Bone mass is a strong determinant of fracture risk, and recent evidence suggests that bone turnover may also be related to fracture risk. Current FDA approved approaches to osteoporosis consist of estrogens, calcitonin, bisphosphonates, and raloxifene. All reduce bone turnover and result in modest increases in bone mass, presumed to be due primarily to reduction in remodeling space. In many individuals with osteoporosis, these gents do not increase bone mass sufficiently to eliminate fractures, indicating a need for agents that are anabolic to the skeleton. In the past funding period, e showed that hPTH increases bone mass especially in the spine in postmenopausal estrogenized women and may be associated with a reduction in vertebral fracture risk. Mechanistically, PTH, in the presence of an anti-resorptive agent, increases bone formation markers within the first weeks of treatment, while resorption markers increase later, after which both are similarly elevated. Our current proposal seeks to evaluate the mechanism of PTH action on human bone physiology. We propose to define the early skeletal response to PTH which underlies the rapid increase in formation biochemistry and bone mass, using histomorphometry. We will evaluate the importance of the anti-resorptive agent in determining the initial bone response and possibly modifying site specific skeletal responses to PTH. Finally, we will determine the skeletal responses to discontinuation of PTH and subsequent rechallenge to determine if a second anabolic response can be mounted by the skeleton. These studies should allow better definition of appropriate clinical protocols for PTH use, as well as defining the mechanisms underlying the short-term and long-term anabolic actions of PTH in the human.

Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
12
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Helen Hayes Hospital
Department
Type
DUNS #
157119244
City
Menands
State
NY
Country
United States
Zip Code
12204
Ascenzi, Maria-Grazia; Liao, Vivian P; Lee, Brittany M et al. (2012) Parathyroid hormone treatment improves the cortical bone microstructure by improving the distribution of type I collagen in postmenopausal women with osteoporosis. J Bone Miner Res 27:702-12
Zhang, Hao; Doty, Stephen B; Hughes, Christine et al. (2007) Increased resorptive activity and accompanying morphological alterations in osteoclasts derived from the oim/oim mouse model of osteogenesis imperfecta. J Cell Biochem 102:1011-20
Dempster, David W; Hughes-Begos, Christine E; Plavetic-Chee, Katarina et al. (2005) Normal human osteoclasts formed from peripheral blood monocytes express PTH type 1 receptors and are stimulated by PTH in the absence of osteoblasts. J Cell Biochem 95:139-48
Cosman, Felicia; Nieves, Jeri; Zion, Marsha et al. (2005) Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med 353:566-75
Iida-Klein, A; Lu, S Shou; Kapadia, R et al. (2005) Short-term continuous infusion of human parathyroid hormone 1-34 fragment is catabolic with decreased trabecular connectivity density accompanied by hypercalcemia in C57BL/J6 mice. J Endocrinol 186:549-57
Kurland, Etah S; Heller, Samantha L; Diamond, Beverly et al. (2004) The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)]. Osteoporos Int 15:992-7
Kim, Chi Hyun; Takai, Erica; Zhou, Hua et al. (2003) Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment. J Bone Miner Res 18:2116-25
Rubin, Mishaela R; Bilezikian, John P (2003) New anabolic therapies in osteoporosis. Endocrinol Metab Clin North Am 32:285-307
Zhou, H; Iida-Klein, A; Lu, S S et al. (2003) Anabolic action of parathyroid hormone on cortical and cancellous bone differs between axial and appendicular skeletal sites in mice. Bone 32:513-20
Dempster, David W (2003) The pathophysiology of bone loss. Clin Geriatr Med 19:259-70, v-vi

Showing the most recent 10 out of 125 publications