Osteoporosis Treatment Options: Which is First Among Equals?

Alvin B. Lin, MD, FAAFP
Dr. Lin is an associate professor of family and community medicine at University of Nevada School of Medicine and an adjunct professor of family medicine and geriatrics at Touro University Nevada College of Medicine. He also serves as an advisory medical director for Infinity Hospice Care and as medical director of Lions HealthFirst Foundation. Dr. Lin maintains a small private practice in Las Vegas, NV. The posts represent the views of Dr. Lin, and in no way are to be construed as representative of the above listed organizations. Dr. Lin blogs about current medical literature and news at


Primus inter pares: First among equals. Who stands out? Governmental agencies and 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 and 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 three 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 average age 64 years. 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 and 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-fashioned 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 and 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 and 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 with 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 with kidney stones and/or hypercalcemia +/- vitamin D toxicity. Bottom line? There's no free lunch! Choose wisely!