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The Silent Fracture: Understanding Osteoporosis

• Dr Gavin Nimon • Season 5 • Episode 72

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The silent, stealthy nature of osteoporosis makes it one of medicine's most challenging conditions. Patients can lose precious bone mass for years with absolutely no symptoms, only discovering their condition after a devastating, life-altering fracture.

With over a million Australians affected and our population steadily aging, understanding how to identify, investigate and treat this condition couldn't be more crucial. Yet despite its prevalence, osteoporosis remains severely underdiagnosed and undertreated in clinical practice.

In this comprehensive episode, Dr Gavin Nimon ( host and Orthopaedic Surgeon) inteviews Endocrinologist Dr Linn Lee brings about this complex topic. She expertly guides us through interpreting those notoriously confusing DEXA scan reports, breaking down T-scores and Z-scores into practical insights you can immediately apply. You'll discover exactly who needs investigating, when to refer to specialists, and how various risk assessment tools like FRAX and Garvan calculators can quantify fracture risk beyond bone density measurements alone.

Dr Lee demystifies the expansive pharmacological landscape – from bisphosphonates to cutting-edge anabolic agents – with particular attention to selecting the right medication for specific patient profiles. She discusses potential complications like osteonecrosis and atypical femoral fractures with refreshing honesty, providing evidence-based context about their prevalence and management strategies to mitigate risks.

Perhaps most valuable is the practical guidance on monitoring treatment efficacy, managing medication side effects, and navigating challenging clinical scenarios like bisphosphonate "drug holidays" and the complexities of stopping denosumab. The discussion extends beyond medications to emphasize the critical role of calcium, vitamin D, and targeted exercise regimens in comprehensive bone health management.

Whether you're a medical student building your foundational knowledge or an experienced GP managing complex cases, this episode delivers the practical insights you need to provide optimal care for patients with this prevalent but often overlooked condition. Subscribe to Aussie Med Ed for more expert-led, pragmatic discussions on core medical topics.

Aussie Med Ed is sponsored by -HealthShare is a digital health company, that provides solutions for patients, General Practitioners and Specialists across Australia.


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Speaker 1:

Osteoporosis is often called a silent disease because it can progress for years without symptoms, only to reveal itself through a sudden devastating fracture. It affects more than a million Australians and is a major cause of morbidity in our ageing population. Yet it's frequently underdiagnosed and undertreated. General practitioners and all doctors play a crucial role in identifying at-risk patients, initiating investigations and starting early treatment to prevent long-term complications. So how do we know who to screen, what medications truly make a difference and how do we know how to navigate the risks and benefits of treatment, especially in elderly or complex patients? Welcome back to Aussie Med Ed, a podcast where we take a pragmatic and relaxed dive into core medical topics designed especially for medical students and general practitioners. I'm your host, dr Gavin Lyman, and today we're unpacking the diagnosis and treatment of osteoporosis with Dr Lynne Lee G'day. And welcome to Aussie Med Ed, the Aussie-style medical podcast, our pragmatic and relaxed medical podcast designed for medical students and general practitioners, where we explore relevant and practical medical topics with expert specialists Hosted by myself, gavin Lyman, an orthopaedic surgeon, this podcast provides insightful discussions to a hunch of clinical knowledge without unnecessary jargon.

Speaker 1:

I'd like to start the podcast by acknowledging the Kaurna people as the traditional custodians of the land on which this podcast is produced. I'd like to pay my respects to the elders, both past, present and emerging, and recognising their ongoing connection to land, waters and culture. I'd like to pay my respects to elders, both past, present and emerging, and recognising their ongoing connection to land, waters and culture. I'd like to say that this podcast is for educational purposes only and does not constitute medical advice. Always refer to clinical guidelines and consult a qualified healthcare professional before making medical decisions. In today's episode, we're discussing the diagnosis and treatment of osteoporosis with Dr Lynne.

Speaker 1:

Lee Lynne is a specialist endocrinologist with a particular interest in bone health, reproductive endocrinology and diabetes management. After graduating from the University of Adelaide, she completed her advanced training in endocrinology at the Lyme Acute Hospital and Flinders Medical Centre and is a fellow of the Royal Australasian College of Physicians. She practices privately as South Australian medical specialist here in South Australia. Dr Lee is also undertaking dual training in chemical pathology, giving her a unique depth of insight into the biochemical basis of endocrine conditions. Welcome, dr Lee. Thank you very much for coming on board for Aussie Med Ed Lynn, and it's great to have you here with us. Perhaps you can tell me a little bit about what osteoporosis actually is and what the difference is between osteoporosis and osteopenia.

