Early Effects of Parathyroid Hormone (PTH) on the Proximal Femur
Condition: Osteoporosis
MeSH terms: Osteoporosis
Study type: Interventional

Summary: 
      Teriparatide is a potent osteoporosis medication that helps prevent fractures, however, the
      investigators know little about its effect on the hip. The investigators will evaluate hip
      bone samples from patients treated with teriparatide before undergoing hip replacement. The
      information will help us understand how teriparatide might help reduce hip fracture risk.
    

Detailed description: 
      Osteoporosis with consequent hip fractures causes substantial disability, morbidity and
      mortality. Teriparatide (TPTD), the aminoterminal fragment of parathyroid hormone (PTH),
      increases bone mineral density (BMD) and bone strength and reduces fracture incidence
      throughout the skeleton, but data confirming specific efficacy against hip fracture will
      never be available. Histomorphometric studies after 18-36 months of TPTD treatment show
      improvements in bone volume and structure in the iliac crest. Both biochemical and
      histomorphometric investigations of the iliac crest at very early time points (within 4-6
      weeks of administration) show that bone formation is dramatically stimulated. Apart from the
      beneficial effect of TPTD on bone density and bone strength by finite element analysis at the
      hip, nothing is known about the mechanism of the effect of TPTD on the proximal femur. While
      BMD changes are smaller and slower in the hip in response to TPTD than in the spine, it is
      possible that stimulation of bone formation on the periosteal bone surface could result in
      expansion of bone size, obscuring the increase in non-invasively measured BMD. The current
      study will provide evidence for or against this possible TPTD-induced periosteal expansion.
      From a clinical perspective, it is unclear whether TPTD would be preferable to other
      osteoporosis medications, such as zoledronic acid, in patients at high risk for hip fracture.
      TPTD induced bone formation in the femur would be expected to improve bone strength and would
      provide a mechanistic basis for the use of TPTD in patients at high risk of hip fracture. The
      proposed project is the only practical and ethical way to obtain information on the effects
      of TPTD on bone formation in the proximal femur in humans. In patients undergoing total hip
      arthroplasty (THA) for degenerative joint disease, the hip samples of greatest interest are
      extracted routinely during the procedure. At the same time, an iliac crest biopsy can be
      taken with minimal added time and risk. The protocol has the following Specific Aims:

      In patients undergoing elective, noncemented total hip arthroplasty (THA): 1. To determine
      the early effects of 1-34hPTH (teriparatide; TPTD 20 mcg) vs placebo, administered
      subcutaneously daily for 6 weeks, on histomorphometric indices of bone formation in
      cancellous and cortical bone of the proximal femur (femoral neck and intertrochanteric bone)
      and iliac crest. 2. To evaluate the association between changes in biochemical indices of
      bone turnover and histomorphometric indices of bone formation in the proximal femur (femoral
      neck and intertrochanteric bone) and iliac crest over 6 weeks of treatment with TPTD vs.
      placebo. 3. To determine if circulating osteoblast precursor cells increase over 6 weeks of
      treatment with TPTD vs Placebo and to compare the change in size of this osteoblast precursor
      pool with the change in a biochemical marker of bone formation and indices of bone formation
      in the femur and iliac crest.
    

Intervention name(s): Teriparatide; placebo
Intervention type(s): Drug; Other
Intervention description(s): six weeks of teriparatide; placebo
Other intervention name(s): forteo
Intervention MeSH terms: Teriparatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: bone formation rate; total hip arthroplasty