This study proposes to use a non-invasive, in vivo model for strain application in the tibiae of rats. It seeks to examine and compare effects of intermittent parathyroid hormone (PTH) administration and mechanical loading on endosteal bone formation. It hypothesizes that there is a common anabolic pathway for the bone responses to PTH and mechanical loading. It will test three hypotheses with in vivo studies in rats: 1) that PTH modulates the responsiveness of bone tissue to mechanical stimuli; 2) that PTH and mechanical loading modulate osteogenesis through two pathways, i.e., one that includes cell proliferation, one that does not; and 3) that nitric oxide and prostaglandins are common paracrine factors involved in the anabolic effects of mechanical loading and PTH. Bone histomorphometry will be used to measure bone formation rates; immunohistochemistry of bromodeoxyuridine to measure cell division; and serum biochemistry to measure blood chemistry and PTH levels. The proposed studies are intended to lay the groundwork for directed research into the paracrine factors and cellular mechanisms involved in the anabolic response in rat bone. The current studies are directed toward characterization of the cellular events following an anabolic stimulus and the identification of paracrines (nitric oxide and prostaglandins) that may be involved in the anabolic response. Once the cell populations and paracrine factors involved in the anabolic response are identified, further studies may be done to assess cell-to-cell paracrine communication, receptor expression, etc. If PTH shares a common anabolic pathway with mechanical loading, this pathway possibly could be accessed directly, with custom molecules, rather than indirectly using systemic hormones or mechanical loads. It is suggested, therefore, that the proposed research into anabolic bone effects might eventually lead to new therapeutics for treating osteoporosis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG4-ORTH (05))
Program Officer
Sharrock, William J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
Zip Code
Robling, Alexander G; Warden, Stuart J; Shultz, Kathryn L et al. (2007) Genetic effects on bone mechanotransduction in congenic mice harboring bone size and strength quantitative trait loci. J Bone Miner Res 22:984-91
Turner, C H; Sun, Q; Schriefer, J et al. (2003) Congenic mice reveal sex-specific genetic regulation of femoral structure and strength. Calcif Tissue Int 73:297-303
Robling, Alexander G; Hinant, Felecia M; Burr, David B et al. (2002) Shorter, more frequent mechanical loading sessions enhance bone mass. Med Sci Sports Exerc 34:196-202
Peacock, Munro; Turner, Charles H; Econs, Michael J et al. (2002) Genetics of osteoporosis. Endocr Rev 23:303-26
Turner, C H (2002) Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int 13:97-104
Robling, A G; Turner, C H (2002) Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. Bone 31:562-9
Ohashi, Naoko; Robling, Alexander G; Burr, David B et al. (2002) The effects of dynamic axial loading on the rat growth plate. J Bone Miner Res 17:284-92
Robling, Alexander G; Hinant, Felicia M; Burr, David B et al. (2002) Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 17:1545-54
Burr, David B; Robling, A G; Turner, C H (2002) Effects of biomechanical stress on bones in animals. Bone 30:781-6
Robling, A G; Burr, D B; Turner, C H (2001) Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol 204:3389-99

Showing the most recent 10 out of 19 publications