High dose teriparatide

Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone.sub.1-34 (rPTH.sub.1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH.sub.1-34 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 rPTH.sub.1-34 (n = 7; 5 [mu]g/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH.sub.1-34 (n = 8; 5 [mu]g/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 rPTH.sub.1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH.sub.1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p