Assessing bone quantity by pQCT.
We have tested the ability of the XCT960A to detect bone loss in OVX-rats, as well as bone gain in the proximal tibial metaphysis of healthy rats treated with hPTH(1-34). The results demonstrated that high precision can be achieved, with CV's for most measurement parameters in the range of 1.6 to 5.9% being obtained in vivo with repositioning of animals. Significant changes in bone parameters in the tibia were observed already at 2 weeks following OVX or PTH-therapy, while whole bone mass measured in the tibia by DEXA ex vivo did not change significantly for up to 24 weeks. For the proximal rat tibia at location 5mm distal to the knee joint was identified as an optimal site. At this location, cortices are fairly parallel thus reducing the partial volume effect, the area is relatively rich in cancellous bone increasing the magnitude of bone gain or loss, and the site (2mm below the growth plate) is relevant for comparisons with histomorphometric measurements. The results demonstrate that pQCT can be adapted for use in small animals such as rats, and that it is a sensitive, reproducible, non-invasive method available to monitor changes in bone mass, bone density, and geometric properties. Future studies should help to establish whether the moment of inertia, moment of resistance and the newly added bone strength index provided by the machine are predictive in any way for bone strength as obtained from biomechanical testing procedures. Peripheral QCT in small animals is an important addition for drug evaluation because it is more sensitive than DEXA and allows for shorter duration of experiments. This non-invasive method can reliably measure changes in cancellous and cortical bone mass over time following ovariectomy or administration of the bone anabolic hormone hPTH(1-34). pQCT should be viewed as a complimentary technique to static and dynamic histomorphometry, which does not replace either of these methods. Its value in the field of basic research should be evaluated.
Gasser
J A
JA
Sandoz Pharma Ltd., Basel, Switzerland.
D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005069:Evaluation Studies as Topic; D005260:Female; D010053:Ovary / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015203:Reproducibility of Results; D019379:Teriparatide; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects*; D014057:Tomography, X-Ray Computed
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019379:Teriparatide