Parathyroid hormone (1-34) increases vertebral bone mass, compressive strength, and quality in old rats.
Human parathyroid hormone 1-34 (PTH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and day 40 of the treatment period, respectively. The PTH treatment did not influence the body weights of the rats, the volumes of whole vertebra, or the vertebral body heights. However, the PTH treatment induced profound changes in the bone structure. Histomorphometric analyses of the vertebral bodies (L-6) revealed an approximate doubling of the cancellous bone volume after PTH treatment from 24.6 +/- 1.3% to 54.9 +/- 2.0% (p < 0.001) as well as a doubling of the trabecular thickness while the bone surface/bone volume decreased by 60%. PTH treatment also increased bone formation as indicated by an increase in mineral apposition rate (from 0.42 +/- 0.01 to 0.89 +/- 0.01 microns/day, p < 0.01), increased mineralizing surface (from 7.8 +/- 1.4 to 43.8 +/- 1.9%, p < 0.01) and an increase in both volume-related and surface-related bone formation rates (5 and 11 times, respectively). The biomechanical properties were analyzed using standardized bone specimens from the vertebral bodies of L-4 by applying cranial-caudal compression in a materials testing machine. The PTH treatment induced a substantial increase in the strength of the vertebral body: ultimate load increased by 66%, ultimate stiffness by 47%, and energy absorption by 98%. The increase in vertebral body strength was also evident after normalizing the parameters to the cross sectional area and the ash content of the vertebral body specimens. PTH treatment increased ultimate stress from 26 +/- 3 to 44 +/- 3 N per mm2 (p < 0.01) and increased ultimate load normalized to ash content per mm specimen height from 59 +/- 4 to 72 +/- 4 N (mm/mg) (p < 0.05). The PTH treatment induced an increase in dry defatted bone density and ash density of both the vertebral body specimen (L-4) and the whole vertebra (L-5). In conclusion, PTH showed a remarkable ability to stimulate bone formation in the vertebral body of old rats. Furthermore, the biomechanical analysis revealed an enhanced compressive bone strength, even after correction for the increased bone mass, indicating an improved bone quality after the PTH treatment.
Ejersted
C
C
Department of Connective Tissue Biology, University of Aarhus, Denmark.
Andreassen
T T
TT
Hauge
E M
EM
Melsen
F
F
Oxlund
H
H
D000375:Aging; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D004548:Elasticity / Q000187:drug effects; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013718:Tensile Strength / Q000187:drug effects
D010281:Parathyroid Hormone