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

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.

- 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