Tuesday, March 14, 2017

Treatment Sequence with Osteoporosis Medications Matters

The effects of medications on bone can be dramatic. Glucocorticoids (e.g. prednisone and dexamethasone) for inflammation, thiazolidinediones (e.g. Avandia and Actos) for type 2 diabetes, and proton pump inhibitors (e.g. Prevacid and Nexium) all can lead to dramatic bone loss. In fact, bone loss can be so profound from drug therapy that it is very important to talk with your doctor about any possible impact on skeletal health when being prescribed a new medication.

Medications specific to osteoporosis treatment can also be very powerful. Many people are aware that drugs for osteoporosis can cause both minor and severe adverse effects. [The most common drugs available for the treatment of osteoporosis are the antiresorptive bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) and Prolia (denosumab), and the anabolic Forteo (teriparatide - TPTD).] Most of these drugs can even lead to increased risk for fracture when taken for three or more years. But what many people don't realize is that these drugs are so powerful that it REALLY matters WHICH medication your doctor prescribes first. He or she needs to choose the RIGHT medication for the job...the FIRST time. Guessing is not good here. Getting it wrong can lead to life-threatening consequences. Unlike an antibiotic that can be changed if the first one doesn't seem to be working to kill off an infection, antiresorptive osteoporosis medications can limit the effectiveness of the anabolic drug TPTD...so order is everything when selecting which of these drugs to use in each individual case.

When someone has severe bone loss and they have sustained fractures, it is common to put them on a sequential treatment program of TPTD (the only anabolic drug therapy currently available) for two years followed by a course of treatment with an antiresorptive bisphosphonate or denosomab. This sequential drug therapy can have dramatic and positive results for reducing fracture risk when drug therapy is warranted.

But what if a person with osteoporosis were to be treated initially with a bisphosphonate and THEN, due to a lack of response (no improvement in bone mineral density (BMD) to the antiresorptive drug, was then prescribed TPTD? Is this a wise protocol? Can this sequence lead to increased fracture risk? This is exactly what Dr. Felicia Cosman of Helen Hayes Hospital in NY set out to evaluate. The importance of proper drug sequencing is the subject of her recent perspective in this months issue of the Journal of Bone and Mineral Research.

In a perspective reviews study, Dr. Cosman concluded the following:

1) When selecting a treatment protocol for someone with severe bone loss, if no osteoporosis drug therapy has been used before, Dr. Cosman recommends TPTD anabolic therapy first (if appropriate) followed by antiresorptive therapy.

2) She goes on to say,"...our observations clearly highlight that the common practice of providing patients with first-line antiresorptive therapy and then only after patients have an inadequate BMD response and/or an intercurrent fracture to switch to TPTD is not the optimal utilization of anabolic treatment." Dr. Cosman explains that this is extremely important especially when someone sustains a hip fracture. She states that to transition to TPTD after a course of antiresorptive therapy "might in fact lead to a transient loss of strength in cortical sites, including the other hip. This is critically important in patients with a recent fracture where we know the risk of a second imminent fracture is extremely high..."(Hip fractures are a common cause of premature death. Over 50% of people who fracture a hip will die within the year.) For these cases she recommends concurrent treatment with an antiresorptive agent and TPTD instead of sequential therapy. 

Cosman, F., Nieves, JW., and Dempster, DW. 2017. Treatment sequence matters: anabolic and antiresorptive therapy for osteoporosis. J Bone Miner Res 32(2):198-202.


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