Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism

Study Overview
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Brief Summary
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This study is designed to answer the question as to whether the sympathetic nervous system is an important determinant of bone metabolism in humans.

Detailed Description
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In postmenopausal women, who have increased sympathetic outflow, to test the hypothesis that treatment with low doses of a non-selective β-blocker (propranolol) will increase serum markers of bone formation and reduce markers of bone resorption (Aim 1a); and using increasingly β1-AR (adrenergic receptor) selective blockers (atenolol and nebivolol), to better define the β-adrenergic receptor selectivity (β1 versus β2) in the regulation of bone turnover by sympathetic outflow in humans.

Official Title
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Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism

Conditions
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Osteoporosis, Age-Related

Intervention / Treatment
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* Drug: Atenolol
* Drug: Nebivolol
* Drug: Propranolol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 anti-hypertensive therapy 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 Resting blood pressure >140/90 mm Hg or those with hypotension (systolic blood pressure <110 mm Hg), heart rate < 60 bpm History of asthma

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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>Sugar pill 2/day for 20 weeks; The once daily groups will receive a placebo as the second dose | Drug: placebo<br>* placebo<br>|
| Active Comparator: Atenolol<br>Atenolol 50 mg 1/day for 20 weeks | Drug: Atenolol<br>* beta blocker<br>|
| Active Comparator: Nebivolol<br>Nebivolol 5 mg/day for 20 weeks | Drug: Nebivolol<br>* beta blocker<br>|
| Active Comparator: Propranolol 40 mg<br>Propranolol 20 mg bid for 20 weeks | Drug: Propranolol<br>* beta blocker<br>|
| Active Comparator: Propranolol 80 mg<br>Propranolol 40 mg bid for 20 weeks | Drug: Propranolol<br>* beta blocker<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of serum bone formation to bone resorption marker | Serum bone formation marker (PINP)/serum bone resorption marker (CTX) | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone formation