Atenolol for the Prevention of Osteoporosis (APO)

• Atenolol 50 MG (Drug), also known as Atenolol: 50 mg Atenolol daily
• Placebo (Drug): one placebo daily

Primary outcomes

• Primary Outcome: Percent change in total hip bone mineral density (BMD) [Baseline, 24 months]: Percent change in total hip bone mineral density (BMD) by DXA

Secondary outcomes

• Secondary Outcomes: Percent changes in lumbar spine and femur neck BMD [Baseline, 24 months]: Percent changes in lumbar spine and femur neck BMD
• Additional secondary outcomes [Baseline, intermediate timepoints, 24 months]: Percent changes in radius and ultra-distal radius BMD using DXA and in bone turnover markers (CTx, PINP).

Sex: Female, ages: 50 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

* Able and willing to provide informed consent
* Postmenopausal women (FSH ≥ 16 IU/L) (no menses for at least one year)
* Aged 50-75 years

Exclusion Criteria:

* Clinical diagnosis of diabetes mellitus requiring insulin
* Clinically significant abnormality in any of the additional screening laboratory studies
* A1c- ≥8
* Calcium - > upper limit lab value per site
* AST- 2x upper normal limit
* FSH- < 16IU/L
* eGFR- < 45 mL/min/1.73m2 based on creatinine
* CBC- Per PI interpretation of each patient
* Presence of (documented clinical diagnosis of any of the following):

  * Significant liver or renal disease
  * Malignancy (current diagnosis including myeloma or melanoma)
  * Radiation (the site PI will determine eligibility on a case-by-case basis)
  * Malabsorption (current clinical diagnosis or actively receiving treatment)
  * Hypoparathyroidism (current clinical diagnosis or actively receiving treatment)
  * Hyperparathyroidism (current clinical diagnosis or actively receiving treatment)
  * Acromegaly
  * Cushing syndrome
  * Hypopituitarism
  * Severe chronic obstructive pulmonary disease
  * Pheochromocytoma (current clinical diagnosis or actively receiving treatment)
  * History of cardiac failure
  * Ejection Fraction <35% (based on most recent EF within the last 12 months, if available)
  * PR interval > 200 msec on screening ECG or known heart block
  * History of bronchospastic disease with treatment (asthma, bronchitis)
  * Gastric Bypass
  * Parkinson's
  * Rheumatoid Arthritis
  * Psoriatic Arthritis
  * Connective Tissue disease
* Undergoing treatment with any medications that affect bone turnover, including the following:

  * adrenocorticosteroids (oral for > 3 months within the past year or year-round use of inhaled corticosteroid use)
  * anticonvulsant therapy for seizures (carbamazepine, phenobarbital, or phenytoin within the previous year) pharmacological doses of: thyroid hormone (causing decline of thyroid stimulating hormone below normal, i.e. < 0.3 miU/L) bisphosphonates (within the past 3 yrs; if taken orally >1 month in past 3 years) denosumab, romosozumab, estrogen therapy (does not include creams or suppositories) or treatment with a selective estrogen receptor modulator, or teriparatide/abaloparatide (> 1 month within the past year); aromatase inhibitors (>1 month within the past year)
  * Current use of digitalis glycosides
  * Thiazides (< 6 months of use prior to screening)
  * Current or within the past 3 months use of beta blockers
* Any recent fracture within the past 6 months prior to screening (other than fingers, toes and facial fractures, which are all acceptable)
* Bilateral hip replacements or metal in both hips
* Patients with serum 25-hydroxyvitamin D levels of < 20 ng/ml, in order to ensure vitamin D sufficiency
* Resting systolic blood pressure < 115 mm Hg, heart rate < 55 bpm (average of 3 readings after a 5-minute rest and one minute between readings with an automatic cuff)

• Informed Consent Form (PDF, 2023-11-17)

• Sundeep Khosla, MD, Principal investigator, Mayo Clinic