Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment.
Bone response under combined mechanical and PTH stimuli is important in osteoporosis. A rat tail animal model with computer modeling was used to examine bone response to loading and PTH. PTH enhances and sustains increased bone formation rate, which directly correlates to mechanical microenvironment, suggesting beneficial effects of combined PTH treatment and exercise in preventing osteoporosis.


BACKGROUND
Using an in vivo rat tail vertebra model combined with a specimen-specific, high-resolution microcomputed tomography (microCT)-based finite element analysis (FEA) technique, trabecular bone response to combined dynamic compressive loading and parathyroid hormone (PTH) stimulation was characterized.


METHODS
Two hundred twenty-four male Sprague-Dawley rats were randomly divided into seven treatment groups: (1) Control, (2) vehicle + 0N, (3) PTH + 0N, (4) vehicle + 50N, (5) PTH + 50N, (6) vehicle + 100N, and (7) PTH + 100N, with three treatment durations (1, 2, or 4 weeks). Rat PTH(1-34) was administered daily in the PTH-stimulated groups approximately 3 h before daily mechanical stimulation with 0, 50, or 100N dynamic compressive loading. microCT-based FEA was performed for each loaded vertebra after death. Bone histomorphometry was performed on trabecular bone with double fluorochrome labeling to assess bone formation.


RESULTS
Daily mechanical loading or PTH administration significantly increased bone formation rate (BFR) compared with control or V + 0N with significant increases in both mineral apposition rate (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical loading, enhanced BFR mainly through a significant increase in MAR after the first week and through a significant increase in LS/BS after 2 and 4 weeks. Synergistic effects in BFR were present when PTH was combined with mechanical loading, especially after 2 and 4 weeks, where the increase in BFR was sustained. However, when either PTH or mechanical loading was the only stimulus, the bone formation response diminished to the level of Control animals after 4 weeks. Furthermore, significant correlations were observed between the bone formation indices and trabecular bone tissue mechanical microenvironments at 1 and 2 weeks, with PTH administration enhancing and sustaining these correlations into 4 weeks.


CONCLUSIONS
The synergistic effects of combined PTH and mechanical stimulation on trabecular bone formation rate suggest a potential benefit for combined PTH administration and exercise in the treatment of osteoporosis.
Kim
Chi Hyun
CH
Department of Biomedical Engineering, Bone Bioengineering Laboratory, Columbia University, New York, New York 10027, USA.
Takai
Erica
E
Zhou
Hua
H
von Stechow
Dietrich
D
Müller
Ralph
R
Dempster
David W
DW
Guo
X Edward
XE
D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010024:Osteoporosis / Q000517:prevention & control; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010805:Physical Conditioning, Animal; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016474:Weight-Bearing
D010281:Parathyroid Hormone