With Deanna Adimoolam, MD, Sundeep Khosla, MD, and Joan A. McGowan, PhD
Results of the “SCOOP” trial, which used the Fracture Risk Assessment Tool (FRAX) to identify high-risk women aged 70 to 85 years in the United Kingdom (UK),1 were published in the journal Lancet. The authors sought to reduce fractures in women at high risk through a community-wide screening intervention.
While it appears that screening for risk of fractures did not attain the primary outcome—reduction in rate of overall fracture occurrence—this systematic, screening approach led to significant reduction in hip fractures, a secondary outcome, over at least five years,1 wrote lead author Lee L. Shepstone, PhD, professor of medicine at the University of East Anglia in Norwich, UK.
These study findings are of value to endocrinologists given an analysis of Medicare claims for women in the US at 65 years of age or over indicated that age-adjusted hip fracture rates from 2013 to 2015 were on the rise, with an increase of 11,000 hip fractures.3
“As well, the National Osteoporosis Foundation predicts that by the year 2020, there will be an expected 14 million people with osteoporosis and over 47 million cases of low bone mass in the USA alone. This increase in women at risk means the number of hip fractures may double or triple by 2040,” said Deena Adimoolam, MD, assistant professor of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai in New York City,
In the first large community-based study to assess possible benefits of a fracture-risk intervention. out of a cohort of nearly 12,500 elderly women from 100 general practitioner practices across the UK, 6,233 women were randomly selected for screening to determine their 10-year hip fracture probability.1
The Fracture Risk Assessment (FRAX) tool was chosen as the screening tool over usual care (which for many meant no assessment) because of its greater sensitivity for identifying fracture risk,2 the authors wrote.
For women in the screening group, 49% were considered at high risk of fracture and invited to have a dual-energy x-ray absorptiometry (DXA) bone scan. The research team determined that women in the high-risk group had a 17.9% risk of hip fractures and 30% risk of major osteoporotic fractures.1 Screened women who were found to be at high risk of hip fracture were given treatment recommendations whereas the women in the control group received usual care.
Among those who participated in the screening program, use of osteoporosis medication increased significantly. Overall, 15% of screened women versus 4% of those in the control group were using osteoporosis medication at the one-year mark.1 Among the subset of women found to be at highest risk, medication use rose to 78% in the first six months.
Yet, women in the intervention group showed no change in osteoporosis-related fractures, no change in clinical fractures, and no difference in overall mortality, anxiety levels, or quality of life parameters. However, the study findings revealed a 28% reduction in hip fractures (hazard ratio 0·72 95% CI 0·59–0·89; P = 0·002).
In another relevant and timely study, peak bone mass—not changes in bone density—appear correlated with the occurrence of fragility factures among post-menopausal, Caucasian women, according to data from the Calgary CaMos Cohort study;4 the study was published the Journal of Bone and Mineral Research.
During this small 5-year prospective study,4 women over 60 years of age enrolled in the study who were known to have had a fragility fracture (incident fracture group, n = 22) was compared to a control group (n = 127), using high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess qualitative skeletal factors.
"Although DXA classifies individuals as being osteoporotic, less than half of all nonvertebral fractures occur in postmenopausal women with an osteoporotic T-score, indicating something other than, or in addition to, [bone mineral density] contributes to fracture risk," according to the research group from McCaig Institute for Bone and Joint Health at the University of Calgary, Canada, lead by Steven K Boyd, PhD, professor of medicine.
In reporting on the findings, the researchers offered the following:4
At the radius, baseline HR-pQCT results indicated that women who had fractures also had lower total bone mineral density (Tt.BMD; 19%), trabecular bone mineral density (Tb.BMD; 25%), and trabecular number (Tb.N; 14%), with higher trabecular separation (Tb.Sp; 19%) than women who did not fracture.
At the tibia, women with a known fracture had lower Tt.BMD (15%), Tb.BMD (12%), cortical thickness (Ct.Th; 14%), cortical area (Ct.Ar; 12%), and failure load (10%) with higher total area (Tt.Ar; 7%) and trabecular area (Tb.Ar; 10%) than women who did not fracture.
