Parameters of Exercise to Prevent Osteoporosis (OSTEOPOROSISEX)

The principal goal of this study is to determine parameters of walking in terms of peak mechanical vertical force, bout duration, and bout spacing that can preserve or increase bone mineral density (BMD) in postmenopausal women. Release of pulses of parathyroid hormone (PTH), growth hormone (GH), and of markers of bone resorption and bone formation will be used as indicators of the osteogenic effects of a short exposure to exercise. When secreted in pulsatile fashion, GH stimulates osteoblast proliferation, particularly in cortical bone (27, 28). Like GH, the pattern of PTH secretion determines the nature of its effect on bone. When it is secreted in pulsatile manner, PTH contributes to bone formation through activation of bone lining cells, differentiation of osteoprogenitor cells, and suppression of bone cell apoptosis .

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Behavioral: Experimental: 40 minute up trial; Behavioral: Experimental: 40 minute down trial; Behavioral: Experimental: Two 20 minute up trials; Behavioral: Experimental: Two 20 min down trials; Behavioral: Active Comparator: Sedentary trial

Detailed Description

A. Hypotheses and specific aims:

Specific aim 1. Measure plasma concentrations of anabolic hormones (parathyroid hormone (PTH) and growth hormone (GH), at sufficient frequency to define the area under the curve (AUC), and of markers of bone formation (osteocalcin, carboxyterminal propeptide of type 1 procollagen (CICP), and bone-specific alkaline phosphatase (ALKP)), and markers of bone resorption (immunoreactive carboxyterminal telopeptide of type I collagen (CTX)) after 40-minutes of treadmill exercise at the relative intensity of 125% of the ventilatory threshold (VT) corresponding to about 1.78 m/sec (4 miles/h), and two intensities of mechanical loading (724, and 1411 N), in healthy postmenopausal women.

Hypothesis 1. Bone formation, as assessed by increases in markers of bone formation and decreases in markers of bone resorption, will be higher in response to dynamic exercise at a level of mechanical loading that produces increased secretion of PTH and GH than to exercise at other loading intensities.

Specific aim 2. Measure plasma concentrations of anabolic hormones), at sufficient frequency to define the area under the curve (AUC), and of markers of bone formation as in specific aim 1, after two 20-minutes of treadmill exercise, separated by 7 h, at the relative intensity of 125% of the ventilatory threshold (VT) corresponding to about 1.78 m/sec (4 mi/h), and two intensities of mechanical loading (724, and 1411 N), in healthy postmenopausal women.

Hypothesis 2. A 7-hour interval separating the two bouts of exercise will have greater bone anabolic effect than the equivalent volume and intensity of exercise performed in a single bout.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Clinical Research Unit United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 50 to 65 years if naturally post-menopausal, or age 47 if surgically postmenopausal
• Dual energy X-ray absorptiometry (DEXA) Z score above -1
• No endocrine or metabolic disease requiring medication except for hormonally corrected hypothyroidism
• No musculo-skeletal disabilities that would preclude treadmill walking
• Normal electrocardiogram (EKG) and heart health history
• BMI between 24 and 30
• Hematocrit above 32 %
• No hormone replacement therapy (HRT)
• Personal health provider's Release Letter

Exclusion Criteria:

• Age and BMI outside of the specified range
• Z score below -1
• Medication for presence of metabolic or endocrine disease
• Musculo-skeletal disabilities that would preclude treadmill walking
• Abnormal electrocardiogram (EKG) and heart health history
• Hematocrit below 32%
• Hormone replacement therapy
• Failure to conform to study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 minute up trial; Subjects were subjected to 40 minutes of treadmill exercise at a 6 degree incline and at 75% of maximal effort between 8:00 and 8:40 am. Isocaloric meals were provided at 7:00, 13:00. and 19:00 h.	Behavioral: Experimental: 40 minute up trial; Other Names: 40 minutes of uphill exercise divided into two 20-minute trials separated by 7 h
Experimental: 40 minute down trial; Subjects were subjected to 40 minutes of treadmill exercise at a 6 degree decline and at 45% of maximal effort between 8:00 and 8:40 am. Isocaloric meals were provided at 7:00, 13:00. and 19:00 h.	Behavioral: Experimental: 40 minute down trial; Other Names: 40 minutes of downhill exercise divided into two 20-minute trials separated by 7 h
Experimental: Two 20 minute up trials; Subjects were subjected to two 20 minutes of treadmill exercise separated by 7 h at a 6 degree incline and at 75% of maximal effort, the first one between 8:00 and 8:40 am and the second one between 15:00 and 15:20 h..Isocaloric meals were provided at 7:00, 13:00. and 19:00 h.	Behavioral: Experimental: Two 20 minute up trials; Other Names: 40 minutes of uphill exercise separated in two 20-min bouts 7 h apart
Experimental: Two 20 min down trials; Subjects were subjected to two 20 minutes of treadmill exercise separated by 7 h at a 6 degree incline and at 45% of maximal effort , the first one between 8:00 and 8:40 am and the second one between 15:00 and 15:20 h. Isocaloric meals were provided at 7:00, 13:00. and 19:00 h.	Behavioral: Experimental: Two 20 min down trials; Other Names: 40 minutes of uphill exercise separated in two 20-min bouts 7 h apart
Active Comparator: Sedentary trial; No exercise day with isocaloric meals provided at 7:00, 13:00. and 19:00 h.	Behavioral: Active Comparator: Sedentary trial; Other Names: A control no-exercise trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ground reaction forces	Sum of pressures on mechanosensitive Novel-Pedar shoe insoles	During last 5 minutes of treadmill walking
Serum osteocalcin	Concentration of osteocalcin measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours
Serum CICP (c-terminal propeptide of type 1 collagen	Concentration of CICP measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours
Serum CTX (c-terminal telopeptide of type 1 collagen	Concentration of CTX measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative aerobic capacity	Percent of maximal aerobic capacity used during uphill and downhill exercise	1 day (measured throughout treadmill exercise bouts)
Serum insulin	Concentration of insulin measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours
Serum cortisol	Concentration of cortisol measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours
Serum GH (growth hormone)	Concentration of GH measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours
serum PTH (parathyroid hormone)	Concentration of PTH measured in serum samples	Hourly blood draws between 8:00 and 22:00 hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University of Wisconsin, La Crosse

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2007
• Primary Completion (Actual): August 19, 2010
• Study Completion (Actual): August 19, 2010

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal
• Other Study ID Numbers: HUM00007202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No