Morse et al. (2008) - SCI causes rapid osteoclastic resorption and GP abnormalities in growing rats

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Summary of Morse et al. 2008 - SCI induced bone loss in growing rats

Method Overview

SCI model - T10 severe contusion (BBB to confirm injury severity)

Rats - 7-week old male Sprague-Dawley (200-225 grams)

Controls - body weight (age) and gender matched (no surgery -not sham)

Sacrificed on Day 10 post-SCI

MicroCT bone imaging

TRAP-staining for mature osteoclast identification

dynamic histomorphometry for bone apposition rate determination.

Here the contusion SCI model is used to determine its impact on bone density, microarchitecture and microenvironment at the distal femoral metaphyses.

intro/justification

SCI causes osteoporosis

leads to increased risk of low trauma fracture

There is evidence that the bone loss is not due just to lack of mobility.

CNS is a major regulator of bone metabolism (bone is highly innervated)

This study suggests an important role of the neural system in regulating bone cell formation and influencing bone homeostasis.

No studies before this on bone loss following contusion SCI.

In-vivo BMD Assessment

Femoral metaphysis chosen for analysis. (clincally relevant)

Distal forelimb (radius/ulna) chosen as supralesional control

in-vivo BMD assessment w/ PIXImus scanner

Assessment areas - (16 x 13 pixels) @ distal femoral metaphysis and (11 x 13) @ distal radius/ulna.

BMD reproducibility (RMS-coefficient of variation) -4% @ dfm and 5% @ dr/u.

MicroCt microarchitecture analysis

µCT scanner - µCT 40 by Scanco.

Indices assessed: TV, BV, MV, BMC, BS, Th, BV/TV. Tb.Th, TB.N, Tb.Sp

Indices reproducibility (precession of error) 0.06 - 2.16% for cortical and 0.59-5.24% for trabecular compartment.[33]

Results - BMD

34%* decrease in BMD in T10 group at dfm. (n = 11) compared to CTR (n = 9) @ 10 days post-injury.

No significant difference in forelimb BMD between groups.

results - microarchitecture

significant alterations due to SCI, as shown in Figure.

48% decrease in trabecular BMC, with an associated decrease in Tb.Th and Conn.D (n = 5) compared to control (n = 5).

mean cortical bone content decreased by 35%, with a significant decrease in Ct.Th.

BS.BC increased in both compartments indicating increased trabecular and cortical bone resoption.

Notes

To obtain bone (apposition) formation rates need biological/chemical tests e.g. a form of histomorphometry.

Also for bone mineralisation, osteoclast/blast activity etc.

Discussion Before study it was assumed rapid bone loss following acute SCI was due to enhanced bone resorption, with normal bone formation. Here report suppressed osteoblast activity for the first time in the development of osteoporosis.