This document compares two dual-energy X-ray absorptiometry (DXA) systems - PIXImus and Insight - for skeletal phenotyping in mice. It finds that while both systems can measure bone mineral density (BMD) and content (BMC) non-invasively and rapidly, they produce somewhat different quantitative results. PIXImus is a portable unit that uses low X-ray energies and high-resolution pixels, allowing measurements in low-density bone, while Insight requires a longer scanning time. Overall, the document evaluates the two DXA systems for analyzing skeletal changes in mouse models of bone disease.
5. WWW.SCINTICA.COM
Microcomputed tomography (µCT) limitations
5
• Requires sacrifice of mice to isolate bones.
• Very slow, days worth of work to process a cohort.
• Measurement thresholds (contouring, segmentation …) set by user.
• Expensive.
• In vivo systems available but expensive and time-consuming.
6. WWW.SCINTICA.COM
• Using 2 X-Rays beams with different energy to measure bone mineral density
(and other parameters).
Strengths:
Non-invasive.
Minimal dose of radiation.
Fast
Cheap
Weaknesses:
No assessment of trabecular bone.
No 3D reconstruction and microarchitecture assessment.
Dual X-ray Absorptiometry (DXA)
6
7. WWW.SCINTICA.COM
Dual X-ray Absorptiometry (DXA)
7
DXA scan in clinics
DXA (PIXImus) for small animals
• Using 2 X-Rays beams with different energy to measure bone mineral density
(and other parameters).
Strengths:
Non-invasive.
Minimal dose of radiation.
Fast
Cheap
Weaknesses:
No assessment of trabecular bone.
No 3D reconstruction and microarchitecture assessment.
8. WWW.SCINTICA.COM
Dual X-ray Absorptiometry (DXA)
8
DXA scan in clinics
DXA (PIXImus) for small animals
• Using 2 X-Rays beams with different energy to measure bone mineral density
(and other parameters).
• Strengths:
• Non-invasive.
• Minimal dose of radiation.
• Fast
• Cheap
Weaknesses:
No assessment of trabecular bone.
No 3D reconstruction and microarchitecture assessment.
9. WWW.SCINTICA.COM
The PIXImus system
• The PIXImus densitometer is a portable unit.
• It uses a stationary anode X-ray tube that generates a cone beam X-ray.
• PIXImus uses low X-ray energies (80/35 kVp at 500 µA).
• The stationary area detector uses ultrahigh resolution pixels (0.18 x 0.18 mm).
• Achieves contrast in extremely low-density bone and for tissue comparison analysis.
9
30 x 63 x 33 cm, ~ 60lbs
10. WWW.SCINTICA.COM
PhD Thesis
Growth Hormone
Hypothalamus
Anterior Pituitary
GHRH Somatostatin
Liver
IGF-I
Metabolism
• Adipose Tissue
• Bone
• Skeletal muscle
Adapted from Thorner MO, et al. In: Williams Textbook of Endocrinology. 9th ed. 1998:249.*
*Clemmons D, Cook D, Kleinberg D
16. WWW.SCINTICA.COM
Actions of IGFBP4
• IGFBP4 inhibits IGF actions in almost all in vitro models:
• Bone cells
• Vascular smooth muscle cells
• Colon cancer cells
• In vivo overexpression of IGFBP4 in bone reduced bone formation.
• Injections of IGFBP4 in mice induced bone formation.
• Surprisingly, IGFBP4 KO mice a growth delay but the knockout was
generated on a mixed background.
IGFBP4
Growth
?
44. WWW.SCINTICA.COM
Inject 12-week-old C57BL6J (n=3) with 3mg/kg BW of Alk4-FC for 2 weeks
95.0
95.5
96.0
96.5
97.0
Ct.
area
/
Total
area
(%)
0.180
0.185
0.190
0.195
0.200
Ct.
Thickness
(mm)
95
100
105
110
Weight
(%
from
Day
0)
p =0.05
65
70
75
80
85
Lean
Mass
(%
from
Day
0)
p =0.03
95
100
105
110
Fat
Mass
(%
from
Day
0)
A B
0.00
0.02
0.04
0.06
BMD
(g/cm
2
)
0.0
0.1
0.2
0.3
0.4
0.5
BMC
(g)
0
5
10
15
20
BV/TV
(%) p =0.05
95.0
95.5
96.0
96.5
97.0
CA/TA
(%)
660 x 581 x 1127 mm, ~ 570lbs
45. WWW.SCINTICA.COM
Inject 12-week-old C57BL6J (n=3) with 3mg/kg BW of Alk4-FC for 2 weeks
95.0
95.5
96.0
96.5
97.0
Ct.
area
/
Total
area
(%)
0.180
0.185
0.190
0.195
0.200
Ct.
Thickness
(mm)
95
100
105
110
Weight
(%
from
Day
0)
p =0.05
65
70
75
80
85
Lean
Mass
(%
from
Day
0)
p =0.03
95
100
105
110
Fat
Mass
(%
from
Day
0)
A B
0.00
0.02
0.04
0.06
BMD
(g/cm
2
)
0.0
0.1
0.2
0.3
0.4
0.5
BMC
(g)
0
5
10
15
20
BV/TV
(%) p =0.05
95.0
95.5
96.0
96.5
97.0
CA/TA
(%)
Secured funding! Project ongoing...
660 x 581 x 1127 mm, ~ 570lbs