Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial

J Clin Endocrinol Metab. 2011 Feb;96(2):394-402. doi: 10.1210/jc.2010-1805. Epub 2010 Dec 15.

Abstract

Context: This is a study extension to evaluate the efficacy and safety of long-term treatment with denosumab in postmenopausal women with low bone mass.

Objective: Our objective was to describe changes in bone mineral density (BMD) and bone turnover markers as well as safety with 6 yr of denosumab treatment.

Design: We conducted an ongoing 4-yr, open-label, single-arm, extension study of a dose-ranging phase 2 trial. This paper reports a 2-yr interim analysis representing up to 6 yr of continuous denosumab treatment.

Setting: This multicenter study was conducted at 23 U.S. centers.

Patients: Of the 262 subjects who completed the parent study, 200 enrolled in the study extension and 178 (89%) completed the first 2 yr.

Intervention: All subjects received denosumab 60 mg sc every 6 months.

Main outcome measures: We evaluated BMD at the lumbar spine, total hip, femoral neck, and one third radius; biochemical markers of bone turnover; and safety, reported as adverse events.

Results: Over a period of 6 yr, continuous treatment with denosumab resulted in progressive gains in BMD in postmenopausal women with low bone mass. Reduction in bone resorption was sustained over the course of continuous treatment. Independent of past treatment and discontinuation period, subjects demonstrated responsiveness to denosumab therapy as measured by BMD and bone turnover markers. The safety profile of denosumab did not change over time.

Conclusions: In this study, denosumab was well tolerated and effective through 6 yr of continuous treatment in postmenopausal women with low bone mass.

Trial registration: ClinicalTrials.gov NCT00325468.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alendronate / therapeutic use
  • Alkaline Phosphatase / blood
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone and Bones / drug effects
  • Bone and Bones / enzymology
  • Bone and Bones / metabolism*
  • Cohort Studies
  • Denosumab
  • Female
  • Hip / diagnostic imaging
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / pathology
  • RANK Ligand / adverse effects
  • RANK Ligand / metabolism
  • RANK Ligand / therapeutic use*
  • Radiography
  • Radius / diagnostic imaging
  • Spine / diagnostic imaging

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Bone Density Conservation Agents
  • RANK Ligand
  • Denosumab
  • Alkaline Phosphatase
  • Alendronate

Associated data

  • ClinicalTrials.gov/NCT00325468