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‘Bone formation best to prevent osteoporotic fractures’
  • By Park Gi-taek
  • Published 2018.06.07 16:06
  • Updated 2018.06.07 16:06
  • comments 0

Osteoporosis is rapidly growing in South Korea. The number of patients suffering the disease rose 12.6 percent over the past five years, from 805,304 in 2013 to 906,631 in 2017, The cost of medical care for osteoporosis also went up 43 percent from 80.5 billion won ($75.3 million) to 111.5 billion won during the same period.

The alarming trend can accelerate with the increase of the aging population. In Korea, the proportion of the elderly aged 65 or more reached 14 percent in 2017. The nation is expected to enter a super-aged society with the ratio of the senior population touching 20.8 percent in 2026.

Then, how should osteoporosis patients manage the disease, at a time when the nation nears a super-aged society?

Gary Krishnan, Eli Lilly’s global lead for external innovation, and Ajou University Hospital’s Endocrinology Professor Jung Yoon-seok said bone formation to prevent fracture is the best method, in an interview with Korea Biomedical Review.

Professor Jung Yoon-seok (right) of Ajou University Hospital’s endocrinology department, and Gary Krishnan, Eli Lilly’s global lead for external innovation, talk in an interview with Korea Biomedical Review.

KBR: What is the status of osteoporosis in Korea?

Jung: The diagnosis rate of osteoporosis has been gradually increasing in Korea because women aged 55 and 65 are obliged to get a state testing for osteoporosis, free of charge. At 55, women enter the postmenopausal period. At 65, they enter the old ages. The percentage of patients receiving the test has risen to 30 percent. However, 70 percent of the entire postmenopausal women are still not examined with a bone density test because either they forget to be tested or are scared to get one.

Among domestic osteoporosis patients, only 9 percent continue to get treated. Most of them take oral medicines for about six months but stop them at discretion. In diabetes and hypertension, stopping the drug causes symptoms to appear. However, in osteoporosis, patients do not have any specific symptoms other than slight back pain. So, osteoporosis patients do not feel the need to continue treatment. If this is repeated for years, they may experience a fracture, caused by osteoporosis. If they visit the hospital with such fractures, they find it challenging to recover quickly because osteoporosis has already progressed significantly.

If people are 70 or older, the health is not good overall, and it is not as easy as it used to be with any treatment. For the seniors, it is best to use bisphosphonates to maintain the already-low bone density.

Krishnan: In the U.S. and Europe, people have a relatively high awareness of osteoporosis or osteoporotic fractures thanks to active campaigns on women's health. However, due to the problem of insurance benefits for dual-energy X-ray absorptiometry (DXA) for measuring bone density, the diagnosis rate has fallen recently. This has resulted in a reduction in overall awareness of the disease. The low treatment rate is a common problem all over the world.

KBR: Korea also had public campaigns to raise awareness of osteoporosis, but questions remain whether they were effective.

Krishnan: Japan is one of the countries that are conducting such campaign actively. The Japanese Society for Bone and Mineral Research (JSBMR) emphasized that doctors explain to patients that “osteoporosis is a disease of silence.” Japanese physicians actively educate patients about osteoporosis and treatment alternatives.

For example, the VERO study provides essential and objective evidence on which treatment is more effective for patients with severe osteoporosis. The study has shown that bone formation stimulators are more effective in treating patients with severe osteoporosis than bisphosphonates. It is clear from this reliable research data that there is a more effective treatment for patients who have osteoporosis.

KBR: Why do both of you highly value the VERO trial?

Jung: The VERO study, which was double-blind and double-dummy, was on 1,360 patients in 14 countries for two years. It was meaningful that the study designed new vertebral fractures as the primary outcome.

Bisphosphonates increase the risk of new fractures, and additional fractures raise the medical expenses including surgery cost. Guardians should keep visiting the hospital with the patients. Given such socioeconomic loss, it is cost-effective to use Forsteo (by Eli Lilly) than bisphosphonates in the long term, although Forsteo is more expensive at the initial stage. The VERO trial confirmed this.

In the future, the paradigm of osteoporosis treatment will change from bisphosphonates to bone formation stimulators, particularly for patients who have already suffered fractures.

KBR: Isn’t it unusual to conduct such kind of study more than 10 years after the launch of Forsteo?

