High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 µg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 µg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

The utility and effectiveness of bone morphogenetic protein in foot and ankle surgery.

UNLABELLED: A review of the use of bone morphogenetic protein in 38 cases in 35 patients at high risk for bone healing complications following foot and ankle surgery was performed. Multiple relevant variables were analyzed with respect to the incidence of healing, including age; diabetes mellitus; Charcot neuroarthropathy; prior infection; type of procedure; and the use of femoral head allograft, electrical bone stimulation, and external fixation. The overall incidence of successful healing was 84.21%. A statistically significant decrease in the incidence of bone healing was observed if the patient was 50 years of age or older (P = .03), and all 16 patients younger than 50 years healed their index operation. If 60 years of age was the benchmark, a statistically significant decrease in the rate of healing was observed (P = .02). Logistic regression showed that a 10-year increase in age almost doubled the risk of not healing (odds ratio = 2.613). Furthermore, 4 (66.66%) of the 6 patients who did not heal had diabetes mellitus and were older than 60 years. This combination of risk factors was associated with a statistically significant decrease in the likelihood of bone healing (P < .01). Of the 10 cases to exhibit postoperative drainage, only 50% of these successfully healed, whereas 96% of the remaining 28 cases successfully healed (P = .0026). The results of this study demonstrate the utility of bone morphogenetic proteins in foot and ankle surgical patients at high risk for bone healing complications. LEVEL OF CLINICAL EVIDENCE: 2.

Laser therapy improves healing of bone defects submitted to autologous bone graft.

OBJECTIVE: The aim of the present study was to assess histologically the effect of low-level laser thrapy (LLLT) (lambda 830 nm) on the healing of bone defects associated with autologous bone graft. BACKGROUND DATA: LLLT has been used on the modulation of bone healing because of the photo-physical and photochemical properties of some wavelengths. The use of correct and appropriate parameters has been shown to be effective in the promotion of a positive biomodulative effect on the healing bone. METHODS: Sixty male Wistar rats were divided into four groups: G1 (control), G2 (LLLT on the surgical bed), G3 (LLLT on the graft), and G4 (LLLT on both the graft and the surgical bed). The dose per session was 10 J/cm(2), and it was applied to the surgical bed (G2/G4) and on the bone graft (G3/G4). LLLT was carried out every other day for 15 days (lambda 830 nm, phi = 0.5 cm(2), 50 Mw, 10 J/cm(2)). The dose was fractioned in four points. The animals were sacrificed 15, 21, and 30 days after surgery; specimens were taken and routinely processed (wax, cut, and stain with H&E and Sirius red stains). Light microscopic analysis was performed by a pathologist. RESULTS: In the groups in which the LLLT was used trans-operatively on the surgical bed (G2/G4), bone remodeling was both quantitatively and qualitatively more evident when compared to subjects of groups G1 and G3. CONCLUSION: The present study indicates that the use of LLLT trans-operatively resulted in a positive biomodulative effect on the healing of bone defects associated with autologous bone grafts.