Bone Mineral Density After Transitioning From Denosumab to Alendronate

David Kendler; Arkadi Chines; Patricia Clark; Peter R. Ebeling; Michael McClung; Yumie Rhee; Shuang Huang; Robert Kees Stad

Disclosures

J Clin Endocrinol Metab. 2020;105(3) 

In This Article

Abstract and Introduction

Abstract

Context: There are few studies on patients transitioning from denosumab to bisphosphonates.

Objective: To investigate patient characteristics and changes in bone mineral density (BMD) after transitioning from denosumab to alendronate.

Design: Randomized, open-label, 2-year crossover Denosumab Adherence Preference Satisfaction (DAPS) study (NCT00518531).

Setting: 25 study centers in the US and Canada.

Patients: Treatment-naïve postmenopausal women with BMD T-scores from −2.0 to −4.0.

Interventions: This post hoc analysis evaluated women randomized to subcutaneous denosumab 60 mg every 6 months in year 1 followed by once-weekly oral alendronate 70 mg in year 2.

Main Outcome Measure: A 3% BMD threshold identified participants who lost, maintained, or gained BMD in year 2 on alendronate.

Results: Of 126 participants randomized to denosumab, 115 (91%) transitioned to alendronate in year 2. BMD increased by 3% to 6% with denosumab in year 1 and by 0% to 1% with alendronate in year 2. After transitioning to alendronate, most participants maintained or increased BMD; 15.9%, 7.6%, and 21.7% lost BMD at the lumbar spine, total hip, and femoral neck, respectively. Few participants fell below their pretreatment baseline BMD value; this occurred most often in those who lost BMD in year 2. Women who lost BMD with alendronate in year 2 also showed a greater percent change in BMD with denosumab in year 1. The BMD change in year 2 was similar regardless of baseline characteristics or adherence to oral alendronate.

Conclusion: Alendronate can effectively maintain the BMD gains accrued after 1 year of denosumab in most patients, regardless of baseline characteristics.

Introduction

Postmenopausal osteoporosis is a chronic disease associated with age-related declines in bone mass, changes in bone microarchitecture, and skeletal fragility. These changes place postmenopausal women at increased risk of fragility fractures, which are linked to significant morbidity, economic cost, and negative impact on health-related quality of life.[1–4] Antiresorptive therapies, including bisphosphonates and denosumab, have been demonstrated to reduce fracture incidence and increase bone mineral density (BMD) in postmenopausal women with osteoporosis,[5–9] although the optimal duration and sequencing of available treatments remain poorly understood. Whereas bisphosphonates bind to bone mineral and become incorporated into bone matrix, denosumab, a monoclonal antibody targeting receptor activator of nuclear factor kappa-B ligand (RANKL), is a reversible therapy. There is a rebound in bone turnover after treatment cessation, leading to loss of the bone density gained on treatment and loss of vertebral fracture protection.[10–12] If denosumab is discontinued, follow-on therapy with a bisphosphonate has been recommended to prevent reversible bone loss,[13,14] although limited data are available on patients transitioning from denosumab to bisphosphonates, such as alendronate.

The Denosumab Adherence Preference Satisfaction (DAPS) study was a 24-month study designed to compare adherence to denosumab with alendronate over 12 months in postmenopausal women with low BMD. Participants were randomized to receive denosumab or alendronate for the first year, after which they crossed over to receive the other treatment for the second year. We previously reported that the primary efficacy endpoints of adherence, preference, and satisfaction favored injectable denosumab over oral alendronate and that alendronate could maintain the gains in BMD achieved with 1 year of denosumab treatment.[15,16] Here we perform a descriptive subanalysis of participants randomized to the denosumab/alendronate sequence to investigate the effect of transitioning to alendronate.

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