Speaker 2:

Absolutely so. Osteoporosis is a condition defined by low bone mass and deterioration in the microarchitectural quality of the bone. It's incredibly common, a huge public health concern, and I guess the easiest way to define it is purely by the radiological kind of definition. So osteopenia is defined by a T-score between minus one and minus 2.5. So that's between one to two and a half standard deviations below what you'd expect for a 30-year-old of the same sex, and osteoporosis is defined as a T-score of lower than minus 2.5. So I guess you could say osteopenia is that sort of milder form, that sort of pre-osteoporosis stage before bone density really gets that low.

Speaker 1:

So 30-year-olds use as a standard, is it?

Speaker 2:

Essentially, yeah. So when you use a T-score, you're comparing it with 30-year-old bone density of the same sex.

Speaker 1:

Yeah, Okay, how common actually is osteoporosis?

Speaker 2:

It's very common. So it's been estimated that in all Australians over the age of 35 years it's about 2.7% of that population and that incidence rises markedly after the age of 75 in women, and it's generally postmenopausal women that have the highest incidence of osteoporosis, but pretty common even in the 35 to 90-year-old population. Yeah, Excellent.

Speaker 1:

It's more common in women than men.

Speaker 2:

Definitely. Yeah, it's probably a lot to do with the fact that women go through menopause so essentially hypogonadal. They lose that estrogen that provides a lot of suppression of bone turnover and they end up developing osteoporosis a lot easier. It's a lot less common in men, but certainly happens as well.

Speaker 1:

So it's not based purely on the fact that men have a higher bone load initially. It's based purely on compared to the same sex.

Speaker 2:

No, that's absolutely a good point. So we know that having a higher body mass generally causes more weight bearing on the bones and leads to achievement of a higher peak bone mass and therefore you tend to have a higher mass to start with. So you lose less and you're less likely to develop osteoporosis. But I think a big part of why women get it more is because of menopause, and we know that postmenopausal women are the biggest group. If you compare premenopausal women, that's a much smaller group.

Speaker 1:

What are the other risk factors for osteoporosis?

Speaker 2:

Yeah, absolutely so. Lots of risk factors. Probably the most common ones to consider when assessing a patient, for example, would be whether there's a family history of osteoporosis, particularly if there's been a family history of hip fracture in either parent. That's actually used in the FRAX calculation score. I always ask my patients about alcohol intake the less the better with regards to bone density, and we consider other things like calcium intake as well, whether that's been adequate, vitamin D deficiency and then significant comorbidities, such as any kind of malabsorption conditions like celiac disease, malnutrition, low bone density and low weight bearing states such as people that are confined to wheelchairs or bed bound. And there are other conditions like inflammatory sort of disorders, like rheumatoid arthritis, glucocorticoid use, of course, diabetes mellitus, chronic kidney disease. A lot of these chronic multi-organ illnesses tend to raise the risk of osteoporosis as well, but those are probably the main ones I tend to ask about.

Speaker 1:

In my reading I was hearing that obviously smoking is a factor and then with smoking and reduced body mass, it's also a factor. Is the cause of smoking being a factor on causing osteoporosis the fact that people who smoke may have a lower body mass because of the appetite suppression or the malabsorption or was it actually a primary effect itself?

Speaker 2:

yeah, I'm not aware that smoking is a primary risk factor and directly interferes with bone metabolism, but certainly those links that you described, I could absolutely see that happening. Lower bone density maybe might be associated with lower nutrition as well, and I do ask that as part of my routine history, but I don't focus on it so much as a risk factor.

Speaker 1:

Yeah, and obviously there's also a lot of medications, too, that can interfere as well with it.

Speaker 2:

So what are?

Speaker 1:

the main ones you would tend to see.

Speaker 2:

Yeah, absolutely so. I already mentioned glucocorticoids. That's a big one, and we have a much lower threshold to treat people with osteoporosis if we know they're on corticosteroids. The other ones I see are women who use certain progesterone-only contraceptions, such as the Depo-Provera. That's the big one, but the Implanon has also been linked to lower bone density. So in vulnerable patient groups we tend to recommend different ones. Oestrogen-containing ones would be ideal. And then the other group of patients are the ones that are on anti-epileptic medications, particularly Valproate. There's been a clear association with low bone mass.

Speaker 1:

Right, you've already mentioned the diagnosis looking at a standard deviation of bone density, yep. That's obviously based on a DEXA score, which I always find very difficult to interpret. It's often two or three pages and there's a bunch of graphs and things. What's the easy way for the medical students and young GPs to try and interpret these results?

Speaker 2:

Yeah. So I wanted to start by actually saying that Healthy Bones Australia has a really nice two-page PDF. It's got like a graphical diagram of how to go about interpreting a Dexan. I thought that was actually quite useful, even for myself, just as something to show people. But I would always start by first of all looking at the age of the patient. That plays a huge role in determining fracture risk.

