Menstrual changes may signal early bone loss in girls, women

Obtaining a menstrual history, particularly from patients with unexplained osteopenia or fractures, is helpful.

Issue: February 2004

Karen K. Winer, MD [photo]

Karen K. Winer is a pediatric endocrinologist who studies the effects of hormonal insufficiencies.

A woman’s overall bone health is closely linked to her menstrual cycle, a fact that should be considered when treating girls and young women who present with no or low impact fractures or unexplained metabolic bone diseases, like osteoporosis and osteopenia.

Because orthopedic surgeons are typically the first clinicians to see these patients, they are in a good position to identify possible reasons for early bone loss, including an altered menstrual cycle, according to experts who spoke with Orthopedics Today.

“Peak bone mass is achieved usually in the late teens or early 20s. The ability to reach an optimal peak bone mass is based upon one’s genetic makeup in addition to various environmental, nutritional and other health factors during childhood. Once this peak bone mass is achieved, there is no further net increase in skeletal mass during the adult years,” said Karen K. Winer, MD, of the Endocrinology, Nutrition and Growth Branch, National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), in Bethesda, Md.

Prolonged menstrual cycle disruptions, chronic illness, excessive stress and some medications in childhood may affect bone mineral accrual and therefore compromise the peak bone mass level. This may lead to bone fractures and osteoporosis later in life, Winer said.

At risk for bone loss

“We’d like to really see the menstrual cycle viewed as a vital sign.”
— Lawrence M. Nelson

“It’s known that if the menstrual cycle is altered, particularly if a woman becomes amenorrheic,” said Sundeep Khosla, MD, professor of medicine and research chair, division of endocrinology and metabolism at the Mayo Clinic College of Medicine in Rochester, Minn. When diagnosing a female patient with signs of unexplained bone loss, the first thing that should be explored is the status of her menstrual cycle.

Knowing the menstrual history is integral to the diagnosis, gynecologist Lawrence M. Nelson, MD, MBA, told Orthopedics Today. “We’d like to really see the menstrual cycle viewed as a vital sign,” said Nelson, investigator, Developmental Endocrinology Branch, NICHD/NIH.

Often, menstrual irregularity lasting for three or more months that arises from premature ovarian failure or other causes goes undiagnosed, he said.

Get a menstrual history

Sundeep Khosla, MD [photo]

Sundeep Khosla studied rising numbers of forearm fractures in children, which may result from insufficient bone mass accrual.

“Part of the routine evaluation of a young woman who is supposed to be menstruating should be asking when was her last menstrual cycle, was it normal and are they coming regularly. We’d like to have that up at the top of the chart,” Nelson said. If the patient’s menstrual cycle is not normal, she should be referred to an endocrinologist, gynecologist or internist to figure out what’s going on, he said. “It might reflect an estrogen deficiency to some degree.”

If a girl or young woman is suspected of having reduced bone mineral density (BMD), Khosla suggested taking the following steps:

Obtain a thorough medical history, including assessment of menstrual history.
Order pertinent blood work, including CBC, blood calcium and phosphorous levels, and a liver and kidney test.
Investigate bone loss with radiographs, DEXA measurements of the spine and hip, etc.
If unexplained fractures or osteopenia are noted, refer the patient to an endocrinologist.

Lawrence M. Nelson, MD, MBA [photo]

Lawrence M. Nelson specializes in studying and treating premature ovarian failure.

“Those things at a minimum would be helpful in terms of speeding up the evaluation,” he said.

An orthopedic surgeon should also look for other factors that could interfere with sex steroid or estradiol production, including chronic diseases, certain medications, and poor dietary habits, all of which could cause a female to not obtain peak bone mass and put her at risk for losing BMD. “Extreme levels of athletic training or any ongoing stress to the body, such as dieting, can potentially interfere with the pituitary-ovarian axis and lead to low levels of estrogen,” Winer said.

The presence of the female athlete triad — the combination of abnormal menses or amenorrhea, eating disorders like anorexia, and stress fractures or early onset of osteoporosis — should be considered suspicious, she said.

According to Khosla, maintaining normal sex steroid and estradiol production is particularly important because it also affects bone mass accrual by aiding overall calcium economy and protecting the skeleton. Sex steroids directly act on bone and other tissues, he said.

Physiological changes

Recent studies into altering the menstrual cycle have identified some of the effects of disrupting sex steroid production, said Khosla, whose current research is in this area. “We’re starting to see reports of bone loss with Depo-Provera (Pfizer) … So anything that disrupts the normal menstrual cycle and causes a low estrogen state is going to cause problems with bone metabolism.”

Abnormal menses is not the only problem. In a study conducted by researchers at the University of Bonn, Germany, changes in bone metabolism markers were detected even during a normal menstrual cycle, according to Khosla. “They’re physiological changes, but they’re probably of importance.”

Without further data it’s hard to speculate whether the incidence of early bone loss due to menstrual problems is increasing, he said. “My clinical impression is it probably is because eating disorders and women being more involved in heavy athletics that lead to amenorrhea are becoming more common.”

For more information:

Zittermann A, Schwarz I, Scheld K, et al. Physiologic fluctuations of serum estradiol levels influence biochemical markers of bone resorption in young women. J Clin Endocrinol Metab. 2000;85:95-101.