title: Repeated in vivo determinations of bone mineral density during parathyroid hormone treatment in ovariectomized mice.
abstract: The recent development of different genetically modified mice with potentially interesting bone phenotypes has increased the demand for effective non-invasive methods to evaluate effects on bone of mice during growth and development, and for drug evaluation. In the present study, the skeleton was analyzed by repeated in vivo scans using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Ovariectomized (ovx) mice treated with parathyroid hormone (PTH) were used as an animal model to evaluate these two techniques at different times after the onset of treatment. Female mice (6 weeks of age) were allocated randomly to four groups: (1) sham-operated+vehicle; (2) ovx+vehicle; (3) sham-operated+PTH(1-84) 150 microg/kg per day; (4) ovx+PTH. Six weeks after ovariectomy the drug treatment began and was continued for 8 weeks. The total body bone mineral content (BMC) and total body areal bone mineral density (BMD) were measured by DXA. Ovariectomy reduced total body BMC and total body areal BMD by 6.2+/-1.7% and 2.6+/-0.9% respectively. No effect of PTH on total body BMC was seen during the treatment period. The trabecular volumetric BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by 52+/-6.7%. The pQCT technique detected a clear effect on trabecular volumetric BMD after 2 weeks of PTH treatment (ovx 94+/-29% and sham-operated 46+/-10% more than vehicle-treated). The cortical bone was measured in a mid-diaphyseal pQCT scan of the tibia. Ovariectomy reduced the cortical BMC by 9+/-2%. PTH treatment for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique is more sensitive than the DXA technique in the detection of bone loss after ovariectomy and increased bone mass after PTH treatment in mice. Notably, the pQCT, but not the DXA, technique detected a dramatic effect as early as after 2 weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring skeletal changes during growth and development, and for drug evaluation in mice.
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden. niklas.andersson@astrazeneca.com
authors.forename: N
authors.initials: N
authors.lastname: Andersson
authors.forename: M K
authors.initials: MK
authors.lastname: Lindberg
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: K
authors.initials: K
authors.lastname: Andersson
authors.forename: B
authors.initials: B
authors.lastname: Ryberg
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D010281:Parathyroid Hormone