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.
Hashimoto
Takahiro
T
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Yamaguchi 755-8505, Japan.
Shigetomi
Mitsunori
M
Ohno
Teruyasu
T
Matsunaga
Tsunemitsu
T
Muramatsu
Keiichi
K
Tanaka
Hiroshi
H
Sugiyama
Toshihiro
T
Taguchi
Toshihiko
T
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