Abstract:
:Bisphosphonates increase bone mass and reduce fracture risk, but their anti-resorptive action may lead to increases in fatigue microdamage. To investigate how bisphosphonate effects influence changes in bone volume and microdamage in the long term, a strain-adaptive model of bone remodeling and microdamage balance was developed for a continuum-level volume of postmenopausal trabecular bone by invoking Frost's mechanostat hypothesis. Both disuse and fatigue microdamage were assumed to stimulate the activation frequency of basic multicellular units (BMUs) such that bone remodeling served to remove excess bone mass and microdamage. Bisphosphonate effects were simulated as follows: low, intermediate, high, or complete suppression of BMU activation frequency either without a change in resorption by the BMU or with an independent decrease in resorption while the bone formation process was unaffected (i.e., formation initially exceeded resorption). Of the bisphosphonate effects, a reduction in resorption relative to formation dictated the long-term gain in bone volume while the potency of activation frequency suppression controlled the rate of gain. A plateau in the bone mass gain that typically occurs in clinical studies of bisphosphonate treatment was predicted by the model because the resultant reduction in strain forced bone formation by the BMU to decrease over time until it matched the reduction in BMU resorption. A greater suppression of activation frequency proportionally increased microdamage, but the accumulation was limited over the long term as long as remodeling was incompletely suppressed. The results of the model suggest creating bisphosphonates that provide minimal suppression of remodeling and a large decrease in BMU resorption because this would minimize damage accumulation and increase bone mass, respectively.
journal_name
Bonejournal_title
Boneauthors
Nyman JS,Yeh OC,Hazelwood SJ,Martin RBdoi
10.1016/j.bone.2004.03.007subject
Has Abstractpub_date
2004-07-01 00:00:00pages
296-305issue
1eissn
8756-3282issn
1873-2763pii
S8756328204001115journal_volume
35pub_type
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