6 at the lumbar spine vs T-score = − 2.2 in the current study). In contrast,
in subjects transitioning from alendronate to a single infusion of zoledronic acid, BMD values remained unchanged at 12 months in those who transitioned to zoledronic acid at 12 months . While the difference in BMD outcomes may be related to suboptimal adherence to previous alendronate treatment in our study, sCTX-1 at study entry was reduced in both treatment groups (< 0.3 ng/mL). Bisphosphonates are currently the most commonly utilized treatment for osteoporosis, and alendronate is generally prescribed as a first-line therapy. Transitioning therapies may occur due to difficult dosing regimens, side effects, or perceived treatment failure, but the incidence is not known. The practice of cycling patients from oral alendronate through multiple, other oral bisphosphonates occurs despite a lack of evidence demonstrating Anti-infection Compound Library mouse additional Depsipeptide supplier benefits in BMD, bone turnover markers, or overall adherence and effectiveness. Thus, studies such as this one can be used not only to assess the pharmacological effects of the drugs, but
also to help physicians choose the best therapeutic strategy. Of particular interest is the observation that subjects with the highest level of remodeling at baseline achieved the greatest gains in BMD, something that was not observed in subjects who were treated with risedronate. Greater reductions in sCTX-1 and greater gains in BMD associated with denosumab treatment have similarly been observed when compared with alendronate in subjects who were treatment-naïve  or pre-treated with alendronate , and when compared with ibandronate in subjects pre-treated
with an oral bisphosphonate . Low BMD is an important and modifiable risk factor for fracture in postmenopausal women, and with denosumab, which has a unique mechanism of action, a strong relationship between BMD increases and anti-fracture efficacy has been shown . The gains in BMD observed in the current study BCKDHA are statistically significant as reflected in the proportion of individuals who had BMD gains ≥ LSC. In this study, there was no BMD-based inclusion criterion, and it was the investigator’s responsibility to assess the appropriateness of the potential study subject to receive prolonged osteoporosis therapy. To better define characteristics of the study population, we developed a higher-risk subgroup by BMD threshold, BMD threshold plus fracture, or baseline sCTX-1 upper limit to identify within the study population a group that would be expected to receive highest priority for prolonged therapy. We found that one-third of this subgroup had prior osteoporosis-related fractures. Interestingly, this subgroup showed BMD responses that were consistent with the overall study cohort, demonstrating consistency of effect of denosumab independently of prevalent fractures.