Bisphosphonates for Prevention of Post-Denosumab Bone Loss
Condition: IOP; Osteoporosis
MeSH terms: Osteoporosis
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary goal of the study is to assess the extent to which bisphosphonate therapy will
      prevent decreases in bone mass that may occur after cessation of denosumab in premenopausal
      women with idiopathic osteoporosis (IOP) enrolled in AAAN0161 (FD05114) "Denosumab for the
      prevention of post-teriparatide bone loss in premenopausal women with idiopathic
      osteoporosis".

      In addition, the investigator will observe participants for a second year off bisphosphonate
      therapy to assess duration of response.

      The hypothesis is that bisphosphonate therapy with alendronate or zoledronic acid, initiated
      after recovery of bone remodeling activity, will prevent significant bone loss after
      discontinuing denosumab.
    

Detailed description: 
      Osteoporosis in premenopausal women with normal menstrual function and no specific cause is
      termed idiopathic osteoporosis (IOP). IOP is a rare disease with an estimated prevalence of
      <200,000 affected premenopausal women in the United States.

      Women with IOP completing at least one year and up to three years of denosumab (Protocol
      AAAN0161) will be offered participation in this open-label study in which they would choose
      whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of
      zoledronic acid 5 mg. Subjects and study personnel will be blinded to BMD outcomes until 12
      months.

      Discontinuation of denosumab is followed by substantial increases in bone turnover markers to
      well above baseline, bone resorption reaching twice baseline levels for about 6 months. Over
      the first 12 months off therapy, all the bone density gained on treatment is lost. Studies
      done at the institution has demonstrated the occurrence of multiple vertebral fractures in
      some patients who have stopped denosumab. Based upon these new fracture data, the Prolia
      label is currently recommending that consideration should be given to transition to another
      antiresorptive drug in patients stopping denosumab. The main goals of this extension study
      are to determine rates of bone loss and incidence of radiographic vertebral fractures during
      one year of bisphosphonate therapy (oral alendronate or intravenous zoledronic acid)
      initiated after completing denosumab.
    

Intervention name(s): Alendronate; Zoledronic Acid
Intervention type(s): Drug; Drug
Intervention description(s): oral alendronate 70 mg weekly for 12 months will be given for the prevention of osteoporosis; single intravenous dose of zoledronic acid 5 mg will be given for the prevention of osteoporosis
Other intervention name(s): fosamax; Reclast
Intervention MeSH terms: Zoledronic Acid; Alendronate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: premenopausal women