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