Speaker 2:

I then look at the T-scores to start with and assess whether or not they have osteopenia or osteoporosis. The Z-score is useful for determining A if the patient has maybe a secondary cause of osteoporosis. Largely speaking, a Z-score under minus two would prompt you to look for a secondary cause. And the reason for that is a Z-score is the number of deviations above or below bone density for an age-matched person. So you're really comparing with other people in that age group and if they've got much lower bone density than other people their age, then you think about whether there's celiac disease or primal hyperparathyroidism or something like that. And the other group that the Z-score is useful for are people that are under the age of 50, because the FRAX tools and all our risk calculations they're really aimed at people who are older. So the Z-score. You can't really use a T-score in that population either. Use the Z-score Then.

Speaker 2:

The next thing I would look at, particularly for people who are on treatment. So when people have already been on treatment and you're following them up with a repeat bone density scan, I tend to look at the percentage change from the last scan and we would consider anything more than 4% in either direction to be a significant change. But most bone density centers will actually tell you whether or not they feel, according to their data, whether it's statistically significant. Significant, but the sort of zero to three percent change that's within what you could naturally find between repeat bone density scans. It might not be significant and that helps me to guide treatment. So I'll know if there's been deterioration despite standard treatment or whether there's been improvement.

Speaker 1:

Excellent. You touched upon the FRAX score and I believe there's also a Garvin score and maybe a few other scores I'm not aware of, but these are two I've heard of. What is the utility of those and how do they help us?

Speaker 2:

Absolutely. Those are the two that I know of as well. So the FRAX tool is more international and it takes into account a few other. It's got a few other questions as part of. It looks at glucocorticoid use, inflammatory conditions, alcohol intake, although I'm not sure to what degree those actually end up changing the FRAX tool, but they certainly are part of the questionnaire. The Garvin I like, particularly for people who have a lot of falls, because it takes into account falls per year and the frax doesn't. So if there's someone who has a lot of falls the frax may actually underestimate that fracture risk because of course if you're not falling you're much less likely to fracture. The other thing is the Garvin is, I think, australia based, so I like using that for our Australian population. I tend to go Garvin and then maybe might do the FRAX as a follow-up.

Speaker 1:

So you do these routinely on your patients.

Speaker 2:

So not routinely.

Speaker 2:

That's a good point that you raised there.

Speaker 2:

It's also worth pointing out that a lot of bone density scan centers will publish automatically their calculated FRAX score based on the bone density they've done on that day, and that's quite helpful.

Speaker 2:

Generally score based on the bone density they've done on that day, and that's quite helpful. Generally, treatment is recommended for people who have a 10-year risk of at least 20% for any osteoporotic site and 3% for the hip, and if you exceed that then antiretroviral is recommended. So sometimes it's a clear-cut case someone who's broken their hip from a minimal trauma event, or a 75-year-old with a t-score of minus three those are clear indications for treatment. When it's a bit less clear for example a 50 year old with no fracture and a t-score of minus 2.5, or maybe a 65 year old with an osteopenia t-score of minus 2.3 those ones that are not clear cut but maybe have an elevated fracture risk I think those are where it's useful. And the other scenario where it might be useful are anxious patients who have a low fracture risk but say a 30 year old with a t-score of minus 2.5 and they're worried. I find that using the fracture calculator is really useful for reassuring them that their fracture risk is really low.

Speaker 1:

And in these scenarios, that perhaps these younger patients particularly what would bring them to have a DEXA scan in the first place.

Speaker 2:

I suppose the times that people may consider it is when there've been significant risk factors, things like. I've seen it done for prolonged periods of untreated hyperthyroidism or premature menopause or what we call primary ovarian insufficiency. In the younger population, and I do see it sometimes done in people who have anorexia nervosa, very low BMIs. I wouldn't say that it's appropriate to do it in those instances, but I can certainly understand why they've been done. The thing is that it may bring to light underlying low bone density. That doesn't end up having any clinical consequences because the risk of fracture is low. Low bone density is not the only determinant of fracture risk but on the other hand one could argue that it does prompt patients maybe to make some lifestyle changes. So get onto their vitamin D and their calcium intake and do more exercise. So I can see the pros and cons of both.

Speaker 1:

So over the age of 50, screening is a tool that's recommended.

Speaker 2:

Absolutely Between the ages of 50 and 65, and talking about the female population here, if they have an additional risk factor for osteoporosis, then screening with a DEXA scan is recommended, definitely Over the age of 65, it's recommended that all women just get a DEXA scan because they are long postmenopausal and the incidence of osteoporosis is very high in that population.

Speaker 1:

Excellent, If we move on to actually further diagnostic tests. What's the role of bone turnover markers? I was actually reading about these and these are blood tests which I've never heard of until I prepared for this talk today.

Speaker 2:

Yep, absolutely so. Look, the two main ones that I think most people will come across are the crosslaps, as we call them. They've got a much longer name, I think it's C-terminal telopeptide, and there's also the P1NP, and, to put it simply, crosslaps are an indicator of bone resorption and P1NP is a marker of bone formation. I don't ever really order a P1NP. It's used a lot in research, of course, and we'll talk a bit later about the bone building agents, and yes, those would be potentially raised, but practically we don't really monitor them. We just trust that the treatment's working.

