RA Denosumab on Bone Microstructure Study
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to compare the effects of denosumab and a current standard treatment
      on cortical and trabecular microarchitecture at the radius and second metacarpal in
      rheumatoid arthritis (RA) patients with low bone mineral density using high resolution
      peripheral quantitative computed tomography (HR-pQCT) during a 6-month open-label randomized
      controlled study. Forty ambulatory Chinese females, who consent to receive alendronate as
      standard treatment subjective to the randomization, will be enrolled in this study. Subjects
      will be randomized to 2 arms receiving: 1) subcutaneous injection of denosumab 60mg (Prolia®)
      every 6 months (n=20), or 2) oral alendronate weekly (Fosamax® once weekly 70 mg, n=20). In
      addition, all patients will be given a daily calcium supplement (1500mg caltrate /day) and 1
      multivitamin tablet per day. Efficacy and safety assessment will be performed at baseline,
      month 3 and month 6. aBMD of lumbar spine, total hip and non-dominant distal radius will be
      measured using dual-energy X-ray absorptiometry (DXA) and microarchitecture of bone is
      measured at the non-dominant distal radius and the second metacarpal bone of the non-dominant
      hand using HR-pQCT.
    

Detailed description: 
      Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease most typical in women.
      Generalized osteoporosis is common in RA, at axial and appendicular skeleton and in females
      and males. Denosumab is a fully humanized IgG monoclonal antibody that targets the receptor
      activator of nuclear factor κB ligand (RANKL). Denosumab prevents the binding and activation
      of the RANK receptors on the osteoclasts and hence inhibits osteoclasts formation,
      activation, function and survival. Denosumab results in more rapid and greater reductions in
      bone remodeling and correspondingly greater increases in areal bone mineral density (aBMD) at
      all skeletal sites. Denosumab was approved by FDA in June 2010 for the treatment of
      postmenopausal women with osteoporosis at high risk of fracture. Denosumab (Prolia®) is also
      licensed in Hong Kong.

      A high-resolution peripheral quantitative computed tomography (HR-pQCT) capable of achieving
      an isotropic voxel size of 80μm at tolerable radiation doses (3μSv) is available for the
      assessment of trabecular and cortical microarchitecture at the distal radius and tibia. This
      technique bears excellent precision for both density and microstructure measures. Denosumab's
      greater potency in suppressing bone remodeling and greater effect on areal BMD than
      alendronate, particularly at predominantly cortical sites such as the distal third of the
      radius, may reflect the differing mechanism of action of these drugs, which, in turn,
      influence bone microarchitecture.

      The aim of this study is to compare the effects of denosumab and a current standard treatment
      on cortical and trabecular microarchitecture at the radius and second metacarpal in RA
      patients with low bone mineral density using HR-pQCT during a 6-month open-label randomized
      controlled study. One bisphosphonate, namely alendronate sodium (or alendronate) is chosen to
      generate a heterogeneous and comparable active control group. This is a 6-month open-label
      randomized controlled clinical trial. Forty ambulatory Chinese females, who consent to
      receive alendronate as standard treatment subjective to the randomization, will be enrolled
      from the rheumatology clinic of the Prince of Wales Hospital in this study. Subjects will be
      randomized to 2 groups receiving: 1) subcutaneous injection of denosumab 60mg (Prolia®) every
      6 months (n=20), or 2) a standard treatment: oral alendronate weekly (Fosamax® once weekly 70
      mg, n=20). In addition, all patients will be given a daily calcium supplement (1500mg
      caltrate /day) and 1 multivitamin tablet per day. Efficacy and safety assessment will be
      performed at baseline, month 3 and month 6. aBMD of lumbar spine, total hip and non-dominant
      distal radius will be measured using dual-energy X-ray absorptiometry (DXA) and
      microarchitecture of bone is measured at the non-dominant distal radius and the second
      metacarpal bone of the non-dominant hand using HR-pQCT.
    

Intervention name(s): Denosumab; Alendronate
Intervention type(s): Drug; Drug
Intervention description(s): Subcutaneous injection of denosumab 60mg every 6 months (1 dose for study period); Alendronate 70mg once weekly
Other intervention name(s): Prolia®; Fosamax®
Intervention MeSH terms: Denosumab; Alendronate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rheumatoid arthritis; Bone density; Bone microarchitecture; HR-pQCT