Screening, treatment of osteoporosis in premenopausal women unclear

Osteoporosis is uncommon in premenopausal women, and most cases have a secondary cause. But recent research suggests that a higher percentage of premenopausal women than previously reported may have idiopathic osteoporosis, in turn experiencing one or more low-trauma fractures and/or having very low bone density.

In a 2009 study published in the Journal of Women’s Health, researchers at Columbia University evaluated 61 premenopausal women at an osteoporosis referral center. Of these women, 39% were considered to have idiopathic osteoporosis, with no known secondary cause identifiable.

“It is important to evaluate premenopausal women for secondary causes of osteoporosis in order to guide treatment of their condition,” Adi Cohen, MD, of the division of endocrinology in the department of medicine at Columbia University College of Physicians and Surgeons, told Endocrine Today. “In some women, no secondary cause can be found — more information is needed to determine appropriate clinical management for these women.”

Adi Cohen, MD, said appropriate clinical management is needed for premenopausal women with low bone density. Photo Courtesy of Jima Ware/New York-Presbyterian Hospital

“There is an important distinction between people diagnosed on the basis of low bone density and those diagnosed based upon fracture. Those who have low trauma fractures are said to have osteoporosis, but those who have only low bone density and no known secondary cause may or may not actually have compromised bone strength,” Cohen added.

Fractures and low bone mass are less common in premenopausal women than postmenopausal women and are usually attributed to secondary causes such as estrogen deficiency, glucocorticoid exposure or hyperparathyroidism, according to Cohen. Low bone mass in premenopausal women may be related to inadequate peak bone mass acquisition or ongoing bone loss.

Little data exist to guide clinical care for premenopausal women with low bone density (z score ,–2) and fragility fractures. Endocrine Today interviewed several experts about premenopausal bone disorders, screening and what can be done to prevent osteoporosis.

Who to screen, who not to screen

Bone density screening by DXA is not routinely recommended to define osteoporosis in premenopausal women.

“Bone density measurements do not clearly predict fracture risk in young premenopausal women the same way that they do in postmenopausal women. Data obtained from a bone density test in a younger woman are not nearly as helpful in determining the need for treatment,” Cohen said.

Steven Petak

Steven Petak, MD, director of the osteoporosis center and bone densitometry unit at the Texas Institute of Reproductive Medicine and Endocrinology in Houston, said in an interview that, “if women have fractures and low bone density or fragility fractures, then they could have osteoporosis, but bone density numbers from the World Health Organization are designed for postmenopausal women and, therefore, we do not use the same classification.”

“I see a few patients each year with low bone mass who are young,” Clifford J. Rosen, MD, senior scientist at Maine Medical Center Research Institute in Scarsborough, told Endocrine Today. “I do not advocate screening in young women — even with positive family history.”

The International Society for Clinical Densitometry recommendations for bone density screening include women aged 65 years and older, postmenopausal women aged younger than 65 years at risk for fracture, women transitioning into menopause with clinical risk factors for fracture, men aged 70 years and older, and men aged younger than 70 years with clinical risk factors for fracture. A number of other major organizations provide recommendations for bone mineral density testing in premenopausal women (see sidebar).

“We all see on referral younger women in whom a bone density has been performed and reported as abnormal,” Michael Kleerekoper, MD, Endocrine Today editorial board member, wrote in an EndocrineToday.com blog.

Kleerekoper said it is a mistake to conduct bone density screening in healthy young women “because by definition 16% of them will have a T-score below –1 and may be given an incorrect diagnosis of osteopenia — a term that should only be used for postmenopausal women. In fact, the ISCD recommends the term ‘low bone mass’ instead of osteopenia for all patients in whom the T-score is between –1.0 and –2.5.”

On the other hand, bone density measurement is recommended for premenopausal women with known secondary causes of osteoporosis or history of fragility fracture.

“There are categories of young women who should have bone density testing, and that includes women who have a secondary cause of osteoporosis, such as glucocorticoid treatment, gastrointestinal malabsorption, anorexia nervosa or other causes of amenorrhea,” Cohen said.

