(Focus - Singapore)
There are some diseases whose symptoms are ignored in the initial stage but taken into consideration when the condition becomes severe. One such disease is osteoporosis, a chronic health condition that makes the bones brittle and prone to fracture. It can be prevented from getting extreme when early-stage symptoms are treated and managed correctly, along with a proper diet containing ample calcium and regular exercise. This is what Dr. Leslie Chi Sern Leong, a renowned orthopedic consultant from Singapore, has to say in his interview with decodeMR.
Dr. Leong Chi Sern Leslie is a Consultant at Orthopaedics International, Director at L3M International, Singapore.
Now in the midst of treating all of this and managing the other medical comorbidities, like their heart, lungs, diabetes, high blood pressure, everything, unfortunately, osteoporosis sometimes gets forgotten. Then, during the follow-up, most of them are seen by an orthopedic surgeon who is now more interested in making sure that the wound has no problems, the fracture is healing well, and the implant has no issues.
When we hear the term osteoporosis, it is usually perceived as a disease that usually happens in older adults. But we do have juvenile osteoporosis that occurs just before the onset of puberty in previously healthy children. So, are there any risk factors that help in timely diagnosis of juvenile osteoporosis?
Dr. Leong - juvenile osteoporosis is not a common problem; it is relatively uncommon compared to osteoporosis in elderly. They may present in a number of ways. When young patients present with multiple fractures, that is one situation that we will look into to exclude osteoporosis. Secondly, we may see patients who present to us with other medical issues. And in some of these patients, they often can be a secondary cause to juvenile osteoporosis. These illnesses include juvenile diabetes, juvenile rheumatoid arthritis, and in some, osteogenesis imperfecta, a genetic problem in bone formation. And of course, there are endocrine issues, for example, Cushing's Syndrome, or they may be on various drugs, for example steroids or drugs that suppress cancer. Some patients may have chronic eating disorders or may not be eating well, leading to malnutrition.
Hence we usually have to exclude a secondary cause of juvenile osteoporosis before simply labeling it as a primary disorder. in some children aged 7 to 11, in a small minority, when there is no other cause for it, you can develop juvenile osteoporosis. But the good news generally is, once they clear that age, they can usually catch up in terms of growth, although there is a slight possibility that they may not be as much bone as they would have had if they did not have the disease. There could be a possibility of a loss of height or some long-term effects from fractures, especially in the spine.
There is a recommendation for pharmacologic therapy after osteoporotic fracture to reduce future fracture risk. But some studies in the US revealed a large treatment gap, with only about 20% of patients receiving treatments following a fracture.[1] What do you think, doctor? What are the reasons behind this treatment gap?
Dr. Leong - There are a few reasons for this treatment gap. Generally, patients present in two ways. One is through the family doctor, or you pick them up from some form of screening. For these patients, it may be a bit easier to treat them and follow up.
The second scenario is that patients that get admitted because they fell and have a spine or hip fracture. Now in the midst of treating all of this and managing the other medical comorbidities, like their heart, lungs, diabetes, high blood pressure and everything else, unfortunately, osteoporosis sometimes gets forgotten. Then, during the follow-up, most of them are seen by an orthopedic surgeon who is now more interested in making sure that the wound has no problems, the fracture is healing well, and the implant has no issues. And as you know, a lot of clinics, the doctors may be quite busy, or maybe the patient is managed by the junior staff who may not be so well in osteoporosis, and that could result in osteoporosis being untreated
Could you comment on the status of post-osteoporotic fracture treatment in Singapore? Is there any treatment gap?
Dr. Leong - Yes, there will be a treatment gap in all countries. That is unfortunate. What people have done to try and mitigate this is from the beginning, when you have an elderly who comes in with a fracture, some people get a geriatrician involved. So, this way we have a medical person who is a bit more aware.
Alternatively, a system can been set up, for example a fracture liaison service (FLS), which is quite now common in our public hospitals in Singapore because of the large number of fractures. The FLS will get involved from the beginning; there is as a nurse, and there are protocols for these hip and spine fracture patients that are being followed to ensure that the osteoporosis is looked after.
The third problem will be, yes, it is looked after but do they(patients) continue medication? In osteoporosis, there are no symptoms until you fall and break your bones. So, some of these patients or their children forget about it, and this is the unfortunate part, which is why I noticed a lot of the drugs only have about 40 to 70% retention use after a 1 - 2 years. Therefore, the problem is making sure the patients remain on continuous follow-up.
