Osteoclast Inhibition and Bone Formation

Effects of Age and Osteoclast Inhibition on Bone Formation

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?

Study Overview

• Status: Completed
• Conditions: Aging; Bone Loss
• Intervention / Treatment: Drug: placebo; Drug: denosumab

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 Type: Interventional
• Enrollment (Actual): 81
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; single subcutaneous injection of placebo (normal saline)	Drug: placebo; subcutaneous saline injection; Other Names: saline
Active Comparator: Denosumab; single subcutaneous injection of denosumab 60 mg	Drug: denosumab; single subcutaneous injection of denosumab 60 mg; Other Names: Prolia
No Intervention: young normal premenopausal women; no intervention

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sundeep Khosla, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2015
• Primary Completion (Actual): October 25, 2016
• Study Completion (Actual): October 25, 2016

Study Registration Dates

• First Submitted: September 17, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimate): September 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 5, 2018
• Last Update Submitted That Met QC Criteria: January 3, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: adrenergic
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 15-002313