Changes in Geometry and Cortical Porosity in Adult, Ovary-Intact Rabbits after 5 Months Treatment with LY333334 (hPTH 1-34) |
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Authors: | T Hirano D B Burr R L Cain J M Hock |
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Institution: | (1) Department of Anatomy and Cell Biology, and Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, US;(2) Lilly Research Laboratories, Indianapolis, Indiana 46285, USA, US |
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Abstract: | The purpose of this study was to determine if the increased cortical bone porosity induced by intermittently administered
parathyroid hormone (PTH) reduces bone strength significantly. Mature ovary-intact New Zealand white rabbits were treated
with once daily injections of vehicle, or PTH(1-34), LY333334, at 10 or 40 μg/kg/day for 140 days. Geometry of the femoral
midshaft was measured to evaluate changes in the cross-sectional moment of inertia (CSMI). Cortical porosity was measured
in the midshaft of the tibia by dividing cortical area into three zones based on equal divisions of cortical diameter: near
endocortical (Zone I), near intermediate (Zone II), and near periosteal (Zone III) regions. Total cortical porosity significantly
increased after PTH treatment from 1.4% in the controls to 6.3% in the higher dose group, but the location of the new porosities
was not randomly distributed. In the controls, porosity of Zones I and II (both 1.7%) was almost twice as much as that of
Zone III (0.9%). In the lower dose group, cortical porosity of Zone I (5.5%) and II (1.8%) was greater than in Zone III (0.9%),
but these differences were not statistically significant. In the higher dose group, cortical porosity of Zone I (11.5%) and
II (6.1%) significantly increased compared with Zone III (1.4%) (P < 0.0005). Histomorphometric measurements showed that bone formation rate on both periosteal and endocortical surfaces increased,
resulting in increased bone area and cortical area in the higher dose group. A model was developed to evaluate the effect
of the changes in geometry and porosity on CSMI in the different zones. This simulation model indicated that CSMI in the higher
dose group was significantly greater than in the other two groups, despite the increased porosity. We speculate the reason
to be that porosity increased near the endocortical surface, where its mechanical effect is small. This increase was more
than offset by apposition of new bone on the periosteal surface. These data suggest that (1) PTH increases cortical porosity
in a dose-dependent manner, primarily near endocortical surfaces; (2) because of this nonhomogeneous distribution, the mechanical
effect of increased porosity is small; (3) the increased cortical porosity associated with PTH treatment is more than offset
by periosteal apposition of new bone, causing an overall increase in the bending rigidity of cortical bone; and (4) these
changes cannot be accurately evaluated using noninvasive methods of bone densitometry, which cannot account for the location
of bone gain and bone loss.
Received: 20 May 1999 / Accepted: 10 January 2000 |
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Keywords: | : PTH — Mechanical strength — Cross-sectional moment of inertia — Cortical porosity — Osteoporosis |
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