Which Daily Injection for Osteoporosis is Better?

For patients with fragile bones, the risk for fracture can be a matter of life and death. I’m James Webb, MD, an Interventional Musculoskeletal Radiologist based in Tulsa, Oklahoma. My goal is to help patients find freedom from pain without invasive surgery or dangerous opioid medications.

For patients with osteoporosis who are at high risk for vertebral fracture, medical therapy can help reduce the risk of future fractures. This is important for the individual for both quality of life and for survival. A new fracture can cause debilitating pain, declining function, and cause expensive hospitalizations.

It becomes even more important when looking at a society level. Symptomatic fragility fractures not only cause increased morbidity and mortality. They are also a drain on healthcare system resources – resulting in increased ER visits, hospitalizations and surgeries. They even cause missed days from work since more and more osteoporosis patients are still in the workforce. However, a comparison of value at a system level is beyond the scope of this article. Let’s instead take a look at what drives decisions in my day-to-day medical osteoporosis treatment practice.

What’s the Best Medical Therapy For Osteoporosis

Traditionally, pharmacologic treatment for osteoporosis focused on preventing fractures in patients who were at higher risk for developing a fracture. While that sounds great, the reality is that many patients never get any treatment until they get a fracture. Once patients do develop a vertebral fragility fracture, their risk for future fractures skyrockets. As such, it’s critical to treat these patients with a holistic approach to reduce their future risk for fracture.

Those of us who treat high risk osteoporosis patients have been advocates of newer anabolic therapies for years. Two significant changes have occurred in this space in the last couple of years. First, two new advanced drugs – Tymlos and Evenity – have been approved by the FDA. Second, the prototypical anabolic therapy, Forteo (teriparatide) has gone off patent.

For the purposes of this article, I want to review some recent data comparing Forteo and Tymlos and which one I think that we should pick for clinical use in 2019 and beyond.

Why Does This Matter?

One of the key statistics we look at when deciding therapy for patients is relative risk reduction (RRR) for fracture. For example, abaoloparatide (Tymlos) was shown in the ACTIVE trial (Abaloparatide Comparator Trial In Vertebral Endpoints) to reduce vertebral fracture risk about 86% when compared to placebo. By contrast, another high-powered IV medication, romosozumab (Evenity) only reduced fracture risk 71%. That means Tylmos is about a 21% better at reducing spinal fractures than even Evenity (15% absolute difference).

Contrast that with data available for the standard therapy, which are oral bisphosphonates (OBP) such as Fosamax and Boniva. Even the best data quoted in the much maligned ICER review showed clearly inferior fracture reduction risks with OBP. Data from the U.S. Preventive Services Task Force (USPSTF) for OBP suggest that these medications only reduce risk 35% for hip fracture after 5 years of treatment.

More to the point for vertebral fractures, the VERT-NA trial (Vertebral Efficacy with Risedronate Therapy-North America) looked at relative risk reduction (RRR) for residronate (Actonel) compared to placebo. Not only was the RRR for this OBP only 65% in the first year, it appears to actually get worse over time (65% RRR in the first year, but only 41% when looking at the first 3 years of treatment).

Since 1) fragility fracture is associated with high mortality risks and 2) there’s a nearly exponential increase in future fracture risk for patients with vertebral fragility fracture – it is important to medically treat these patients to reduce their risk.

Remember that the majority of OBPs are prescribed to reduce fracture risk in asymptomatic patients. Once a patient sustains a fragility fracture, they have gone from a theoretical risk to an actual and high risk. It is imperative that treatment shifts from preventative to active risk reduction at this point.

A More Recent Study Comparing Tymlos and Forteo

A recent study by Reginster et al. compared outcomes in osteoporosis patients treated by the most powerful medications available to fight fracture. The study compared the two anabolic agents – abaloparatide (Tymlos) and teriparatide (Forteo).

The authors looked at data from the ACTIVE trial which was the study proving abaloparatide reduced the risk of fractures. They took the data a little further and combined with other studies to calculate the number needed to treat (NNT) to reduce fracture risk in both Tymlos and Forteo for new fractures including vertebral, non-vertebral (hip, wrist, etc.) as well as all clinical and major osteoporotic fracture (MOP).

The number needed to treat, or NNT, is a different way to look at how effective a therapy is at reducing fracture risk. For example, we can look at the data from the ACTIVE trial in Table 1. If we look in the row with VCF, you’ll notice that the NNT for vertebral fractures for Tymlos and Forteo is 30 and 28 respectively. That means you need to treat 30 patients with Tymlos to prevent a vertebral fracture, and only 28 with Forteo.

NNT Tymlos vs. Forteo

While Forteo is slightly better than Tymlos is the number needed to treat for spinal fracture, it’s not as good in preventing clinical VCF. You see, the conventional wisdom is that 2/3 of vertebral fractures are non-clinical or ‘morphometric.’ That means that about 2/3 of vertebral fractures never present to a doctor—either because the patient never felt it, or it got better before they sought treatment.

A big advantage for Tymlos is that it seems to be better at reducing “major osteoporotic fracture” or MOP. MOP basically means a major fracture caused by osteoporosis that came to clinical attention—a symptomatic vertebral fracture, or a fracture of the wrist, hip or humerus. And for me, that’s a major benefit. Even though I mostly treat vertebral fractures, it’s important to treat patients to reduce their overall fracture risk.

When looking at major osteoporotic fractures, you would need to treat 75 patients to prevent one with Forteo, but only 34 with Tymlos.

Conclusions

In patients I see who have sustained fragility fractures, we generally go with the medications that offer the most fracture risk reduction in terms of RRR. That’s because in these patients, it’s not a question of IF another fracture will occur, but WHEN. Until the arrival of Tymlos, Forteo had been RRR champion. While Tymlos might not be as great as Forteo in reducing painful vertebral fractures, the data suggests it appears to be even better at both RRR (reducing risk for all vertebral fractures) and the overall NNT (number needed to treat) for major osteoporotic fractures in particular.

Furthermore, with teriparatide going off-label and support from the manufacturer drying up, Forteo no longer seems to be a viable option for many patients at the moment. That’s why in my practice, I’ve switched the majority of my high risk patients to Tymlos.

Of course, this discussion is focused on high risk patients such as those who have already had a fragility fracture, or have other medical considerations that make them high risk (such as medical conditions or long term use of certain medications).

SELECTED REFERENCES

• Harris, ST et al. “Effects of Risedronate Treatment on Vertebral and Nonvertebral Fractures in Women With Postmenopausal Osteoporosis: A Randomized Controlled Trial.” JAMA. 1999;282(14):1344-1352. doi:10.1001/jama.282.14.1344
• Miller PD, et al. “Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.” JAMA 2016;316(7):722-33. doi:10.1001/jama.2016.11136.
• Reginster JY et al. “Abaloparatide is an Effective Treatment Option for Postmenopausal Osteoporosis: Review of the Number Needed to Treat Compared with Teriparatide.” Calcif Tissue Int. 2018;103(5):540–545. doi:10.1007/s00223-018-0450-0
• Institute For Clinical And Economic Review. “Anabolic Therapies for Osteoporosis in Postmenopausal Women: Effectiveness and Value.” Final Evidence Report.
• USPSTF. “Screening for osteoporosis in postmenopausal women: Recommendations and rationale.” Ann. Int. Med. 2002;137:526–8.

– James Webb, MD