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AAOS Now

Published 6/1/2018
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Peter Pollack

Preventing Fractures in High-risk Women

According to Susan V. Bukata, MD, among postmenopausal women who are at high risk for fracture, treatment with abaloparatide can reduce clinically significant vertebral and nonvertebral fractures compared to both placebo and treatment with teriparatide.

Dr. Bukata presented her findings in two scientific posters displayed at the AAOS 2018 Annual Meeting.

“Abaloparatide is a parathyroid hormone-related protein similar to teriparatide,” Dr. Bukata continued. “One of the notable things about our study is that it directly compares abaloparatide not only to placebo, but to teriparatide as well. There aren’t many osteoporosis studies that offer direct comparison of two treatment options.”

One trial, two studies

The researchers conducted a single trial of a single patient population. Of the two posters, the first compared the preventative effects of the two medications and placebo on clinical vertebral fractures, using a primary endpoint of radiographically identified new vertebral fractures, evaluated at baseline and at the end of study. The second poster compared the effects of treatment on nonvertebral fractures based on a composite endpoint comprising fractures of the hip, pelvis, femur, proximal tibia (excluding the knee and ankle), ribs, proximal humerus (upper arm or shoulder), and wrist/forearm, while excluding fractures linked to high trauma.

“Vertebral fractures are a little bit different from nonvertebral fractures,” Dr. Bukata noted, “in that we know only about a third of vertebral fractures actually present with clinical symptoms. Patients tend to seek medical help only when they’ve had a certain amount of pain over a long enough period. In about two-thirds of cases, the patient might have back pain for a few days, but it doesn’t necessarily persist and they rarely present to a physician.

“On the other hand, while vertebral fractures are a common sign of osteoporosis, patients with osteoporosis suffer far more nonvertebral fractures, and those are more likely to require surgery,” she continued.

The research team conducted a prospective, randomized, placebo-controlled study of 2,463 women with osteoporosis (mean age, 69 years; range, 49–86 years), who were treated with double-blind daily subcutaneous injection of either 80 µg abaloparatide (n = 824) or placebo (n = 821), or open-label 20 µg teriparatide (n = 818), for 18 months.

They used the Kaplan-Meier method to assess the incidence of clinical vertebral fracture and major nonvertebral fracture and estimated relative fracture rates using an intent-to-treat analysis.

Over a three-year follow-up period, Dr. Bukata and her colleagues found that nine of 821 patients in the placebo group experienced a new clinical vertebral fracture during the study period, compared with one of 824 patients in the abaloparatide group, and three of 818 patients in the teriparatide group. Hazard ratios (HRs) were 0.11 for abaloparatide versus placebo and 0.33 for teriparatide versus placebo.

Similarly, over the same three-year follow-up, the researchers found that abaloparatide was associated with a 53 percent reduction in risk of major nonvertebral fracture versus placebo (HR 0.47), but the effect of teriparatide was not significant compared with placebo (HR 0.73).

An effective, preventive approach

Overall, the research team found that abaloparatide reduced both clinical vertebral fracture risk and risk of major nonvertebral fractures among postmenopausal women with osteoporosis. Combined with previous evidence, they write that the results “indicate broad antifracture efficacy with abaloparatide, including reduced risk of fragility fractures that are commonly associated with surgical repair, hospital admissions, increased mortality, and reduced quality of life.”

“In the end, our goal was to determine if we could reduce or prevent fractures that may clinically present to the orthopaedic surgeon,” said Dr. Bukata. “A lot of osteoporosis studies use standardized radiographs and imaging, and everything is focused on the total number of vertebral fractures. It’s important if you can impact what you see on radiography, but the soul of this is: Can we prevent the fractures that become clinically symptomatic and problematic for patients? These studies both suggest that abaloparatide may be an effective preventative regimen for at-risk patients.”

Dr. Bukata’s coauthors are Lorraine A. Fitzpatrick, MD; Greg Williams, PhD; Gary Hattersley, PhD; Ming-Yi Hu, PhD; Bruce H. Mitlak, MD; and Paul D. Miller, MD. The trial received funding from Radius Health, Inc.

Peter Pollack is the senior staff writer for AAOS Now. He can be reached at ppollack@aaos.org.

Bottom Line

  • Researchers conducted two studies based on a single-patient population, comparing abaloparatide to teriparatide and placebo.
  • The studies focused on clinically symptomatic fractures instead of radiographic findings.
  • Abaloparatide is a parathyroid hormone-related protein similar to teriparatide.
  • Compared to teriparatide and placebo, treatment with abaloparatide was linked to a reduction in clinical vertebral fractures and major nonvertebral fractures among postmenopausal women with osteoporosis.
  • Based on the current and previous studies, the researchers state that the data indicate broad antifracture efficacy associated with abaloparatide.