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I don't think this is quite what I was asked to talk about, but I've put in things that I wish all orthopedic consultants knew, I suppose, um, thinking about what referrals I get. So I'll talk about those kind of things. So it's not just um metabolic bone disease. Um And um if you get to the next slide, actually, I'm talking through three cases and these, um so these sides and these letters are all from an ish. So this is kind of what I um you know, he's clearly an excellent example of what you shouldn't do what, no, what exactly what you should be thinking about. Um I don't think we've got probably enough time to talk through all of this. But effectively this, this girl was seen over several years by a Knish. Initially, she presented with Junior Val Gum and Tibial Talk shin um and was been seeing about flat feet. So if you read through this a little bit, um she had this, this little girl had a subdural hematoma when she was very young has flexible feet, but not much else to find except for blue sclera, which mom has as well and no other signs of being hyper mobile. Um and couldn't find anything which suggested a collagen disorder, a neuromuscular disorder. So if you get to the next slide, um so she came back at four um and nothing's changed, she's not broken anything. So she gets discharged at this point if you go to the next one. Um and then she gets referred back. Um And at this point, she's got lots of aches and pains. Um She's still got blue scare and she's got a triangular pain and she's got back pain. And I think this immediately highlight something which lots of people don't always take seriously, particularly actually in the pediatric world. Um And so it's really important if you're thinking about osteoporosis in Children to do a lateral vertebral image and this might be something that you're all brilliant at. But I know that my pediatric colleagues aren't all great that so you get to the next slide. Um I just wanted to talk about what we're doing at. I'm, I'm sorry, you'll have to keep clicking through. Um So what I want to think about is what you can see on the radiograph of the spine. So, is it completely normal or is there a fracture or are there multiple fractures? And what level of fracture is it? Um And I'll talk about the grades of fracture afterward. But so yeah, if you go back to that image, have a look at it for a bit and this is important to be able to do because um they don't always get reported accurately, natural vertebral or for Matori images. Guess again, you guys are super good at looking at X rays. Um And maybe this happens with other imaging, but it definitely happens quite commonly with natural vertebral images that they're not always reported in the way I'd expect them to be. So if you go down, we'll have a look down one more. Um So this child has got a severe fertile factor, which is grade three. So they're graded. This is the gannon system. So mild fracture is grade one and that's a loss of vertebral height of 20 to 25% moderate is 25 to 40 and severe is more than 40. Um In reality, it's really difficult to score them. And I've sat in a room with multiple pediatric endocrinologist looking at images all the time and we all score them slightly differently. And so actually, the severity isn't that important because your management just depends on whether there is a fracture there or not, but that's just how we'd expect it to be scored. So this child does have a vertebral fracture and that therefore impact uh on what we do next with them. Did you go to the next slide? Um And then this child also has a couple of fractures. So the next, this one and then in the next slide and I'm not going to talk through these, your way, more expert at looking at fractures than me. Um that raises um the query in an issues mind again about the bone disorder, which was thought about earlier on. Um And so this child is then referred to see me. Um So if you can't go to the next slide, um and what it's always worth having in your mind, what an acceptable number of fractures is. Um And when you should be thinking about osteoporosis, so two factors, less than 10 years with appropriate trauma and three fractures, less than 18 with appropriate trauma. Um And so the things that I know that you guys will ask are what age people have their first fractures, that the number of fracture sites and timing and the apparent causation and this, although you all know to do it, it doesn't always happen because I do see Children who have had more than this number of fractures or fractures with really low trauma who don't necessarily get referred and doesn't get, always get a thought about. So actually, even one fracture where it really doesn't fit with the mechanism, it's worth thinking about it or unusual fractures just like you think about N A I. So this girl came to see me um and she'd have three factors at this point. So what do we do next? So you go to the next slide. Um We think about things that might suggest underlying bone fragility. So there's lots of risk factors associated with early on in life. So being premature, um things like having necrotizing enterocolitis, having prolonged parental nutrition, having conjugated, jaundiced or chronic lung disease, being treated with frozen might. So, I mean, from your perspective, are they premature? Um and then osteogenesis imperfecta is inherited dominantly. So it's really helpful to ask about family history but lots of families don't necessarily know they have. Oh I, so actually it's saying, how many fractures have you had? Are you hyper mobil? Do you get lots of pain when you're moving around any early onset deafness? What your teeth like? Those kind of questions and early onset osteoporosis and that can give you clues, say next one. Um and then um thinking about other causes of low bone density. So looking at biochemical things like vitamin D P th calcium phosphate and alkaline phosphatase. So next slide. So I am quite simple when I think about bone biochemistry. Um and I think about it um in terms of bricks and mortar and I'll explain that in a minute, but the bricks are effectively the building blocks, the calcium and phosphate. Um um if you go to the next slide and, and then the collagen is sort of holding, holding it together if that makes sense, that's your mortar. So you can get problems with your bricks. Um And these are the three main things that can cause rickets in osteo Malaysia. So you can have a lack of bricks, um lack of the mineral supplies. So that's calcium and phosphate. So calcium deficiency, phosphate deficiency, phosphate deficiency is actually very rare outside of the neonatal period or outside of significant nutritional deficiency because it's pretty much in everything. Um So that's unusual. Um You can have a problem with the supplier. So you're fan that's bringing the calcium um from the bloodstream to the bones, um can be not working. So that's fit what vitamin D does. Um or you can have the builders not working and doesn't lay down those minerals appropriately in the bone. So, um an example of that would be hypophosphatasia next slide. Um So in this child, there's a problem with the mortar. Um And, and it's osteogenesis imperfecta, which is a collagen disorder. You can see on the left hand image you've got normal bone looks like and on the right, a magnified bone in a child with, oh I um and effectively the holes are