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Delayed remodeling in the
early period of fracture healing in spontaneously diabetic BB/OK
rats depending on the diabetic metabolic state
N. Follak1, I. Klöting2, E. Wolf3
and H. Merk1
1Orthopedic Research Laboratories, Department
of Orthopedic Surgery, Ernst Moritz Arndt University, Greifswald,
Germany, 2Institute for Pathophysiology, Division of Laboratory
Animal Science, Karlsburg, Ernst Moritz Arndt University, Greifswald,
Germany and 3Institute for Pathology, Klinikum Stralsund, Germany
Offprint requests to: Dr. N. Follak, MD, Orthopedic Research
Laboratories, Department of Orthopedic Surgery, Erns Moritz Arndt
University, F. Sauerbruch Str. 17487 Greifswsald, Germany. Fax:
+49-3834-867052. e-mail: follak@mail.uni-greifswald.de
Summary. Several
clinical series, analyzing fracture healing in patients with
insulin-dependent type 1 diabetes (IDDM) demonstrated significant
incidence of delayed union, non-union, and pseudarthrosis. The
purpose of this study was to examine the detailed histomorphometry
and histology of bone formation and remodeling during fracture
healing depending on the diabetic metabolic state in spontaneously
diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents
a close homology to IDDM in man.
A standardized fracture model was chosen and based on blood-glucose
values at the time of surgery (mg%), postoperative blood-glucose
course (mg%) and postoperative insulin requirements (IU/kg),
100 spontaneously diabetic BB/OK rats were divided into groups
with well-compensated (n=50, 167±77 mg%; 244±68
mg%; 1.8±1.9 IU/kg) or poorly compensated (n=50, 380±89
mg%; 415±80 mg%; 6.0±1.0 IU/kg) metabolic state.
Fifty LEW.1A rats served as the normoglycemic controls (97±15
mg%). Ten animals from each group were killed 1, 2, 3, 4 and
6 weeks after fracture and specimens were processed undecalcified
for quantitative histomorphometry and for qualitative light microscopy.
In terms of bone histomorphometry, within the first four weeks
after fracture, severe mineralization disorders occurred exclusively
in the rats with poorly compensated diabetic metabolic states
with a significantly decrease of all fluorochrome-based parameters
of mineralization, apposition, formation and timing of mineralization
in comparison to the spontaneously diabetic rats with well-compensated
metabolic states and to the control rats. This was confirmed
histologically.
Early fracture healing in the spontaneously diabetic BB/OK rats
is delayed exclusively in poorly compensated diabetic metabolic
states, and 6 weeks after fracture, histomorphometrically significant
deficits in the measured and dynamically calculated parameters
remain. This study suggests that strictly controlled insulin
treatment resulting in well-compensated diabetic metabolic states
will ameliorate the impaired early mineralization and cell differentiation
disorders of IDDM fracture healing. Histol. Histopathol. 19,
473-486 (2004)
Key words: Spontaneously
diabetic rats, Fracture healing, Histomorphometry, Diabetes,
Remodeling
DOI: 10.14670/HH-19.473
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