Bones in the balance

In the beginning, there’s soft cartilage. Then the cells go to work. Calcium salts and phosphorus are pulled from the blood and made to crystallize. The crystals are laid onto a lattice of fibers, hardening and strengthening the skeleton.

It’s called bone mineralization, and it must last a lifetime, because once bone mass reaches its peak – by the time we turn 18 – it can never increase. It can only be lost.

Catherine Gordon, MD, MSc, director of the Bone Health Program at Children’s Hospital Boston, is seeing more and more children who are missing key windows for bone mineralization because of disease, medication side effects or nutritional deficiencies. No one really knows what will happen when children with bone loss enter adulthood and old age.

Researchers – Gordon among them – are only beginning to figure out how best to measure bone mineral density in children, how to interpret the readings and whether existing treatments for adults will be beneficial. But Gordon fears that these children are tomorrow’s elderly patients with osteoporosis.

“It’s a young field,” Gordon says. “Even 10 years ago, pediatricians were not thinking about bone loss as a serious concern.” A missing vitamin Amazingly, bone loss can begin in infancy, the first crucial period for laying down bone. For a variety of reasons, many babies don’t get enough calcium or vitamin D, a critical vitamin that helps bones absorb calcium.

Last year, during construction of Children’s new clinical building, workers uncovered a long copper box. It was a time capsule, placed when the neighboring Bader building was completed in 1929. Among its contents was an article from The New England Journal of Medicine that argued the value of ultraviolet light, from the sun or artificial sources, in treating rickets. Rickets – a softening of the bones leading to fractures, stunted growth and skeletal deformities such as a curved spine and bowed legs – was then a common disease. A dedication letter in the box decreed that the Bader building’s top floor would house a solarium for “light therapy.” The hospital’s 1929 annual report advertised, “Every bed in every ward can be wheeled out of doors in a few seconds.”

Within the decade, it became known that although sunlight is important, the true cause of rickets was a lack of vitamin D. Ultraviolet light helps the body manufacture this critical vitamin. In the 1940s, the U.S. government mandated milk fortification with vitamin D, and rickets virtually disappeared.

But in recent decades, vitamin D deficiency has reemerged to become a hidden epidemic. Several years ago, when Gordon and her colleagues tested over 300 healthy adolescents, 42 percent had insufficient vitamin D levels, 24 percent were frankly deficient and 5 percent were severely deficient.

The indoor generation

Gordon is now conducting a similar study in infants; so far, about 10 percent have proven to be vitamin D-deficient. Rickets itself is also cropping up. In her 15 years at Children’s, Gordon has seen about 20 cases. “In young children, the bones’ growth plates – the areas where tissue is still developing – are open,” Gordon says. “When children with rickets bear weight on their bones, they bend. In the worst cases, a child may have trouble walking because of their bow-legs and generalized muscle and skeletal weakness.

“Ironically, two recent public health campaigns – one to get people to avoid sun exposure, and another to promote breastfeeding – are partially to blame for vitamin D deficiency. Deficiency is most prevalent in northern locales like Boston that receive less sunlight, and in dark-skinned children, whose pigmentation reduces absorption of ultraviolet rays. (In Gordon’s study of adolescents, 39 percent of African Americans were vitamin D-deficient, versus 13 percent of whites.)

Heeding public health warnings about skin cancer, parents are limiting their children’s sun exposure and slathering them with stronger and stronger sunblocks. But in the medical community, the question of whether sun exposure is bad is under hot debate. “The dermatologists say that no one should be out in the sun,” Gordon says. “I, and other endocrinologists, advocate a few minutes of sun daily for most patients before applying sunblock, to allow for vitamin D synthesis.

Except for people with a history of skin cancer, a reasonable recommendation is 10 to 15 minutes for fair-skinned people and 15 to 20 minutes for those who are darkly pigmented.”

Fear of cancer isn’t the only factor reducing kids’ sun exposure. They’re also spending more time indoors than a generation ago, lured by TV, movies and computer games. In poor urban neighborhoods, there may be few places to safely play outside, or working parents may be unable to supervise them. “A lot of moms we see are single mothers, and they’re just so busy that their child doesn’t get out enough,” says Stephanie Bristol, a research assistant on Gordon’s study of infant vitamin D deficiency. Reduced consumption of vitamin-D-fortified milk is compounding the situation.

