Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice

To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights （0.5, 1 and 1.5 m） and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT （μ-CT） analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus （bone strength）, was reduced by 30% （P 〈 0.05） at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV （r2 = 0.14 and 0.16, P 〈 0.05）. In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.

Local treatment of osteoporosis with alendronate-loaded calcium phosphate cement

Background A new treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures.We term this strategy as the ＂local treatment of osteoporosis＂.The study was performed to investigate the effect of alendronate-loaded calcium phosphate cement （CPC） as a novel drug delivery system for local treatment of osteoorosis.Methods An in vitro study was performed using CPC fabricated with different concentrations of alendronate （ALE,0,2,5,10 weight percent （wt％））.The microstructure,setting time,infrared spectrum,biomechanics,drug release,and biocompatibility of the composite were measured in order to detect changes when mixing CPC with ALE.An in vivo study was also performed using 30 Sprague-Dawley rats randomly divided into six groups：normal,Sham （ovariectomized （OVX） ＋ Sham）,CPC with 2％ ALE,5％ALE,and 10％ ALE groups.At 4 months after the implantation of the composite,animals were sacrificed and the caudal vertebrae （levels 4-7） were harvested for micro-CT examination and biomechanical testing.Results The setting time and strength of CPC was significantly faster and greater than the other groups.The ALE release was sustained over 21 days,and the composite showed good biocompatibility.In micro-CT analysis,compared with the Sham group,there was a significant increase with regard to volumetric bone mineral density （BMD） and trabecular number （Tb.N） in the treated groups （P ＜0.05）.Trabecular spacing （Tb.Sp） showed a significant increase in the Sham group compared to other groups （P ＜0.01）.However,trabecular thickness （Tb.Th） showed no significant difference among the groups.In biomechanical testing,the maximum compression strength and stiffness of trabecular bone in the Sham group were lower than those in the experimental groups.Conclusions The ALE-loaded CPC displayed satisfactory properties in vitro,which can reverse the OVX rat vertebral trabecular bone microarchitecture and biomechanical properties in vivo.