A novel autologous bone graft substitute comprised of rhBMP6 blood coagulum as carrier tested in a randomized and controlled Phase I trial in patients with distal radial fractures.

Bone morphogenetic proteins (BMPs) are known to induce new bone formation in vivo but treating trabecular bone defects with a BMP based therapeutic remains controversial. Here, we evaluated the safety and efficacy of a novel Autologous Bone Graft Substitute (ABGS) comprised of recombinant human BMP6 (rhBMP6) dispersed within an autologous blood coagulum (ABC) as a physiological natural carrier in patients with a closed distal radial fracture (DRF). We enrolled 32 patients in a randomized, standard of care (SoC) and placebo (PBO) controlled, double-blinded Phase I First in Human (FiH) clinical trial. ABGS was prepared from peripheral blood as 250 µg rhBMP6/mL ABC or PBO (1 mL ABC containing excipients only) and was administered dorsally via a syringe injection into the fracture site following closed fracture fixation with 3 Kirschner wires. Patients carried an immobilization for 5 weeks and were followed-up for 0 to 26 weeks by clinical examination, safety, serial radiographic analyses and CT. During the 13 weeks follow-up and at 26 weeks post study there were no serious adverse reactions recorded. The results showed that there were no detectable anti-rhBMP6 antibodies in the blood of any of the 32 patients at 13- and 26-weeks following treatment. Pharmacokinetic analyses of plasma from patients treated with ABGS showed no detectable rhBMP6 at any time point within the first 24 h following administration. The CT image and radiographic analyses score from patients treated with AGBS showed significantly accelerated bone healing as compared to PBO and SoC at 5 and 9 weeks (with high effect sizes and P = 0.027), while at week 13 all patients had similar healing outcomes. In conclusion, we show that intraosseous administration of ABGS (250 µg rhBMP6/mL ABC) into the distal radial fracture site demonstrated a good tolerability with no serious adverse reactions as well as early accelerated trabecular bone healing as compared to control PBO and SoC patients.

Comparison of ultrasonographic and intraoperative findings in Achilles tendon rupture.

The purpose of the study was to assess the value of ultrasonography in the diagnosis of Achilles tendon rupture, by comparing initial ultrasonographic scans and direct intraoperative findings, as well as to follow up the healing process in operatively and conservatively treated patients. Ultrasound examination was performed in 100 patients (91 males and 9 females, with mean age of 46 years) with clinically suspicious Achilles tendon ruptures. Ultrasonographic findings were compared with intraoperative findings. Eighty-eight patients underwent surgery and twelve patients were treated conservatively. Complete ruptures were diagnosed by ultrasound in 88 patients, and partial ruptures in 12 patients. The length of the tendon (Pearson r = 0.973, p < 0.001, Spearman p = 0.972, p < 0.001) and the size of the rupture (Pearson r = 0.940, p < 0.001, Spearman p = 0.905, p < 0.001) measured before surgery by ultrasound and directly during surgery showed a high correlation. Out of 88 operatively treated patients, 86 had a complete rupture and two had a partial rupture. All patients were examined 3, 5, 8, and 12 weeks after injury or after surgery. In the first five weeks, there were statistically significant differences noted between these two groups. Operatively treated tendons healed more quickly, but after eight and twelve weeks this difference had disappeared. Our study showed that ultrasound is an excellent imaging method for confirming the clinical diagnosis of Achilles tendon rupture as well as for following up the process of tendon healing.