Deprescribing Bisphosphonates: The Crowdsourced Opinion

Charles P. Vega, MD

Disclosures

July 24, 2019

Recently I posted a case, drawn from my own clinical practice, involving bisphosphonate deprescribing. I presented the rationale for my decision to suggest that my patient take a 2- to 3-year drug holiday. And I asked all of you to describe your thinking about the case, especially if you disagreed with me.

As many of you noted, this case posed issues that affected the patient's bone health beyond her age-related osteoporosis and use of alendronate. Several of you commented that vitamin D levels should be assessed in patients with known osteoporosis. But we have to keep in mind that frequent testing may not be covered by health insurance plans. The suggestion to evaluate the patient's parathyroid hormone level is also reasonable, given her chronic kidney disease. Those results could suggest the need for a different dose or form of vitamin D. Finally, discontinuing pioglitazone is a good idea as well. Other antidiabetic drugs that don't have an impact on bone health could be substituted, although drug cost might be a consideration in this choice as well.

And the Winner Was...

Most of you also advocated for a bisphosphonate holiday, ideally after repeat DEXA testing. The Endocrine Society would agree with this approach. They published new guidelines for the pharmacologic management of osteoporosis among postmenopausal women in May 2019. Fracture risk should be reassessed after 3-5 years of therapy, and those women who continue to be at high risk for fracture should continue on treatment. The most obvious case for continued treatment would be a patient who suffers an osteoporosis-related fracture while taking a bisphosphonate. In patients with such a history or who fail to at least maintain bone mineral density while on a bisphosphonate, consideration should be given to switching to a drug such as denosumab. I find that it is very important to revisit drug adherence in these cases; oral bisphosphonates will not work if a patient is missing the majority of doses.

Most women taking bisphosphonates fall into the low-to-moderate fracture risk category, and a drug holiday should be considered. A retrospective cohort study[1] including 39,502 women treated with a bisphosphonate for at least 3 years found a very small overall increase in the risk for osteoporosis-related fractures among women taking a drug holiday vs persistent users of bisphosphonates, but the rate of hip fracture was similar in the two groups. Moreover, women on a drug holiday experienced significantly better fracture outcomes compared with women who continued to receive bisphosphonate prescriptions but were less than 50% adherent to the dosing schedule. These data emphasize the importance of patient preference, motivation, and adherence.

Women who take a drug holiday should have their fracture risk reassessed in 2-4 years, and those who experience a substantial increase in risk should be restarted on therapy.[2] Although the data to support a drug holiday are limited, a retrospective comparing patients with atypical femoral fractures and a control group found that the risk for fractures declined by 70% each year after discontinuing bisphosphonate therapy.[3]

Clinician and patient in this case should discuss the potential benefits and risks of continued bisphosphonate therapy, and shared decision-making about this option should be documented. A commenter quite rightly pointed out that this patient should continue lifestyle interventions to improve her bone health as well as reduce her risk for falls. It will also be important to monitor her baseline renal function in case a bisphosphonate is considered in the future. This case offers an opportunity in deprescribing, but only after a careful assessment and conversation with the patient.

That caution applies equally well to the next case in this series, which will showcase the issues in deprescribing antidiabetic agents.

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