Krishnan: I will explain that in two ways. First, the current treatment guidelines recommend Forsteo for patients with severe osteoporosis. Since several years ago, however, people started to question whether it was more useful to inhibit bone resorption or to help form bone in treating such patients. To have an answer to this question, the VERO study began. The study proved that it was more effective to stimulate bone formation than to inhibit bone resorption.

Second, I should mention the change in the paradigm in treating osteoporosis. In the past, we examined bone density to treat the disease. Nowadays, however, we measure bone strength using the “finite element method” that engineers use to measure the strength of bridges and buildings. Bone fracture is caused not by a problem in bone density but a problem in bone strength. The VERO study has been designed to meet the needs of the shift in treatment paradigm and concluded that Forsteo was conducive to enhancing bone strength.

KBR: Does Forsteo have any safety concern?

Jung: Patients may have slight dizziness or discomfort when they take Forsteo injections at first. Such side effects appear in the first month or so. After that, there is no big problem because patients get accustomed to it.

Krishnan: A study reported that rodents developed osteosarcoma after using Forsteo for a lifetime. However, an independent data monitoring committee found that the global incidence of osteosarcoma was not significantly different between patients who were treated with Forsteo and those who were not.

Some patients with the severe renal disease should not use parathyroid hormone because the symptoms can worsen if they do. However, patients with moderate kidney disease can use the parathyroid hormone at the discretion of medical staffs.

Patients with orthostatic hypertension may experience dizziness for a month after using Forsteo. If they adjust to the medication, they can continue the treatment without a problem.

Globally, a considerable number of patients are prescribed with Forsteo and using it. Also, the drug’s safety has been confirmed sufficiently.

KBR: It sounds as if bone formation stimulators could be used as the first-line treatment.

Jung: If bisphosphonates as the first-line treatment do not stop the declining of bone density for a year, physicians recommend a second-line treatment. However, the second-line treatment is almost useless to those whose disease has progressed too seriously.

Rather than making choices by price only, we should consider the cost-effectiveness of the drugs. The comparisons should involve whether the remedy improves symptoms and whether it can prevent additional fractures that will cost more time and money of the guardian.

Krishnan: We should also consider things that cannot be economically converted. Forsteo has a significant meaning that it can help the patient restore self-esteem, lead an independent life, and participate in social activities. Because the drug promotes bone formation, a one-month medication reduces back pain quickly. Patients recover their confidence by feeling that their bones are getting stronger again. Indeed, I have seen a patient, who used to lie on the bed all day long due to severe osteoporosis, began walking after Forsteo treatment.

KBR: We heard that even if a patient stops taking Forsteo, its therapeutic effect continues. Is it true?

Krishnan: According to the PRINCE study, Forsteo reduced fracture risk for more than 30 months after stopping the treatment. Some patients use other treatments after stopping Forsteo under the treatment guidelines. However, Forsteo helps generate new healthy bone, which maintains the efficacy to reduce fracture risk for a long-term. Another study SHOTZ showed that bone scans a few days before the discontinuation of the Forsteo treatment showed that bone formation was very active.

Jung: If you use Forsteo, you develop new bones. Your bone will not disappear but continue to exist (even after the cessation of treatment). If you use Forsteo for two years, you will have new bones sufficiently. The new bones can last for more than 30 months as long as you maintain other treatments after stopping the Forsteo therapy.

KBR: Do you have any more comment?

Jung: I hope that the regulator will ease or improve the criteria for Forsteo reimbursement so that patients who need it the most could get the timely treatment. Forsteo received insurance benefit in December 2016 under too strict conditions. Patients have to use the first-line treatment for a year and have two osteoporotic fractures to benefit from insurance. They also should be 65 years old or older, and the bone density measured by dual-energy X-ray absorptiometry on the central bone should be minus 2.5 or less.

Few patients meet all these conditions at the same time. Such conditions are a huge barrier to patients who need the treatment.

The VERO study was in postmenopausal women aged 45 or more. The average age of osteoporosis patients is in the 60s range. If we allow reimbursements for younger people who suffered more than two fractures with serious osteoporosis, however, Forsteo covered by insurance will make more active treatments possible amid effective therapeutic benefits.

Krishnan: With aging, the number of osteoporotic fracture patients is surging. As we have confirmed evidence that bone formation stimulators are more effective than other treatments for patients with fractures, I hope that the Korean government will make the right decision for patients later on.


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