Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

Review of soft tissue coverage options in distraction osteogenesis of the extremity

Aim:To review the choices of soft tissue coverage in distraction osteogenesis of the extremity.Methods:A PubMed literature search yielded 14 articles included for systematic review.Data were extracted from each article if available(sample size,patient age,surgical indications,type of flap,use of additional modalities,method of bone osteogenesis,postoperative events,follow-up,satisfaction,weight-bearing status,and success rate).Unpaired t-tests were performed to compare complication rates.A retrospective review of three cases was also conducted.Results:Fourteen articles discussed 145 patients with a mean age of 33.4 years and 146 extremity injuries followed over 3.3 years on average.Indications included chronic osteomyelitis or nonunion(58.2%)and acute trauma(41.8%).Average time from injury was 1.1 years.Ilizarov frame was used in 12 articles.Free flaps(88.0%)or rotational flaps(12.0%)were used,with muscle flaps(96.7%)being most common.Most extremities received free latissimus dorsi or rectus abdominis flaps.Bone grafts and antibiotic beads were often used in conjunction.Although complications and reoperations were not uncommon(up to 30%),98.8%of patients on average were ultimately weight bearing and all articles reported>91%success rate.Additionally,the rates of any complication were not statistically different between"fix and flap"protocol and flap or frame first.Lastly,a three-patient case series is presented.Conclusion:Bone transport with soft tissue reconstruction remains an excellent choice for patients with large bony defects or who are unable to undergo autologous bone grafting.Not one surgical approach to limb salvage is superior,and decision should be made on a case by case basis between the surgeon and the patient.

Preparation and Characterization of Hydroxyapatite-Coated Selenium Nanoparticles and their Interaction with Osteosarcoma(SaOS-2) Cells

Nanotechnology has taken a firm step to revolutionize the field of orthopedic implants. Current research on bone implants focuses to develop implants with multifaceted functions viz., osteoinduction, chemoprevention, antimicrobial action etc., especially for cancerous bone resection. The objective of the present study was to synthesize a novel composite for bone implants, possessing the above properties. Selenium was selected owing to its chemopreventive and chemotherapeutic properties. Hydroxyapatite was selected owing to its bioactivity and similarity in composition to bone mineral properties. Selenium nanoparticles were prepared by chemical reduction method and coated with hydroxyapatite.Hydroxyapatite-coated selenium nanoparticle（HASnp） was characterized physico-chemically using fourier transform infrared spectroscopy, X-ray diffractometry, scanning electron microscope, and energy-dispersive X-ray spectroscopy.HASnp was analysed in vitro using SaOS-2 cell line. Enhanced cell proliferation and alkaline phosphatase activity were observed in HASnp-treated cells. The results indicate that HASnp is highly suitable for the use in orthopedic applications.