AS652 - Measuring muscle mass in postmenopausal women using the creatine dilution method

Investigator Names and Contact Information

Hailey Banack (hrbanack@buffalo.edu)

Introduction/Intent

There is strong evidence linking sarcopenia with a myriad of poor health outcomes in older adults. Sarcopenia was previously defined simply as age-related loss of muscle mass, but newer definitions of sarcopenia include an assessment of muscle strength and/or performance. One of the greatest challenges in studying and understanding the relationship between sarcopenia and health outcomes is the difficulty in obtaining valid and accurate measurements of skeletal muscle mass. In clinical settings or research studies, muscle mass is typically measured by CT, MRI or DXA scan, but each of these methods require access to expensive specialized equipment and trained personnel. In this pilot study, we propose to use a novel yet simple measure of muscle mass known as the creatine dilution method. There are no known risks associated with using the creatine dilution method in older adults. Our study will be the first to evaluate the feasibility of using this method in a sample of community dwelling postmenopausal women. We will additionally use this direct measure of muscle mass to study the cross sectional relationships between muscle mass, muscle strength, and muscle function. The sample will include 100 women from the WHI Buffalo Clinical Center. Participants will be mailed a single dose of a pill called D₃-creatine. They will be asked to take the pill at home, and then 3 to 6 days later will be scheduled to come into the WHI Clinic at the University at Buffalo to provide a fasting morning urine sample. While in the clinic, women will be asked to complete a blood draw, anthropometric measures, measures of physical strength and performance (handgrip strength and short physical performance battery), and dual energy x-ray absorptiometry scan. We hypothesize that our results will demonstrate that this method is a simple, low-cost, and non-invasive way to measure muscle mass in postmenopausal women. Our long term objective is to use the results of this pilot study to provide preliminary data to support a grant that will allow us to include the creatine dilution method as part of a home visit for the Long Life Study 2.

SPECIFIC AIMS

Sarcopenia is a geriatric syndrome that is strongly predictive of adverse health outcomes, such as physical disability, falls, fractures, and mortality.^1-3 It is associated with a marked increase in healthcare utilization through emergency department visits, hospitalization, and use of short- and long-term skilled nursing care facilities. Sarcopenia is an important public health problem associated with enormous direct and indirect healthcare costs ($18.5 billion/year).³ Although sarcopenia is reported to be highly prevalent in postmenopausal women, research on sarcopenia prevention and treatment is hampered by the fact that there is no broadly accepted clinical definition, diagnostic criteria, or treatment guidelines for sarcopenia.^1,2,4

Sarcopenia was previously defined simply as age-related loss of muscle mass, but newer definitions of sarcopenia also include an assessment of muscle strength and/or performance.^1,2 One of the greatest challenges in studying and understanding the clinical relevance of sarcopenia is the difficulty in obtaining valid and accurate measurements of skeletal muscle mass. Assessment of muscle strength and muscle performance are relatively straightforward and inexpensive, however assessment of muscle mass is neither straightforward nor inexpensive. Measuring muscle mass requires expensive, specialized equipment, and highly trained technicians. Up to this point, it has not been possible to directly measure muscle in large-scale health research studies and this has severely limited our ability to fully understand the health implications of this critically important aspect of healthy aging.

Recently, a novel method of measuring skeletal muscle mass was developed.⁵ This new method, called the creatine dilution method, is a simple and direct measure of muscle mass. Participants are given a single oral dose of D₃-creatine, which is then metabolized in skeletal muscle to D₃-creatinine. Three to six days after the oral dose, participants are asked to provide a single morning urine sample. Urinary concentrations of D₃-creatinine are used as a direct measure of total skeletal muscle mass. It has several advantages over traditional methods: it can be used to measure muscle mass at home with mailed or drop off specimen collection, is low cost, and does not expose participants to radiation. Moreover it measures muscle mass directly, as opposed to lean body mass approximated from a DXA scan. There are no known risks associated with taking creatine and the dose (30mg) is far lower than the amount typically consumed from dietary sources. This method was recently used in a sample of older adults in the MrOs study and there were no adverse events or side effects reported.⁴

We propose to use the creatine dilution method to measure muscle mass in the Buffalo-area participants of the Women’s Health Initiative (WHI). The overall objective of this pilot study is to collect preliminary data and demonstrate the feasibility of using the creatine dilution method in WHI participants. Our long term goal is to use the results of this pilot study to support a grant application to use this method in participants joining the Long Life Study 2 (LLS-2) study and home visit. As such, our specific aims are:

Specific Aim 1. Use the creatine dilution method to measure muscle mass in a community dwelling sample of WHI postmenopausal women using a combination of standardized inhome and clinic- based measures.

Specific Aim 2. Characterize the cross-sectional associations between muscle mass, muscle strength, and physical functioning in community dwelling WHI postmenopausal women.