'Preventing Osteoporosis With Drug Therapy'

 Prevention of osteoporosis should be considered before a bone break occurs, and many patients at risk for the chronic bone condition may benefit from pharmacologic options.

"Most current guidelines focus on fracture risk stratification with the idea that we use non-pharmacological therapy for low-risk patients, antiresorptive therapy for high risk, and we consider anabolic therapy for very high-risk patients," said E. Michael Lewiecki, MD, of the University of New Mexico Health Sciences Center in Albuquerque.

"But I think an argument can certainly be made for drug treatment to prevent osteoporosis in women with T-scores above -2.5 [the threshold for osteoporosis] who have not had a fracture and are not at high risk," he said at the American Society for Bone and Mineral Research annual meeting.

Rationale for Prevention

Interventions for osteoporosis are necessary to prevent bone loss and the irreversible deterioration of bone microarchitecture, especially during the menopausal years, said Lewiecki.

In a recent review, Ian Reid, MD, of the University of Auckland in New Zealand, and Michael McClung, MD, of the Oregon Osteoporosis Center in Portland, argued that doctors "should move away from making treatment decisions based solely on T-scores, but focus on identifying and treating patients at increased risk of fracture based on the totality of their clinical picture."

While a T-score of -2.5 or lower denotes osteoporosis, bone mineral density (BMD) between -2.5 and -1.0 fall within the range of osteopenia.

"Although fracture risk is often lower in osteopenic women than in those with osteoporosis, their greater number means that most fractures occur in osteopenic individuals," wrote Reid and McClung. "Fracture risk varies widely in the osteopenic range, depending on factors including BMD, age, fracture history, and nationality and ethnicity."

FDA-Approved Preventive Therapies

Many of the currently approved antiresorptive treatments for osteoporosis also have indications for the prevention of osteoporosis. While some are dosed the same for prevention and treatment, some may be dosed lower or less frequently when used for prevention.

Drugs that can be used for prevention include hormonal options like estrogen and estrogen-progesterone, as well as the selective estrogen receptor modulator raloxifene.

The American Association of Clinical Endocrinology (AACE) 2020 osteoporosis clinical practice guidelines point out that while estrogen is FDA-approved for osteoporosis prevention in postmenopausal women, it comes with the added caveat that "when prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate."

Other approved prevention options include denosumab, as well as bisphosphonates like alendronate, risedronate, ibandronate, and zoledronic acid, also known as zoledronate.

For women early in menopause, and especially those with vasomotor symptoms, a hormonal option like estrogen may be a preferred prevention strategy, Lewiecki noted. But if breast cancer is a concern and vasomotor symptoms aren't, he said bisphosphonates may be the preferred choice.

"Especially attractive in a lot of patients ... is zoledronic acid because of its infrequent dosing intervals, [with data] suggesting it works well for 5 years or even longer," he said, referring to a landmark randomized trial published earlier this year that included 1,054 early postmenopausal women with average T-scores at the lumbar spine or hip indicating normal BMD at baseline.

Over 10 years of follow-up, a new morphometric vertebral fracture occurred in 6.3% of women who received a dose of zoledronate at baseline and again at 5 years, in 6.6% of those who received a dose of zoledronate at baseline and then placebo at 5 years, and in 11.1% of those who received placebo at both time points.

Study author Mark Bolland, MBChB, PhD, of the University of Auckland, previously told MedPage Today that clinicians should discuss infrequent zoledronate dosing as a primary prevention strategy with their patients at low or intermediate risk of fracture, as opposed to waiting until they are at high risk.

When it comes to using drugs for prevention, Reid and McClung said patient motivation for receiving medication for fracture prevention "varies widely."

"In those who are enthusiastic, the doctor's responsibility is to ensure that treatment is safe for the particular individual, and that the intervention meets the thresholds for cost-effectiveness," they wrote. "The low cost of these agents does not mean that all patients should be actively encouraged to take these medicines, even if they are cost-effective, because in those with a very low fracture risk, the number needed to treat to prevent a fracture makes the effort of regular medication difficult to justify for a reluctant patient, and the risk of atypical femoral fractures could outweigh any benefit."

"Such judgements are subjective and, when fracture risk is low, should be patient-led for optimal adherence," they added.

Beyond antiresorptive medications, anabolic bone-building medications, including teriparatide, abaloparatide (Tymlos), and romosozumab (Evenity), should be considered for those at high risk for fracture, said Reid and McClung. However, these agents are only approved for the treatment of -- and not the prevention of -- osteoporosis.

Disclosures

Lewiecki reported relationships with Amgen, Ascendis, Ardius, and Ultragenyx.

Reid reported relationships with Amgen, Abbott, and Medison Pharma.

McClung reported relationships with AbbVie, Theramex, Alexion, Amgen, Radius Health, Bristol Myers Squibb, the International Osteoporosis Foundation, and the Menopause Society.

Bolland reported a relationship with the Health Research Council of New Zealand.

https://www.medpagetoday.com/spotlight/asbmr-osteoporosis/117887