Premenopausal Osteoporosis Poses Special Clinical Challenges

A woman being examined for bone density.
GagliardiPhotography / shutterstock.com

ATLANTA—Osteoporosis in premenopausal women is uncommon compared with its frequency in post-menopausal women, but when it is suspected, it poses some difficult questions for clinicians: How should it be diagnosed in this understudied population? If found, should it be treated—and how?

Elizabeth Shane, MD, professor of medicine at Columbia University and attending physician at New York-Presbyterian/Columbia University Medical Center, who gave the Oscar S. Gluck, MD, Memorial Lecture at the 2019 ACR/ARP Annual Meeting, said that although the data for osteoporosis in premenopausal women are limited, important points can help guide its assessment and management.

Limits of Bone Density Scores

She cautioned against an overreliance on bone density scores in premenopausal women in their diagnosis.

In women younger than 50 a low bone mineral density (BMD) score could be due to a low peak bone mass or just due to a small stature, Dr. Shane said, and is not necessarily a sign of a problem requiring medical intervention. “It may be that this person just comes from a family with low bone density.”

And a low BMD in women younger than 50 doesn’t carry the same risk of fracture; young women have more muscle mass than older women and fewer falls, for example.

Dr. Shane

What’s more, BMD score cut-off points for a diagnosis of normal bone mass, low bone mass and osteoporosis in post-
menopausal women were “never intended and shouldn’t be used” for diagnosis of premenopausal women, Dr. Shane said.

The International Society for Clinical Densitometry (ISCD) recommends that Z scores, which compare a patient’s bone density to that of a person of the same age and gender, be used in the assessment of premenopausal women instead of T scores, which compare a patient’s bone density to an average 30-year-old adult.

The ISCD recommendations for diagnosis of osteoporosis in premenopausal women are a BMD Z score of -2.0 or less plus a secondary cause of osteoporosis, or a history of vertebral or non-vertebral low-trauma fractures at a major site, whether or not the BMD is low.

Secondary Causes

The goal of an evaluation in this population is to identify secondary causes of osteo­porosis, particularly causes that are treatable.

“In my opinion, anybody who has a low T or Z score deserves an evaluation to make sure that there’s nothing going on that could be rectified, and perhaps improve their bone density by a targeted inter­vention,” Dr. Shane said. “If I see one hip fracture, that’s it for me.”

Common causes of osteoporosis in premenopausal woman include excessive gluco­corticoid use, premenopausal estrogen deficiency, gastrointestinal disease and effects of other medications, such as anti-epileptic drugs. But many cases are idiopathic, she said.

Tetracycline-labeled transiliac bone biopsy, primarily a research tool, may be indicated in patients who have unexplained low-trauma fractures and can help guide therapy in some cases, Dr. Shane said.

In a cross-sectional study, 64 women with idiopathic premenopausal osteoporosis—some with a fracture history and some with a low BMD—underwent central skeletal quantitative computed tomography (QCT) along with 40 healthy controls. Those with low BMD had a worse volumetric BMD and bone strength compared with controls than those with a fracture history.¹

Diagnosis is just the first tricky hurdle, Dr. Shane said. “The dilemma is whether you should treat at all, and then [the next step] if you decide that you must treat—for whatever reason you choose—is to decide how to treat,” she said.

Treatment Limits

Conservative steps, such as better nutrition, increased calcium and smoking cessation, all make sense, but they have minimal effects on BMD, she said, and this requires counseling. “You have to prepare them; this would … prevent them from getting worse [not make] them a lot better,” Dr. Shane explained.

Finding the secondary cause is the goal of the evaluation because “this often yields the largest improvements in bone density,” she said. “In some situations, like celiac disease, like hyperparathyroidism, it can be very effective to diagnose the underlying cause and treat it specifically.”

But generally, Dr. Shane said, “I think it’s rarely justified to treat a premenopausal woman [with osteoporosis] unless there are certain conditions. This is just my opinion.” For her, these conditions include fractures, ongoing bone loss or extremely low BMD scores—possibly –3.0 or worse.

Bisphosphonates should be used with caution in young women; teriparatide and denosumab are contraindicated in pregnancy; and selective estrogen receptor modulators (SERMs) should not be used to treat osteoporosis in premenopausal women, Dr. Shane warned.²

Bisphosphonates and teriparatide have been found to improve BMD in premenopausal women with secondary osteoporosis, but they’re only approved in women who are taking glucocorticoids, and no data suggest these drugs actually prevent fractures in these women.

In an open-label observational study at Dr. Shane’s center on teriparatide, among premenopausal women with idiopathic osteoporosis, researchers saw increases in BMD of the lumbar spine, hip and femoral neck, but a wide range in effects was seen.³

“It was quite a variable responsiveness to teriparatide,” Dr. Shane said. “We had four of the 21 [who] didn’t have any change in bone density at the spine by 12 months. They did come up a little bit by 18 months, but didn’t continue up.” The nonresponders had a significantly lower bone formation rate on baseline biopsy.

In a not-yet-published, federally funded, randomized, controlled trial of teriparatide in 41 premenopausal women with idiopathic osteoporosis, researchers found the treatment led to increased BMD, but 20% of women didn’t respond, she said.

The period after teriparatide treatment also poses a challenge, Dr. Shane noted.

“Do we need to treat premenopausal women afterward to prevent bone loss? It makes sense to me that we probably need to do it, but we don’t know what anti-
resorptive should be used,” she said. “I think it really depends on the individual situation. If it’s a woman who’s 48, not going to have any more children, you could definitely use a bisphosphonate. … If it’s somebody much younger and wants to have children, then you might want to avoid it. You might want to give estrogen in some situations.”

Thomas R. Collins is a freelance writer living in South Florida.

References

1. Cohen A, Dempster DW, Recker RR, et al. Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2011 Oct;96(10):3095–3105.
2. Eng-Wong J, Reynolds JC, Venzon D, et al. Effect of raloxifene on bone mineral density in premenopausal women at increased risk of breast cancer. J Clin Endocrinol Metab. 2006 Oct;91(10):3941–3946.
3. Cohen A, Stein EM, Recker RR, et al. Teriparatide for idiopathic osteoporosis in premenopausal women: A pilot study. J Clin Endocrinol Metab. 2013 May;98(5):1971–1981.