In the JournalsPerspective

Two-thirds of all fractures not attributable to osteoporosis

Only 16% of fractures in women and 15% in men are attributable to low bone mineral density, suggesting that treatment of people based on a diagnosis of osteoporosis is unlikely to reduce a large number of fractures in the overall population, according to an analysis of Australian adults published in The Journal of Clinical Endocrinology & Metabolism.

Tuan V. Nguyen

“We cannot predict with certainty who will fracture from a measurement of bone mineral density alone,” Tuan V. Nguyen, DSc, PhD, a professor of osteoporosis research, bone biology division, at the Garvan Institute of Medical Research at St Vincent’s Clinical School, University of New South Wales, and professor of predictive medicine at the University of Technology Sydney, told Endocrine Today. “Therefore, the assessment of fracture risk for an individual should move beyond bone mineral density to take into account important factors such as fracture history, prior falls, smoking and comorbidities. Tools such as the Garvan Fracture Risk Calculator and Fracture Risk Assessment Tool (FRAX) can help doctors to evaluate a patient’s risk of fracture based on multiple risk factors.”

Low BMD vs. advancing age

Nguyen and colleagues analyzed data from 3,700 adults (2,320 women; mean age, 69 years) aged at least 50 years, participating in the Dubbo Osteoporosis Epidemiology study, an ongoing, population-based prospective cohort of residents in Dubbo, New South Wales, Australia. Researchers assessed low-trauma fractures via X-ray reports and mortality data via the Birth, Death and Marriage Registry. Primary outcome was fragility fracture, defined as any fracture resulting from a fall from standing height or less, assessed via X-ray reports. Participants underwent DXA measurements of the lumbar spine and femoral neck at baseline. Researchers estimated the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD by calculating the prevalence of low BMD (stratified by T-scores of less than –2.5, –2 and –1.5) and the strength of the association between low BMD and fracture using Cox proportional hazard models. Within the cohort, 21% of women and 11% of men had osteoporotic BMD, defined as a T-score of less than –2.5. During follow-up, 864 women (37%) and 273 men (20%) sustained a fragility fracture, with most observed at the vertebrae (48% of all fractures in both sexes), followed by hip (22%) and wrist (9%).

Researchers found that, among women, approximately 20% of fractures were attributable to osteoporosis within the first year of follow-up, decreasing to 17% by year 5, further decreasing to 14% by year 10 and rising to 19% by year 20. Among men, 13% of fractures were attributable to osteoporosis within the first year of follow-up, decreasing to 8% after 20 years, according to researchers. In analysis stratified by fracture type, researchers found that the attributable fraction of fracture was highest for hip fracture, with 41% of hip fractures in women and 22% of hip fractures in men attributable to low BMD.

In analyses accounting for advancing age (defined as age 70 years or older), researchers found that 34% and 35% of total fractures in women and men, respectively, were attributable to advancing age and/or low BMD.

“However, a decomposition analysis reveals that the majority of this attributable fraction was ascribed to advancing age,” the researchers wrote. “For instance, out of the 34% attributable fraction in women, approximately 19% were ascribed to advancing age and low BMD, and another 9% due to advancing age alone. A similar trend was also observed in men.”

Reduced survival after fracture

The researchers noted that approximately 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis and fracture; however, most of the attributable proportion was accounted for advancing age.

“Another important implication from the study is that patients with a fracture have reduced survival,” Nguyen said. “At present, there are effective anti-osteoporosis therapies that can reduce the risk of mortality among patients with a fracture. However, the reality is that most (approximately 70%) patients with fracture do not receive any treatment, and that is a crisis. Our finding implies that many lives can be saved if doctors initiate treatment early.”

Nguyen said predictive tools for the individualized assessment of fracture risk, such as the Garvan Fracture Risk Calculator and FRAX, are useful; however, a randomized controlled trial is needed to determine whether antiresorptive treatment could reduce fractures among those deemed to be high risk.

“Fracture is partly due to hereditary factors, and over the past 10 years or so, we have identified many genes that were associated with fracture risk,” Nguyen said. “The next step is to develop a test that combines the information of these genes to identify high-risk individuals much earlier, even at birth.” – by Regina Schaffer

For more information:

Tuan V. Nguyen, DSc, PhD, can be reached at the Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; email: t.nguyen@garvan.org.au.

Disclosures: The authors report no relevant financial disclosures.

Only 16% of fractures in women and 15% in men are attributable to low bone mineral density, suggesting that treatment of people based on a diagnosis of osteoporosis is unlikely to reduce a large number of fractures in the overall population, according to an analysis of Australian adults published in The Journal of Clinical Endocrinology & Metabolism.

