Phase 4
N=69
Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women
Osteoporosis, Post-menopausal
Bottom Line
View on ClinicalTrials.gov: NCT00927186 ↗Enrolled (actual)
69
Serious AEs
7.2%
Results posted
Mar 2012
Primary outcome: Primary: Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months — 5.60; 0.16 percentage of surface — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Teriparatide (Drug); Zoledronic Acid (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- Female
- Sponsor
- Eli Lilly and Company
- Primary completion
- Oct 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
5.60; 0.16 | <0.001 sig |
| SECONDARY Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
3.00; 0.07 | 0.002 sig |
| SECONDARY Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
18.64; 0.30; 5.82; 0.00 | <0.001 sig |
| SECONDARY Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.37; 0.01; 0.37; 0.01 | <0.001 sig |
| SECONDARY Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.19; 0.00; 0.18; 0.00 | 0.002 sig |
| SECONDARY Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.83; 0.00; 0.83; 0.01; 0.25; 0.00 | <0.001 sig |
| SECONDARY Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.0116; 0.0002; 0.0116; 0.0002 | <0.001 sig |
| SECONDARY Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.0057; 0.0000; 0.0057; 0.0001 | 0.002 sig |
| SECONDARY Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.0307; 0.0000; 0.0307; 0.0003; 0.0093; 0.0000 | <0.001 sig |
| SECONDARY Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.56; 0.35; 0.56; 0.33 | <0.001 sig |
| SECONDARY Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.44; 0.00; 0.43; 0.30 | 0.020 sig |
| SECONDARY Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.50; 0.00; 0.50; 0.30; 0.43; 0.00 | <0.001 sig |
| SECONDARY Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.34; 0.02; 0.34; 0.02 | <0.001 sig |
| SECONDARY Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.13; 0.00; 0.12; 0.02 | 0.050 |
| SECONDARY Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.41; 0.00; 0.41; 0.03; 0.35; 0.00 | <0.001 sig |
| SECONDARY Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
13.63; 75.72; 13.63; 75.72 | <0.001 sig |
| SECONDARY Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
38.84; 45.67; 45.33; 128.37 | 0.906 |
| SECONDARY Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
12.63; 26.97; 12.63; 26.70; 15.67; 42.86 | 0.049 sig |
| SECONDARY Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
9.99; 9.05; 9.99; 9.05 | 0.502 |
| SECONDARY Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
13.42; 17.38; 13.52; 13.92 | 0.077 |
| SECONDARY Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
10.57; 11.27; 10.57; 11.34; 12.30; 14.94 | 0.647 |
| SECONDARY Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.24; 1.46; 0.24; 1.46 | <0.001 sig |
| SECONDARY Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.60; 0.51; 0.68; 2.62 | 1.00 |
| SECONDARY Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.24; 0.43; 0.24; 0.54; 0.27; 0.62 | 0.022 sig |
| SECONDARY Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months |
0.15; 0.16; 0.15; 0.16 | 0.154 |
| SECONDARY Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months |
0.19; 0.19; 0.19; 0.25 | 0.906 |
| SECONDARY Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.20; 0.20; 0.20; 0.28; 0.23; 0.22 | 0.979 |
| SECONDARY Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
3.19; 0.02; 4.13; 0.07 | <0.001 sig |
| SECONDARY Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
2.25; 0.15; 1.69; 0.00 | 0.006 sig |
| SECONDARY Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
5.56; 0.25; 13.46; 0.00; 3.75; 0.00 | <0.001 sig |
| SECONDARY Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
0; 12; 0; 2; 0; 3 | <0.001 sig |
| SECONDARY Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
0; 4; 1; 3; 0; 0 | 0.033 sig |
| SECONDARY Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
0; 14; 0; 9; 0; 0 | <0.001 sig |
| SECONDARY Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
0.35; 0.24 | 0.002 sig |
| SECONDARY Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
0.23; 0.29 | 0.906 |
| SECONDARY Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
0.34; 0.30; 0.27; 0.30 | 0.536 |
| SECONDARY Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
1.32; 0.24 | <0.001 sig |
| SECONDARY Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
1.33; 0.18 | 0.002 sig |
| SECONDARY Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