Speaker 2:

To be honest, crosslaps do have a major role in the management of osteoporosis. Crosslaps reduce quite quickly after starting anti-resorptive treatment. So within one to two weeks of starting a bisphosphonate, for example, cross-lapse will reduce by 50%, and for Prolia Denosumab, within a few days it will reduce quite significantly as well, and it's a really good indicator of reassuring ourselves that the anti-resorptive therapy is working. And I find that particularly useful in a few scenarios. The main one would be when you're treating someone with an oral bisphosphonate.

Speaker 2:

Now, oral bisphosphonates are well known to be not the best absorbed drug. It's got a very low oral bioavailability and even in the best of scenarios, with a big glass of water, 30 minutes empty stomach. It may not be the best absorbed drug and it's useful to have cross-laps to do to reassure yourself that it's actually working and we aim for a cross-lapse under 400 to tell us that it's therapeutic. We'll talk a little bit later as well about the issues with prolia and stopping prolia, and we do use cross-laps as well to monitor the rebound reduction in bone density that occurs after the cessation of prolia and stopping prolia. And we do use cross-laps as well to monitor the rebound reduction in bone density that occurs after the cessation of prolia and how that guides us with managing those patients.

Speaker 1:

Yeah, okay, so for the average person? Obviously most osteoporotic patients would be treated by their GP. We'll talk through the treatment methods in a minute, but there'll be occasional patients that may have greater osteoporosis or there may be some concern. What's the average patient that we referred to an endocrinologist for osteoporosis?

Speaker 2:

Yeah, I see patients mainly who may be not satisfied with the standard treatments that are available bisphosphonates and or Prolia and they may want to explore things like hormone replacement therapy. They just want to get a second opinion. That's pretty common. We do get a lot of referrals for failure of treatment or patients who would benefit from zoledonic acid because there's quite a lack of accessibility for giving these infusions and I completely understand getting referrals for that. And with just going back to treatment failure, that's defined as patients who either have a deterioration in bone density or a minimal trauma fracture despite 12 months of adequate treatment. We do now have treatments that require specialist review for prescription on the PBS and we see those patients as well quite a lot, and I suppose any patient where they have osteoporosis and too many other things going on on CKD is the big one where we just need maybe more of a bigger picture.

Speaker 1:

So balancing the kidney disorders with the osteoporosis and try to coordinate the calcium resorption and reabsorption from the kidneys?

Speaker 2:

Yeah, absolutely so. We tend to see those quite a bit as well.

Speaker 1:

Okay, excellent, we'll move on to the treatment of osteoporosis. I understood. You know, obviously, as a north big surgeon, about calcium and taking vitamin d and getting sunlight very important and that's about as much as I knew. I've heard about biphosphonates in the last few years, but when you look at it, there's a lot to it. There's so many different forms of treatment yeah we start off with the simple things first. Obviously, obviously preventative would be important reducing alcohol intake and doing exercise. Where do you go from there?

Speaker 2:

Yeah, and look, I'm glad you brought up exercise. It's actually really important to also prescribe the type of exercise that should be done. A lot of the patients that you take a history from will say, yeah, I walk every day and the walking's good, but if they've already had a fall and a fracture, we really need to be looking at what more we can do for these patients and Healthy Bones. Australia actually has a really nice PDF again about exercise and they cover exercises for weight bearing and they also cover resistance training and balance training. So these are the three sort of categories of exercise, and balance training is really important for these patients, especially the ones who are falling over just ensuring that they can write themselves better if they trip and things like that and I think exercise physiology referral is absolutely reasonable as well.

Speaker 2:

So with regards to finishing up on the lifestyle things, I guess I always make sure that patients are having adequate calcium, so the recommendation is at least 1200 milligrams for a postmenopausal woman per day, and that can look like different things. I usually have a little chart of calcium foods and there's also online calculators that people can use to make sure they're getting enough calcium and vitamin D. I think labs quote 60 is the normal range, but we know that you need sometimes need up to 80 to completely eliminate any sort of bone resorption. That's going on, yeah, and most of us need vitamin D supplementation. We're all indoors, so yeah. So that's the kind of we've covered the lifestyle things, the dietary things, and then moving on to pharmacological management. So I always split them up into two categories the bone, the antiresorptives, so the ones that prevent osteoclast action, and the bone building agents, or the anabolic agents. So, in terms of the antiresorptives, you mentioned the bisphosphonates. That's the oldest one we have, with the most data comes in oral form. Obviously, you've got weekly tablets, monthly tablets. Actonel, fosamax are the two main ones that we tend to prescribe, and then we've also got zoledronic acid, which is an intravenous infusion that we use yearly. Bisphosphonates, like I said, they're very old. They're very old medications. We've got lots of data on them. They work really well. The main side effect with the oral bisphosphonates are the gastrointestinal side effects and, like I mentioned before, the low bioavailability. So really emphasizing to patients that the mode of administration is really important, sticking to the advice provided by the pharmacy, and I tend to avoid it in patients who have had upper gastrointestinal surgeries or esophageal strictures, anything where that drug might get stuck. I don't, yeah, I don't recommend it.

