Overview

The goal of this clinical trial is to learn if veverimer will reduce urinary net acid excretion leading to reduced bone resorption in healthy adults with osteopenia. The main questions it aims to answer are:

• How much does each dose of veverimer (vs. placebo) reduce 24-hr urinary net acid excretion.
• Describe the safety of veverimer based on changes in serum bicarbonate and potassium.
• Assess the changes in bone resorption.
• Assess the changes in bone formation.
• Explore the effect of veverimer on physical performance.

Participants will:

• Take veverimer or placebo every day or every other day for 8 weeks
• Visit the clinic a total of 8 times (including screening) for checkups and testing
• Keep a medication diary tracking each day they take the study drug

Eligibility

Inclusion Criteria:

1. Community dwelling adults age 50 years and older (approximately equal numbers of men and women).
2. Men should be sterile or agree to use contraception throughout the study.
3. Women must be postmenopausal, defined as no menses in the last 5 years (to reduce variability in change in bone resorption since menopause prompts a rapid increase in bone resorption).
4. Osteopenia will be defined as a bone mineral density (BMD) T-score at the lumbar spine, femoral neck, or total hip lower than -1 or higher than -2.5.
5. On a prescreening interview, candidates must report a usual diet associated with an acid load by our validated short questionnaire.
6. Estimated glomerular filtration rate (eGFR) must be 45 ml/min or greater.
7. Participants must agree not to change their exercise pattern or medication use during the study.
8. Participants must agree not to change their pattern of supplement use and not to use antacids during the study because most calcium supplements and other antacids add alkali.
9. Participants must agree to not change their eating habits or intentionally change their weight.

Exclusion Criteria:

1. Normal BMD T-scores at all spine and hip sites, osteoporosis based on BMD T-score of -2.5 or less
2. Respiratory illness in last month
3. Chronic obstructive pulmonary disease (COPD)
4. Asthma
5. Nausea/vomiting in last month
6. Dysphagia
7. Malabsorption
8. Inflammatory bowel disease
9. Chronic diarrhea (defined as loose bowel movements daily) or constipation (≤ 2 stools per week)
10. Insulin-requiring diabetes or fasting plasma glucose \>125 mg/dl
11. Untreated thyroid disease
12. Cirrhosis
13. Current unstable heart disease
14. Malignancy (except non-melanoma skin cancer) or cancer therapy in last year
15. Alcohol use \>2 drinks/day.
16. Individuals who are unable to provide informed consent due to cognitive impairment.