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

Condition(s) targeted: Low Bone Mass; Low Bone Mineral Density; Osteoporosis; Postmenopausal Osteoporosis

Intervention: Bone Biopsy (Procedure)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Amgen

Official(s) and/or principal investigator(s):
MD, Study Director, Affiliation: Amgen

Overall contact:
Amgen Call Center, Phone: 866-572-6436

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

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

Study design: Supportive Care, Open Label, Single Group Assignment, Safety Study

Primary outcome: The primary endpoint is bone histology as part of the qualitative assessment of bone. Normal bone histology will be characterized by normal lamellar bone, mineralization and osteoid as well as absence of osteomalacia, marrow fibrosis or woven bone.

Secondary outcome:

Bone histomorphometry variables including cancellous bone volume, trabecular number, separation and thickness, cortical width, surface density, osteoblast-osteoid interface, osteoid surface, width and volume, wall thickness, eroded surface, osteoclast

The biochemical markers of bone turnover CTX-1 and PINP.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Ambulatory postmenopausal women

- Received denosumab and completed study 20050179, completed study 20050141, completed

study 20060237, completed study 20030216 but did not enroll in study 20060289. Subjects who will participate in the off-treatment imaging study for 20080747 also are eligible.

- Completed participation in eligible studies (4. 1.2) ≥ 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.

- Subjects 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).

- Subject 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 subject to give written informed consent and/or comply with study procedures.

Amgen Call Center, Phone: 866-572-6436

Research Site, Quebec, Canada

AmgenTrials clinical trials website

Starting date: June 2009
Ending date: March 2010
Last updated: July 30, 2009