Speaker 2:

Intravenous bisphosphonates. So the main one we use obviously is zoledronic acid. I like that it bypasses the gastrointestinal tracts, are really good for those that do get reflux and symptoms like that. The main side effect is flu-like symptoms. In some patients it can be pretty severe as well. They can get this really run down malaise. They can get the headaches and body aches and joint pains and things and it can be quite off-putting. If they've not expected it, I generally tell patients to take paracetamol three days prior leading up to the infusion and on the day of as well. They can take it after as well if they want, and that's actually been shown in the literature to be useful. I have also seen in clinical practice patients who have really severe reactions. The next one they might take a small one-off dose of a corticosteroids, so 25 milligrams of prednisolone or something like that. But yeah, those would be the main side effects. So those are the bisphosphonates.

Speaker 2:

The other anti-resorptive that we see a lot of is Prolia, the denosumab. So denosumab is a monoclonal antibody against rank ligand and it's a very potent inhibitor of osteoclastic action. It works extremely well, but the main downside is that it only works while it's in the system, so it has to be given every six months pretty strictly, and it also can't be stopped. So it's meant to be in an indefinite treatment and cessation is not recommended unless it's covered by something else, and even then there are nuances issues with that.

Speaker 2:

And if it is seized without anything to replace it, you can get a pretty profound bone density rebound, bone density loss.

Speaker 2:

There's also an increased risk of multiple vertebral fractures in the spine and actually by two years post-cessation it's almost like you've never been on any prolia at all. So you actually go back to being on essentially similar to placebo, yeah, yeah. So quite a profound and significant issue there with the denosumab and I see it prescribed a lot in the younger population it's such a convenient drug you inject it and forget it. But I am now actually seeing more and more gps, I think, being made aware of the issues with denosumab, and we do get a lot more referrals now for people who have been started on denosumab either by a different GP or a specialist or hospital and they're saying can you please help us get this patient off denosumab because they're way too young to be on it Anyone over the age of 80 or someone who's got a lower life expectancy. I think very reasonable to be on denosumab. We've got data going up to 10 years for the safety and efficacy, but we don't have much beyond that.

Speaker 1:

So in these osteoclastic reduction, osteoclastic activity they don't obviously increase the actual bone density, they just reduce the actual loss. Is that correct?

Speaker 2:

So it yes, it doesn't affect the osteoblast, so it doesn't actually cause any bone formation. But by reducing osteoclastic activity alone that can, I guess, improve you could say the balance between the two. And we do see increases in in bone density. We do see that particularly with prolia in the spine. It's got quite a marked improvement.

Speaker 1:

But we see that with bisphosphonates as well yeah, so that leads to a change in their percentage. They may move from a lower t value or z value, depending on their age group to a change in their percentage. They may move from a lower T value or Z value, depending on their age group, to a higher T value in that situation I would be satisfied if they just didn't lose bone.

Speaker 2:

But very often we do see and expect them to gain some bone as well, right, yep.

Speaker 1:

Okay, Moving away from those osteoclastic drugs are there any other we need to look at, or is that the main ones?

Speaker 2:

Well, there are the ones that we use less commonly in women. So we've got raloxifene, which is a selective estrogen receptor modulator and it's an estrogen agonist on bone, but it's an antagonist on breast and uterine tissue. It's an oral medication and it's indicated for postmenopausal women with osteoporosis. We tend not to use it in people who've had venous thromboembolisms or people at a higher clotting risk, because it can potentially increase the risk of VTE or venous thromboembolism.

Speaker 2:

And the last one, just to mention in passing as well, is tibalone. So tibalone is a synthetic steroid that has estrogenic and progestogenic effects. It's also an oral medication and it's also indicated for postmenopausal osteoporosis and we tend to choose this one. For women who also have vasomotor symptoms of menopause they get a lot of hot flushes but for whatever reason they can't have HRT then tibalone might be something that we can consider. And of course, we should mention HRT. Estrogen is a very good suppressor of bone resorption. We don't recommend using it as first line treatment in someone who needs anti-resorptive treatment, but if they have troubling vasomotor symptoms of menopause and they've got an increased risk of fracture although not a very high risk of fracture then HRT is a great option for those women.

Speaker 1:

Excellent. So there's numerous different options depending on the scenario. Obviously, it's not one size fits all. What about the osteoblastic drugs? Are these newer agents? Because I've not really heard too much about these.