Although there are many conditions, diseases and medications that may prompt a bone density test, “for the otherwise young, healthy woman who does not have these risk factors, women should be reassured that their risk for osteoporosis is small, even if their bone density is low,” Petak said.

The most important issue is ordering the correct test or procedure in the correct patient, according to Kleerekoper, an endocrinologist at St. Joseph Mercy Hospital in Ann Arbor, Mich. “Bone density measured by DXA is a valuable tool, but technology will change dramatically in the next 20 years, so it may be pointless for young, premenopausal women to undergo this testing.”

Medical record review

In the Journal of Women’s Health study, Cohen and colleagues reviewed medical records for all premenopausal women with low BMD and/or low-trauma fracture evaluated at the Columbia University referral center during 2005 (n=61; mean age, 37 years; 93% white). Fifty-seven percent of women had a family history of osteoporosis and 43% had been given bisphosphonates. The researchers aimed to estimate the proportion of premenopausal women with idiopathic osteoporosis as opposed to secondary osteoporosis.

The most common secondary causes of osteoporosis were amenorrhea (34%), anorexia nervosa (16%) and glucocorticoid exposure (13%). After exclusion of secondary causes, 39% of the overall cohort and 48% of women with fractures had idiopathic osteoporosis.

“A certain percentage of the group did not have any cause after extensive evaluations,” Cohen said. “We learned a lot from this chart review.”

In addition, women with known secondary causes had lower BMD z scores at the spine and hip compared with those with idiopathic osteoporosis. Women with low BMD and no fractures had shorter stature and weighed less than women with fractures. “The smaller stature of women diagnosed only on the basis of BMD criteria raises the question of whether their areal BMD measurements are spuriously low because of smaller bone size,” the researchers wrote.

Two details from this study stand out, Kleerekoper wrote in a related blog posting. “The first is that smaller women tended to have lower BMD, underscoring the limitations of this 2-D approach to ‘density.’ The second is that a substantial proportion of the women identified as having secondary osteoporosis or idiopathic osteoporosis had been prescribed bisphosphonate therapy prior to referral, including six of the 10 with low bone mass, no identified secondary cause for bone loss and no history of fracture.”

Other risk factors for bone loss

Michael Kleerekoper

“The list of secondary causes of low bone mass in premenopausal women is quite long but not too different from the list that applies to postmenopausal women,” Kleerekoper wrote in his blog. Factors associated with low bone mass in premenopausal women include estrogen deficiency, age, weight changes, physical activity, BMI, smoking, alcohol intake, calcium and vitamin D deficiency, a family history of osteoporosis and pregnancy.

Treatment in women taking glucocorticoids may require special consideration. Data suggest that vertebral fractures can occur despite normal BMD in this population. In a Journal of Rheumatology study conducted by Kumagai and colleagues, seven of 16 premenopausal women treated with high-dose glucocorticoids had evidence of vertebral fractures despite normal BMD.

When looking at bone density in premenopausal women it is also important to consider reproductive history because of decreases that occur during pregnancy and breastfeeding. Results of some studies have suggested that normal pregnancy and lactation lead to bone loss in about 5% to 10% at the spine and hip. Bone loss reverses after weaning but may take as long as 18 months or more to be restored to baseline levels.

“Timing of pregnancy should be taken into account whenever one interprets bone density measurements in a premenopausal woman,” Cohen said. “Bone density measured 18 months postpartum or about one year after weaning may give a better idea of what the baseline is.”

Women with eating disorders, female athletes who develop exercise-induced amenorrhea and women who have been assigned to chemotherapy or who have hematologic disease are also at increased risk for osteoporosis. Others at risk include women with gastrointestinal disorders, celiac disease, Cushing’s disease and those who have undergone bariatric surgery and have vitamin D absorption problems, according to Petak.

According to Cohen’s data published on UpToDate.com, in women who are not having regular periods, one of the first things to do to help treat low bone density, fractures or osteoporosis would be to restore estrogen, according to Cohen.

