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

Osteoporosis Clinical Trial

Official title:

Early Effects of PTH on the Proximal Femur

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01309399
• Other study ID #: 09-09
• Secondary ID: R01AR059204-01
• Status: Completed
• Phase: N/A
• First received: March 4, 2011
• Last updated: November 22, 2016
• Start date: August 2010
• Est. completion date: August 2015

Study information

• Verified date: November 2016
• Source: Health Research, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 2015
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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).

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• Teriparatide
six weeks of teriparatide

Other:
• placebo
placebo

Locations

Country	Name	City	State
United States	Helen Hayes Hospital	West Haverstraw	New York

Sponsors (3)

Lead Sponsor	Collaborator
Health Research, Inc.	Hospital for Special Surgery, New York, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone formation rate	At the time of surgery, the femoral neck and a small piece of bone will be obtained and measured for indices of bone formation in the femur and iliac crest in both placebo or teriparatide groups.	6 weeks
Secondary	Blood samples will be analyzed for indices of bone formation (serum P1NP) and resorption (serum CTX) after treatment with placebo or teriparatide Biochemical markers of bone	Blood samples will be analyzed for indices of bone formation (serum P1NP) and resorption (serum CTX) after treatment with placebo or teriparatide	six weeks