WEBVTT
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Osteoporosis is often called a silent disease because it can progress for years without symptoms, only to reveal itself through a sudden devastating fracture.
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It affects more than a million Australians and is a major cause of morbidity in our ageing population.
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Yet it's frequently underdiagnosed and undertreated.
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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.
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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?
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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.
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I'm your host, dr Gavin Lyman, and today we're unpacking the diagnosis and treatment of osteoporosis with Dr Lynne Lee G'day.
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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.
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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.
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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.
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I'd like to pay my respects to elders, both past, present and emerging, and recognising their ongoing connection to land, waters and culture.
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I'd like to say that this podcast is for educational purposes only and does not constitute medical advice.
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Always refer to clinical guidelines and consult a qualified healthcare professional before making medical decisions.
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In today's episode, we're discussing the diagnosis and treatment of osteoporosis with Dr Lynne.
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Lee Lynne is a specialist endocrinologist with a particular interest in bone health, reproductive endocrinology and diabetes management.
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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.
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She practices privately as South Australian medical specialist here in South Australia.
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Dr Lee is also undertaking dual training in chemical pathology, giving her a unique depth of insight into the biochemical basis of endocrine conditions.
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Welcome, dr Lee.
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Thank you very much for coming on board for Aussie Med Ed Lynn, and it's great to have you here with us.
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Perhaps you can tell me a little bit about what osteoporosis actually is and what the difference is between osteoporosis and osteopenia.
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Absolutely so.
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Osteoporosis is a condition defined by low bone mass and deterioration in the microarchitectural quality of the bone.
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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.
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So osteopenia is defined by a T-score between minus one and minus 2.5.
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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.
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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.
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So 30-year-olds use as a standard, is it?
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Essentially, yeah.
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So when you use a T-score, you're comparing it with 30-year-old bone density of the same sex.
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Yeah, Okay, how common actually is osteoporosis?
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It's very common.
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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.
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Yeah, Excellent.
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It's more common in women than men.
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Definitely.
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Yeah, it's probably a lot to do with the fact that women go through menopause so essentially hypogonadal.
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They lose that estrogen that provides a lot of suppression of bone turnover and they end up developing osteoporosis a lot easier.
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It's a lot less common in men, but certainly happens as well.
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So it's not based purely on the fact that men have a higher bone load initially.
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It's based purely on compared to the same sex.
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No, that's absolutely a good point.
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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.
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So you lose less and you're less likely to develop osteoporosis.
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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.
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If you compare premenopausal women, that's a much smaller group.
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What are the other risk factors for osteoporosis?
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Yeah, absolutely so.
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Lots of risk factors.
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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.
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That's actually used in the FRAX calculation score.
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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.
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And there are other conditions like inflammatory sort of disorders, like rheumatoid arthritis, glucocorticoid use, of course, diabetes mellitus, chronic kidney disease.
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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.
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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.
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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?
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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.
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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.
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Yeah, and obviously there's also a lot of medications, too, that can interfere as well with it.
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So what are?
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the main ones you would tend to see.
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Yeah, absolutely so.
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I already mentioned glucocorticoids.
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That's a big one, and we have a much lower threshold to treat people with osteoporosis if we know they're on corticosteroids.
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The other ones I see are women who use certain progesterone-only contraceptions, such as the Depo-Provera.
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That's the big one, but the Implanon has also been linked to lower bone density.
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So in vulnerable patient groups we tend to recommend different ones.
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Oestrogen-containing ones would be ideal.
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And then the other group of patients are the ones that are on anti-epileptic medications, particularly Valproate.
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There's been a clear association with low bone mass.
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Right, you've already mentioned the diagnosis looking at a standard deviation of bone density, yep.
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That's obviously based on a DEXA score, which I always find very difficult to interpret.
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It's often two or three pages and there's a bunch of graphs and things.
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What's the easy way for the medical students and young GPs to try and interpret these results?
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Yeah.
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So I wanted to start by actually saying that Healthy Bones Australia has a really nice two-page PDF.
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It's got like a graphical diagram of how to go about interpreting a Dexan.
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I thought that was actually quite useful, even for myself, just as something to show people.
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But I would always start by first of all looking at the age of the patient.
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That plays a huge role in determining fracture risk.
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I then look at the T-scores to start with and assess whether or not they have osteopenia or osteoporosis.
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The Z-score is useful for determining A if the patient has maybe a secondary cause of osteoporosis.
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Largely speaking, a Z-score under minus two would prompt you to look for a secondary cause.
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And the reason for that is a Z-score is the number of deviations above or below bone density for an age-matched person.
