Sequential treatment with intermittent low-dose human parathyroid hormone (1-34) and bisphosphonate enhances large-size skeletal reconstruction by vascularized bone transplantation.
Vascularized bone transplantation enables reconstruction of large skeletal defects, but this process needs a long time. Since short-term intermittent parathyroid hormone (PTH) enhances rat fracture healing, we investigated the effects of 4-week intermittent low-dose (10 microg/kg/day) or high-dose (100 microg/kg/day) PTH followed by 4-week vehicle, low-dose or high-dose intermittent PTH, or zoledronic acid (ZOL, 2 micro/kg/week), a potent bisphosphonate, on large skeletal reconstruction by vascularized tibial grafting in rats. Compared to 8-week vehicle, 8-week low-dose PTH did not significantly increase the serum osteocalcin level as well as the urinary deoxypyridinoline level, while 4-week low-dose or high-dose PTH followed by 4-week ZOL decreased both of these levels. Eight-week PTH increased the bone mass of the graft and strength of the reconstructed skeleton in a dose-dependent manner; notably, the reconstructed skeleton showed an obviously higher response to PTH compared to the contralateral nonoperated femur. In contrast, 4-week PTH followed by 4-week vehicle reduced these effects and caused local bone loss at the host-graft junctions. Four-week PTH followed by 4-week ZOL did not induce such bone loss; however, 4-week high-dose PTH followed by 4-week ZOL caused a large callus in the distal cortical junction. Four-week PTH followed by 4-week ZOL increased the bone mass and strength similarly to 8-week PTH. These preliminary findings suggest, for the first time, that sequential treatment with short-term intermittent low-dose PTH and bisphosphonate as well as long-term intermittent low-dose PTH treatment enhance large skeletal reconstruction by vascularized bone transplantation, though early timing of sequential antiresorptive treatment could result in delay of bone repair.
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan.
Takahiro
T
Hashimoto
Mitsunori
M
Shigetomi
Teruyasu
T
Ohno
Tsunemitsu
T
Matsunaga
Keiichi
K
Muramatsu
Hiroshi
H
Tanaka
Toshihiro
T
Sugiyama
Toshihiko
T
Taguchi
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016025:Bone Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000098:blood supply / Q000187:drug effects*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000628:therapy*; D006801:Humans; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew
D004164:Diphosphonates; D010281:Parathyroid Hormone; D010446:Peptide Fragments