Changes in Bone Mineral Density after Alendronate Treatment May Be Caused by Increased Degree of Mineralization

Introduction: In patients with low initial bone mass, alendronate treatment causes small increases in DXA derived areal bone mineral density (BMD) and large decreases in fracture incidence. An increase in bone balance (the difference between bone formed and that resorbed per remodeling cycle) is often cited as the primary cause of increased BMD in clinical trials. Although some evidence exists suggesting that bone balance can change during alendronate treatment, these changes are not seen in all patients taking alendronate1. Recent findings that alendronate treatment increases the degree of mineralization of bone tissue have led to a theory that the increase in BMD and decrease in fracture incidence in clinical trials is due to increases in the ash fraction (ash mass/dry mineralized bone mass) of the bone tissue2. Increased ash fraction occurs when bone accumulates more mineral before being resorbed during a subsequent remodeling event. This can occur when the rate of mineral accumulation is increased or the rate of bone turnover is decreased. Mineral accumulation occurs in two phases, a quick primary mineralization phase lasting only a few days and a secondary mineralization phase that is estimated to last from months to years3, 4. Bone turnover is commonly measured by the activation frequency, a parameter known to decrease in response to alendronate treatment1. The objective of this study is to determine whether the changes in ash fraction caused by alendronate treatment can account for the observed changes in BMD.