Abstract
Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies.
Highlights
IntroductionOsteoporosis is a common health problem characterized by low bone mass and structural deterioration of bone resulting in an increased susceptibility to fractures [1]
Osteoporosis is a common health problem characterized by low bone mass and structural deterioration of bone resulting in an increased susceptibility to fractures [1].Bone matrix formations as well as general bone health are largely affected by mechanical loading and nutrition
On the other hand breaking load of the femur (Fig. 2C) increased in the OVX+Diet at 3 M, whilst bending stiffness showed no significant difference in femora between the two groups (Fig. 1D)
Summary
Osteoporosis is a common health problem characterized by low bone mass and structural deterioration of bone resulting in an increased susceptibility to fractures [1]. Bone matrix formations as well as general bone health are largely affected by mechanical loading and nutrition. Most important of these are calcium and vitamin D. Disorder of calcium balance could lead to Hypercalciuria which is often accompanied bone demineralization and vitamin D deficiency [2]. Beside its critical role in bone metabolism, vitamin D insufficiency was reported to add a significant additional fracture risk for osteoporosis. Limited or permitted nutritive diets can determine bone mass
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