Parathyroid hormone (PTH) administered intermittently is a bone-building peptide. In joint replacements, implants are unavoidably surrounded by gaps despite meticulous surgical technique and osseointegration is challenging. We examined the effect of human PTH(1-34) on implant fixation in an experimental gap model. We inserted cylindrical (10 × 6 mm) porous coated titanium alloy implants in a concentric 1-mm gap in normal cancellous bone of proximal tibia in 20 canines. Animals were randomized to treatment with PTH(1-34) 5 μg/kg daily. After 4 weeks, fixation was evaluated by histomorphometry and push-out test. Bone volume was increased significantly in the gap. In the outer gap (500 μm), the bone volume fraction median (interquartile range) was 27% (20-37%) for PTH and 10% (6-14%) for control. In the inner gap, the bone volume fraction was 33% (26-36%) for PTH and 13% (11-18%) for control. At the implant interface, the bone fraction improved with 16% (11-20%) for PTH and 10% (7-12%) (P = 0.07) for control. Mechanical implant fixation was improved for implants exposed to PTH. For PTH, median (interquartile range) shear stiffness was significantly higher (PTH 17.4 [12.7-39.7] MPa/mm and control 8.8 [3.3-12.4] MPa/mm) (P <0.05). Energy absorption was significantly enhanced for PTH (PTH 781 [595-1,198.5] J/m(2) and control 470 [189-596] J/m(2)). Increased shear strength was observed but was not significant (PTH 3.0 [2.6-4.9] and control 2.0 [0.9-3.0] MPa) (P = 0.08). Results show that PTH has a positive effect on implant fixation in regions where gaps exist in the surrounding bone. With further studies, PTH may potentially be used clinically to enhance tissue integration in these challenging environments.