Osteoporosis with consequent hip fractures causes substantial disability, morbidity and mortality. Teriparatide (TPTD), the aminoterminal fragment of parathyroid hormone, increases 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.

Public Health Relevance

Teriparatide is a potent osteoporosis medication that helps prevent fractures, however, we know little about its effect on the hip. We 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR059204-03
Application #
8242642
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Chen, Faye H
Project Start
2010-05-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
3
Fiscal Year
2012
Total Cost
$368,570
Indirect Cost
$132,326
Name
Helen Hayes Hospital
Department
Type
DUNS #
157119244
City
Menands
State
NY
Country
United States
Zip Code
12204