Radius Loading in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone
(PTH) and high blood calcium, is one of the most common endocrine disorders.

PHPT is seen most often in post-menopausal women. Kidney stones and bone deformities were
prominent manifestations of the disease in the past, however, PHPT is now primarily
asymptomatic due to incidental detection of high blood calcium levels.

Many patients with PHPT, however, have low bone mineral density (BMD) when bone mass is
measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm.

There is no effective medical therapy which increases bone density at the forearm in
patients with PHPT. PTH both builds and breaks down bone, and the pathways by which PTH
mediates these actions are beginning to be identified. Prior research suggests that
mechanical loading shifts PTH towards building bone. Arm exercise is an attractive option
for the treatment of low forearm BMD in patients with PHPT since it is often the site most
affected by excess PTH.

Inclusion Criteria:

Inclusion criteria for primary hyperparathyroidism group:

1. Primary hyperparathyroidism (defined by an elevated serum calcium and concomitantly
elevated or inappropriately normal PTH)

2. Female sex, postmenopausal status for at least five years, ages 45-80

3. English- or Spanish-speaking

4. DXA T-score less than -1.0 at the one-third radius

5. Physically capable of exercise

6. 25-hydroxyvitamin D >20 ng/mL. The latter inclusion criterion will lead to the
enrollment of some individuals whose vitamin D stores will not be frankly low. We
feel, however, that it is better to study subjects in their usual state rather than
replacing them with vitamin D which could add another variable that would further
complicate this pilot study.

Inclusion criteria for the osteopenic control:

1. Female sex, postmenopausal status for at least five years ages 45-80

2. English- or Spanish-speaking

3. DXA T-score less than -1.0 at the one-third radius

4. Physically capable of exercise

5. Normal serum calcium and PTH level

6. 25-hydroxyvitamin D >20 ng/mL

Exclusion Criteria:

1. Men, premenopausal women, women less than age 45 or greater than age 80

2. Familial hypocalciuric hypercalcemia

3. Current or prior use of bisphosphonates (alendronate or risedronate (within 12
months), ibandronate (within 6 months), other bisphosphonate (2 years)

4. Current use of cinacalcet

5. Current or prior use of estrogen replacement therapy (within 2 years)

6. Planned parathyroidectomy (within one year)

7. Planned initiation of bisphosphonates

8. DXA T-score greater than -1.0 at the one-third radius

9. Cardiovascular disease or uncontrolled hypertension

10. Exercise-limiting pulmonary diseases

11. Malignancy other than non-melanomatous skin cancer or microscopic thyroid cancer
(within 5 years)

12. Renal failure

13. Secondary hyperparathyroidism

14. Celiac disease

15. Physical/orthopedic disabilities and neurologic disorders or vasculopathies that
would place the subjects at risk or limit their ability to perform exercise (eg.
arthritis, carpal tunnel syndrome, rotator cuff injury, etc)

16. Moderate or high physical activity (category 2 or 3) as assessed by the IPAQ
questionnaire. This latter exclusion criterion is a measure of baseline physical
activity and looks to exclude those who would have a lower likelihood of benefit by
baseline participation in an exercise program.

17. Protected individuals (institutionalized), prisoners, and any other prospective
participant who might not be able to give voluntary informed consent.