title: Parathyroid hormone 1-34 enhances titanium implant anchorage in low-density trabecular bone: a correlative micro-computed tomographic and biomechanical analysis.
abstract: The use of endosseous titanium implants is the standard of care in dentistry and orthopaedic surgery. Nevertheless, implantation in low-density bone has a poor prognosis and experimental studies show delayed implant anchorage following gonadectomy-induced bone loss. Intermittently administered human parathyroid hormone 1-34 [iahPTH(1-34)] is the leading bone anabolic therapy. Hence, this study assessed whether iahPTH(1-34) enhances titanium implant integration in low-density bone. Threaded titanium implants, 0.9 mm in diameter, were inserted horizontally into the proximal tibial metaphysis of 5-month-old rats, 7 weeks postorchiectomy (ORX). Subcutaneous administration of iahPTH(1-34), at 5, 25 and 75 microg/kg/day commenced immediately thereafter and lasted for 8 weeks. Quantitative micro-computed tomography (muCT) at the implantation site was carried out at 15 microm resolution using high energy and long integration time to minimize artifacts resulting from the high implant radiopacity. Osseointegration (OI) was calculated as percent implant surface in contact with bone (%OI) quantified as the ratio of "bone"-to-total voxels in contact with the implant. Additionally, the trabecular bone volume density (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and connectivity density (Conn.D) were measured in the peri-implant bone. All microCT parameters were stimulated by iahPTH(1-34) dose-dependently; the percent maximal enhancement was %OI = 143, BV/TV = 257, Tb.Th = 150, Tb.N = 140 and Conn.D = 193. The maximal values of %OI, BV/TV and Tb.Th in iahPTH(1-34)-treated ORX rats exceeded significantly those measured in the implantation site of untreated sham-ORX controls. The same specimens were then subjected to pullout biomechanical testing. The biomechanical parameters were also enhanced by iahPTH(1-34) dose-dependently, exceeding the values recorded in the sham-ORX controls. The percent iahPTH(1-34)-induced maximal enhancement was: ultimate force = 315, stiffness = 270 and toughness = 395. Except for the BV/TV and Tb.Th, there was no significant difference between the effect of the 25 and 75 microg/kg/day doses. There was a highly significant correlation between the morphometric and biomechanical parameters suggesting the use of quantitative CT as predictive of the implant mechanical properties. These findings demonstrate that iahPTH(1-34) effectively stimulates implant anchorage in low-density trabecular bone and thus the feasibility of administering iahPTH(1-34) to improve the clinical prognosis in low-density trabecular bone sites.
authors.affiliation: Bone Laboratory, The Hebrew University of Jerusalem, PO Box 12272, Jerusalem 91120, Israel.
authors.forename: Yankel
authors.initials: Y
authors.lastname: Gabet
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Jay
authors.initials: J
authors.lastname: Levy
authors.forename: Richard
authors.initials: R
authors.lastname: Dimarchi
authors.forename: Michael
authors.initials: M
authors.lastname: Chorev
authors.forename: Itai
authors.initials: I
authors.lastname: Bab
authors.forename: David
authors.initials: D
authors.lastname: Kohavi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D015519:Bone Density; D004305:Dose-Response Relationship, Drug; D020007:Implants, Experimental; D008297:Male; D008422:Materials Testing / Q000295:instrumentation / Q000379:methods*; D009919:Orchiectomy; D016348:Osseointegration / Q000187:drug effects; D010024:Osteoporosis / Q000209:etiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength; D014025:Titanium / Q000737:chemistry*; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D014025:Titanium