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CHAPTER
25
Bon
e Histomorphom
etry
Frank Rauch
Shriners Hospital for Children, Montreal, QC, Canada
INTRODUCTION
added in one remodeling cycle is called “remodeling bal-
ance.” The remodeling balance is typically close to zero so
that there is no or little net effect on the amount of bone.
However, the remodeling process renews the bone tissue
and thereby prevents tissue damage from accumulating.
9
Bone growth in width occurs through a differ-
ent mechanism, called modeling.
5,6,8,10
Bone modeling
involves the same set of effector cells as bone remodeling:
osteoclasts and osteoblasts. However, while in remod-
eling both cell types are sequentially active on the same
bone surface, osteoclasts and osteoblasts act on different
surfaces during modeling. During bone growth in width,
osteoblasts are typically located on the outer (periosteal)
surface of a bone cortex, where they deposit bone matrix
and later mineralize it. Thereby, the outer circumfer-
ence of a long bone or a vertebral body is increased. At
the same time, osteoclasts located on the inner (endo-
cortical) surface of the cortex resorb bone, thus increas-
ing the size of the marrow cavity. Since osteoblasts are
active without interruption in bone modeling, much more
rapid increases in the amount of bone tissue can occur in
modeling than in bone remodeling. Osteoclasts usually
remove less bone tissue than is deposited by osteoblasts
during modeling.
5,8
Therefore, modeling leads to a net
increase in the amount of bone tissue. For example, the
difference between osteoblastic matrix deposition and
osteoclastic bone resorption leads to cortical thickening.
Many different mutations in a variety of genes can
give rise to osteogenesis imperfect (OI), but the common
denominator of all types of OI is osteoblast dysfunction.
1
As osteoblasts are the cells that form extracellular bone
matrix, their functional deficit leads to the production of
abnormal bone tissue. To elucidate the pathogenesis of
OI, it is therefore essential to evaluate the tissue-level fea-
tures of OI bone.
The best tool to study bone on the tissue level is bone
histomorphometry, which can be used for both human
and animal studies.
2-4
This technique represents the quan-
titative evaluation of bone tissue, which in clinical studies
is usually obtained from the ilium (transiliac bone biopsy
specimen). Both the activity of bone cells and the amount
and distribution of bone tissue can be analyzed. When tet-
racycline labeling is performed prior to biopsy, bone histo-
morphometry offers the unique possibility to study bone
cell function
in vivo
. Importantly for pediatric use, the
growth process does not directly interfere with the mea-
surements. The osteoblast dysfunction in OI affects two
basic aspects of tissue-level mechanisms of bone develop-
ment: bone remodeling and bone modeling. These two
processes therefore must be briefly introduced here.
Bone is continuously renewed by remodeling.
5-8
Remodeling consists of successive cycles of bone resorp-
tion and formation on the same bone surface, either tra-
becular or cortical. The basic features of this process are
identical for trabecular and cortical bone.
5
A group of
osteoclasts removes a small quantity (“packet”) of bone
tissue, which after a reversal phase is replaced by a team
of osteoblasts. The entire group of cells involved in this
process is named remodeling unit or basic multicellular
unit. The fact that osteoblast activity is linked to previous
osteoclast action has been named “coupling.”
5
The dif-
ference in the amounts of bone which are removed and
THE BONE TISSUE LEVEL IN
CLASSICAL OI
Modeling and Remodeling Defects in OI Types I,
III and IV
In a study on 70 children with OI types I, III and IV
between 1.5 and 13.5 years of age, it was observed that
