ENDO 2019: 101st Annual Meeting of the Endocrine Society:

Bone Density Assessment Tools Fall Short in Supporting Fracture Prevention

With Mone Zaidi, MD, PhD, Joy N. Tsai, MD, and Kenton R. Kaufman, PhD

Most fractures occur in older women who do  not have a frank diagnosis of ostoeporosis.This sobering statement was the opening salvo in a session marked by data that is likely to prompt an adjustment in perceptions of fracture risk and falls,2 on the first day of the 101st Annual Meeting of the Endocrine Society in New Orleans, Louisiana.

Low bone density increases the risk of osteoporosis and osteopenia, leading to bone fractures.  However, most postmenopausal women who experience an osteoporotic fracture had non-osteoporotic bone mineral density scores, highlighting the need for clinicians to consider risk factors independent of T-scores alone.2

At least one in four individuals are likely to experience a second fracture in the first year following an initial fracture,2said Peter R. Ebeling, MD, professor, and head of the department of medicine at Monash University in Australia.

Given these disquieting statistics, there was good reason to reconsider the efficacy of current approaches to fracture risk assessment, including the use of the fracture risk assessment tool (FRAX) and dual-energy x-ray absorptiometry (DXA).2

DXA Fails to Capture Many Individuals At Risk for Fractures

Older males who presented with vertical fractures and whose DXA findings appeared normal, are just one of the examples offered by Joy N. Tsai, MD, assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital, in this presentation on Imaging: Beyond BMD in whom treatment would be beneficial but wasn’t initiated.2

Is DXA the best way to assess bone density?  Relying on the results of DXA in determining when many individuals who do not have osteoporosis based on the guidelines should be questioned, said Dr. Tsai.“In fact, the majority of fractures occur in women with osteopenia, not osteoporosis."  

The reason for this, she said, is that DXA providing 2-dimensional images but bone density is a 3-dimensional process that is impacted both positively and negatively by a variety of factors and artifacts such as osteoarthritis and bone thickness.

“Also, there is no distinction made in the analysis between trabecular and cortical bone tissue. In essence, DXA does not fully capture changes in bone architecture,” she said.  These factors represent important contributions to bone strength and would help discrimination between osteopenia and osteoporosis.

Of those who experienced a fracture, 86% of these events occurred after having had a DXA scan that did not suggest osteoporosis.3 While there is certainly room for improvement in the current methodology for fracture prediction, DXA remains just one assessment tool, Dr. Tsai said. That said, “clinically, it is still important to consider bone mineral disorders and differences in bone architecture when evaluating a patient’s bone fracture risk.”

Diabetes Independently Intensifies Bone Density Losses 

Postmenopausal women with diabetes represented a specific subpopulation who may benefit from a minimally invasive procedure known as impact micro-indentation.4

Alternately, use of DXA and a T-score adjusted FRAX score may improve the estimated fracture risk and is most useful for those deemed at borderline risk [for fracture];5 but using the T-score alone is not recommended in clinical bone treatment planning, she said. This method is also not recommended for those receiving bisphosphonates or a denosumab/teriparatide regimen.6

“FRAX falls short in estimating low bone density when failing to account for the temporal nature of increased fracture risk and underestimating absolute fracture risk given good bone density,” said Dr. Ebeling.

As such, the FRAX score should not be considered a reliable assessment tool in the following at-risk groups: 

  • Type 2 diabetes: risk of falls is elevated due to peripheral neur9pathy and muscle weakness, and their risk of fracture is double
  • Does not account for ethnic differences
  • Multiple vertebral or other fragility fracture fractures
  • Recent or imminent fragility fracture
  • High-dose glucocorticoid therapy
  • Post-transplant-induced osteoporosis
  • Obesity
  • Sarcopenia
  • Aromatase inhibition therapy for breast cancer
  • Androgen deprivation therapy for prostate cancer

Given the vast number of patients who have a high risk of fracture but who fall outside the standard diagnostic criteria, it is strongly recommended that anti-osteoporosis treatments not be withheld based solely on a false low absolute FRAX fracture risk estimate, he said.

Falls Are Multifactorial and Fail Common Clinical Predictions

Contrary to popular belief, the frequency of falls is greatest not in the middle of the night or during the winter as one might expect. Rather, most falls happen during the middle of the day and in the summer—likely because these are the occasions in which people are most active.

In addition, the frequency of falls usually occurs most often at home and away, and inside or out, and on an even surface,said Kenton R. Kaufman, PhD, PE, professor of biomedical engineering in the Motion Analysis Lab at the Mayo Clinic in Rochester, Minnesota, during the session on fracture risk assessment.

Dr. Kaufman then refuted another common misnomer about the reasons for most falls.

“There are two important factors that are needed to prevent falls—sufficient strength to be able to support oneself and the ability to instantaneously reposition oneself to retain the center of mass over the base of support,” Dr. Kaufman told EndocrineWeb. “Since falls happen so fast—in 500 milliseconds— a person’s response has to be automatic in order to be able to avoid going down.” The reason for this is simple—when the center of body mass goes outside the basis of support, the individuals lose balance, leading to a forward fall (a trip) or a backward fall (a slip).

Here are some statistics to support the prevalence of falls.7

  • 46% forward falls and 41% falls to the side (Trips)
  • 33% backward falls and 17% falls to the side (Slips)
  • 23% of slips and trips resulted in a fracture  

When falls occur, one in three individual over age 65 years, and 50% of individuals over age 80 will fall, with 20-30% experiencing a fracture, specifically of the hip and forearm,2 according to Dr. Kaufman.

