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Completed

NCT Number: NCT00887965

A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab

To characterize the effects of discontinuation of denosumab therapy on variables of bone histology in postmenopausal women with low bone mass or osteoporosis. Patients who have received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341) will be included in this study. Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) are also eligible.

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Key information

Conditions

Low Bone Mass Bone Diseases Bone Diseases, Metabolic Low Bone Mineral Density Metabolic Diseases Musculoskeletal Diseases Nutritional and Metabolic Diseases Osteoporosis Osteoporosis, Postmenopausal Postmenopausal Osteoporosis

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Ambulatory postmenopausal women
  • Received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341). Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) also are eligible.
  • Completed participation in eligible studies ≥ 12 and ≤ 36 months prior to screening
  • Provide signed informed consent

Exclusion criteria

  • Did not receive denosumab in studies 20050141, 20060237, 20030216, or 20050179.
  • Discontinued investigational product before end of study visit for studies 20050141, 20060237, 20030216, or 20050179.
  • Received > 1 month osteoporosis treatment since having completed studies 20050141, 20060237, 20030216, or 20050179.
  • Received zoledronic acid at any time after ending study participation in parent studies 20050141, 20050179, 20030216, or 20060237.
  • Newly diagnosed with any of the following conditions during the intervening period since completing studies 20050141, 20060237, 20030216, or 20050179:
  • Hyperthyroidism (stable on anti-thyroid therapy or post-ablation is allowed, if the Thyroid Stimulating Hormone is within the normal range)
  • Hypothyroidism (stable on thyroid replacement therapy is allowed, if the Thyroid Stimulating Hormone is within the normal range)
  • Hyper- or hypoparathyroidism
  • Osteomalacia
  • Paget's disease of bone
  • Other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta)
  • 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.
  • Permanently non-ambulatory subjects (use of assistive device eg cane, walker is permitted).
  • Has known or suspected sensitivity or contraindication to tetracycline derivatives.
  • Received any investigational product other than denosumab.
  • Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone analogue, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone.
  • Has undergone bilateral transiliac crest bone biopsy in the past.
  • Current use of medications that, in the opinion of the investigator, cannot be discontinued and may compromise the safety of the subject when undergoing the bone biopsy procedure (eg, aspirin, warfarin, high-dose heparin).
  • Current use of systemic glucocorticoid therapy (topical or nasal steroids are permitted).
  • Evidence of coagulopathy that in the opinion of the investigator, may compromise patient safety when subjected to the bone biopsy procedure.
  • Any disorder that, in the opinion of the investigator, may compromise the ability of the participant to give written informed consent and/or comply with study procedures.

Treatment and study plan

Previous denosumab

Drug

Participants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative.

Primary outcomes

  1. Number of Participants With Normal/Abnormal Bone Histology

    Time frame: 25-34 days post-Day 1

    The number of participants with normal/abnormal bone histology as assessed by bone biopsy samples at the central histomorphometric facility. Normal bone histology is characterized by: - normal lamellar bone, - normal mineralization or - osteoid (the organic matrix of bone; young bone that has not undergone calcification). Biopsies with abnormal bone histology are characterized by: - osteomalacia, - marrow fibrosis, - clinically significant marrow abnormality or - woven bone.

Secondary outcomes

  1. Bone Histomorphometry: Cancellous Bone Volume

    Time frame: 25-34 days post-Day 1

    Cancellous (trabecular) bone volume (Tb.V) is the relative volume of total cancellous bone measured (TV), expressed as percentage, that is occupied by trabeculae. Cancellous bone volume was measured using Fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.

  2. Bone Histomorphometry: Trabecular Number

    Time frame: 25-34 days post-Day 1

    Trabecular number (Tb.N) is the number of trabeculae present per lineal mm and is calculated as trabecular bone volume/trabecular thickness. Tb.N is a measure of trabecular connectivity and decreases with bone loss.

  3. Bone Histomorphometry: Trabecular Separation

    Time frame: 25-34 days post-Day 1

    Trabecular separation (Tb.Sp) is the mean distance in mm between trabeculae (measured by integrated computer graphics). Tb.Sp increases with trabecular bone loss.

  4. Bone Histomorphometry: Trabecular Thickness

    Time frame: 25-34 days post-Day 1

    Mean trabecular thickness (Tb.Th) is a measure of trabecular structure and is calculated as the reciprocal of total bone (trabecular) surfaces. Tb.Th is reduced by aging and osteoporosis.

  5. Bone Histomorphometry: Cortical Width

    Time frame: 25-34 days post-Day 1

    Cortical width correlates with dual photon absorptiometric (DPX) measurements of bone density.

  6. Bone Histomorphometry: Surface Density

    Time frame: 25-34 days post-Day 1

    Surface density is calculated by total bone (trabecular) surfaces / total tissue volume.

  7. Bone Histomorphometry: Osteoblast - Osteoid Interface

    Time frame: 25-34 days post-Day 1

    Osteoblast - osteoid interface is calculated as osteoblast surface / osteoid surface * 100.