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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.
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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.
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So the Z-score.
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You can't really use a T-score in that population either.
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Use the Z-score Then.
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The next thing I would look at, particularly for people who are on treatment.
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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.
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But most bone density centers will actually tell you whether or not they feel, according to their data, whether it's statistically significant.
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Significant, but the sort of zero to three percent change that's within what you could naturally find between repeat bone density scans.
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It might not be significant and that helps me to guide treatment.
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So I'll know if there's been deterioration despite standard treatment or whether there's been improvement.
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Excellent.
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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.
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What is the utility of those and how do they help us?
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Absolutely.
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Those are the two that I know of as well.
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So the FRAX tool is more international and it takes into account a few other.
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It's got a few other questions as part of.
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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.
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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.
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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.
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The other thing is the Garvin is, I think, australia based, so I like using that for our Australian population.
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I tend to go Garvin and then maybe might do the FRAX as a follow-up.
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So you do these routinely on your patients.
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So not routinely.
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That's a good point that you raised there.
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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.
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Generally score based on the bone density they've done on that day, and that's quite helpful.
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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.
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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.
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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.
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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.
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I find that using the fracture calculator is really useful for reassuring them that their fracture risk is really low.
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And in these scenarios, that perhaps these younger patients particularly what would bring them to have a DEXA scan in the first place.
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I suppose the times that people may consider it is when there've been significant risk factors, things like.
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I've seen it done for prolonged periods of untreated hyperthyroidism or premature menopause or what we call primary ovarian insufficiency.
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In the younger population, and I do see it sometimes done in people who have anorexia nervosa, very low BMIs.
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I wouldn't say that it's appropriate to do it in those instances, but I can certainly understand why they've been done.
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The thing is that it may bring to light underlying low bone density.
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That doesn't end up having any clinical consequences because the risk of fracture is low.
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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.
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So get onto their vitamin D and their calcium intake and do more exercise.
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So I can see the pros and cons of both.
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So over the age of 50, screening is a tool that's recommended.
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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.
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Excellent, If we move on to actually further diagnostic tests.
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What's the role of bone turnover markers?
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I was actually reading about these and these are blood tests which I've never heard of until I prepared for this talk today.
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Yep, absolutely so.
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Look, the two main ones that I think most people will come across are the crosslaps, as we call them.
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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.
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I don't ever really order a P1NP.
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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.
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We just trust that the treatment's working.
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To be honest, crosslaps do have a major role in the management of osteoporosis.
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Crosslaps reduce quite quickly after starting anti-resorptive treatment.
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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.
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And I find that particularly useful in a few scenarios.
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The main one would be when you're treating someone with an oral bisphosphonate.
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Now, oral bisphosphonates are well known to be not the best absorbed drug.
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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.
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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.
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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.
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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.
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Yeah, okay, so for the average person?
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Obviously most osteoporotic patients would be treated by their GP.
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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.
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What's the average patient that we referred to an endocrinologist for osteoporosis?
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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.
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They just want to get a second opinion.
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That's pretty common.
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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.
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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.
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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.
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So balancing the kidney disorders with the osteoporosis and try to coordinate the calcium resorption and reabsorption from the kidneys?
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Yeah, absolutely so.
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We tend to see those quite a bit as well.
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Okay, excellent, we'll move on to the treatment of osteoporosis.
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I understood.
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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.
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I've heard about biphosphonates in the last few years, but when you look at it, there's a lot to it.
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There's so many different forms of treatment yeah we start off with the simple things first.
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Obviously, obviously preventative would be important reducing alcohol intake and doing exercise.
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Where do you go from there?
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Yeah, and look, I'm glad you brought up exercise.
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It's actually really important to also prescribe the type of exercise that should be done.
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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.
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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.
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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.
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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.
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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.
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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.
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That's going on, yeah, and most of us need vitamin D supplementation.
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We're all indoors, so yeah.
00:18:59.560 --> 00:19:05.859
So that's the kind of we've covered the lifestyle things, the dietary things, and then moving on to pharmacological management.
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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.
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So, in terms of the antiresorptives, you mentioned the bisphosphonates.
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That's the oldest one we have, with the most data comes in oral form.
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Obviously, you've got weekly tablets, monthly tablets.
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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.
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Bisphosphonates, like I said, they're very old.
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They're very old medications.
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We've got lots of data on them.
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They work really well.
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The main side effect with the oral bisphosphonates are the gastrointestinal side effects and, like I mentioned before, the low bioavailability.
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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.
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I don't, yeah, I don't recommend it.