Although some physicians may offer oral contraceptives as a form of treatment, Michelle Warren, MD, professor of medicine and obstetrics and gynecology at Columbia University, said that this is not effective.

“It’s time to take another look at why we are using oral contraceptives for patients who have nutritionally based problems with their bones. The physiology is different and the treatment is improving nutrition, not giving medication,” she said in an interview. “Oral contraceptives are not a ‘quick fix’ in preventing bone loss in premenopausal women; it needs to be looked at on a case-by-case issue.”

Petak added that birth control may be useful in women in a hypoestrogenic state, “but if the patient has anorexia, their nutritional needs are much more important.”

History of fracture

Personal history of fracture is a significant factor in premenopausal osteoporosis, according to Kleerekoper.

In some women who have multiple fractures, treatment with a medication may be indicated. Currently, bisphosphonates are the only FDA-approved medication for use in premenopausal women, but only in those taking steroids. Cohen expressed “great caution” for bisphosphonate use in premenopausal women “because the long-term effects, in particular the effect on future pregnancies, are not entirely known.” Kleerekoper would also not recommend bisphosphonate treatment in premenopausal women in most circumstances.

In the Columbia University study, 38% of women with a fracture history and 47% of women with low BMD and no fractures had been prescribed bisphosphonates. Cohen said she and colleagues “were surprised to see that many women who did not have a fracture history had been treated with bisphosphonates … more than what we expected, given the potential risk of this medication in premenopausal women.” A more conservative approach to therapy is preferable in this group, according to the researchers.

Cohen and colleagues are currently recruiting women aged 20 to 48 years for an interventional study of idiopathic osteoporosis. Participants will be assigned 18 months of teriparatide, and researchers will assess treatment effects on BMD and microstructure, bone mechanical competence and bone turnover. The hypothesis is that teriparatide will significantly increase bone density and improve bone structure in premenopausal women with idiopathic osteoporosis.

Preventing, treating low bone mass

Lifestyle modification is encouraged for all women with low bone mass. Data have indicated that an increase in sedentary lifestyles among young children has contributed to the increase in low bone density, according to Petak.

“Peak bone mass does not occur until one is in their mid-to-late 20s, and it is very important in childhood and young adulthood to have sufficient calcium, vitamin D and exercise so that a person can achieve as much bone as they are genetically supposed to,” Petak said.

“The amount of bone put in the ‘bone bank’ during the childhood and teenage years is pretty much all we will deposit. Osteoporosis has been described as a childhood disease that presents in adulthood because people may not be achieving the amount of bone they need for later in life.”

Despite routine screening not recommended for premenopausal women, in a 1999 study conducted by Jamal et al, whose results were published in the Journal of Bone Mineral Research, researchers found an increase in positive lifestyle changes when bone density testing was combined with bone health education among 669 premenopausal women. Twelve months after the study intervention, women were less likely to use alcohol, cigarettes or caffeine, and those with low BMD were more likely to take calcium and vitamin D supplements.

On a related note, data published in Pharmacotherapy this year indicate that more premenopausal women are seeking evaluation for osteoporosis from health care providers.

“It is more common today from previous years to find patients with low bone density,” Petak added. “We are seeing more of these consultations, and what is contributing to this is the increase in awareness and the use of bone densitometry. People are becoming more and more aware of what is out there and available for them.” – by Jennifer Southall

How has DXA reimbursement affected your practice?

For more information:

• Cohen A. J Womens Health. 2009;18:79-84.
• Jamal SA. J Bone Miner Res. 1999;14:2143.
• Kleerekoper M. Osteoporosis in premenopausal women. Endocrine Today website. endocrinetoday.com/comments.aspx?rid=41724. Published July 16, 2009. Accessed Sept. 17, 2009.
• Kumagai S. J Rheumatol. 2005;32:863-869.
• UpToDate website. uptodate.com. Accessed Sept. 17, 2009.
• Vondracek SF. Pharmacotherapy. 2009;29:305-317.