Phase 4
N=69
Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis
Osteoporosis
Bottom Line
View on ClinicalTrials.gov: NCT01753856 ↗Enrolled (actual)
69
Serious AEs
5.8%
Results posted
Oct 2015
Primary outcome: Primary: Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies — 12.43; -2.51 percentage of BS — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Teriparatide (Drug); Denosumab (Drug); Demeclocycline (Drug); Tetracycline (Drug); Calcium Supplement (Drug); Vitamin D (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- Female
- Sponsor
- Eli Lilly and Company
- Primary completion
- Jun 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies |
12.43; -2.51 | <0.001 sig |
| SECONDARY Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies |
31; 24; 0; 0; 0; 9 | <0.001 sig |
| SECONDARY Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies |
26.12; -2.97; 9.39; -6.70; 2.40; -0.39 | <0.001 sig |
| SECONDARY MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug |
18.73; 0.96; 39.50; 5.42; 21.69; 3.05 | <0.001 sig |
| SECONDARY Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies |
89.02; 90.83; 10.98; 9.17; 83.33; 100.00 | 0.740 |
| SECONDARY Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies |
16.67; 0.87; 2.06; 0.09; 32.92; 5.42 | — |
| SECONDARY Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies |
17.74; 0.00; 21.98; 0.00; 0.00; 0.00 | <0.001 sig |
| SECONDARY Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
0.19; 0.05; 0.25; 0.03; 0.18; 0.02 | <0.001 sig |
| SECONDARY Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
0.00; -0.04; 0.01; -0.06; 0.03; -0.07 | 0.004 sig |
| SECONDARY Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
0.0280; -0.0056; 0.0275; -0.0055; 0.0509; -0.0069 | <0.001 sig |
| SECONDARY Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies |
15.44; 1.28; 10.44; 0.22; 24.24; 7.18 | <0.001 sig |
| SECONDARY Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH) |
-26.89; 72.24; -32.16; 46.68; -40.18; 30.40 | <0.001 sig |
| SECONDARY Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) |
134.38; -11.56; 213.15; -66.64; 284.22; -68.24 | <0.001 sig |
| SECONDARY Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin |
90.53; -6.56; 123.66; -45.70; 187.29; -50.53 | <0.001 sig |
| SECONDARY Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) |
6.09; -90.70; 73.04; -90.77; 89.13; -82.50 | <0.001 sig |
| SECONDARY Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest |
1.41; 0.10; 1.41; 0.06; 2.77; 0.35 | <0.001 sig |
| SECONDARY Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest |
0.58; 0.21; 0.58; 0.14; 0.76; 0.65 | 0.002 sig |
| SECONDARY Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest |
2.58; 0.39 | <0.001 sig |
| SECONDARY Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest |
20.51; 3.46; 30.85; 6.95; 17.81; 4.34 | <0.001 sig |
| SECONDARY Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest |
6.12; 3.78; 6.99; 4.33; 7.08; 4.68 | <0.001 sig |
| SECONDARY Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest |
26.29; 24.03; 31.88; 30.08; 38.25; 37.80 | <0.001 sig |
| SECONDARY Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest |
3.73; 1.52; 3.79; 1.65; 11.19; 1.27 | <0.001 sig |
Summary
The purpose of this study is to determine how teriparatide or denosumab affects the bone of postmenopausal women with osteoporosis after 3 months of treatment, as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis).
Eligibility Criteria
Inclusion Criteria
- Ambulatory, postmenopausal women (no vaginal bleeding for at least 2 years prior to screening) with osteoporosis
- Bone mineral density (BMD) T-score of at least -2.5 at femoral neck (FN), total hip (TH), or lumbar spine (LS) (Lumbar vertebrae L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture after menopause, OR
- BMD T-score of at least -1.5 at FN, TH, or LS (L1-L4, with at least 2 evaluable vertebrae), and 1 or more atraumatic fractures after menopause (vertebral or nonvertebral). Nonvertebral fracture sites allowed are wrist, hip, pelvis, rib, humerus, clavicle, leg (femur, tibia, and fibula, excluding ankle)
- Laboratory values for serum calcium, parathyroid hormone (PTH), and alkaline phosphatase must be within the normal reference range
Exclusion Criteria
- Has an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton
- Has an allergy or intolerance to teriparatide or denosumab and/or is a poor candidate for teriparatide or denosumab treatment (investigator should refer to local product prescribing information)
- Has a history of exposure to DEM or TET therapy in the 12 months prior to screening or a known allergy to DEM or TET
- Has a condition that could put the participant at additional risk of an adverse event (AE) due to the bone biopsy procedure (for example, bleeding disorder)
- Has undergone 2 previous iliac crest bone biopsies (1 in each iliac crest)
- Has a 25-hydroxyvitamin D concentration of <10 nanograms per milliliter (ng/mL)
- Has currently active or suspected (within 1 year prior to enrollment) diseases that affect bone metabolism, other than osteoporosis (such as renal osteodystrophy, hyperthyroidism, osteomalacia, or hyperparathyroidism)
- Has a history of certain cancers within 5 years prior to trial entry
- Current or recent (within 1 year prior to enrollment) celiac disease, inflammatory bowel disease, gastric bypass, or other malabsorption syndrome
- Has significantly impaired hepatic or renal function
- Has had treatment with systemic glucocorticoids in doses ≥5 mg/day prednisone/day or equivalent in the 6 calendar months prior to screening
- Has taken any intravenous osteoporosis medication
- Has had prior treatment with other bisphosphonates and not been off of them for a specific period of time before trial entry
- Has participated in any other clinical trial studying teriparatide, PTH, PTH analog, or denosumab, or prior or current treatment with teriparatide, PTH, PTH analog, or denosumab
Data sourced from ClinicalTrials.gov (NCT01753856). 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.