clinical studies and meta-analyses have shown that calcium and vitamin D supplementation reduces osteoporotic fractures, and a strong correlation exists between vitamin D status and fracture risk. Vitamin D supplementations improve calcium balance in the body; however, it remains unclear whether vitamin D directly affects bone metabolism. Recently, eldecalcitol (ELD), an active form of vitamin D analog, has been approved for the treatment of osteoporosis in Japan. A 3-year clinical trial showed ELD treatment increased lumbar spine bone mineral density (BMD) and reduced fracture risk in patients with osteoporosis. To evaluate the mechanism of ELD action in bone remodeling, ovariectomized cynomolgus monkeys were treated with 0.1 or 0.3 μg/day of ELD for 6 months. This treatment increased lumbar BMD by 4.4% and 10.2%, respectively, and suppressed ovariectomy-induced increases in bone turnover markers compared to OVX-vehicle control. Histomorphometric analysis of bone revealed that both bone formation parameters and bone resorption parameters in the trabecular bone of the lumbar vertebrae were suppressed by ELD treatment. ELD treatment also improved biomechanical properties of the lumbar vertebrae and the femoral neck in the ovariectomized cynomolgus monkeys. These results indicate that, in a bone-remodeling animal model, ELD increases BMD and improves bone biomechanical properties by normalizing bone turnover. Therefore, ELD has a direct and potentially beneficial effect on bone metabolism.

Link to Article

http://dx.doi.org/10.1016/j.bone.2013.06.005

The Effect of Implant Shape and Screw Pitch on Microdamage in Mandibular Bone

Authors

Chendi Xu BDS, MS, Zhong Wei BS, Nizhou Liu BDS, MS, Fei Sun BDS, MS, Hui Chen BDS, Tingting Lin BDS, MS, Baowei Zhang DDS, Tingting Tang MD, PhD, Eryi Lu DDS, PhD

Abstract

The aim of this study was to investigate the effect of implant shape and screw pitch on microdamage in bone during insertion of dental implants. Thirty custom-made implants (length, 10 mm; diameters, 4.1 mm; cylindrical, tapered, and taper-cylindrical shapes; screw pitches, 1.25 and 0.8 mm; classified as 1.25C, 0.8C, 1.25T, 0.8T, 1.25TC, 0.8TC) were placed with a surgical device in the mandibles of eight goats. Two implant sites were prepared in the edentulous area on each side of the mandible. Implants were placed in a randomized order. Immediately after placement of the implants, the bone blocks with the implants were collected, bulk stained with basic fuchsin, embedded in methyl methacrylate, and sectioned. Histomorphometric quantification of the microcrack length (Cr.Le, μm); microcrack surface density (Cr.Le/B.Ar, μm/mm2), and damaged bone area fraction (DB.Ar/B.Ar, %) were measured. The Cr.Le, Cr.Le/B.Ar, and DB.Ar/B.Ar values of 0.8TC group were 80.96 ± 17.55, 478.75 ± 51.85, and 4.40 ± 0.36, respectively. All these parameters of microdamage induced by 0.8TC were significantly lower than those induced by other five types of implants (p < .05). Taper-cylindrical implants with 0.8 mm screw pitch caused the least microdamage to the bone in comparison with the other five types of implants during placement of implants.

Link to Article

http://dx.doi.org/10.1111/cid.12100