Osteoclast Inhibition and Bone Formation

Study Overview
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Brief Summary
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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
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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?

Official Title
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Effects of Age and Osteoclast Inhibition on Bone Formation

Conditions
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Bone Loss, Aging

Intervention / Treatment
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* Drug: placebo
* Drug: denosumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adrenergic