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1.  Systemic intermittent parathyroid hormone treatment improves osseointegration of press-fit inserted implants in cancellous bone 
Acta Orthopaedica  2012;83(4):411-419.
Background and purpose
Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically.
Material and methods
We examined the effect of human PTH (1–34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1–34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure.
Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile range) 15% (13–18)) in the PTH group and 11% (7–13) in control. The fraction of lamellar bone was unaltered. No significant difference in bone or fibrous tissue was observed in the circumferential regions of 0–500, 500–1,000, and 1,000–2,000 μm around the implant. Mechanically, the implants treated with PTH showed no significant differences in total energy absorption, maximum shear stiffness, or maximum shear strength.
Intermittent treatment with PTH (1–34) improved xhistological osseointegration of a prosthesis inserted press-fit at surgery in cancellous bone, with no additional improvement of the initial mechanical fixation at this time point.
PMCID: PMC3427634  PMID: 22880714
2.  Parathyroid Hormone Treatment Increases Fixation of Orthopedic Implants with Gap Healing: A Biomechanical and Histomorphometric Canine Study of Porous Coated Titanium Alloy Implants in Cancellous Bone 
Calcified Tissue International  2011;88(4):294-303.
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/m2 and control 470 [189–596] J/m2). 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.
PMCID: PMC3059756  PMID: 21253714
Parathyroid hormone; Prostheses and implants; Canine; Biomechanics; Histomorphometry
3.  Effect of local TGF-β1 and IGF-1 release on implant fixation: comparison with hydroxyapatite coating 
Acta Orthopaedica  2009;80(4):499-504.
Background and purpose Hydroxyapatite (HA) coating stimulates the osseointegration of cementless orthopedic implants. Recently, locally released osteogenic growth factors have also been shown experimentally to stimulate osseointegration so that bone fills gaps around orthopedic implants. Here, we have compared the effect of local release of TGF-β 1 and IGF-1 with that of hydroxyapatite coating on implant fixation.
Method Weight-bearing implants with a 0.75-mm surrounding gap were inserted bilaterally in the knees of 10 dogs. Growth factors were incorporated in a biodegradable poly(D,L-lactide) coating on porous coated titanium implants. Plasma-sprayed HA implants served as controls. The dogs were killed at 4 weeks and the implants were evaluated by mechanical push-out test and by histomorphometry.
Results There was no difference in any of the mechanical parameters. Bone ongrowth was 3-fold higher for HA-coated implants (p < 0.001). For growth factor-coated implants, bone volume was 26% higher in the inner half of the gap and 28% higher in the outer half compared to HA (p < 0.03).
Interpretation- The mechanical fixation of porous-coated titanium implants with local growth factor release is comparable to that of HA coating. While HA mainly stimulated bone ongrowth, local release of TGFβ 1 and IGF-1 stimulated gap healing.
PMCID: PMC2823183  PMID: 19634022

Results 1-3 (3)