Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.
Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.
Verhaeghe
J
J
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Belgium.
Suiker
A M
AM
Einhorn
T A
TA
Geusens
P
P
Visser
W J
WJ
Van Herck
E
E
Van Bree
R
R
Magitsky
S
S
Bouillon
R
R
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000502:physiology*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000032:analysis / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000502:physiology; D006801:Humans; D006811:Humerus / Q000737:chemistry / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D015675:Osteocalcin / Q000032:analysis / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000473:pathology*; D010052:Ovariectomy / Q000009:adverse effects; D010710:Phosphates / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D013977:Tibia / Q000473:pathology / Q000502:physiology
D015415:Biomarkers; D010710:Phosphates; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol; D002118:Calcium