Should you use Forteo for osteoporosis?
I keep an eye on the various drug treatments for osteoporosis, watching to see how the latest and greatest drug therapy pans out. I just took a second look at one of them: Forteo™ (teriparatide). And I’m still not liking what I see.
Imagine osteoporosis as a scale that’s out of balance. If you were to add an ounce or two of weight to the lighter side, perhaps you’d bring it back into balance. Well, using Forteo is the equivalent of dropping 1 pound onto the higher side. You’ve accomplished your goal — the lighter side is now heavier — but now you’ve not only put the scale more out of balance, you might even flip the scale over entirely!
Forteo tricks the body
It’s important to understand how Forteo works: It mimics a natural process that promotes bone building in order to trick the body into building more bone. Forteo is a synthetic form of parathyroid hormone (PTH) found naturally in the body. PTH increases the number of osteoblasts (it both causes more to be produced and delays their natural death) and encourages more bone remodeling activity by enhancing RANKL production from osteoblasts.
Basically, this boils down to a drug that tricks the body into using its own processes to build bone.
Does Forteo work?
At first glance, this deception seems to be effective: multiple studies report that a 2-year course of Forteo increased lumbar spine bone density by 8.8–13.1% and hip bone density of 1–6.2%, accompanied by a 9% absolute reduction in fracture incidence.
These are fantastic numbers, and considerably better than you find with bisphosphonates like Fosamax, Actonel, or Boniva, which act to halt bone breakdown. It even beats other powerful bone drugs like Prolia. So why am I hesitating? In a word: Safety. It’s not enough for a medication to be effective. It has to provide more benefit than harm. And I’m not sure Forteo does.
Is Forteo safe?
Even though Forteo has been on the market almost two decades, all of the studies that produced these glowing numbers were only six months to two years in duration. This is because in the animal studies prior to its approval in 2001, Forteo was shown to cause a high incidence of osteosarcoma (a rare malignant, often fatal, bone tumor), as well as osteoblastoma (abnormal mass of tissue in bone) and osteoma (small, benign bone lesions). As a result, guidelines were set to limit the duration of its use in humans to two years, and the FDA required a “black box” label warning, clearly stating the increased cancer risk.
But the downside of this caution is that we have no information about long-term effects of taking Forteo — and, once the two-year limit is up, what’s the next step? You guessed it: more bone drugs, side effects included (because the benefits just don’t last).
Does Forteo cause cancer?
A registry created to determine whether Forteo was causing osteosarcoma has found no clear evidence that it is. But osteosarcoma is a very rare cancer — in the U.S., only about 900 people get it each year, and 90% of those are under age 30. And Forteo is not a commonly prescribed drug (according to one analysis, only 40,000 of 35 million [0.1%] Medicare subscribers are taking Forteo). It’s statistically unlikely that at these numbers, you’d see signs of osteosarcoma in the population even if the incidence is increased. Even a single case in the existing population of Forteo patients would represent a 12-fold increase in risk! So if Forteo increases risk by, say, 3 to 5 times, or even 10 times, we’d still be unlikely to see even one case in the literature — and keep in mind, although 54,804 people enrolled in the registry as of 2016, participation is voluntary, so it likely does not include all patients who’ve taken Forteo.
On the other hand, an association between Forteo and other bone cancers — such as multiple myeloma — can be found in the medical literature. Multiple myeloma is known to be a malfunction of the RANKL/OPG system, the very system Forteo manipulates to cause its bone-building effects. This makes me wonder if the surveillance isn’t too narrowly focused on osteosarcoma. If the registry were to look for all bone cancers in people using Forteo, what would it find?
More unanswered questions
But the potential for cancer isn’t the only cause for concern. PTH, which Forteo mimics, and RANKL have important roles in the immune system. One role is to encourage proliferation of T cells. Ironically, osteoclasts are naturally kept in check by T cells suppressing RANKL — which means Forteo is working against the immune system. PTH receptors are also found on other immunologic cells (neutrophils and B cells). If you fiddle with PTH by using Forteo, what does it mean for your immune system’s functioning? And what of the many other roles that PTH and RANKL play in the body, known and unknown?
It bears mentioning that using Forteo is expensive. Without insurance coverage, Forteo costs approximately $3600 a month —out of reach for most people. That seems like a pricey proposition for something that has many unanswered and worrisome questions and that doesn’t provide a lasting solution for osteoporosis and fracture prevention.
I’ve always maintained that it’s better to work with nature than against it. My mistrust of Forteo centers upon the fact that it hijacks a normal molecular pathway for bone metabolism and sends it into overdrive to produce a change in bones — and we still don’t know what its long-term impact will be. And, of course, once you’re done with it, you have to move on to yet another bone drug with more and different side effects.
Is there a better way to increase bone strength and reduce needless osteoporotic fractures? Is there a way that does not run the risk of causing cancer, or lead to excessive new bone formation — a way that is not only safe, but also good for the entire body? One that average people can afford to use without breaking the bank — and doesn’t mean going from one drug to another to another for a lifetime?
To learn more on the topic of osteoporosis and bone loss, read our additional articles here:
Do you really need a drug for your bones?
20 key nutrients for bone health
6 ways to stop bone loss during the menopause transition
Andrews E.B., Gilsenan A., Midkiff K., Harris D. Challenges in studying very rare cancer outcomes and infrequent exposures: example of teriparatide and osteosarcoma. Ann. Epidemiol. 2016;26:751–753.
Forslund T., Koski A.-M., Koistinen A., Sikiö A. Malignant Myeloma in a Patient After Treatment for Osteoporosis with Teriparatide; a Rare Coincidence. Clin Med Case Rep. 2008; 1: 119–122.
Geara A.S., Castellanos M.R., Bassil C., et al. Effects of Parathyroid Hormone on Immune Function. Clin Dev Immunol. 2010; 2010: 418695.
Published online 2010 Sep 16. doi: 10.1155/2010/418695
Koski A.M., Sikiö A., Forslund T. Teriparatide treatment complicated by malignant myeloma. BMJ Case Rep. 2010 Aug 13;2010. pii: bcr0120102681. doi: 10.1136/bcr.01.2010.2681.
Kwon Y.D., Lee D.W., Choi B.J., et al. Short-term teriparatide therapy as an adjunctive modality for bisphosphonate-related osteonecrosis of the jaws. Osteoporos Int. 2012 Nov;23(11):2721-5. doi: 10.1007/s00198-011-1882-9. Epub 2012 Jan 5.
Lindsay R. Krege J. H., Marin F. Jin L., Stepan J. J. Teriparatide for osteoporosis: importance of the full course. Osteoporos Int. 2016; 27: 2395–2410.
Lorentzon M. Treating osteoporosis to prevent fractures: current concepts and future developments. J Intern Med. 2019 Apr;285(4):381-394. doi: 10.1111/joim.12873. Epub 2019 Jan 18.
Mumford E.R., Raffles S., Reynolds P. Coexistent osteoporosis and multiple myeloma: when to investigate further in osteoporosis. BMJ Case Rep. 2015; 2015: bcr2015210896.
Zhang W., Yang G.-J., Wu, S.-X., et al. The guiding role of bone metabolism test in osteoporosis treatment. Am J Clin Exp Immunol. 2018; 7(2): 40–49.