This is a three-year study to evaluate the effect of sequential therapy of Forteo (teriparatide) and denosumab on bone density at the spine, hip, leg and forearm.

In order to maximize the early anabolic effect with teriparatide (TPTD), and to avoid the development of tachyphylaxis to the continued daily administration of TPTD beyond 6 months, cyclic therapy might be optimal. Since Denosumab (Prolia) is a potent antiresorptive agent with a rapid off-effect, it might be the optimal agent to help maximize bone gains with cyclic TPTD/antiresorptive therapy. Our primary hypothesis is that the increment in bone density of the spine by DXA will be greater in women randomized to receive the cyclic sequential regimen (three separate 6 month cycles of daily subcutaneous TPTD, each followed by one subcutaneous injection of Denosumab) compared with daily sequential therapy (18 months of daily subcutaneous TPTD followed by Denosumab therapy for 18 months).

Inclusion Criteria:Subjects should be postmenopausal >age 45, and of any racial origin. They must not be on any osteoporosis medication. They should be willing to participate for the duration of the study and have no physical or psychological illness that would prohibit them from participating. Pregnant women, protected individuals (institutionalized), and those unable to give informed consent will not be recruited. Exclusion criteria are detailed below.

Subjects who meet initial pre-screening criteria will present for an on site screening visit and have a full medical history, brief physical exam, BMD and lab evaluation to confirm eligibility. Osteoporosis will be defined by DXA BMD T-Score < -2.5 at lumbar spine (at least 2 evaluable vertebrae between L1 and L4), or total hip or femoral neck. In addition, women with confirmed vertebral deformity on radiograph or lateral DXA image, or prior osteoporosis-related fracture at age >45 along with a DXA BMD T-Score < -1.5 at one or more skeletal sites will be eligible to participate.

Exclusion Criteria:

• The use of drugs known to affect skeletal or calcium homeostasis.

• Multiple vertebral fractures or severe lumbar degenerative changes with fewer than 2 evaluable lumbar vertebrae

• Current use of anti-resorptive medicines

  • Use of Hormone/Estrogen Therapy, raloxifene or calcitonin within the past 3 months
  • Use of oral bisphosphonate for more than 4 months within the past 2 years or more than 5 years total cumulative bisphosphonate use in the past 10 years
  • Use of intravenous ibandronate within the past 18 months
  • Use of intravenous zoledronic acid within the past 4 years
  • A history of a symptomatic renal stone within the past 3 years or history of multiple symptomatic renal stones
  • Skeletal Disorders other than osteoporosis including: Hypercalcemia, hyperparathyroidism, Paget's Disease or osteomalacia
  • Untreated or uncontrolled thyroid disease
  • Elevated Bone Specific Alkaline Phosphatase level
  • History of external or internal radiation therapy
  • Renal insufficiency with estimated GFR below 30 ml/min
  • Liver function tests (ALT/AST) more than 1.5 times the upper limit of normal
  • Clinically significant hyperuricemia or active gout
  • Any contraindications to receipt of Teriparatide or Denosumab (including hypocalcemia)
  • History of an atypical fracture of the femoral shaft