Dataset Information

Bone Mineral Density After Transitioning From Denosumab to Alendronate.

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.

SUBMITTER: Kendler D

PROVIDER: S-EPMC7112973 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Bone Mineral Density After Transitioning From Denosumab to Alendronate.

Kendler David D Chines Arkadi A Clark Patricia P Ebeling Peter R PR McClung Michael M Rhee Yumie Y Huang Shuang S Stad Robert Kees RK

The Journal of clinical endocrinology and metabolism 20200301 3

<h4>Context</h4>There are few studies on patients transitioning from denosumab to bisphosphonates.<h4>Objective</h4>To investigate patient characteristics and changes in bone mineral density (BMD) after transitioning from denosumab to alendronate.<h4>Design</h4>Randomized, open-label, 2-year crossover Denosumab Adherence Preference Satisfaction (DAPS) study (NCT00518531).<h4>Setting</h4>25 study centers in the US and Canada.<h4>Patients</h4>Treatment-naïve postmenopausal women with BMD T-scores ...[more]

PMID: 31665314

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Project description:Romosozumab is a therapy that stimulates bone formation and reduces bone resorption. In this study of postmenopausal women with low BMD, a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options. INTRODUCTION:In patients with high fracture risk, therapies that stimulate bone formation provide rapid BMD gains; currently available agents, parathyroid hormone receptor agonists, are limited to a 2-year lifetime exposure and generally used for a single treatment course. However, for long-term osteoporosis management, a second treatment course may be appropriate. Romosozumab, a therapy with the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. Here, we report efficacy and safety of a second romosozumab course. METHODS:In this phase 2, dose-finding study, postmenopausal women with low bone mass (T-score???-?2.0 and ??-?3.5) received romosozumab or placebo (month 0-24) followed by placebo or denosumab (month 24-36); participants then received a year of romosozumab (month 36-48). RESULTS:Of 167 participants who entered the month 36-48 period, 35 had been initially randomized to romosozumab 210 mg monthly. In participants who received romosozumab 210 mg monthly followed by placebo, a second romosozumab course (n?=?19) increased BMD by amounts similar to their initial treatment (month 0-12) at the lumbar spine (12.4%; 12.0%, respectively) and total hip (6.0%; 5.5%, respectively). Following denosumab, a second romosozumab course (n?=?16) increased BMD at the lumbar spine (2.3%) and maintained BMD at the total hip. Safety profiles were similar between first and second romosozumab courses. CONCLUSIONS:After 12 months off-treatment, a second romosozumab course again led to rapid and large BMD gains. Following denosumab, BMD gains with romosozumab were smaller than with initial treatment. No new safety findings were observed during the second course.

Project description:Abstract Despite clinical strides in the treatment of osteoporosis in several diverse medical conditions, the ability to maintain bone has proven to be exceedingly difficult in individuals with severe immobilization. Fifty to 60% of bone mineral density (BMD) at the epiphyseal and metaphyseal regions of the long-bones of the lower extremities may be lost over the first couple of years after spinal cord injury (SCI). Once a large amount of bone has been lost, it would be challenging to restore BMD, trabecular architectural integrity, and mechanical strength to provide protection against long-bone fractures of the lower extremities. Persons with neurologically complete forms of SCI have marked loss of BMD of the lower extremities, predisposing to fracture, especially at the knee. Denosumab, a commercially available human monoclonal antibody of the IgG2 immunoglobulin isotype with a high affinity and specificity for binding RANKL to antagonize its action, may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty-six patients with motor-complete SCI [International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) grade A and B] were randomized to receive denosumab or placebo at baseline (BL), 6, and 12 months. Ten participants in the denosumab group and 8 participants in the placebo group completed the 18-month clinical trial [ClinicalTrials.gov (NCT01983475)]. Dual energy x-ray absorptiometry (DXA; Lunar Prodigy Advance, all software version 12.20.023; EnCORE, GE Medical Systems, Madison, WI) and peripheral quantitative computed tomography (pQCT; Stratec XCT 3000; STIM designs, Carmel, CA) imaging were performed. Within group paired analysis revealed a significant decrease for areal BMD (aBMD) from BL in the placebo group that started at month 3 for the distal femoral epiphysis (DFE), distal femoral metaphysis (DFM), and total hip (TH) and at month 6 for the femoral neck (FN), and at month 12 for the proximal tibial epiphysis (PTE); the loss in aBMD progressed to 18 months for all the skeletal regions of interest (ROI). At 18 months, the percent change at the ROI for the denosumab vs. placebo groups were: DFE (1.1% ± 7.5 vs. -30.0% ± 11.9, respectively, p<0.001 and p<0.001), DFM (1.2% ± 6.4 vs. -17.2% ± 14.2, p<0.01), TH (3.3% ± 8.7 vs. -25.6% ± 7.6, p < 0.001), and PTE (-1.7% ± 8.2 vs. -24.1% ± 12.3, p<0.001). At 18 months, pQCT at the 4% tibial region confirmed the DXA findings at proximal tibial; at the 38% tibial region, a trend toward loss of total volumetric BMD (vBMD) was observed (-0.7% ± 4.5 vs. -16.9% ± 20.0, p<0.09), but cortical vBMD was similar between the denosumab and placebo groups, suggesting trabecular loss at the tibial shaft. In summary, the findings suggest that denosumab, if treatment is initiated within 3 months of acute SCI, appears to be an efficacious approach to maintain BMD at the knee and hip regions.

Dataset Information

Bone Mineral Density After Transitioning From Denosumab to Alendronate.

Publications

Bone Mineral Density After Transitioning From Denosumab to Alendronate.

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