Odds ratios (ORs) at the radius revealed every SD decrease of Tt.BMD (OR = 2.1), Tb.BMD (OR = 2.0), and Tb.N (OR = 1.7) was associated with a significantly increased likelihood of fragility fracture. At the tibia, every SD decrease in Tt.BMD (OR = 2.1), Tb.BMD (OR = 1.7), Ct.Th (OR = 2.2), Ct.Ar (OR = 1.9), and failure load (OR = 1.7) were associated with a significantly increased likelihood of fragility fracture.4
The findings suggested that baseline bone density, microarchitecture, and bone strength offered a better predictive measure than changes occurring over time,4 Dr. Boyd and his colleagues wrote.
“We need to follow up on our earlier success that drove the risk of hip fracture down over a couple of decades. In that time, increased knowledge about the threat and consequences of osteoporotic fractures and how to prevent them, the availability of effective medications, and some good tools to assess the risk of fracture in individuals, certainly helped to reduce fractures,” said Joan A. McGowan, PhD, director of the division of Musculoskeletal Diseases at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland
“To me, the benefit of screening age-appropriate women with a bone density scan (which has very limited side effects or risks) largely outweighs the risk of that person potentially having osteoporosis and sustaining a significant osteoporosis-related fracture that can be detrimental to their health and quality of life,” said Dr. Adimoolam, a sentiment that her colleagues endorsed.
While Dr. Adimoolam doesn’t foresee changing her clinical practice based on results of the SCOOP trial,1 as she already recommends screening for osteoporosis in all women after the age of 65, in addition to women with risk factors for osteoporosis (ie, fracture history, long-term use of steroids, low body weight). “It’s important to recognize that [the SCOOP] study focused on screening women aged 70-85, which is older than the patients who we should begin screening,” she said.
“The problem in the United States, is that we’ve gone from testing many, even most, women for osteoporosis in the late 1990s and early 2000s and aggressively treating even those with osteopenia to the complete opposite scenerio – not even adequately testing those who have had a fracture, and with most patients rejecting treatment— in response to bad press about side effects of bisphosphonates,” said Sundeep Khosla, MD, professor of medicine and of physiology at the Mayo Clinic in Rochester, Minnesota.
There is a big disconnect in the field of bone health. “At present, about 3-20% of women after a hip fracture are getting the recommended evaluation and treatment, whereas a person who is hospitalized for a heart attack, is discharged with a beta blocker, aspirin, an antihypertensive agent, a statin, and other appropriate medications to reduce the risk of a recurrence,” said Dr. Khosla, “Yet, an osteoporotic fracture is the same or even worse for mortality risk.”
“Women have become innocent bystanders, not getting the needed treatment,” he said, “Yet, we’ve learned a lot more about how to use bisphosphonates wisely,” such as putting women on a one to two year drug holiday after five-years of treatment. Clinicians need to become more aggressive in educating their patients.
Dr. Khosla shared with EndocrineWeb two more points for clinicians to include in their discussion with patients in an effort to allay any fears about taking bisphosphonates, and to enhance their clinical outcomes:
In effect, clinicians should be responsive to any patient who presents with a complaint about new hip or back (spine) pain; these patients should receive an immediate work-up for a possible hip or vertebral fracture, according to Dr. Khosla.
The net take-away is that for most women, the risk of any potential for side effects from taking bisphosphonates is so much less than the chance of sustaining a potentially life-threatening fracture. Clinicians will serve their patients best by “educating those at risk as to the necessity of regular assessments and adherence to treatment to avoid future fractures,” Dr. Khosla said.
“We now need to harness all the evidence we have and improve the information available to physicians and the public about the appropriate use and timing of diagnosis and treatment to prevent fractures,” Dr. McGowan told EndocrineWeb, “Part of this will come from a better understanding of the risks and benefits of various strategies and good communication tools to inform physicians and motivate high-risk patients to follow an effective course of action.”