Speaker 2:

Yeah, they definitely tend to be ones that endocrinologists prescribe. The two that we have on the market are teriparatide. So teriparatide is a synthetic PTH analog. It's been around for ages, although under continuous parathyroid hormone stimulation, bones tend to become osteoporotic. What they've found is that when you expose bone to intermittent PTH stimulation, it actually helps build bones, actually got an osteoblastic activity. So that's how teriparatide works.

Speaker 2:

It's a daily subcutaneous injection which, as you can imagine, brings its own challenges with getting patients to agree to have it, but it's pretty safe. We've got lots of data, long-term data, on it. It's safe in a wide range of kidney functions and it's safe in people that have a higher cardiovascular risk as well. So it's a really good option there as well, and it's given for 18 to 24 months. So it's PBS subsidized for 18 months, but it's been proven to be beneficial beyond that, up to 24 months.

Speaker 2:

After 24 months there is a black box warning for development of osteosarcoma. We always stop at 24. So the main limitation with prescribing on the PBS is the fact that you need very severe osteoporosis, so a T-score of minus 3.0 or less, and you need to have had at least two minimal trauma fractures, and one has to be on standard treatment and lots of barriers there, but we do see patients who qualify and I've prescribed it certainly a few times Yep, and but it's usually well tolerated, usually very well tolerated they self-administer the injections themselves right yep, so it's definitely been shown to significantly increase bone density, and both anabolic agents of teriparatide and romisazumab, which we'll talk about next, both of these need to be consolidated.

Speaker 2:

When we say that, we mean you need to lock it in with either Prolia or a bisphosphonate in order to secure that bone building and prevent sort of loss of what was gained.

Speaker 1:

So it's used at the same time, or once the first one stops, you start the second one.

Speaker 2:

Classically we stop the anti-resorptive, put on the anabolic agent, finish the course and then consolidate. But there have been some people that have been looking at using teriparatide and denosumab together and that's been. There's been some positive results there. Obviously that wouldn't work on the PBS because you can't be on an anti-resorptive when you're on an anabolic. But if one, if a person, if an individual was happy to self-fund one or the other, then technically it could be done.

Speaker 1:

But apart from teriparatide with denosumab together, I'm not familiar with any other concurrent treatments okay, so classically one than the other okay, and then one last drug to go through is that's it so romisosumab.

Speaker 2:

That's the newest one that we have. It's a fast drug to go through, isn't it? That's it. So romisozumab that's the newest one that we have. It's a monthly injection. It's actually two injections for whatever reason, but you inject them at the same time in two different sites and it's a monthly injection for a total of 12 months. And they've never done head-to-head trials between teriparatide and romisozumab. But just looking at numbers alone, it's suggesting that the romisozumab is probably more efficacious in increasing bone density.

Speaker 2:

The main issue with romisozumab is that there is a small but theoretical risk of increased cardiovascular events. Now, it wasn't found to be statistically significant. I think the numbers were something like 2.5% in the romisozumab population versus 1.9% in the alendronate. So it wasn't statistically significant, but it was enough to make people worried and certainly enough for the company to put out a warning that they wouldn't recommend prescribing this drug in anyone with a heart, a cardioinfarction or a cerebrovascular event in the last 12 months, and certainly in the older, more frail, comorbid population. I am very hesitant and would probably opt for the teriparatide instead because of that warning.

Speaker 2:

But apart from that, it is easy to administer. You just get them to book it in with their nurse and they usually tolerate it really well. I usually just check their calcium at the six month mark just to make sure that's not risen significantly. But it's a listed thing to look at but never really seen it be an issue. And then after the 12 months again they need to have consolidation. The slight difference with romisozumab is that there's really good evidence that upfront, first-line romisozumab so they've never had any anti-resorptive is actually the most beneficial and PBS in the last little while have started subsidizing romisozumab as first-line treatment. But again there are some strict criteria, again relating to very low T-scores and having specific symptomatic fractures within the last 24 months. But certainly if a patient fits that brief, absolutely would recommend being on romisozumab if they can Brilliant.

Speaker 1:

All these drugs are trying to reduce the amount of bone resorption or increase the bone formation, and they're the numbers we're looking at, that we actually have figures, and how will they actually prevent fractures or reduce the complications of fractures at all?

Speaker 2:

yep, yep, absolutely. You're absolutely right. So, at the end of the day, why do we care about improving bone density? It's not just to have a number go up, it's actually to reduce fracture risk. So I know for a fact that bisphosphonates have fracture risk in individuals. I always tell them. It doesn't make them bulletproof, though, so they still need to be really careful. If you have fractured before, you can fracture again, even with the best treatment. But yes, bisphosphonates have fracture risk. I don't know off the top of my head the numbers for the other agents, but they've all been shown to reduce fractures and not just improve bone density.

Speaker 1:

Excellent. You've mentioned some of the side effects of the drugs as we've gone, obviously the one that a lot of people might've heard about, the bisphosphonates, the risks of osteonecrosis of the jaw or unusual femoral fractures as well. What are your thoughts on those?

