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

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

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

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