The literature says that if you have had a cardiovascular accident in the past year, you should not use it. And, if you probably have uncontrolled heart disease, it may not be a good indication. Many elderlies will have these issues, so that will be a problem.
Several clinical trials have shown that romosozumab followed by denosumab may be a promising regimen for treating osteoporosis. [2] [3] What are your thoughts on this combination?
Dr. Leong - Yes, we have seen the trials, and I think it is very promising. Prior to romosozumab there was Forteo (teriparatide) and of course, abaloparatide. Studies at that time show that if you take teriparatide together with antiresorptive, they will be synergistic instead of taking one or the other.
Also, in the old days, we used to reserve teriparatide for the treatment failures, as it was quite costly, thinking that if the patient did not do well with antiresorptive, we would resort to a bone-building drug [osteoanabolic]. These new trials have shown us that it is better for severe osteoporotic patients and in patients with multiple fractures, to treat them with an osteoanabolic first and then continue with an anti-resorptive, rather than the other way around.
The studies have also shown that if you start anti-resorptive, and then you put them on an osteoanabolic the results are not as great as starting with an osteoanabolic first
How will it impact the osteoporosis treatment landscape of Singapore?
Dr. Leong - I think this is pretty new. Evenity (romosozumab) is only launched recently. So right now, there isn't a huge impact. But going forward, I think it will help patients who have multiple fractures, who are elderly with multiple co-morbidities or severe osteoporosis. A rapid increase in bone mass may also help prevent further fractures better than a slow increase. The only fly in the ointment is the price.
It is not exactly a cheap drug. But we know from the results that one year of romosozumab plus one year of denosumab equals six to seven years of denosumab. So, if you look at it that way, in terms of pricing, you could say that, yes, you either pay your money over seven years, or you do it upfront. It is just a matter of where you want to put the cost and your budget.
Is there any limitation that you foresee apart from the cost of this treatment combination?
Dr. Leong - Yes. We know from the trials that there are some issues with this treatment combination if you have recent heart attacks or stroke. The literature says that if you have had a cardiovascular accident in the past year, you should not use it. And, if you probably have uncontrolled heart disease, it may not be a good indication. Many elderlies will have these issues, so that will be a problem. An option would be to use teriparatide instead.
Talking about treatment approaches, we have ongoing clinical trials on the combination and sequential therapies in osteoporosis, as the effects of bone-forming treatments may be improved and maintained with combined or sequential treatments. [4] [5] So which approach do you follow or prefer, doctor?
Dr. Leong - If I am using teriparatide, I will use a combination, which means teriparatide for the first 1 - 2 years, along with an antiresorptive because that has been shown to be synergistic. However, if it is romosozumab, that will be sequential because romosozumab by itself has both antiresorptive and analog properties.
Do you see any concerns with these treatment options doctor?
Dr. Leong - I do not have any huge concerns. As I mentioned earlier, the contraindications for romosozumab are the only thing. So, in that sense, for that group of patients, teriparatide may be the better option if they cannot take romosozumab.
Before we conclude our session, what are your key takeaway message to osteoporosis patients or their caregivers, especially during this COVID pandemic?
Dr. Leong - Unfortunately, osteoporosis tends to get left out in the cold simply because there are no symptoms. And by the time you have symptoms, it may be too late because when you break a bone, you may have to go for surgery. Also, the risk of further fractures is severely elevated for the next year and remains somewhat elevated for the next several years.
To avoid this problem, make sure you get sufficient calcium in the diet, vitamin D, either from sunshine or pills, and exercise that doesn't just include cycling and swimming; it means walking, jogging, and resistance exercise as well. And if you have confirmed osteoporosis, please get it treated, and put a reminder on your fridge door to get yourself tested every 1 - 2 years and continue your drugs
Thank you very much for your time and your insights.
Reference:
1. https://pubmed.ncbi.nlm.nih.gov/25112720/
2. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.3622
3. https://www.frontiersin.org/files/Articles/717065/fphar-12-717065-HTML/image_m/fphar-12-717065-t003.jpg 4. https://www.frontiersin.org/files/Articles/717065/fphar-12-717065-HTML/image_m/fphar-12-717065-t005.jpg
5. https://www.frontiersin.org/files/Articles/717065/fphar-12-717065-HTML/image_m/fphar-12-717065-t004.jpg