Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice

Citation
Jm. Alexander et al., Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice, J BONE MIN, 16(9), 2001, pp. 1665-1673
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF BONE AND MINERAL RESEARCH
ISSN journal
0884-0431 → ACNP
Volume
16
Issue
9
Year of publication
2001
Pages
1665 - 1673
Database
ISI
SICI code
0884-0431(200109)16:9<1665:HPH1RB>2.0.ZU;2-2
Abstract
The experimental work characterizing the anabolic effect of parathyroid hor mone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) ani mals, mainly rats. A major drawback of these animal models is their inacces sibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermi ttently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral b ones were evaluated by microcomputed tomography (mu CT) followed by histomo rphometry. A tight correlation was observed between trabecular density (BV/ TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. P TH induced a similar to 35% recovery of this loss and a similar to 40% reve rsal of the associated decreases in trabecular number (Tb.N) and connectivi ty. PTH also caused a shift from single to double calcein-labeled trabecula r surfaces, a significant enhancement in the mineralizing perimeter and a r espective 2- and Mold stimulation of the mineral appositional rate (MAR) an d bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thicknes s also were increased with a high correlation between these parameters. The se data show that OVX osteoporotic mice respond to PTH by increased osteobl ast activity and the consequent restoration of trabecular network. The Swis s-Webster mouse model will be useful in future studies investigating molecu lar mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.