Osteoporosis
Conditions
Keywords
bone biopsy, tetracycline, demeclocycline, total hip replacement
Brief summary
The primary objective of this study is to determine the incidence of modeling-based bone formation in the femoral neck in participants who have received denosumab and are undergoing total hip replacement (THR).
Interventions
OTHERTetracycline
Treatment during cycle 1 consists of a total oral dose of 1000 mg of tetracycline daily for a total of 3 days.
OTHERDemeclocycline
Treatment during cycle 2 consists of a total oral dose of 600 mg of demeclocycline daily for 3 days.
PROCEDURETotal Hip Replacement
Participants entering this study were prescheduled to undergo elective THR due to osteoarthritis. Surgery was to be performed according to local standard of care. During THR a fragment of femoral bone was acquired for histomorphometry evaluation.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures * Ambulatory postmenopausal women and men with osteoporosis * Scheduled to undergo elective THR due to osteoarthritis of the hip * Received at least 2 doses of denosumab 60 mg subcutaneously over 18 months * Last dose of denosumab within 6 months of scheduled THR
Exclusion criteria
* Received treatment for osteoporosis other than denosumab in one year prior to THR * Subjects with current diagnosis of any of the following conditions are excluded * Current, uncontrolled hypo- or hyperthyroidism (subjects who have controlled hypo- or hyperthyroidism may be eligible, provided that they have been on a stable therapy for at least 3 months \[per subject report\]) * Current, hypo- or hyperparathyroidism * Osteomalacia * Paget's disease of bone * Other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta) * Severe chronic kidney disease (CKD), defined as CKD stage 4 or greater * Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma) * Self-reported alcohol or drug abuse within the previous 12 months * Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) * Other investigational procedures while participating in this study are excluded * Subject has known sensitivity to any of the products to be administered (eg, tetracycline, demeclocycline) during study * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck | Days 22-58 (at the time of hip replacement surgery) | Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The percentage of participants with fluorochrome labeling present in the cancellous or periosteal, or endocortical surfaces of the femoral neck indicative of modeling-based bone formation is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modeling Based Formation Units in the Femoral Neck | Days 22-58 (at the time of hip replacement surgery) | Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The number of modeling based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface. |
| Overfilled Remodeling-based Formation Units in the Femoral Neck | Days 22-58 (at the time of hip replacement surgery) | Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling-based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of overfilled remodeling-based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported as units per mm of bone surface. |
| Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck | Days 22-58 (at the time of hip replacement surgery) | Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of remodeling based formation units including overfilled units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at one center in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Osteoarthritis Participants Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after the last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Osteoarthritis Participants |
|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The percentage of participants with fluorochrome labeling present in the cancellous or periosteal, or endocortical surfaces of the femoral neck indicative of modeling-based bone formation is reported.
Time frame: Days 22-58 (at the time of hip replacement surgery)
Population: All enrolled participants who had an evaluable biopsy for fluorochrome labeling.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osteoarthritis Participants | Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck | 100 percentage of participants |
Secondary
Modeling Based Formation Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The number of modeling based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time frame: Days 22-58 (at the time of hip replacement surgery)
Population: Enrolled participants who had an evaluable biopsy for fluorochrome labeling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Osteoarthritis Participants | Modeling Based Formation Units in the Femoral Neck | Cancellous Region | 0.1455 units/mm | Standard Deviation 0.2097 |
| Osteoarthritis Participants | Modeling Based Formation Units in the Femoral Neck | Endocortical Region | 0.2223 units/mm | Standard Deviation 0.2306 |
| Osteoarthritis Participants | Modeling Based Formation Units in the Femoral Neck | Periosteal Region | 0.1990 units/mm | Standard Deviation 0.1409 |
Secondary
Overfilled Remodeling-based Formation Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling-based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of overfilled remodeling-based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported as units per mm of bone surface.
Time frame: Days 22-58 (at the time of hip replacement surgery)
Population: Enrolled participants who had an evaluable biopsy for fluorochrome labeling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Osteoarthritis Participants | Overfilled Remodeling-based Formation Units in the Femoral Neck | Cancellous Region | 0.0038 units/mm | Standard Deviation 0.0062 |
| Osteoarthritis Participants | Overfilled Remodeling-based Formation Units in the Femoral Neck | Endocortical Region | 0.0108 units/mm | Standard Deviation 0.0138 |
| Osteoarthritis Participants | Overfilled Remodeling-based Formation Units in the Femoral Neck | Periosteal Region | 0.0000 units/mm | Standard Deviation 0 |
Secondary
Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility. Remodeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of remodeling based formation units including overfilled units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time frame: Days 22-58 (at the time of hip replacement surgery)
Population: Enrolled participants who had an evaluable biopsy for fluorochrome labeling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Osteoarthritis Participants | Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck | Cancellous Region | 0.0285 units/mm | Standard Deviation 0.0174 |
| Osteoarthritis Participants | Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck | Endocortical Region | 0.0323 units/mm | Standard Deviation 0.0318 |
| Osteoarthritis Participants | Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck | Periosteal Region | 0.0033 units/mm | Standard Deviation 0.0065 |