New ACP Guidelines on the Treatment of Osteoporosis

Pam Harrison

May 08, 2017

Physicians should treat women with osteoporosis with one of the three main bisphosphonates or the biologic denosumab for a duration of 5 years, during which time monitoring of bone-mineral density (BMD) is not necessary, according to new clinical guidelines from the American College of Physicians (ACP).

The ACP also advises physicians to prescribe generics over brand-name drugs whenever possible and to discuss medication adherence with their patients, especially for bisphosphonates.

The recommendations were published online May 8 in the Annals of Internal Medicine, and have been endorsed by the Academy of Family Physicians

At the same time, the ACP does not recommend physicians use hormone-replacement therapy (HRT), given either as estrogen alone or in combination with progestogen, citing a lack of evidence supporting its effectiveness to prevent fracture in postmenopausal women with osteoporosis, and "serious harms — such as increased risk for cerebrovascular accidents and venous thromboembolism — [that] significantly outweigh the potential benefits."

It also recommends against the selective estrogen-receptor modulator (SERM) raloxifene for the same indication, citing risks of cardiovascular disease (CVD) and thromboembolic events as reason enough to argue against its use.

But not everyone is in complete agreement with these latest guidelines, particularly with regard to the recommendation not to use HRT. In addition, some observers don't approve of the ACP's decision not to recommend use of the anabolic agent teriparatide.

In Support of HRT for Osteoporosis

In an accompanying editorial, while Eric Orwoll, MD, Oregon Health and Science University, Portland, Oregon, concurs with ACP's strong recommendation to offer treatment with a bisphosphonate or the biologic denosumab to women with osteoporosis, he takes issue with their recommendation not to employ HRT for the same indication.

In his view, HRT can be a reasonable option in select patients. "Estrogen replacement reduces fractures in postmenopausal women overall, and it is likely to do the same in osteoporotic women," he writes.

"Therefore, although estrogen should not be the first choice for osteoporosis therapy, if a woman is using estrogen for other reasons (such as menopausal symptoms), skeletal benefits can be expected without the addition of a second osteoporosis drug," Dr Orwoll observes.

And JoAnn Pinkerton, MD, University of Virginia Health System in Charlottesville, Virginia, and executive director, the North American Menopause Society (NAMS) told Medscape Medical News that her organization is about to release a position statement on the role of hormone therapy in the treatment of menopausal symptoms as well as osteoporosis.

"We reviewed all the literature and we can tell you that hormone therapy has been shown to be safe and effective for symptomatic menopausal women with benefits exceeding risk in healthy women who are under the age of 60 or within 10 years of menopause," she said.

"And in addition to relieving hot flushes, night sweats. and sleep disruption, hormone therapy — whether it's estrogen by itself, estrogen with progestogen for women with a uterus, or the new conjugated estrogen combined with the [SERM] bazedoxefine — all have been shown to prevent bone loss and reduce fractures as well," Dr Pinkerton stressed.

On the other hand, NAMS does not recommend hormone therapy for women who are over the age of 60 or who are more than 10 years out from menopause, because the absolute risk of heart disease, blood clots, and dementia is greater with age and thus the risk/benefit ratio for HRT is less favorable for these specific groups of women, she noted.

First ACP Recommendations on Osteoporosis in Almost a Decade

The ACP last issued guidance on the management of low bone density, or osteoporosis (T scores less than -2.5 or those who have experienced fragility fractures), for fracture prevention in men and women in 2008.

"One new biologic, denosumab [Prolia, Amgen], a human monoclonal antibody approved by the [US] FDA for treatment of osteoporosis has been added since publication of the 2008 guideline," lead author of the guidelines, Amir Qaseem, MD, PhD, American College of Physicians, Philadelphia, Pennsylvania, and colleagues write. "And the target audience for this guideline includes all clinicians and the target patient population includes men and women with low bone density and osteoporosis."

