People with CF are at risk for developing osteopenia, a reduction in bone mineral. This can progress to osteoporosis-a disease in which bones become weak and brittle-which can lead to painful and debilitating fractures of the spine, ribs or hips.
In the human being, bone mass increases though childhood, reaching maximum levels by later adolescence or early adulthood. This peak bone mass serves as a bone bank for the rest of adult life. As we age and our sex steroid levels decrease, our bodies make withdrawals of bone mineral from this bone bank. In some people, this process may result in osteopenia and osteoporosis.
What are the risk factors for osteopenia? Why do the bones of some CF patients become less dense while others remain denser and thus healthier? Does reduced bone density result from inadequate bone acquisition during the growing years? Or does CF speed up the loss of bone mineral?
Based on research to date, it is known that several factors may contribute to osteopenia in CF patients. The malabsorption and poor nutrition associated with CF can cause poor growth, low body mass and low levels of fat soluble vitamins, including vitamin D, which is essential for calcium absorption. These can result in reduced bone mass in children. Hormones also play a role. Puberty is frequently delayed in CF patients, and low levels of sex steroids-estrogen in females and testosterone in males-can lead to loss of bone mass. Chronic illness and respiratory acidosis may interfere with mineralization. Taking medication such as prednisone (another kind of steroid, not to be confused with sex steroids) can also lead to loss of bone mass. Dr. Laura K. Bachrach of Stanford University Medical Center is studying this issue with the intention of eventually creating effective preventive and therapeutic programs for CF patients at risk for osteoporosis.
In a study funded by CFRI and conducted at Lucile Packard Children's Hospital at Stanford, Dr. Bachrach is currently analyzing bone mineral acquisition by comparing the bone densities of 49 CF children and adults with that of healthy control subjects.
One year into her study, Dr. Bachrach has discovered that the majority of the 49 CF patients measured-young patients as well as adults-had significantly reduced bone densities. These results were seen at all three regions of the skeleton studied: whole body, lumbar spine, and the femoral neck (a narrow part of the hip bone). About one-third of the CF patients' bones scored in the normal range (plus- or minus- one standard deviation). But the great majority have less-dense bones than their healthy counterparts, and thus are at a greater risk of fractures. Especially vulnerable sites for fractures in CF are the ribs, the hip and the spine.
In an attempt to define risk factors for osteopenia and osteoporosis, many measures of the subjects have been taken: age, body mass, pubertal status, calcium intake, exercise, Schwachman score (a clinical score that assesses the severity of CF symptoms), forced vital capacity, and history of taking certain medications.
All participants in the study are being interviewed about eating habits to assess current dietary calcium intake. They are also assessed for pubertal development; young women give information about menstrual history and young men are tested for testosterone levels in the blood. Height and weight are measured from which a body mass indexis calculated. The subjects have their bone density measured by a dual x-ray absorptiometer, a painless, low-radiation procedure.
With information from the study, some predictions are already confirmed: prednisone use is correlated with lower bone density, as is lower body mass. The early results have yielded a few surprises, too. Several CF patients in the study show a deficiency in vitamin D even when they take their daily ADEK supplements.
Now they are taking still more vitamin D, and Dr. Bachrach will be measuring their bone density over several years to see if it improves. Several of the adult patients discovered they were deficient in sex steroids though they had not experienced any problems, except for irregular periods in the women. They have begun taking estrogen or testosterone to see if this treatment can enhance bone mineral or prevent further loss.
Low calcium intake is a risk factor for low bone density, but how it interacts with CF has not yet been studied. "There's a lot going on here," Dr. Bachrach said in a recent interview. "We ask people about calcium intake, but we don't measure how much calcium is actually absorbed nor how much is excreted."
This is the first study to look at the bone densities of a broad range spectrum of people with CF-children through adults. It should yield insights into how to maintain a healthier skeleton. "Our goal is to follow these people for three or four years," Dr. Bachrach said. "This will give us a much better picture of what's going on." The 49 subjects of the bone mineral acquisition study by Dr. Bachrach represent a broader spectrum of age and disease severity than CF patients reported in earlier studies. Many are outpatients doing well at Lucile Packard Children's Hospital at Stanford. However, as a group, their bone mineral density is much less than expected.
In this chart, bone mineral density in males is shown as triangles; females are represented by circles. A z-score of zero indicates that bone density is normal for age and sex. A standard deviation of -1 means twice the risk of fractured bones. A standard deviation of -2 means four times the risk of fractured bones. This might explain why some people with CF can fracture a rib just by coughing.
Researchers have found that decreased bone density is associated with low body mass, low levels of sex hormones, and a history of glucocorticoid (prednisone) medication.
Editor's Note: CFRI has donated $9,565 this year and $14,150 last year to pay for a research assistant for Dr. Bachrach's research; Dr. Bachrach donates her time; and the bone density scans, valued at $350 per person, are donated by Stanford University Medical Center. For the data on normal bone density, the NIH has made available the results of a $500,000 study. Dr. Bachrach is currently applying to the NIH for funding for a longer-term project.
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