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

Phase 4

Completed

Conditions: Osteoporosis

Interventions: Other: Tetracycline
Other: Demeclocycline
Procedure: Total Hip Replacement

Registration Number: NCT02576652

Lead Sponsor: Amgen

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Osteoarthritis Participants	Demeclocycline	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.
Osteoarthritis Participants	Total Hip Replacement	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.
Osteoarthritis Participants	Tetracycline	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.