Tuan V. Nguyen

“We cannot predict with certainty who will fracture from a measurement of bone mineral density alone,” Tuan V. Nguyen, DSc, PhD, a professor of osteoporosis research, bone biology division, at the Garvan Institute of Medical Research at St Vincent’s Clinical School, University of New South Wales, and professor of predictive medicine at the University of Technology Sydney, told Endocrine Today. “Therefore, the assessment of fracture risk for an individual should move beyond bone mineral density to take into account important factors such as fracture history, prior falls, smoking and comorbidities. Tools such as the Garvan Fracture Risk Calculator and Fracture Risk Assessment Tool (FRAX) can help doctors to evaluate a patient’s risk of fracture based on multiple risk factors.”

Low BMD vs. advancing age

Nguyen and colleagues analyzed data from 3,700 adults (2,320 women; mean age, 69 years) aged at least 50 years, participating in the Dubbo Osteoporosis Epidemiology study, an ongoing, population-based prospective cohort of residents in Dubbo, New South Wales, Australia. Researchers assessed low-trauma fractures via X-ray reports and mortality data via the Birth, Death and Marriage Registry. Primary outcome was fragility fracture, defined as any fracture resulting from a fall from standing height or less, assessed via X-ray reports. Participants underwent DXA measurements of the lumbar spine and femoral neck at baseline. Researchers estimated the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD by calculating the prevalence of low BMD (stratified by T-scores of less than –2.5, –2 and –1.5) and the strength of the association between low BMD and fracture using Cox proportional hazard models. Within the cohort, 21% of women and 11% of men had osteoporotic BMD, defined as a T-score of less than –2.5. During follow-up, 864 women (37%) and 273 men (20%) sustained a fragility fracture, with most observed at the vertebrae (48% of all fractures in both sexes), followed by hip (22%) and wrist (9%).

Researchers found that, among women, approximately 20% of fractures were attributable to osteoporosis within the first year of follow-up, decreasing to 17% by year 5, further decreasing to 14% by year 10 and rising to 19% by year 20. Among men, 13% of fractures were attributable to osteoporosis within the first year of follow-up, decreasing to 8% after 20 years, according to researchers. In analysis stratified by fracture type, researchers found that the attributable fraction of fracture was highest for hip fracture, with 41% of hip fractures in women and 22% of hip fractures in men attributable to low BMD.

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In analyses accounting for advancing age (defined as age 70 years or older), researchers found that 34% and 35% of total fractures in women and men, respectively, were attributable to advancing age and/or low BMD.

“However, a decomposition analysis reveals that the majority of this attributable fraction was ascribed to advancing age,” the researchers wrote. “For instance, out of the 34% attributable fraction in women, approximately 19% were ascribed to advancing age and low BMD, and another 9% due to advancing age alone. A similar trend was also observed in men.”

Reduced survival after fracture

The researchers noted that approximately 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis and fracture; however, most of the attributable proportion was accounted for advancing age.

“Another important implication from the study is that patients with a fracture have reduced survival,” Nguyen said. “At present, there are effective anti-osteoporosis therapies that can reduce the risk of mortality among patients with a fracture. However, the reality is that most (approximately 70%) patients with fracture do not receive any treatment, and that is a crisis. Our finding implies that many lives can be saved if doctors initiate treatment early.”

Nguyen said predictive tools for the individualized assessment of fracture risk, such as the Garvan Fracture Risk Calculator and FRAX, are useful; however, a randomized controlled trial is needed to determine whether antiresorptive treatment could reduce fractures among those deemed to be high risk.

“Fracture is partly due to hereditary factors, and over the past 10 years or so, we have identified many genes that were associated with fracture risk,” Nguyen said. “The next step is to develop a test that combines the information of these genes to identify high-risk individuals much earlier, even at birth.” – by Regina Schaffer

For more information:

Tuan V. Nguyen, DSc, PhD, can be reached at the Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia; email: t.nguyen@garvan.org.au.

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Rachel Pessah-Pollack

    Rachel Pessah-Pollack

    This study provides important information that many fractures are occurring in patients that do not meet BMD criteria for osteoporosis, and often have osteopenia, defined as a T-score between –1.0 and –2.5.  

    Given the majority of fractures are occurring in the non-osteoporotic population, it is necessary to assess a patient's risk factors outside of BMD, including glucocorticoid use, premature menopause, family history of hip fracture, advancing age, use of aromatase inhibitors and low body weight. Unfortunately, pharmacological treatment of osteoporosis has declined in recent years due to numerous concerns including medication side effects; however, this study emphasizes the substantial mortality risk associated with fracture. It is a public health problem that can be improved by providing education to medical professionals and patients to identify non-osteoporotic patients at high-fracture risk, in order to offer treatment to reduce the risk for future fractures and increased mortality.

    • Rachel Pessah-Pollack, MD, FACE
    • Clinical Assistant Professor of Medicine
      Icahn School of Medicine at Mount Sinai

    Disclosures: Pessah-Pollack reports she receives speaking and advisory board fees from Boehringer Ingelheim and Eli Lilly and previously served as a speaker and advisor for Radius Health Care.