00:20:13.571 --> 00:20:15.215
Intravenous bisphosphonates.
00:20:15.215 --> 00:20:17.180
So the main one we use obviously is zoledronic acid.
00:20:17.180 --> 00:20:23.932
I like that it bypasses the gastrointestinal tracts, are really good for those that do get reflux and symptoms like that.
00:20:23.932 --> 00:20:27.760
The main side effect is flu-like symptoms.
00:20:27.760 --> 00:20:30.948
In some patients it can be pretty severe as well.
00:20:30.948 --> 00:20:33.954
They can get this really run down malaise.
00:20:33.954 --> 00:20:38.574
They can get the headaches and body aches and joint pains and things and it can be quite off-putting.
00:20:38.574 --> 00:20:47.442
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.
00:20:47.442 --> 00:20:53.019
They can take it after as well if they want, and that's actually been shown in the literature to be useful.
00:20:53.019 --> 00:20:58.554
I have also seen in clinical practice patients who have really severe reactions.
00:20:58.554 --> 00:21:04.195
The next one they might take a small one-off dose of a corticosteroids, so 25 milligrams of prednisolone or something like that.
00:21:04.195 --> 00:21:07.092
But yeah, those would be the main side effects.
00:21:07.092 --> 00:21:09.416
So those are the bisphosphonates.
00:21:09.537 --> 00:21:14.175
The other anti-resorptive that we see a lot of is Prolia, the denosumab.
00:21:14.175 --> 00:21:22.256
So denosumab is a monoclonal antibody against rank ligand and it's a very potent inhibitor of osteoclastic action.
00:21:22.256 --> 00:21:36.262
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.
00:21:36.262 --> 00:21:45.234
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.
00:21:45.977 --> 00:21:54.142
And if it is seized without anything to replace it, you can get a pretty profound bone density rebound, bone density loss.
00:21:54.471 --> 00:22:02.761
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.
00:22:02.761 --> 00:22:08.643
So you actually go back to being on essentially similar to placebo, yeah, yeah.
00:22:08.643 --> 00:22:20.413
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.
00:22:20.413 --> 00:22:43.743
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.
00:22:43.743 --> 00:22:46.393
I think very reasonable to be on denosumab.
00:22:46.393 --> 00:22:51.383
We've got data going up to 10 years for the safety and efficacy, but we don't have much beyond that.
00:22:51.829 --> 00:23:00.777
So in these osteoclastic reduction, osteoclastic activity they don't obviously increase the actual bone density, they just reduce the actual loss.
00:23:00.777 --> 00:23:01.759
Is that correct?
00:23:01.890 --> 00:23:08.769
So it yes, it doesn't affect the osteoblast, so it doesn't actually cause any bone formation.
00:23:08.769 --> 00:23:15.835
But by reducing osteoclastic activity alone that can, I guess, improve you could say the balance between the two.
00:23:15.835 --> 00:23:18.582
And we do see increases in in bone density.
00:23:18.582 --> 00:23:21.298
We do see that particularly with prolia in the spine.
00:23:21.298 --> 00:23:23.885
It's got quite a marked improvement.
00:23:23.925 --> 00:23:28.601
But we see that with bisphosphonates as well yeah, so that leads to a change in their percentage.
00:23:28.601 --> 00:23:30.923
They may move from a lower t value or z value, depending on their age group to a change in their percentage.
00:23:30.923 --> 00:23:39.219
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.
00:23:39.410 --> 00:23:44.561
But very often we do see and expect them to gain some bone as well, right, yep.
00:23:44.982 --> 00:23:50.298
Okay, Moving away from those osteoclastic drugs are there any other we need to look at, or is that the main ones?
00:23:56.470 --> 00:23:57.712
Well, there are the ones that we use less commonly in women.
00:23:57.712 --> 00:24:06.921
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.
00:24:06.921 --> 00:24:11.878
It's an oral medication and it's indicated for postmenopausal women with osteoporosis.
00:24:11.878 --> 00:24:23.060
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.
00:24:24.269 --> 00:24:27.102
And the last one, just to mention in passing as well, is tibalone.
00:24:27.102 --> 00:24:32.901
So tibalone is a synthetic steroid that has estrogenic and progestogenic effects.
00:24:32.901 --> 00:24:40.153
It's also an oral medication and it's also indicated for postmenopausal osteoporosis and we tend to choose this one.
00:24:40.153 --> 00:24:49.799
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.
00:24:49.799 --> 00:24:52.271
And of course, we should mention HRT.
00:24:52.271 --> 00:24:56.163
Estrogen is a very good suppressor of bone resorption.
