Early Effects of Parathyroid Hormone (PTH) on the Proximal Femur

NCT ID: NCT01309399

Last Updated: 2016-11-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2015-08-31

Brief 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.

Conditions

Osteoporosis

Keywords

bone formation rate; total hip arthroplasty

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

teriparatide

six weeks of teriparatide

Group Type: ACTIVE_COMPARATOR

Teriparatide

Intervention Type: DRUG

six weeks of teriparatide

placebo

placebo identical in appearance to teriparatide

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

placebo

Interventions

Teriparatide

six weeks of teriparatide

Intervention Type: DRUG

placebo

placebo

Intervention Type: OTHER

Other Intervention Names

forteo

Eligibility Criteria

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).

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospital for Special Surgery, New York

OTHER

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Health Research, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Felicia Cosman, M.D.

Medical Director, Clinical Research Center, Helen Hayes Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felicia Cosman, M.D.

Role: PRINCIPAL_INVESTIGATOR

Helen Hayes Hospital

Locations

Helen Hayes Hospital

West Haverstraw, New York, United States

Countries

United States

Other Identifiers

R01AR059204-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-09

Identifier Type: -

Identifier Source: org_study_id