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How do bisphosphonates prevent fractures?
  1. JONATHAN H TOBIAS
  1. Rheumatology Unit, Bristol Royal Infirmary
  2. Bristol BS2 8HW

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Why do fractures occur in osteoporosis?

In osteoporosis, changed bone remodelling causes loss of bone tissue and a deterioration in skeletal microstructure, which leads to an increase in skeletal fragility and risk of fracture.1These microstructural changes largely consist of a deterioration in skeletal microarchitecture, which affects both trabecular and cortical bone.2 ,3 In particular, the high bone turnover frequently seen in osteoporosis can produce the following changes: thinning, perforation, and complete removal of trabeculae; expansion of the medullary cavity, thereby reducing cortical thickness; an excess of partially completed cortical bone remodelling units, so increasing the proportion of cortical bone consisting of Haversian canals—that is, cortical porosity.

Recent evidence also suggests that changes in the material composition of bone may also contribute to the increase in skeletal fragility seen in osteoporosis. For example, accumulation of fatigue damage within bone, and a reduction in collagen crosslink concentration, have both been suggested to increase skeletal fragility.4 ,5 Several other independent determinants of fracture risk have also been identified, such as overall size and shape of the skeleton,6 ,7 and factors related to the risk of falling such as postural instability.8 However, unlike skeletal microstructure, these other factors are not thought to be influenced either by bone remodelling, or by therapeutic agents like bisphosphonates.

Summary of effects of bisphosphonates on bone

Bisphosphonates have been used to treat patients with osteoporosis since the 1980s. They are similar in structure to inorganic pyroposphate, and bind avidly to bone where they act to inhibit osteoclast activity,9 although the precise mechanisms responsible for this action remain to be elucidated. Studies involving biochemical markers of bone turnover in humans have confirmed that bisphosphonates are potent suppressors of bone resorption.10 As a consequence of this action, bisphosphonates are effective at preventing further bone loss, and can …

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