Bone Histomorphometry in Postmenopausal Men and Women With Osteoarthritis Undergoing Total Hip Replacement

Study Overview
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Brief Summary
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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).

Official Title
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Bone Histomorphometry of the Proximal Femur in Denosumab-treated Subjects Undergoing Total Hip Replacement

Conditions
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Osteoporosis

Intervention / Treatment
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* Other: Tetracycline
* Other: Demeclocycline
* Procedure: Total Hip Replacement


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Osteoarthritis Participants<br>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 last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline. | Other: Tetracycline<br>* Treatment during cycle 1 consists of a total oral dose of 1000 mg of tetracycline daily for a total of 3 days.<br>Other: Demeclocycline<br>* Treatment during cycle 2 consists of a total oral dose of 600 mg of demeclocycline daily for 3 days.<br>Procedure: Total Hip Replacement<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 22-58 (at the time of hip replacement surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 22-58 (at the time of hip replacement surgery) | 
| 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. | Days 22-58 (at the time of hip replacement surgery) | 
| 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. | Days 22-58 (at the time of hip replacement surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone biopsy, tetracycline, demeclocycline, total hip replacement