Speaker 2:

Yeah, yep, so we'll start with the osteonecrosis of the jaw. So everyone's really worried about it, and that's reasonable. It can be catastrophic and treatment can be prolonged and difficult. Osteonecrosis of the jaw is actually really uncommon in the osteoporosis population. It's better described in the oncology population, where they get much bigger doses and more frequent doses of these medications. But the incidence in the osteoporotic population is something between 0.001 to 0.15%. So it is a pretty unusual complication to have and if you know how to prevent it and which populations are most at risk, then it's very avoidable.

Speaker 2:

The biggest risk factors are, of course, being on an anti-resorptive, but apart from that, having poor dentition or active suppurative dental disease. So periodontal disease and things like that, those would be the main risk factors, and also having a recent dental extraction. That's one of the biggest risk factors as well. So it's always about prevention. Whenever you're about to start someone on treatment, always have a quick look in their mouth. If they're happy to get a dental review, that would be the best, but as long as they've not had any active dental issues, it's not the end of the world. I now get most patients just to do a dental review, because you never know when there's something that's asymptomatic that gets picked up, they can have that fixed before they then go down the route.

Speaker 2:

Like I said, if they need something done emergently, it can be done. Now we don't have any good ways of knowing when's the best time. I guess it makes sense that you would aim to do it just before the next dose for Prolia, because you can't stop it. You would do it maybe month four, so that they've got a whole month to recover before their next dose With bisphosphonates. If they're on an oral bisphosphonate, definitely stop it. It's no rebound bone loss, so that's fine. And with the zoledronic acid I don't think there's any hard and fast rule, but I would maybe aim to do it maybe six months, at least three to six months after their last dose, before they have any dental work done.

Speaker 2:

But if they can have it, all done before starting, then it eliminates a lot of issues after.

Speaker 1:

So these risks are for all the anti-resorptive medications is it Essentially.

Speaker 2:

Yes, so bisphosphonates and denosumab equally Okay.

Speaker 1:

Right, okay, what about the femoral shaft fractures? The proximal subtrochanteric type fractures that we will see occasionally? Yes, the proximal subtrochondriac type fractures that we will see occasionally?

Speaker 2:

Yes, absolutely so. I'll probably start by just saying a little bit about atypical femoral fractures or AFFs. So AFFs are generally no trauma or minimal trauma fractures that occur in generally the femoral shaft. They have quite specific radiological features that help us to differentiate it from your typical femoral fractures, have quite specific radiological features that help us to differentiate it from your typical femoral fractures. They tend to start laterally in the cortex and then move inwards, either transversely or obliquely. And you can also get some incomplete ones that just show as like a little bit of beaking at the side. That can be quite subtle, but they are associated with prolonged bisphosphonate use. Now the risk of AFFs go up even within the first year of bisphosphonate use. Now, the risk of AFFs go up even within the first year of bisphosphonate use, but goes up significantly after five years. And in saying that, once you stop bisphosphonates, the risk of AFF also drops quite significantly after cessation. So that's good to know. All the antiresorptives are associated with AFFs, but it appears that bisphosphonates more so than denosumab. The other thing to note is that AFFs in general are rare. They're very rare and they're difficult to study because they're so rare. And the other thing to note is that patients who have osteoporosis are also more likely to have AFFs. Anyway, you can have AFFs without being on bisphosphonates and we do see that happen sometimes.

Speaker 2:

I think this brings us to our next kind of topic about drug holidays, because that's something that's discussed a lot and GPs do ask me a lot of questions about drug holidays. So a drug holiday basically means, after a period of time of being on a bisphosphonate, taking one to two years off the bisphosphonate to reduce the risk of AFFs. Now drug holidays are recommended in people with a low to intermediate risk of fracture. If they've, say, had a T-score of minus 2.5 and then you treated them with a bisphosphonate and now they're just osteopenic, they've not had any fractures you could definitely consider a drug holiday. But official guidelines actually say not to consider it if they're still at a high risk of fracture, so they've had a recent fracture or t-scores are still below minus 2.5. They actually recommend that you keep going because even at the 10-year mark of being on a bisphosphonate for most of the population, even then the risk of fracture from a from minimal trauma typical fracture would be higher than the risk of an AFF. So that's something to be aware of.

Speaker 1:

Yeah, I think it's quite commonly known that a person who breaks their hip has got a high risk of mortality in the first year after that.

Speaker 2:

Absolutely, absolutely. So we'd rather prevent that than an incomplete AFF, say. And the other thing to mention is that we can be on the lookout for these. So if you've got a patient who's on long-term bisphosphonates, just always asking them about groin pain, and if they do mention any groin pain, just doing a bilateral x-ray, you can then refer them on to our colleagues, like yourself, and see whether they'd be suitable for fixation.

