Hanover, NH—For many Americans aged 65 years and older, improvements in quality of life and longevity are tied to use of modern medications.
A study in JAMA Network Open points out, however, that many prescription medications also heighten the likelihood of a bone fracture in older patients. Dartmouth University researchers focused on the association between the number of fracture-associated drugs (FADs) older patients receive and their risk of sustaining a broken bone.
Commonly prescribed drugs, such as opioid pain killers, antidepressants, antacids, and sleep aids, can increase falls, weaken bones, or both, which leads to an increased fracture risk. Especially at risk are patients who already have osteoporosis.
“With older adults consuming, on average, five medications simultaneously, we suspected that a good number of seniors are likely to use more than one of these fracture-associated drugs at a time,” explained lead author Rebecca Emeny, PhD, MPH, a research scientist at The Dartmouth Institute for Health Policy and Clinical Practice and lead author on the study. “We wanted to determine how that increased exposure would impact their risk for hip fractures, which are among the most painful, debilitating, deadly, and costly fractures one can experience.”
With the effect of taking multiple fracture-associated drugs (FADs) unknown, researchers sought to quantify the risks of hip fracture.
To do that, they conducted a cohort study using a 20% random sample of Medicare fee-for-service administrative data for age-eligible beneficiaries from 2004 to 2014. The focus was on hip-fracture risk associated with current receipt of one, two, or three or more of 21 known FADs. The study team also looked at the risk associated with each FAD, as well as two-way FAD combinations versus no FADs. Analyses began in November 2018 and were completed April 2019.
Overall, 11.3 million person-years were observed, involving 2.6 million patients with a mean age of 77.2 years. Participants were 61.1% women and 80.7% white.
Results indicate that about 2.8 person-years (25.1%) involved receipt of one FAD; about 1.3 million person years (11.7%), involved two FADs; and about 955,000 person years (8.5%) involved three or more FADs.
“In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P <.001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P <.001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P <.001),” the authors write. “Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P <.001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P <.001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P <.001).”
The study adds that, for females, two individual FADs were associated with HRs greater than 3.00, with 80 pairs of FADs exceeding that threshold.
Researchers reveal that common, risky pairs among women included:
• Sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P <.001)
• Serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P <.001)
• Proton-pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P <.001)
In addition, they write, receiving one, two, or three or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P <.001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P <.001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P <.001).
“Among older adults, FADs are commonly used and commonly combined,” the authors conclude. “In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (e.g., sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.”
The most commonly used FADs were opioids, 55%; diuretics, 40%; and proton-pump inhibitors, 35%, according to the study. Researchers write that they were surprised that, while, on average, taking any one of these drugs doubled a patient’s risk, the risks jumped up so quickly—taking any two almost tripled it, and taking three or more increased fracture risk four-fold.
“This is an important consideration for patients, if any of their medications are optional and thus can be eliminated with no negative consequences,” noted corresponding author Nancy Morden, MD, MPH. “In any case, the results of our cohort study suggest caution when combining FADs, especially when use is discretionary, alternatives exist, or baseline fracture risk is high.”
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A study in JAMA Network Open points out, however, that many prescription medications also heighten the likelihood of a bone fracture in older patients. Dartmouth University researchers focused on the association between the number of fracture-associated drugs (FADs) older patients receive and their risk of sustaining a broken bone.
Commonly prescribed drugs, such as opioid pain killers, antidepressants, antacids, and sleep aids, can increase falls, weaken bones, or both, which leads to an increased fracture risk. Especially at risk are patients who already have osteoporosis.
“With older adults consuming, on average, five medications simultaneously, we suspected that a good number of seniors are likely to use more than one of these fracture-associated drugs at a time,” explained lead author Rebecca Emeny, PhD, MPH, a research scientist at The Dartmouth Institute for Health Policy and Clinical Practice and lead author on the study. “We wanted to determine how that increased exposure would impact their risk for hip fractures, which are among the most painful, debilitating, deadly, and costly fractures one can experience.”
With the effect of taking multiple fracture-associated drugs (FADs) unknown, researchers sought to quantify the risks of hip fracture.
To do that, they conducted a cohort study using a 20% random sample of Medicare fee-for-service administrative data for age-eligible beneficiaries from 2004 to 2014. The focus was on hip-fracture risk associated with current receipt of one, two, or three or more of 21 known FADs. The study team also looked at the risk associated with each FAD, as well as two-way FAD combinations versus no FADs. Analyses began in November 2018 and were completed April 2019.
Overall, 11.3 million person-years were observed, involving 2.6 million patients with a mean age of 77.2 years. Participants were 61.1% women and 80.7% white.
Results indicate that about 2.8 person-years (25.1%) involved receipt of one FAD; about 1.3 million person years (11.7%), involved two FADs; and about 955,000 person years (8.5%) involved three or more FADs.
“In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P <.001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P <.001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P <.001),” the authors write. “Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P <.001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P <.001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P <.001).”
The study adds that, for females, two individual FADs were associated with HRs greater than 3.00, with 80 pairs of FADs exceeding that threshold.
Researchers reveal that common, risky pairs among women included:
• Sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P <.001)
• Serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P <.001)
• Proton-pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P <.001)
In addition, they write, receiving one, two, or three or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P <.001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P <.001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P <.001).
“Among older adults, FADs are commonly used and commonly combined,” the authors conclude. “In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (e.g., sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.”
The most commonly used FADs were opioids, 55%; diuretics, 40%; and proton-pump inhibitors, 35%, according to the study. Researchers write that they were surprised that, while, on average, taking any one of these drugs doubled a patient’s risk, the risks jumped up so quickly—taking any two almost tripled it, and taking three or more increased fracture risk four-fold.
“This is an important consideration for patients, if any of their medications are optional and thus can be eliminated with no negative consequences,” noted corresponding author Nancy Morden, MD, MPH. “In any case, the results of our cohort study suggest caution when combining FADs, especially when use is discretionary, alternatives exist, or baseline fracture risk is high.”
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