Fracture risk is increased with opioids, SSRIs and glucocorticoids, but decreased with statins and TNFi

Some treatments for rheumatoid arthritis may help lower the risk of spinal fractures.

Rheumatoid arthritis is a chronic inflammatory disease that affects a person’s joints, causing pain and disability. Rheumatoid arthritis is more common in older people, but there is also a high prevalence in young adults and even children, and it affects women more frequently than men.

People with rheumatoid arthritis are twice as likely to get osteoporosis or to have bone fractures compared to people of the same age without the disease. This increased risk can be due to the inflammation causing the disease itself, or by the use of some types of medicines such as glucocorticoids (sometimes called steroids). In the general population, some other common medicines such as opioids, anti-depressants, statins, proton pump inhibitors (heartburn inhibitors; often shortened to PPIs) and seizure and anxiety medicines (so-called psychotropic drugs), have been shown to influence the fracture risk – some make fractures more likely, but some seem to decrease the risk.

What did the authors hope to find?
The authors wanted to find out how different medicines affect the risk of getting a fracture in people with rheumatoid arthritis.

Who was studied?
The study looked at over 11,000 people with rheumatoid arthritis being treated at clinics in the US. Everyone was over the age of 40, and nobody had a fracture at the start of the study.

How was the study conducted?
This was a longitudinal prospective observational study. The authors collected information twice a year in a questionnaire, which asked whether people had fractured their finger, wrist, arm, elbow, toe, foot, ankle, lower leg, knee, hip, pelvis, rib, skull, face, or spine in the past 6 months. The questionnaire also collected information about what medicines people were taking, so it was possible to work out the fracture risk linked to different medicines. The authors also calculated people’s FRAX scores. This is a tool that predicts whether someone will get an osteoporotic fracture within the next 10 years.

What were the main findings of the study?
The main finding was that opioids and some types of anti depressants (selective serotonin reuptake inhibitors or SSRIs) increased the risk of fractures. The risk of fracture was higher with strong opioids (methadone, morphine, oxycodone, meperidine, and fentanyl) than weaker ones (hydrocodone, tramadol, codeine), and the effect was seen even with very short-term use (less than 1 month). Some medicines used to treat rheumatoid arthritis called glucocorticoids were associated with more fractures. This risk increased when the glucocorticoids were taken for more than 3 months, or at doses higher than 7.5 mg per day. The fracture risk in the first month of taking opioids is probably higher because of falls. Longer use of opioids and SSRIs gives a bigger risk, probably because of decreases in bone density.

A group of medicines called statins were found to decrease the risk of spinal (vertebral) fracture by 23%. Some medicines used to treat rheumatoid arthritis (infliximab, adalimumab, etanercept, golimumab, certolizumab) were also shown to decrease these kinds of spinal fractures compared to another medicine for rheumatoid arthritis called methotrexate, but the same effects were not seen for other bone fractures.

The authors did not find any fracture risk change with proton pump inhibitors, seizure or anxiety drugs, or with any other medicines used to treat rheumatoid arthritis.

Are these findings new?
Previous studies have looked at the risk of fractures with opioids and other painkillers in people with rheumatoid arthritis, but this is the first to investigate the risk of fractures with antidepressants, statins, proton pump inhibitors and other psychotropic medications in people with rheumatoid arthritis. Also, this study differs from others in some of the measures used, as well as having the fracture risk assessed with the FRAX score.

What are the limitations of the study?
As an observational study, the study has some limitations. It is known that doctors make treatment decisions based on people’s individual characteristics, and this might have affected the results.

An important factor that was not included in the study was the risk of people having a fall, and so it is possible that the increased risk seen with opioids or SSRI anti-depressants was due to an increase in fall risk. The study also did not collect any data about the trauma that caused the fracture. However, these new fracture rates were comparable to those reported in previous studies.

What do the authors plan on doing with this information?
The authors plan to collect more data to try and work out whether the increased risk of fractures is affected by some medicines making it more likely for people to have falls.

What does this mean for me?
If you have rheumatoid arthritis, you are more likely to get bone fractures than other people your age. You are also more at risk of osteoporosis, but you can take steps to minimise the impact of your disease.

Keeping your rheumatoid arthritis under control will help to reduce the inflammation in your body, and will reduce the need to use glucocorticoids or opioid painkillers. If you do need to use these medicines, you should closely follow your doctor’s instructions, and do not take them for longer than prescribed, or at a high dose. If you have any concerns about your disease or its treatment, you should talk to your doctor. It is important that you do not stop taking any medicine you have been prescribed without getting proper medical advice.

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Date prepared: July 2019
Summary based on research article published on: 15 May 2019
From: Ozen G, et al. Medications associated with fracture risk in patients with rheumatoid arthritis. Ann Rheum Dis 2019;78:1041–1047. doi:10.1136/annrheumdis-2019-215328

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