Bisphosphonates and PTH for Preventing Fractures - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 156

Fig. 4 Overview of
determinants of structural
biomechanical properties and
how bisphosphonates affect
the key material properties of
bone
to control animals [ 28 , 55 - 57 ]. This decline in toughness was initially thought to
be related to the well-documented accumulation of microdamage that was observed
in lumbar vertebrae and other bones in dogs treated with BPs [ 28 , 56 , 57 ], although
changes to both mineralization and collagen cross-linking have also been shown to
occur. More recent data show that toughness in BP-treated animals continues to
decline with long-term treatment without a change in microdamage accumulation
or a further increase in mineralization [ 55 ]. This suggests that neither microdamage
nor mineralization is completely responsible for the progressive deterioration in the
bone's material properties leaving progressive changes to collagen, or the inter-
action among all these properties, as the cause of this progressive toughness
decline.
4.1 Mineralization
Both pre-clinical and clinical studies show that by reducing the turnover of bone
and thereby increasing mean tissue age, BP treatments lead to a significantly
higher average tissue mineralization [ 58 , 59 ] and lower heterogeneity of miner-
alization across the bone matrix [ 60 ]. These changes probably occur predomi-
nately within the first 2-3 years of treatment, and then change little with continued
treatment [ 61 , 62 ]. Increased mineralization with BP treatment occurs for two
reasons. Under normal conditions, bone remodeling preferentially renews the more
highly mineralized bone matrix, a process that takes about a year [ 63 ] or longer
[ 64 ]. Thus by suppressing remodeling, BPs allow more highly mineralized regions
to persist for a longer time. Moreover, suppression of remodeling allows more of
the newly formed bone to become fully mineralized without replacement.
An unresolved question is whether BPs alter either the rate of mineralization, or
the eventual degree of mineralization, of a specific BMU. One or both of these
changes would be expected to have a significant effect on the biomechanical
properties at the tissue level. Early data using FTIR [ 59 ] imply that BPs may