Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats.
Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.
Department of Orthopaedics, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. qing.zhang@yale.edu.
Qing
Q
Zhang
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. christopher.p.miller@yale.edu.
Christopher
C
Miller
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. jesse.bible@yale.edu.
Jesse
J
Bible
Department of Biology, Indiana University Purdue University Indianapolis, 723 West Michigan Street, SL306, Indianapolis 46202, IN, USA. jilili@iupui.edu.
Jiliang
J
Li
Department of Orthopaedics, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. xqing011@yahoo.com.
Xiaoqing
X
Xu
Unigene Laboratories, Inc. 81 Fulton Street, Boonton 07005, NJ, USA. nmehta@unigene.com.
Nozer
N
Mehta
Unigene Laboratories, Inc. 81 Fulton Street, Boonton 07005, NJ, USA. JGilligan@tarsatherapeutics.com.
James
J
Gilligan
Department of Orthopaedics, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. agnes.vignery@yale.edu.
Agnès
A
Vignery
Section of Comparative Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven 06510, CT, USA. jodi.carlson@yale.edu.
Jodi A Carlson
JA
Scholz