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Use of medications associated with rising osteoporosis risk
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The use of medications associated with the development of osteoporosis has steadily increased across Denmark in the past 16 years, particularly by those most at risk for fracture, such as postmenopausal women and older adults, according to findings from a registry study published in Bone.
“We know from population demographics that the number of elderly people is going to double in many industrialized countries over the next 20 years,” Bo Abrahamsen, MD, PhD, a professor and consultant endocrinologist at the Institute of Clinical Research at the University of Southern Denmark and Holbæk Hospital, Denmark, told Endocrine Today. “Fortunately, the risk of osteoporotic fractures, such as hip fractures in the elderly, is currently declining due to a combination of better health, falls prevention and improved treatment of osteoporosis. However, several old and new drugs increase the risk of osteoporotic fractures and some of these drugs have now seen high and increasing usage in the population. When looking at medication sales in Denmark between 1999 and 2016, we noted high and increasing usage of proton pump inhibitors and anti-depressants, such as selective serotonin reuptake inhibitors (SSRI) and venlafaxine; increases of 460%, 110% and 600%, respectively.”
Abrahamsen and colleagues conducted a literature search to identify medications associated with an increased risk for osteoporosis, and then identified and mapped relevant prescription codes for the retrieval of public domain prescription data through an open-access database in Denmark. Medications were thiazolidinediones, proton pump inhibitors, warfarin, heparin, glucocorticoids, cyclophosphamide, methotrexate, gonadotropin-releasing hormone agonists, aromatase inhibitors, calcineurin inhibitors, phenobarbital, phenytoin, carbamazepine, valproate, SSRIs, venlafaxine and duloxetine.
Between 1999 and 2016, researchers assessed user rate per 1,000 capita, stratified by sex and age group; total sale per year for both sexes and all age groups, given in defined daily dose; and sale per 1,000 capita per day, based on total sale across both sectors and on population statistics, given in defined daily dose.
Researchers classified medications according to use and change in dose, as given by sale per 1,000 capita per day and the change in sale per 1,000 capita per day from 1999 to 2016, respectively. Low use was defined as a sale per 1,000 capita below one defined daily dose per day in 2016; moderate use was from one to 10 defined daily doses per 1,000 capita per day in 2016 and high use was defined as above 10 defined daily doses per 1,000 capita per day in 2016.
Researchers observed high use of several drugs associated with secondary osteoporosis, including proton pump inhibitors, SSRIs, venlafaxine and glucocorticoids. The pattern of sales rates for glucocorticoids was stable during the study period, according to researchers; however, there was an increasing sales pattern observed for SSRIs and venlafaxine between 1999 and 2016.
“It is worth noting that the absolute change in sale per 1,000 capita per day was particularly large for [proton pump inhibitors], which increased 54.9 [defined daily dose] per 1,000 capita per day, and SSRI, which increased 25.1 [defined daily dose] per 1,000 capita per day,” the researchers wrote.
During 2016, 9% of all men and 11.4% of all women collected at least one prescription for a proton pump inhibitor, according to researchers, vs. 3% and 3.4%, respectively, in 1999. The increase in usage rate was matched by an increase in the sale per 1,000 capita, they noted.
Researchers observed an increase in the uptake of SSRIs until 2010, followed by a decrease during which most age groups returned to a level comparable to their 1999 level. Exceptions were observed for men and women aged 40 to 64 years, who demonstrated a 37% and 34% increase from 1999 to 2016, respectively. The usage rate for SSRIs was nearly twice as high for women vs. men.
In assessing use of glucocorticoids, researchers found that the usage rate in general was stable during the observation period; however, an increase was seen among older adults (aged at least 80 years) of 21% for men and 16% and women.
Researchers observed moderate use of six medications in 2016, including warfarin, duloxetine, methotrexate, aromatase inhibitors, gonadotropin-releasing hormone agonists and valproate.
“A causal link between these medications and osteoporotic fractures has been proposed but remains controversial,” Michael K. Skjødt, MD, of the department of medicine at Holbaek Hospital, Denmark, told Endocrine Today. “However, even if use of these medications is an indicator of fracture risk rather than a cause of fractures, this increasing use suggests that fracture rates may not continue to decline over the coming decades. This would have serious implications for the health services as we rely on a continuous decrease in fracture rates to offset the health consequences of aging in the population.”
Abrahamsen added that the use of glucocorticoids — which have a very strong link to high fracture risk — continues to increase, with widespread use in older adults. – by Regina Schaffer
For more information:
Bo Abrahamsen, MD, PhD, can be reached at the Institute of Clinical Research at the University of Southern Denmark, Winsløwparken 19, 3, Sal, Odense C, Denmark, 5000; email: b.abrahamsen@physician.dk.
Michael K. Skjødt, MD, can be reached at Hospital of Holbaek, Department of Medicine, Region Zealand, Smedelundsgade 60, 4300 Holbaek, Denmark; email: michael.skjoedt@gmail.com.
Disclosure: Abrahamsen reports he has institutional research contracts with Novartis and UCB. Skjødt reports no relevant financial disclosures.
Perspective
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The takeaway message of this research is that there is a growing list of therapies that can have deleterious effects for bone. Some of these drugs have been growing in their frequency of use in recent years, in particular, drugs to manage breast cancer and prostate cancer. The good news is that people are living longer with serious medical problems. The bad news is that, as you live longer with serious medical problems like breast cancer, prostate cancer or HIV, you run more risk for getting into trouble with conditions like osteoporosis.
The solution is when a patient is taking a medicine that has known deleterious effects on the bone, the clinician needs to be aware of this, and, either alone or in consultation with a clinician who specializes in bone health, evaluate bone density and assess other risk factors to avoid the risk for fractures. This used to be a problem predominantly with glucocorticoids, but now we have a whole host of other medications that we should be thinking about.
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