Nitrates and Bone Turnover; Nitrates and Bone Turnover Bisphosphonate Sub-Study
Condition: Osteoporosis
MeSH terms: Osteoporosis
Intervention: Nitrates (NABT Main trial); Placebo
Intervention description: nitroglycerin; isosorbide mononitrate; Placebo ointment
Intervention MeSH terms: Nitroglycerin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 265.0
Sex: Female
Minimum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: postmenopausal; osteoporosis; bone turnover; nitrate; headache

Summary:

      Purpose: NABT: To compare five widely available nitrate formulations: (1) 15 of nitroglycerin
      (NTG) ointment, (2) 0.3 mg and (3) 0.6 mg of sublingual NTG, (4) 20 mg of isosorbide
      mononitrate (an oral tablet), and (5) 160 mg of glycerol trinitrate (a patch), for their
      efficacy on markers of bone formation and resorption and for the incidence and severity of
      headache they cause.

      Hypothesis: There is one ideal nitrate preparation which balances the clinical efficacy in
      bone remodeling against the common side effect of headache.

      NABT-B: To determine if nitrates affect markers of bone formation (serum BALP and P1NP) and
      resorption (serum CTX and urine NTX) in women who have recently discontinued treatment with
      alendronate, risedronate or zoledronate.
    

Eligibility criteria:

        Inclusion Criteria:

        NABT:

          -  Women aged 50 years and older whose last menstrual period occurred at least 3 years
             ago

          -  Women without a uterus will be eligible after age 55

        NABT-B:

          -  Women aged 50 years and older whose last menstrual period occurred at least 3 years
             ago

          -  Women without a uterus will be eligible after age 55

          -  Previously treated with alendronate but stopped within 2 years of study commencement;
             or previously treated with risedronate but stopped within 1 year of study
             commencement; or previously treated with zoledronate.

        Exclusion Criteria:

        NABT:

          -  A previous fracture of the hip, wrist, spine or ankle within the last 3 months; or a
             diagnosis of osteoporosis;

          -  A history of bone disorders such as hyperparathyroidism or Paget's disease;

          -  Treatment within 12 months of study entry with any agent that may influence bone
             metabolism including any hormone, anti-estrogen or raloxifene and prednisone
             (equivalent to 5 mg/d for 12 months or greater);

          -  Treatment with any antiresorptive agent, including alendronate, risedronate,
             etidronate or denosumab use for at least four weeks within the last three years;

          -  Previous treatment with intravenous zoledronate or parathyroid hormone;

          -  Current treatment with nitrates;

          -  A history of migraine headaches;

          -  A history of angina or cardiovascular disease;

          -  Inability to give informed consent;

          -  Hypersensitivity to nitroglycerin.

        NABT-B:

          -  A previous fracture of the hip, wrist, spine or ankle; or a self-reported diagnosis of
             osteoporosis;

          -  A history of bone disorders such as hyperparathyroidism or Paget's disease;

          -  Treatment within 12 months of study entry with any agent that may influence bone
             metabolism including any hormone, anti-estrogen or raloxifene and prednisone
             (equivalent to 5 mg/d for 12 months or greater);

          -  Treatment with etidronate or denosumab use for at least four weeks within the last
             three years and any previous treatment with parathyroid hormone;

          -  Current treatment with nitrates;

          -  A history of migraine headaches;

          -  A history of angina or cardiovascular disease;

          -  Inability to give informed consent;

          -  Hypersensitivity to nitroglycerin.