Combination Risedronate - Parathyroid Hormone Trial in Male Osteoporosis
Condition: Osteoporosis
MeSH terms: Osteoporosis
Intervention: Risedronate; Teriparatide; Placebo Teriparatide; placebo Risedronate
Intervention description: weekly risedronate; daily teriparatide; daily placebo of teriparatide; weekly placebo of Risedronic Acid
Intervention MeSH terms: Teriparatide; Risedronic Acid; Etidronic Acid; Parathyroid Hormone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: Male
Minimum age: 30 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: osteoporosis; male

Summary:

      The purpose of this study is to develop new treatment options for osteoporosis in men. The
      Investigators will study two medications and three treatment regimens. First, risedronate
      (FDA approved) will be studied as monotherapy. Second, the investigators will study
      injectable parathyroid hormone (PTH 134, teriparatide; FDA approved), as a therapy for male
      osteoporosis. PTH, a naturally occurring hormone produced by the parathyroid glands, is one
      of the most important regulators of bone metabolism. The drug being studied in this protocol,
      teriparatide, is the first aminoterminal 34 amino acids of the native 84amino acid peptide.
      Teriparatide contains all of the classical biological activities of native PTH. In studies of
      postmenopausal women, in a small study of 23 men with osteoporosis and a larger study of 437
      men treatment with teriparatide led to significant increases in bone density. Although
      teriparatide and actonel are now approved for osteoporosis in men additional studies of these
      medications are needed in order to establish how best to use these drugs. This study is
      focused on an entirely new treatment approach, namely the combination of two medications for
      the treatment of osteoporosis risedronate with teriparatide to evaluate whether combination
      therapy is superior to therapy with either medication alone. This study is also designed to
      assess the extent to which risedronate maintains increases in bone density after a course of
      mono or combination therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males, ages 30-85 with osteoporosis.

          2. Osteoporosis can be due to hypogonadism, past steroid use, or idiopathic.

          3. Patients with hypogonadism can be included if their replacement dosage of testosterone
             has been stable for at least 18 months.

          4. Bone mineral density must be 2 or more standard deviations below (T-score 2.0) the
             young adult peak for men at the lumbar spine, the hip or the radius.

          5. Normal renal (glomerular filtration rate >= 60 ml/min) and liver (less than or equal
             to twice the normal limits for ALT and AST) function.

        Exclusion Criteria:

          1. Use of any specific osteoporosis drug in the previous 6 months.

          2. Known or suspected metabolic bone diseases (such as renal osteodystrophy,
             osteomalacia) other than osteoporosis.

          3. Preexisting hypercalcemia or an underlying hypercalcemic disorder, such as primary
             hyperparathyroidism.

          4. Secondary hyperparathyroidism.

          5. Paget's disease of bone or fibrous dysplasia. Teriparatide should not be given to
             patients with these conditions due to an increased risk of osteosarcoma.

          6. Patients with any elevations of alkaline phosphatase that are secondary to bone
             disease, as such individuals may be at risk for osteosarcoma.

          7. History or presence of any malignancy, except dermatological, but including melanoma.
             Known or suspected bone metastasis, or a history of skeletal malignancies.

          8. Prior radiation therapy. Patients with prior radiation therapy should be excluded from
             treatment with teriparatide.

          9. Any medical condition, which in the opinion of the investigator could preclude study
             participation, including but not limited to cardiovascular, gastric, renal and hepatic
             disorders, or abnormal PSA test. In particular, patients with active or recent (within
             the last 2 years) urolithiasis will be excluded.

         10. History of previous major bowel surgery including bowel resection.

         11. Oral use of systematic glucocorticoids for two or more weeks in the previous six
             months.

         12. Parenteral use of systemic glucocorticoids on more than two occasions in the previous
             six months.

         13. Use of anticonvulsant drugs.

         14. History of uncontrolled diabetes mellitus (Patient with Type 2 diabetes who have
             HbA1C< 8 are permitted to be enrolled).

         15. Hypercalciuria (> 4 mg/kg/day).

         16. Impaired liver function (>twice the upper normal limits for ALT and AST).

         17. Hyperadrenalism as assessed by physical examination.

         18. Any other clinically significant laboratory abnormalities, which are deemed relevant
             to the design of the protocol.

         19. Patients with known hypersensitivity to any of the test materials (teriparatide or
             risedronate) or related components (metacresol, mannitol, glacial acetic acid, sodium
             acetate).

         20. Use of any investigational or unlicensed drug in the previous 30 days.

         21. Patients who may be unreliable for the study, including those engaging in excessive
             alcohol consumption or drug abuse or patients who are unable to return for scheduled
             follow-up visits.

         22. Patients who are unable or unwilling to comply fully with the protocol.

         23. Inability to stand or sit upright for at least 30 minutes

         24. Those with history of esophagitis, Barrett's esophagus, esophageal/peptic ulcers or
             esophageal motility disorders

         25. Hypocalcaemia

         26. Renal dysfunction (GFR <60)

         27. Patients planning invasive dental work such as implants, extractions or procedures
             involving the jaw bone or patients with poor oral hygiene

         28. Use of digitalis.

         29. Patients with HIV/AIDS.