Clinical trial NCT00927186: Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women
Official title: Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis, Post-menopausal
Keywords: osteoporosis
teriparatide
zoledronic acid
histomorphometry
bone biopsy
postmenopausal
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-06-24
Enrollment: 69
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 Months
measure: Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 24 months
measure: 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
timeFrame: 6 and 24 months
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 24 months
measure: 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
timeFrame: 6 and 24 months
measure: Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months
timeFrame: 6 months
measure: Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months
timeFrame: 24 months
measure: Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months
timeFrame: 6 and 24 months
measure: Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint
timeFrame: Baseline, 1, 3, 6 months
measure: Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint
timeFrame: Baseline, 12 months
measure: Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint
timeFrame: Baseline, 1, 3, 6 months
measure: Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint
timeFrame: Baseline, 12 months
measure: Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint
timeFrame: Baseline, 1, 3, 6 months
measure: Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint
timeFrame: Baseline, 12 months
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Colorado
city: Atlanta
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Georgia
city: Gainesville
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Georgia
city: Bethesda
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Maryland
city: Detroit
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: Omaha
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Nebraska
city: Albuquerque
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: New Mexico
city: West Haverstraw
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: New York
city: Madison
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Wisconsin
city: Calgary
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Alberta
city: Vancouver
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: British Columbia
city: Sainte-Foy
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Dempster DW, Zhou H, Recker RR, Brown JP, Bolognese MA, Recknor CP, Kendler DL, Lewiecki EM, Hanley DA, Rao SD, Miller PD, Woodson GC 3rd, Lindsay R, Binkley N, Alam J, Ruff VA, Gallagher ER, Taylor KA. A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial. J Bone Miner Res. 2016 Jul;31(7):1429-39. doi: 10.1002/jbmr.2804. Epub 2016 Mar 8.