11.34; 2.51 | <0.001 sig |
| SECONDARY Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
11.19; 1.26 | 0.008 sig |
| SECONDARY Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
16.33; 1.87; 7.48; 1.55 | <0.001 sig |
| SECONDARY Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
4.92; 3.77 | <0.001 sig |
| SECONDARY Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
5.71; 3.98 | 0.079 |
| SECONDARY Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
4.94; 3.70; 5.23; 3.53 | <0.001 sig |
| SECONDARY Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
31.29; 28.63 | 0.014 sig |
| SECONDARY Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
31.37; 29.26 | 0.079 |
| SECONDARY Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
36.30; 32.39; 34.00; 32.45 | 0.027 sig |
| SECONDARY Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months |
4.59; 2.71 | <0.001 sig |
| SECONDARY Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months |
4.44; 2.39 | 0.025 sig |
| SECONDARY Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months |
4.06; 1.87; 3.43; 1.88 | 0.012 sig |
| SECONDARY Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint |
0.06; -0.37; 0.26; -0.35; 0.31; -0.32 | <0.001 sig |
| SECONDARY Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint |
0.42; -0.23 | <0.001 sig |
| SECONDARY Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint |
65.50; -15.00; 66.00; -39.00; 84.00; -37.50 | <0.001 sig |
| SECONDARY Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint |
93.50; -33.00 | <0.001 sig |
| SECONDARY Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint |
22.35; -3.39; 29.93; -12.30; 30.85; -14.06 | <0.001 sig |
| SECONDARY Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint |
32.98; -12.32 | <0.001 sig |
Summary
The purpose of this study is to investigate how teriparatide or zoledronic acid affects the bone of postmenopausal osteoporotic women after 6 months of treatment as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis). After completing 12 months of treatment all participants are eligible to participate in an additional 12-month open label extension.
Eligibility Criteria
Inclusion Criteria
- Ambulatory, postmenopausal women with osteoporosis (no vaginal bleeding for at least 2 years prior to trial entry)
- Free of severe or chronically disabling conditions other than osteoporosis that will impair ability to complete the trial
- Bone mineral density (BMD) T-score of at least -2.5 at the femoral neck, total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture or,
- Bone mineral density (BMD) T-score of at least -1.5 at the femoral neck, or total hip, or lumbar spine (L1-L4, with at least 2 evaluable vertebrae), and either 1 or more atraumatic vertebral fracture(s) or an atraumatic nonvertebral fracture in the opinion of the investigator. Nonvertebral fracture sites allowed are wrist, hip, pelvis, ribs, humerus, clavicle, leg (femur, tibia, and fibula, excluding the ankle).
- Serum calcium, parathyroid hormone (PTH), alkaline phosphatase must be within normal reference range
Exclusion Criteria
- Have an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton
- Are allergic or cannot tolerate teriparatide or zoledronic acid or any of their ingredients or components
- Are allergic to tetracycline
- Have a history of exposure to tetracycline therapy in the 3 months prior to trial entry
- Have participated in a prior PTH clinical trial or received prior treatment with teriparatide, PTH, or other related medications
- Have a vitamin D level below 10 nanogram/milliliter (ng/mL)
- Have a condition that could possibly put one at risk for an adverse event due to the bone biopsy procedure (e.g. bleeding disorder)
- Have undergone two previous iliac crest bone biopsies (one in each iliac crest)
- Have taken any intravenous (IV) osteoporosis medication
- Have taken other oral osteoporosis medications and have not been off of them for a specific period of time before trial entry
- Have a history of certain cancers in the 5 years prior to trial entry
- Have active liver disease
- Have significantly impaired kidney function
- Currently have active or suspected diseases that affect the bones, other than osteoporosis
- Have active or recent history of significant gastrointestinal (stomach or intestinal) disorders
- Have been treated with certain glucocorticoids for more than 30 days in the past 1 year prior to trial entry
Data sourced from ClinicalTrials.gov (NCT00927186). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.