Mineralization of bone matrix implies two successive steps, a primary mineralization on the calcification front followed by a slow process of secondary mineralization progressively adding about 50-60% of the mineral content on bone matrix. Our model is that antiresorptive agents prolong the lifetime of the basic structural units (BSUs) by causing a marked reduction in the birth rate of basic multicellular units (BMUs), and increase the degree of mineralization of bone (DMB) by allowing a more complete secondary mineralization. Conversely, agents or events provoking an augmentation of the birthrate of BMUs and a decrease of the lifetime of BSUs lead to resorption of new BSUs before they have fully completed their secondary mineralization, leading to the presence of incompletely mineralized BSUs and a low mean DMB value, as measured by quantitative microradiography. Measurements of DMB (distribution and mean value) under circumstances with various remodeling activities favor our model. In postmenopausal osteoporotic women treated during 2 or 3 years with alendronate (10 mg/day), an increase of the mean DMB of approximately 7 to 10% was found, due to a marked reduction in the bone remodeling. In contrast, an activation of bone remodeling as in primary hyperparathyroidism lowered the mean DMB.
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