Karen Johnson, MD—professor of preventive medicine and principle investigator of the WHI site in Memphis, and Laura Carbone, MD professor of medicine—said it is the largest study of postmenopausal women ever conducted. Johnson and Carbone led three clinical trials and an observational study, publishing the results earlier this year in the Archives of Internal Medicine.

 

"It's important to follow these women to try to elucidate what makes them healthier, improves their quality of life over time, and how that can inform our medical practice," said Johnson.

 

Previous research revealed that bone and heart health are two major concerns for postmenopausal women. Dr. Johnson estimates that "over half of all postmenopausal women will experience an osteoporosis related fracture in their lifetime." These fractures can be caused by such minor trauma as a fall, sneeze or cough. A fracture that would heal normally in a cast might require a longer time in the cast or even surgery for patients with osteoporosis.

 

The UTHSC study results revealed a 16 percent increase in fracture risk among postmenopausal women who used loop diuretics for three or more years. Loop diuretics, named for the mechanism of action at the loop of Henle in the kidney, act much more quickly than other diuretics, and are often prescribed for hypertension, high blood calcium, and congestive heart failure.

 

Loop diuretics inhibit the absorption of calcium and magnesium, preventing the urine from becoming concentrated and disrupting the generation of a hypertonic renal medulla. Without a concentrated medulla, urine production increases. These diuretics remove excess water from the body, allowing the heart to pump blood more efficiently. However, they also cause calcium and sodium elimination through the urine. Excessive loss of calcium in urine, known as hypercalciuria, can decrease bone mineral density and increase the overall risk of fractures. Other diuretics, which do not cause hypercalciuria, may be prescribed.  Johnson cautions patients not to suddenly discontinue loop diuretics without first consulting their physician.

 

Loop diuretics such as Lasix, Demadex and Bumex, are prescription-class diuretics, different from over the counter diuretics, often referred to as "water pills."

 

Fractures were recorded in study participants for an average of 7.7 years. Bone mineral density was recorded for 300 loop diuretic users and 9,124 non-users at the beginning and third year of the study. No significant association was found with shorter-term use of loop diuretics and bone loss or fracture. Johnson stressed that the increase of fractures was caused by long-term use of loop diuretics—of three years or more.

 

Johnson suggests that postmenopausal women, and all women over 65, talk to their primary care provider about bone health, especially when using loop diuretics. She recommends a densitometry, or DEXA scan, to check bone mineral density. The scan can help determine whether bones are healthy, or in the osteoporotic or osteopenic range. 

 

A DEXA scan uses special X-rays to measure grams of calcium and other bone minerals contained in a segment of bone. These tests also help physicians predict which patients are at increased risk of fractures based on the scan results. Patients with a bone mineral density in the osteoporotic range are approximately five times more likely to suffer an osteoporosis related fracture.

 

The WHI sponsors clinical trials to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancers in women. The next studies planned at UTHSC will focus on the effects of other medications on bone health, including effects of different over-the-counter and seizure medicines.

 

The three main components of the WHI are clinical trials for unproven approaches to prevention, observational studies to predict the likelihood of disease, and researching community approaches for developing healthful behaviors. The WHI is funded by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, and will continue tracking study participants until 2010.