Additional recommendations from this latest ACP 2017 publication include the following:

  • The ACP recommends that physicians offer men with osteoporosis treatment with a bisphosphonate to reduce the risk of vertebral fracture. "The evidence specifically for men is spare," Jack Ende, MD, ACP president says in a statement. "However, the data did not suggest that outcomes associated with drug treatment would differ between men and women if based on similar bone-mineral density, so treatment for men may be appropriate." Physicians may choose alendronate, risedronate, or zoledronic acid when using a bisphosphonate to treat osteoporosis in men or in women.

  • The ACP recommends that physicians decide whether or not to treat osteopenic women 65 years of age and older who are at high risk for fracture based on their individual fracture profile and patient preference.

The guideline authors also reviewed evidence on the role of calcium and vitamin D on fracture risk as well as the effect that physical activity might have on the same end point and concluded that evidence is insufficient to recommend calcium, vitamin D, or physical activity on their own as a means of preventing fracture in any group of patients.

They also point out that the evidence does not support frequent monitoring of women with normal BMD for osteoporosis, as most of these women do not develop osteoporosis over time.

 "As a general rule, physicians should prescribe generic drugs as a way to keep treatment costs down and to improve adherence because cost is part of adherence as well. Medication adherence is an important part of treatment because patients with osteoporosis often do not feel any symptoms while taking medications," Dr Ende added.

Anabolic Agents Should Be Considered, Says ASBMR

Commenting further on the treatment of osteoporosis in his accompanying editorial, Dr Orwoll points out that while the ACP guideline committee did not feel that evidence supporting teriparatide, an anabolic agent, was adequate enough to recommend it as first-line treatment, "teriparatide may be particularly attractive in the setting of sequential therapy," Dr Orwoll observes.

Furthermore, abaloparatide (Tymlos, Radius Health), a similar drug to teriparatide that has just been approved by the FDA for osteoporosis patients at high risk of fracture, will provide physicians with yet another option if they wish to treat patients with an anabolic agent.

"Clinicians should take into account more than BMD in judging risk and in guiding therapeutic decisions….[That] is absolutely critical," Dr Orwoll cautions.

"Further, these guidelines are but one of several that exist, [and] clinicians must carefully examine the considerable differences among them," he suggests.

Asked by Medscape Medical News to comment on the new ACP guidelines, Benjamin Leder, MD, of Harvard Medical School, Boston, Massachusetts, and chair of the American Society of Bone and Mineral Research (ASBMR) Professional Practice Committee, congratulated the ACP for issuing new recommendations for the treatment of osteoporosis, if only to raise awareness that patients with this undertreated chronic disease deserve to be screened and treated for it.

For specialists, however, the fact that teriparatide was not listed as part of the recommended armamentarium for osteoporosis is an oversight, Dr Leder felt, as most would agree that anabolic therapy can play a role in specific types of patients.

Similarly, the SERM raloxifene was also not recommended by the ACP for use in any context. "Again, I think most specialists who treat osteoporosis would find that for a subgroup of patients, raloxifene is a very good medication," Dr Leder observes. Like all medications, raloxifene has side effects, but it has the added benefit of reducing the risk of breast cancer, he pointed out.

"And while raloxifene doesn't have hip-fracture efficacy, in a younger population where hip fracture is not an immediate concern, I think a lot of endocrinologists and rheumatologists would find its use beneficial," he observed.

Finally, in terms of the ACP's recommendation to limit the duration of therapy to 5 years, "I think some would say that's a bit strict."

"Obviously some patients should be treated for longer than 5 years while others should not be treated for the full 5 years, as they may reach their goals earlier, and continued therapy wouldn't be indicated," he concluded.

The guidelines were made possible by funding provided by the ACP. Dr Leder declared he receives research funding from Eli Lilly and Amgen and he has consulted for Merck, Eli Lilly and Amgen in the past as well.

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Ann Intern Med. Published online May 8, 2017. Article

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