Current guidelines recommend at least 200 international units of vitamin D daily for children, and Gordon advises at least 400. Many children, substituting juices and soft drinks for milk, aren’t meeting either target. Juice consumption has increased in preschoolers, and almost 90 percent of 1-year-olds drink juice, most of which isn’t fortified with vitamin D. In addition, with greater awareness of milk allergy and lactose intolerance, more babies and toddlers are drinking soy milk, rice milk and other milk substitutes that often lack vitamin D. And then there are the exclusively breastfed babies, who receive no fortified milk or formula.

Breast (plus vitamin D) is best

You can’t visit Children’s Primary Care Center without seeing the posters: “Making milk is easy!” Or “Breastfeeding: Simply the healthiest choice.” Jessica Roman, mother of 1-year-old Secarra Little, firmly agrees. “Breast is best,” she says. “Jessire, my older daughter, was breastfed until she was 2 years and 9 months old. Neither she nor Secarra have ever had ear infections or a fever for more than a day.”

Yet Secarra was found to have an alarmingly low vitamin D level that might have been missed had she not had a well-baby visit at the age of 9 months, while Gordon’s vitamin D study was underway. Secarra entered Gordon’s study and began receiving vitamin D and calcium supplements. After six weeks, her levels returned to normal and are being maintained with a multivitamin. Roman now wants to have Jessire’s vitamin D levels tested. “We are watching Jessire more carefully,” she says. “The study made us more aware of their calcium and vitamin D intake and the foods that we choose.”

Working on nothing

As puberty approaches, children have another window to build up their bone mass. During adolescence, they acquire more than half the bone calcium they will have as adults. “Adolescence is a critical period for lifetime bone health,” says Gordon. “It’s also when anorexia typically strikes.”

It struck Caroline Dragani, now a second-grade teacher, at age 13. Originally slightly overweight at 150 pounds and 5’4″, and fueled by depression and anxiety, she began to lose weight precipitously. Just before she was to start high school, Caroline’s weight fell from 115 to 102 in a single week, leading to her first hospitalization.

“I was not eating anything,” she recalls. “I was walking, running, on the exercise bike, doing sit-ups, exercising any time I could. I was not drinking milk – my body was working on nothing.”

Caroline kept losing weight, hitting 91 pounds, then 86 and ultimately 78 pounds at age 15. “That’s when a lot of the bone loss started to take place,” she says.

Hormonal havoc

In her emaciated state, Caroline stopped menstruating – in fact, she’d had only one period before her anorexia struck. Her Children’s physician, Estherann Grace, MD, put Caroline on birth control pills to adjust her hormone levels so she’d start menstruating again.

Estrogen, a hormone that regulates the menstrual cycle, is made by fat tissue and often declines with severe weight loss. Too much exercise can also shut down estrogen production. Caroline’s estrogen levels were so low they couldn’t be measured. The low estrogen and other hormonal changes were depleting Caroline’s bones. Bones constantly remake themselves, periodically breaking down old bone, a process called resorption, and replacing it with new bone. Normally, hormones keep resorption and formation in balance. But anorexic patients are low in

Bones constantly remake themselves, periodically breaking down old bone, a process called resorption, and replacing it with new bone. Normally, hormones keep resorption and formation in balance. But anorexic patients are low in estrogen, which reduces bone resorption; high in cortisol, which increases bone resorption; and low in androgens, which promote bone formation. As bone loss outpaces formation, their bones become extremely brittle, increasing their fracture risk seven-fold. But Caroline had more life-threatening problems. “My electrolytes were all thrown off,” she says. “My blood pressure was wacky, and when I hit 80 pounds, my heart rate was in the 30s, which is about as low as you can go.” A negative affirmation At this point, Grace was monitoring Caroline weekly. In her sophomore year of high school, Caroline – severely depressed and apathetic about her health – spent a week in the hospital for bed rest, IV fluids and heart monitoring. “I just wanted to be thin,” she says. “If you had told me then that I had bone loss, it would have been another affirmation for me that I was abusing myself. The disease is about self-destruction.” It was around this time that Caroline first met Gordon. “She knew what she needed to do. But she couldn’t bring herself to eat,” Gordon recalls. I was really worried about her.” Since the greatest gains in bone density come from simply gaining weight, Caroline embodied the core problem in trying to treat bone loss in anorexic patients. Gordon wondered if she might have more success with hormonal therapies.

