Osteoclast Inhibition and Bone Formation

Early Phase 1

Completed

• Conditions: Bone Loss; Aging
• Interventions: Drug: placebo; Drug: denosumab

• Registration Number: NCT02554695
• Lead Sponsor: Mayo Clinic

Brief Summary

This protocol addresses: 1) How gene expression changes in bone cells are affected by aging? 2) Is aging associated with decreased signaling between bone cells? 3) How does treatment with the osteoporosis medication denosumab affect bone cell signaling?

Detailed Description

This protocol collectively addresses the following goals: 1) What are the changes in gene expression in osteoblasts and osteocytes that lead to impaired bone formation with aging; 2) Since recent work from the investigators' group has demonstrated that osteoclasts produce a number of growth factors and cytokines (coupling factors) that enhance osteoblast proliferation and/or differentiation, is aging associated with reduced osteoclast coupling factor production; and 3) If osteoclasts are markedly reduced using the FDA-approved medication for osteoporosis, denosumab, how does that effect the quantity of coupling factors in the bone microenvironment and the target genes of these coupling factors in osteoblasts?

Study Timeline

• Study First Submitted: 2015-09-17
• Study First Submitted QC: 2015-09-17
• Study First Posted: 2015-09-18
• Study Start: 2015-10-20
• Primary Completion: 2016-10-25
• Study Completion: 2016-10-25
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-03
• Last Update Posted: 2018-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 81

Inclusion Criteria

• normal premenopausal women aged 25-40 years
  • normal postmenopausal women aged 60-80 years
  • at least 5 yrs since their last menses
  • follicle stimulating hormone (FSH) > 20 IU/L

Exclusion Criteria

• Abnormality in any of the screening laboratory studies

  • Presence of significant liver or renal disease
  • Malignancy (including myeloma)
  • Malabsorption
  • Diabetes
  • Hypoparathyroidism
  • Hyperparathyroidism
  • Acromegaly
  • Cushing's syndrome
  • Hypopituitarism
  • Severe chronic obstructive pulmonary disease
  • Undergoing treatment with any medications that affect bone turnover, including the following:

• adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)

• anticonvulsant therapy (within the previous year)

• pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)

• calcium supplementation of > 1200 mg/d (within the preceding 3 months)

• bisphosphonates (within the past 3 yrs)

• denosumab

• estrogen (E) therapy within the past year

• treatment with a selective E receptor modulator within the past year

• teriparatide within the past yr

  • Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm)
  • Recent (within the past 6 months) fracture
  • Serum 25-hydroxyvitamin D levels of < 20 ng/ml

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	single subcutaneous injection of placebo (normal saline)
Denosumab	denosumab	single subcutaneous injection of denosumab 60 mg

Primary Outcome Measures

Name	Time	Method
Gene expression changes in bone cells	3 months	Ratio of selected genes as expressed between each of the 3 arms (i.e. relative runx2 gene expression levels in each arm).

Secondary Outcome Measures

Name	Time	Method
Osteoclast-osteoblast coupling factor changes	3 months	Ratio of selected genes as expressed between each of the 3 arms (i.e. relative runx2 gene expression levels in each arm).

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States