  8. Bone Histomorphometry: Osteoid Surface

    Time frame: 25-34 days post-Day 1

    Osteoid surface is expressed as a percentage total bone surface.

  9. Bone Histomorphometry: Osteoid Width

    Time frame: 25-34 days post-Day 1

    Osteoid thickness (width; O.Th) is the mean thickness of osteoid seams on cancellous surfaces. O.Th is normally <12.5 µm. Increased O.Th suggests abnormal mineralization (osteomalacia).

  10. Bone Histomorphometry: Wall Thickness

    Time frame: 25-34 days post-Day 1

    Wall thickness is the average thickness of trabecular bone structural units (BSU) and is used to assess the overall balance between resorption and formation.

  11. Bone Histomorphometry: Eroded Surface/Bone Surface

    Time frame: 25-34 days post-Day 1

    Eroded surface is expressed as a percentage of total bone surface.

  12. Bone Histomorphometry: Osteoclast Number - Length Based

    Time frame: 25-34 days post-Day 1

    Osteoclast number expressed per mm of bone. Osteoclast number was measured using fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.

  13. Bone Histomorphometry: Osteoclast Number - Surface Based

    Time frame: 25-34 days post-Day 1

    Osteoclast number expressed per bone surface area. Osteoclast number was measured using fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.

  14. Bone Histomorphometry: Single-label Surface

    Time frame: 25-34 days post-Day 1

    Single-label surface is expressed as a percentage of total bone surface. The presence of a single label indicates that mineralization was occurring during only one labeling period.

  15. Bone Histomorphometry: Double-label Surface

    Time frame: 25-34 days post-Day 1

    Double-label surface is expressed as a percentage of total bone surface. The presence of double labels indicates that normal bone mineralization was actively occurring over the labeling interval.

  16. Bone Histomorphometry: Total Mineralizing Surface

    Time frame: 25-34 days post-Day 1

    Total mineralizing surfaces (MS) include all double and half of single-labeled surfaces. MS is expressed as a percentage of total bone surface.

  17. Bone Histomorphometry: Mineral Apposition Rate

    Time frame: 25-34 days post-Day 1

    The mineral apposition rate (MAR) is the avarage rate at which new bone mineral is being added on any actively forming surface. MAR is calculated as the average distance between visible labels, divided by the labeling interval.

  18. Bone Histomorphometry: Adjusted Mineral Apposition Rate

    Time frame: 25-34 days post-Day 1

    The mineral apposition rate (MAR) is the avarage rate at which new bone mineral is being added on any actively forming surface. Adjusted MAR is calculated as: (average distance between visible labels / labeling interval) * (total mineralizing surface/total bone surface).

  19. Bone Histomorphometry: Bone Formation Rate - Surface Based

    Time frame: 25-34 days post-Day 1

    Bone formation rate - surface based (BFR/BS) is the calculated rate at which cancellous bone surface is being replaced annually. BFR/BS is derived from the Mineral Appositional Rate * 365 * (relative mineralizing surface /total bone surface).

  20. Bone Histomorphometry: Bone Formation Rate - Volume Based

    Time frame: 25-34 days post-Day 1

    Bone formation rate - volume based (BFR/BV) is the calculated rate at which cancellous bone volume is being replaced annually. BFR/BV is derived from the Mineral Appositional Rate * 365 * (relative mineralizing surface / total bone volume).

  21. Bone Histomorphometry: Formation Period

    Time frame: 25-34 days post-Day 1

    The formation period is the duration of an interval when a place on the bone surface is actively forming bone. The formation period is calculated as the wall width (thickness of new bone made in one cycle) divided by the mineral apposition rate.

  22. Bone Histomorphometry: Activation Frequency

    Time frame: 25-34 days post-Day 1

    The average time that it takes for a new remodeling cycle to begin on any point on a cancellous surface is called the activation frequency (Ac.f). Activation frequency is calculated as the bone formation rate / wall width.

  23. Bone Histomorphometry: Osteoid Volume

    Time frame: 25-34 days post-Day 1

    Osteoid volume is expressed as a percentage of total bone volume.

  24. Bone Histomorphometry: Mineralization Lag Time

    Time frame: 25-34 days post-Day 1

    The mineralization lag time is the time interval between osteoid secretion and its subsequent mineralization, in days.

  25. C-Telopeptide (CTX-1)

    Time frame: Day 3 or Day 20

    C-Telopeptide is a biochemical marker for bone turnover. Blood samples were drawn for assessment of CTX-1 levels on either Day 3 or Day 20, within 24 hours of the last dose of the respective tetracycline cycle.

  26. Procollagen Type 1 N-terminal Peptide (P1NP)

    Time frame: Day 3 or Day 20

    Procollagen Type 1 N-terminal Peptide is a biochemical marker of bone turnover. Blood samples were drawn for assessment of P1NP levels on either Day 3 or Day 20, within 24 hours of the last dose of the respective tetracycline cycle.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Important dates

Study start
2009
Primary completion
2010
Study completion
2010
First posted
Apr 24, 2009
Registry last updated
Nov 15, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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