Primus inter pares. First among equals. Who stands out? Governmental agencies & other third party payers would like comparative effectiveness studies to determine which option is best. But as would be expected, Big Pharma doesn't typically pit its blockbuster against another lest there be an upset. Or if it does, it handicaps the competition, say by comparing its maximal dose to the competitor's half maximum dose. You get the idea. No one wants to lose. So typically, it's up to the government to sponsor the study, which is just as well since you don't want any potential bias based upon funding support.
So what about treatment of osteoporosis? Which is best? This question comes up in the preceptor room more often than I'd care to admit. We have a wealth of options now whereas once we only had those oldies but goodies, calcium & vitamin D. Now we have Bisphosphonates. Selective estrogen receptor modulator (SERM). Recombinant parathyroid hormone (PTH). And the newest kid on the block, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor. Admittedly, we only have one example of each of the last 3 classes.
Well, in a
study published online in Journal of Clinical Endocrinology & Metabolism prior to print in June, the authors analyzed 116 trials lasting an average of 2 years involving 139.647 patients of whom 4 out 5 were Caucasian women avg 64yo. Their conclusion? It's a tie! While teriparatide (recombinant PTH) demonstrated the greatest fracture reduction, statistically speaking, denosumab (RANKL inhibitor) and the bisphsophonates were equivalent to teriparatide. Raloxifene (SERM) may have been a little less effective but the data was sparse. And even calcium & vitamin D was deemed effective but only if given together (as in one doesn't work without the other).
So how do (we help) our patients chose? Well, a good old fashion wallet biopsy helps! After all, it doesn't matter if it's the best thing since sliced bread, because if the patient can't afford it, it's no use. Second, consider route & frequency of administration. Some patients may refuse intravenous administration, even if only annually (zolendronate comes to mind), much less quarterly (ibandronate). And I suspect that if you can't convince a patient to undergo a semi-annual subcutaneous injection (think denosumab), then a daily subcutaneous injection (teriparatide anyone?) is going to be an impossible sell. Raloxifene is available only as an oral daily medication while the oral bisphosphonates are available in daily, weekly & monthly forms. It's an embarrassment of riches, I tell you!
So third, it's now time to consider risks. Denosumab is too new to the market to have developed a bad reputation, unlike the bisphosphonates which require a very strict regimen and have now been associated w/
atypical femur fractures,
osteonecrosis of the jaw, and
as of just yesterday, inflammatory eye disease. Teriparatide has only been studied out to 2 years but gave concern to rats who developed osteosarcoma at a greater rate compared to placebo. Raloxifene trades off prevention of invasive breast cancer against increase thrombus formation, including stroke. As for calcium & vitamin D,
if you take too much, you could end up w/kidney stones and/or hypercalcemia +/- vitamin D toxicity. Bottom line? There's no free lunch! Choose wisely!
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