Osteopenia Warrants Treatment—Selectively—to Reduce Fracture Risk

Post-menopausal women who do not meet the definition of osteoporosis may be candidates for earlier intervention with bisphosphonate therapy.

With Ian R. Reid, MD, and Ethel Siris, MD

That osteoporosis represents a growing health concern is unequivocal.1 Despite the elevated risks of morbidity and mortality associated with fragility fractures, there are no current recommendations regarding treatment for post-menopausal women with osteopenia.2,3

Need to treat older Women with osteopenia advocated with new evidence.

The evidence suggests a need to reconsider the role of and risks associated with osteopenia in aging women.

The reason—the vast majority of fractures occur in women who are diagnosed as having osteopenia, which is defined as a T-score ranging from -1 to -2.5.4,5 Many of these women will be at elevated risk for fracture, not necessarily because they have low T scores but because, in addition to low T scores, they present with other relevant risk factors—older age, postmenopausal status, and history of prior fracture.

The clinical trend has been evolving as to the right timing for initiating bone density treatment based on absolute fracture risk,1and that tipping point—demonstrating treatment efficacy for women with osteopenia at higher risk—has arrived.

“Osteopenia, frequently considered just a risk factor, when combined with an elevated FRAX score that confirms an elevated risk of fracture, will lead to a clinical diagnosis of osteoporosis,” said Ethel Siris, MD, the Madeline C. Stabile Professor of Clinical Medicine in the Department of Medicine at the College of Physicians and Surgeons of Columbia University, and the Director of the Toni Stabile Osteoporosis Center of the Columbia University Medical Center in New York City.

Osteopenia is not a very useful term, according to Nelson B. Watts, MD, professor of medicine and Director of the University of Cincinnati Bone Health and Osteoporosis Center in Ohio who has been advocating for the elimination of this term as a diagnostic measure for more than a decade.

While the shift in managing low bone density has been slow, clinical consideration is beginning to shift away from waiting for a diagnosis of osteoporosis before initiating treatment in women deemed at risk for fracture defined solely by a bone mineral density (BMD) score, which, until now, has been considered the more reliable and only diagnostic means of identifying significant risk for fracture.7,8

Data Supports Treating Some Women with Osteopenia

While bisphosphonates are demonstrated to reduce fracture risk in women with overt osteoporosis, most fractures occur in post-menopausal women diagnosed with osteopenia. Until now, the efficacy of treating these at-risk patients remains uncertain.

Taking on this clinical question, a team of researchers from Auckland University examined the efficacy of zoledronate (ZOL) compared with placebo to assess for a difference in fracture risk in a six-year, double-blind clinical trial.9

Ian R. Reid, MD, and colleagues followed 2000 postmenopausal women, ages >65 years, who had a T score of −1.0 to −2.5 at either the total hip or femoral neck. Participants were randomized to receive either zoledronate (5 mg) or placebo (a saline solution) at 18-month intervals.9

These women also received vitamin D supplements—a single oral dose of cholecalciferol one week before their first infusion and then once a month throughout the trial duration— if they were not already taking them; calcium supplementation was recommended but not required. The investigators selected zoledronate because it is administered via intravenous (IV) injection no more than once annually, and has a satisfactory safety profile.9

At baseline, the mean age of the enrolled women was 71.5 years; the mean T score at the femoral neck was -1.64 (+0.5) and -1.27 at the total hip, and the median 10-year risk of hip fracture was 2.3%. A total of 312 fragility fractures were recorded in 190 women receiving placebo and 122 women in the ZOL group (< 0.001).

The group receiving ZOL also had a significantly lower risk of nonvertebral fragility fractures, symptomatic fractures, vertebral fractures, and height loss.9

Twice as many women discontinued the trial after the first infusion of ZOL (n=86) versus placebo (n=42 ). During the trial, 115 women in the placebo group and 33 women in the treatment group initiated oral bisphosphonate treatment (subsequent study treatments were discontinued but these patients remained in the study).9

The women in the treatment group also appeared to gain added protection against cancer, stroke, and cardiovascular events, with a 35% reduced risk for death with zoledronate.  

Forming a Better Management Strategy for Bone Fragility

In a conversation with EndocrineWeb about the study findings, Ian R. Reid, MD, professor of medicine on the Faculty of Medical and Health Sciences at the University of Auckland, New Zealand, said, “the benefits of zoledronate were quite substantial.”

The investigators chose to prescribe zoledronate every 18 months, rather than every 12 months as has been the case for standard management of osteoporosis,9 said Dr. Reid, who explained that infusions every 18 months proved a very convenient and effective protocol for treating older women who were considered at risk for fragility fractures. 

Dr. Siris said, “this well-designed, well-conducted prospective clinical trial demonstrated that zoledronate works to prevent fractures in older (> 65 years) osteopenic postmenopausal women at elevated risk of fracture.”

However, she cautioned clinicians against giving zoledronate (or other bisphosphonates) indiscriminately to every woman who presents with osteopenia. Women with confirmed osteopenia but without any other risks for fracture are not candidates for this approach to preventive treatment.

“Most women in their early 50’s have a very low risk of fractures in the next five to 10 years, whereas most fragility fractures occur after age 65,” said Dr. Reid.

Both Dr. Reid and Dr. Siris agreed that this study provides an excellent opening to explore the timing of treatment in post-menopausal women and to begin filling in missing data, as the results of this study clearly demonstrated fracture risk reductions with this specific pharmacotherapy in a group of older osteopenic patients at risk for fracture.

Clinicians now have evidence to support the benefits of treating osteopenia to avoid fractures, in the many women who may be at risk in the rapidly growing baby-boomer population.

When to Treat?  Wait for Changes in Age, T Score, Other Risks 

Younger women, under 50 years, and those who have not yet reached menopause remain at low risk for fracture even with osteopenia. There is no evidence that treating these patients will reduce their risk because it’s already low,  Dr. Siris said, “and medications are not without risks.”

However, should the risk of fracture increase—change in age, lower T score, a decline in FRAX score— such that the patient profile meets the NOF criteria for clinical osteoporosis, it would be appropriate and justifiable to initiate treatment for fracture prevention, according to both Dr. Reid and Dr. Siris.

It bears repeating, as patients may inquire about treatment—a diagnosis of osteopenia is not indicative of a need for active intervention, in and of itself. Only when the patient’s risk changes would it be warranted to revisit the decision to treat. It is not about waiting for a fracture to occur but rather seeing if the fracture risk changes before clinicians might justify treatment, said Dr. Siris.

Facing Concerns of Osteopenia in Your Patients 

When the patient has osteopenia and an elevated FRAX score or is deemed at high risk for fracture, this would be considered a clinical diagnosis of osteoporosis, according to the NOF, who would likely benefit from treatment with zoledronate, Dr. Siris told EndocrineWeb.

The findings of this study, supported by the National Osteoporosis Foundation guidelines, should become sufficient for insurance reimbursement in patients with a current diagnosis of osteopenia deemed at risk for fracture, and fitting the proposed profile for pharmacological intervention.  

Neither clinician has any known financial conflicts with regard to this study. The trial was supported by grants from the Health Research Council of New Zealand. Trial medication was supplied by Novartis.

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