Radius Loading in Primary Hyperparathyroidism

Study Overview
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Brief Summary
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The purpose of the study is to determine the effect of forearm exercise on forearm bone density in post-menopausal women with or without primary hyperparathyroidism. The investigators hypothesize that forearm exercise will increase forearm bone density in patients with primary hyperparathyroidism more so than in patients without primary hyperparathyroidism.

Detailed Description
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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.

Official Title
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Effect of Mechanical Loading on Radius Bone Density and Microarchitecture in Primary Hyperparathyroidism

Conditions
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Primary Hyperparathyroidism, Bone Diseases, Metabolic, Osteoporosis, Postmenopausal, Bone Loss, Postmenopausal

Intervention / Treatment
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* Other: Forearm exercise program
* Other: Walking program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for primary hyperparathyroidism group: Primary hyperparathyroidism (defined by an elevated serum calcium and concomitantly elevated or inappropriately normal PTH) Female sex, postmenopausal status for at least five years, ages 45-80 English- or Spanish-speaking DXA T-score less than -1.0 at the one-third radius Physically capable of exercise 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: Female sex, postmenopausal status for at least five years ages 45-80 English- or Spanish-speaking DXA T-score less than -1.0 at the one-third radius Physically capable of exercise Normal serum calcium and PTH level 25-hydroxyvitamin D >20 ng/mL Exclusion Criteria: Men, premenopausal women, women less than age 45 or greater than age 80 Familial hypocalciuric hypercalcemia Current or prior use of bisphosphonates (alendronate or risedronate (within 12 months), ibandronate (within 6 months), other bisphosphonate (2 years) Current use of cinacalcet Current or prior use of estrogen replacement therapy (within 2 years) Planned parathyroidectomy (within one year) Planned initiation of bisphosphonates DXA T-score greater than -1.0 at the one-third radius Cardiovascular disease or uncontrolled hypertension Exercise-limiting pulmonary diseases Malignancy other than non-melanomatous skin cancer or microscopic thyroid cancer (within 5 years) Renal failure Secondary hyperparathyroidism Celiac disease 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) 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. Protected individuals (institutionalized), prisoners, and any other prospective participant who might not be able to give voluntary informed consent.

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PHPT/ Walking + Forearm exercise<br>Ten participants with PHPT will be randomized to the intervention of 52 weeks of the forearm exercise program plus walking. | Other: Forearm exercise program<br>* Participants assigned to forearm exercise will receive training in forearm strengthening exercises from a doctoral occupational therapy student. Participants will be taught 8 exercises and are performed at home. The exercise program is designed to take about 30 minutes per session.<br>* Other names: Mechanical Loading;|
| Placebo Comparator: PHPT/ Walking alone<br>Ten participants with PHPT will be randomized to the intervention of 52 weeks of the walking program alone. Walking will consist of 30 minutes at a moderate pace every other day for 52 weeks. | Other: Walking program<br>* Walking will consist of 30 minutes at a moderate pace every other day for 52 weeks. The walking program for all participants constitutes the control/placebo comparator.<br>* Other names: Walking;|
| Active Comparator: Osteopenia/ Walking + Forearm exercise<br>Ten healthy, postmenopausal women with osteopenia will be randomized to the intervention of 52 weeks of the forearm exercise program plus walking. | Other: Forearm exercise program<br>* Participants assigned to forearm exercise will receive training in forearm strengthening exercises from a doctoral occupational therapy student. Participants will be taught 8 exercises and are performed at home. The exercise program is designed to take about 30 minutes per session.<br>* Other names: Mechanical Loading;|
| Placebo Comparator: Osteopenia/ Walking alone<br>Ten healthy, postmenopausal women with osteopenia will be randomized to the intervention of 52 weeks of the walking program alone. Walking will consist of 30 minutes at a moderate pace every other day for 52 weeks. | Other: Walking program<br>* Walking will consist of 30 minutes at a moderate pace every other day for 52 weeks. The walking program for all participants constitutes the control/placebo comparator.<br>* Other names: Walking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with improved bone mass and bone quality at the 1/3 radius | The primary outcome is proportion of subjects with improved bone mass and bone quality at the 1/3 radius over one year. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperparathyroidism, Primary, Bone Diseases, Metabolic, Osteoporosis, Postmenopausal, Bone Loss, Postmenopausal