Early Effects of Parathyroid Hormone (PTH) on the Proximal Femur
Early Effects of Parathyroid Hormone (PTH) on the Proximal Femur
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.
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.
Inclusion Criteria:

 -  Age 50-90 years old.

 -  Male or postmenopausal (women who have had no menses for one year)

 -  Degenerative joint disease of the hip (osteoarthritis) requiring total hip
 arthroplasty, based on radiologic and clinical impression.

 Exclusion Criteria:

 -  Any contraindications to use of TPTD.

 -  Age younger than 50, greater than 90 years old.

 -  Metabolic bone disease other than osteoporosis.

 -  History of hyperparathyroidism without surgical correction.

 -  Unexplained hypercalcemia.

 -  Paget's disease (or unexplained elevated bone alkaline phosphatase level).

 -  History of any metastatic cancer or osteosarcoma.

 -  Prior radiation treatment.

 -  Secondary hyperparathyroidism due to vitamin D deficiency or renal disease. Active
 hyperthyroidism or excessive thyroid hormone replacement (with TSH below normal
 range).