But Caroline had more life-threatening problems. “My electrolytes were all thrown off,” she says. “My blood pressure was wacky, and when I hit 80 pounds, my heart rate was in the 30s, which is about as low as you can go.”

A negative affirmation

At this point, Grace was monitoring Caroline weekly. In her sophomore year of high school, Caroline – severely depressed and apathetic about her health – spent a week in the hospital for bed rest, IV fluids and heart monitoring. “I just wanted to be thin,” she says. “If you had told me then that I had bone loss, it would have been another affirmation for me that I was abusing myself. The disease is about self-destruction.” It was around this time that Caroline first met Gordon. “She knew what she needed to do. But she couldn’t bring herself to eat,” Gordon recalls. I was really worried about her.” Since the greatest gains in bone density come from simply gaining weight, Caroline embodied the core problem in trying to treat bone loss in anorexic patients. Gordon wondered if she might have more success with hormonal therapies.

Estrogen replacement, the same therapy used in postmenopausal women, is often used in anorexic patients, but its effectiveness in treating bone loss is unclear. So Gordon decided to study dehydroepiandrosterone (DHEA), a hormone that is at low levels in anorexic patients.

Perhaps replacing it could help these emaciated young women regain their bone mass. Grace urged Caroline to enroll in the DHEA study, and Caroline figured she had nothing to lose.

“I knew bone loss wasn’t healthy, but I wasn’t really that concerned,” she says. “I figured it was an old people thing. But Dr. Gordon made me want to be healthy. She made me feel like I was helping her, and that made me feel good about myself.”

A wake-up call

On entering Gordon’s study, Caroline had a bone scan with dual-energy X-ray absorptiometry, a relatively new technology that measures bone density at the hip and spine. “Her bone mass was at least 20 percent below where it should have been,” Gordon says. “It was approaching the range that, in an adult, would be considered osteoporosis.”

The study randomly assigned 61 young women to take DHEA or conventional estrogen therapy. Over the course of a year, both groups gained weight, improved their hip bone density and maintained their spinal bone density. But the DHEA group also had improved psychological measures and more markers of bone formation in their blood.

Hoping to get greater gains in bone density, Gordon has begun a new study combining DHEA with standard estrogen therapy. Caroline, one of those who received DHEA in the initial study, gained weight, became less depressed, started menstruating again and built back 11 percent of her bone.

“I was rejoicing,” she says. “I had a boyfriend, I had aspirations. I didn’t want to be 30 and start having a dowager’s hump. I wanted to be healthy.”

DHEA treatment was one of many factors that were gradually helping Caroline recover from her anorexia. An important factor was learning that low estrogen levels would make it hard to get pregnant, and that osteoporosis would make pregnancy dangerous since the growing fetus can deplete its mother’s bone calcium.

Today, at 26, Caroline’s bone density is in the normal range. “Being in the study had a role in my recovery,” she says. “Getting all this health information kind of brought me to my senses.”

Little old lady bones

A variety of other factors can cause children to lose bone, but before programs like Gordon’s, bone density scanners could only be found at adult hospitals. When bone loss was even recognized as a possibility in children, they would often have to wait for their bone scans in a room with elderly women, and then be told, “Your bones are like a little old lady’s.”

“Sometimes I feel funny as a pediatrician, going to seminars on osteoporosis and postmenopausal women,” Gordon says. “Most of my training in the past decade has come from adult endocrinologists and geriatricians and I try to translate that to children. This whole field has evolved in a very short period of time.”

(Source: Children’s Hospital Boston: Nancy Fliesler: October 2006.)