Does Exercise Ameliorate Falls Risk in the Elderly?

In a meta-analysis of more than 20,000 adults,8 published in JAMA Internal Medicine, the researchers reported that “usual exercise appeared effective in reducing the risk of falls by up to 20%,” said Dr. Kaufman.  

While the authors found that exercise helped to reduce the risk of falls and injurious falls, regular physical activity did not significantly decrease the risk of fracture or lessen the rate of related morbidity and mortality.8

“Given the paucity of trainings choices, the best approach to reduce the risk of falls and associated injury in older adults, particularly among those with diabetes and cardiometabolic disease and neurological deficient, is to commit to doing moderate intensity, multicomponent activities that incorporate balance training a few times a week to reducing the risk of falls,” he said.

While exercise is the best available method to reduce fall risk by building strength and stability,9 there is growing evidence of more substantial fall reduction with interventional training. This process of postural perturbation training incorporates two components: sufficient strength and practice in building a neuromuscular response to control the center of mass—which reduces falls,  particularly trips and slips, by 50 %,10,11 according to Dr. Kaufman.

Postural training is successful in graded fashion by taking patients to the limits of their ability and beyond so they are able to stay upright becomes an automatic response, rather like when we learn to ride a bike, he said, “we fall and fall until at some point our bodies learn to find that center of gravity allowing us to stay upright as we move forward, he told EndocrineWeb.

Building on this concept, Dr. Kaufman and his research team designed an interventional training program to teach war veterans with amputations to respond to postural perturbations to reduce their risk of falling, Interventional training essentially taught the subjects to maintain body stability resulting in fewer stumbles and falls.11

"That learning has been tested in clinical trials with individuals at high risk of falls. The fall training takes two weeks and has proven very effective in prospectively reducing falls that is sustained for at least one year. and is scalable to patient tolerance, " Dr. Kaufman said, and it is slowing being adopted by physical therapy groups.

The Next Hurdle for Clinicians: How Do We Frame Treatment

Talking to patients about absolute versus relative risks associated with treatment for osteoporosis, with regard to osteonecrosis of the jaw or atypical femoral fracture, is counterproductive.12

Rather than having the standard conversation about the risks and benefits of anti-osteoporosis medications given the inherent negative biases, clinicians are urged to talk to patients about the harms of not receiving treatment.

When recommending fracture prevention treatment, patients respond more favorably when the clinician emphasizes the advantages that come with avoiding the hazards of osteoporosis, including the adverse effects of a fracture such as severe pain, reduced quality of life, and increased mortality with repeat fractures.12

And, patient education should continue to include the importance of dietary sources of vitamin D and calcium, smoking cessation whenever an issue, and the need for daily exercise.

In effect, optimum clinical management of osteoporosis will require shared care with the greatest emphasis on primary practice engagement and some patient education. Abrahamson  And, once treated is established, clinicians should actively follow patients closely for at least one to two years to assure satisfactory adherence and good response.2

“In patients with diabetes whose hazard ratio for falls—after correcting for age, race, sex, body mass index, and education—is 3.0, and whose risk of trips and slips is 50-60% greater than the otherwise healthy population, the clinicians’ focus must be on good glucose management to prevent injurious fall,” Dr. Kaufman told EndocrineWeb.

“Clinicians must impress upon patients that good glucose control is the most important factor in reducing their fall risk, followed by the other known benefits of exercise,” he said.

Why Wait?—Focus on Osteopenia to Curtail Bone Loss  

Once bone is lost, it cannot be replaced and then all we can do is slow the process of bone turnover, Mone Zaidi, MD, PhD, professor of Medicine at the Icahn School of Medicine at Mount Sinai in New York City, told EndocrineWeb. “The sooner anti-osteoporosis therapy is initiated in at-risk individuals, the better.”

While this statement may seem obvious, management guidelines focus solely on postmenopausal women with osteoporosis and essentially miss women who might benefit most: those with osteopenia.  Dr. Zaidi offered his rationale for changing the treatment to focus as much on osteopenia as osteoporosis in women at high risk of fractures:


 

“Osteopenia is really an epidemiological definition of bone loss in women and men, which was derived from data generated about 20 years ago and relates to the trabecular bone score (T-score), which represents the number of standard deviations above and below the mean for a reference female population). T-score values between -1 and a -2.5 are defined as osteopenia, whereas T-scores of less than -2.5 is considered overt osteoporosis.”

“A couple of key points: First, women suddenly do not become osteoporotic; they must progress through the osteopenic range in order to become osteoporotic. This is indicative of a progression from normal bone density through osteopenia to osteoporosis.

“Secondly, more recent evidence suggests that a woman loses bone most rapidly in the early years of menopause when she has primary osteopenia, which also causes a loss of bone that predisposes to fractures,” said Dr. Zaidi. “Therefore, in considering the general population, there are more fractures in women who are diagnosed with osteopenia not because there’s a greater risk of fracture but because there are simply more women who fall into the osteopenic range for T-score values and experience fractures with the same kind of frequency.”

“The idea is that we want to initiate treatment to slow bone loss sooner—in perimenopause—when the greatest bone turnover is occurring, rather than wait until a significant amount of bone is already lost; in other words, it is better to lessen bone loss than treat lost bone,”13 he said.

 

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