Speaker 1:

Lynn, once you've got these patients on the medications treating them, how should these patients be monitored, and what are the red flags for treatment failure in these scenarios too, that you need to take into account?

Speaker 2:

Yep, absolutely. So. We touched on brain turnover markers. So cross-laps I would recommend doing cross-laps at least three months into treatment just to, particularly with the oral bisphosphonates, just to make sure that they're doing their job For the duration of treatment. I also do regular, at least six-monthly, biochemistry to check their renal function, because there are limitations on treatment with bisphosphonates, so you're not meant to use them, the bisphosphonates, particularly with an EGFR under 30.

Speaker 2:

I still use oral bisphosphonates in that CKD population, but cautiously. And of course the risk of side effects with denosumab goes up quite a bit. If you've got CKD you can develop hypocalcemia which can send patients to ICU and be very symptomatic. So that's something to look out for as well, always monitoring the renal function. I do also monitor their vitamin D, particularly before a denosumab dose or a zoledronic acid dose, and give them high dose vitamin D to boost them up quickly, to make sure that we also reduce that risk of hypocalcemia after treatment. And I would also just check their calcium just to make sure they're not hypocalcemic for whatever reason to start with, because we would definitely need to manage that before they get something that could potentially make them even more hypocalcemic.

Speaker 1:

And the DEXA scans. I think you said every couple of years after you've started treatment.

Speaker 2:

Yes, so if you've just started treatment, you can get a MBS-rebatable DEXA scan within one year. Otherwise, the other scans are generally every two years. So I'd be happy to do one after one year of treatment. Usually, patients are quite keen to see how their bone density is doing as well. So that would be reasonable.

Speaker 1:

Excellent, all right. What's the difference between treating a female patient and a male patient? Is there any difference you look into? Obviously, some of the medications we talked about are indicated in postmenopausal ladies. That may not be the scenario for men. Does that affect how you treat them?

Speaker 2:

So ultimately, the same principles still apply for treatment. It's all about whether they've had a fracture, how low their bone density is and what their calculated fracture risk is using those tools that we discussed. I think the main differences are actually with regards to maybe the more nuanced conditions around osteoporosis. For example, if we look at hypogonadism, a common secondary cause of osteoporosis in men is testosterone deficiency. Now, men may benefit from testosterone replacement for other reasons energy, libido, things like that but it's actually not been shown that testosterone replacement improves fracture risk, and in fact, it's been shown that it goes the other way around, and we don't know if that's because men just get so much energy they're jumping around falling over, but it does increase bone density, but that has not translated to fracture risk, whereas for women who have had estrogen deficiency, we know that it prevents fractures and it improves bone density. So that's probably one of the main things to be aware of.

Speaker 1:

Okay, that's an interesting fact to know. So where do you think things are heading for the future in the treatment of osteoporosis? I know we focus on calcium as a major issue. Where do you think things will be in the future?

Speaker 2:

Yeah, there's lots of things on the horizon, as with, I'm sure, every field of medicine, so we could talk a little bit about trabecular bone score. So trabecular bone score is a measurement of bone microarchitecture and it's taken as a measurement of the lumbar spine, which is obviously it is mainly trabecular bone, and it just adds more information to help the clinician assess fracture risk. Most centers don't offer a trabecular bone score, but there are some that do and that can certainly be used to help with decision-making, particularly in intermediate risk patients or patients who are just on the threshold of indications for treatment, and I think as we learn more about how to use it, it will become a more useful tool. And then I believe there are also on the horizon. There's also the development of other anabolic treatments, potentially dual action agents as well, to address both osteoclastic activity and osteoplastic activity, and also looking at different sorts of bone markers that can help us.

Speaker 1:

Excellent.

Speaker 2:

Hopefully one day these people, will be bulletproof and we'll be a lot less work for ourselves in orthopaedics. Absolutely absolutely.

Speaker 1:

Thank you very much, Lynn. It's been fantastic having you here.

Speaker 2:

Thank you for having me.

Speaker 1:

And it's been really great hearing about these different agents. The main thought that came through my head, and a lot of the way through, was the bifosfinates. I was remembering when they were just being released. An old agent shows how old I am. It's all good fun.

Speaker 2:

They've always been in my textbooks.

Speaker 1:

Thank you very much for coming on. Aussie Med Ed. It's been great to have you, it's been a pleasure, thank you. Thank you very much. Thank you, dr Lynn Lee. I'd like to remind you that all the information presented today is just one opinion and there are numerous ways of treating all medical conditions. It's just general advice and may vary depending upon the region in which you are practicing or being treated. The information may not be appropriate for your situation or health condition and you should always seek the advice from your health professionals in the area in which you live. Also, if you have any concerns about the information raised today, please speak to your GP or seek assistance from health organisations such as Lifeline in Australia. Thanks again for listening to the podcast and please subscribe to the podcast for the next episode. Until then, please stay safe.

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