Purpose

In this clinical trial, we evaluated the safety and efficacy of rhBMP6 undergoing HTO. The systemic pharmacokinetics (PK), safety, acceleration of new bone formation, and tolerability were examined.

Methods and Materials

We assigned 20 HTO patients into this randomized, controlled, blinded Phase I-II clinical trial (EudraCT number 2015-001691-21). RhBMP6 or placebo were implanted into the tibial wedge-defects. Patients were followed for 24 months by clinical examination, x-rays and CT scans. Efficacy outcome was defined as percentage of defect filled with newly formed bone, based on x-ray analyses of day 1, week 6 and 24, month 12, 18 and 24. The bone mineral density (BMD), as well as bone formation in the defect area, was measured on CT scans by ITK-SNAP program transferring voxels into BMD (mgs/cm³) by using a bone 3 CT calibration phantom at weeks 9 and 14 post-surgery.

Results

CT scans from HTO defects of patients treated with rhBMP6/ABC (n=10) showed an accelerated bone healing when compared to placebo treated patients (n=10). BMD gain was higher in the treatment group after 9 and 14 weeks: 47.8 ± 24.1 vs. 22.2 ± 12.3 (P=0.008) and 89.7 ± 29.1 vs. 53.6 ± 21.9 (P=0.006). X-rays from day 1, weeks 6 and 24, and months 12, 18, 24 confirmed the enhanced bone formation in rhBMP6/ABC treated patients. The use of rhBMP6/ABC was not associated with serious adverse events during the entire 24 months follow-up. The availability of rhBMP6 was detected in the plasma of only one out of 10 patients (8.3 mg/ml) from locally administered rhBMP6/ABC implants within the first 15 minutes after implantation. As measured on CT scans, the BMD increased distally from the osteotomy wedge in rhBMP6/ABC treated patients.

Conclusion

rhBMP6/ABC at a dose of 100 µg/ml accelerated the bone formation rate without serious adverse events, with a good tolerability and no systemic distribution.

Purpose

Analysis and quantification of bone healing after open wedge high tibial osteotomy

Methods and Materials

Study Phase 1:High tibial osteotomy was performed on six lower extremities of human body donors and experimental X-rays and CT scans were applied. Different techniques were evaluated by 3 specialists for best representation of the osteotomy gap.

Study Phase 2: Optimized radiological techniques were used for follow-up on 12 patients. The radiographs were examined by 3 specialists measuring 10 different parameters. The CT scans were analyzed with semi-automatic computer software for quantification of bone ossification.

Results

The osteotomy gap was best represented in 30° of flexion in the knee and 20° internal rotation of the leg. There were significant changes of the medial width over time (p < 0.001) as well as of the length of fused osteotomy, the Schröter score, sclerosis, trabecular structure and zone area measurements. Sclerosis, medial width of the osteotomy and area measurements were detected as reproducible parameters. Bone mineral density was calculated using the CT scans, showing a significantly higher value 12 weeks postoperatively (112.5 mg/ccm) than at baseline (54.6 mg/ccm). The ossification of the gap was visualized by color-coding.

Conclusion

Sclerosis and medial width of the osteotomy gap as well as area measurements were determined as reproducible parameters for evaluation of bone healing. Quantification of bone ossification can be calculated with CT scans using a semi-automatic computer program and should be used for research in bone healing.