bigger. Um And you've got reduced cortical and trabecular bone volume. So it breaks more easily and you also have reduced bone mass. Um She didn't have any history, didn't have biochemistry. So actually, her diagnosis was made through genetics to go to the next slide. Um And also um you know, we, we know that her mom had blues clearer and she had these blues clearer that lasted for longer than six months. Um And in her, there weren't on other findings but you can look for things like dented Guinness imperfecta, which is found in a proportion, limb deformity and large anterior fontanel. Um Next slide. So, oh, I is a rare condition. Um It feels like it's not particularly rare in Norfolk, but maybe that's gonna normal, normal for Norfolk. Um It's mainly dominantly inherited and it's the majority are due to collagen mutate genes and mutations in collagen type one. Um And then there's other rarer forms um which I don't think we need to go into today and please shout if you've got questions by the way. So the next case, um we can go into the next one. Um So I'm, I don't suppose you see huge numbers of Children outside of the factor management with, with Duchenne muscular dystrophy. But I just want to talk a little bit about the path of physiology of bone fragility and Duchennes because it gives quite a good example of the things that can be really helpful to think about. Um And also of some of the management things that apply to all Children with bone health problems. Um So this is a 12 year old boy. Um You'll just have to click through them. Um And he's very typical of Children with Duchennes. Um So he's started on a steroid eight years and that's now every day. So he's had a steroid exposure for four years. He's got cardiac problems. Um And they often come and see me at the point that they have back pain. Um So following a fall and he's also non ambulant. Um So, injections, which is an excellent recessive disease, which affects males. Most Children are diagnosed because they have difficulties with mobility and early childhood. Um It's because of a loss of function mutation in the dystrophin gene. Um And if it's untreated Children will stop walking by the age of 10 and die an early adulthood with muscle deterioration. Um There's not huge amounts of effective treatments or haven't been historically. Um So the mainstays been using glucocorticoids, which obviously aren't brilliant for your bones. So they extend life expectancy and ambulate ambulation, they reduce scoliosis and help with cardiac and respiratory function. Um But they are not good for your bones. So they double the risk of fractures have started before the age of five. Um But I think what's interesting about Descends and bones is it lets you think a little bit about other things that are important in bones because it's not just the steroids that are impacting negatively on bone strength. Um So you click on the next one. Um So the other thing that's happening in these Children is that you need mechanical challenges to lay down strong bone. Um And they obviously don't have the strain same muscle strength and then many of them are then in wheelchairs. Um The other thing that happens that's really important to think about in all Children is the injections, you get delayed puberty, which means you don't get exposed to testosterone and testosterone gets aromatase to estrogen. And estrogen is really good for bone strength. So all of that is delayed. So their bone is effectively weaker because of delayed puberty. They also often have quite poor nutrition, which again impacts on bone strength and then if you click on to the next one, um yeah, we probably don't need to go through this. You can just get to the next slide and the next one it's fine. So the fact that they have thinner bones that break more easily, unfortunately, unlike the first child that we saw lots of these Children um only get to see me once they've got multiple vertebral fractures, which is quite late on in what we call a vertebral fracture cascade. So they'll often have had one vertebral fracture. Um but that's not picked up. Um And so I see them quite late. Um And about 50% of patient's will have symptomatic vertical fractures about two years after starting steroids. But that means about 50% of vertical fractures are a symptomatic which is worth bearing in mind if you're ever worried about osteoporosis in a child because just examining their back and saying it's not painful, doesn't necessarily mean there's not a fracture there. Um In this group, vertebral fractures are associated with not having a premature loss of ambulation, which is really bad for long term prognosis. If you go to the next slide um then you can go to the next one that's just an image of um if we can pick Children up early. So if you do see Children and you're managing their fractures, um And they're not seeing someone else, please just do kind of think about the bigger picture in these Children. So, next slide um so these slides are really relevant, not just two Children with Duchennes, but any child, really any child that you're seeing with a fracture. These sort of things are important to talk about. Um So additions particularly you'd think about bone health on term, long term, both bone health monitoring, but we also do that in any one that's got osteoporosis. I want to talk a little bit about osteoporosis stabilization and what that might mean. Um Sorry, just go back up for a sec. Um and then bone health maintenance and what what that means. So the goal of preserving any clinical gains you get through, through stabilization. So, through ongoing bone targeted therapy. So if you go to the next slide, sorry. Um So minimizing risk is really important and these are things that the more of us that talk about them, hopefully, the more they'll get taken on board. So appropriate exercise, vitamin D calcium puberty um and then bone health monitoring next slide. So when you see someone with a fracture, it's worth asking a little bit about their diet and whether they take calcium or not because there's a surprising number of Children and it's probably increasing that have really particular diets and often don't take anything and they've got calcium in and this is super simple to do and I'll show you how on the next slide. Um um and then talk a bit about vitamin D deficiency because if you don't have enough vitamin D, you're not going to be able to absorb the calcium. So both of those things go together. So the next slide, um so the easiest way to assess calcium into, to use this, it's a five item food questionnaire. Um And it was developed as a really easy quint clinic screen. So I literally say, you know, how much milk do you have? How much cheese, yogurt bread and vegetables? And you get a super clear idea. I mean, the ones that you're going to want to pick up of those that aren't having really any of that. Um And in those Children that's really helpful to identify and say you're not really having any calcium in your diet. Some people then say, oh, I hadn't realized I'm really happy to add cheese in every day. Cheese is the thing that you can see, he's got the highest calcium. So it's sort of the easiest to start taking. And other people say, well, I'm never going to eat any of those things. And then, um, it's helpful just to start some calcium just you can buy over the counter calcium supplements or ask your GP just to follow it up next slide, please. Um, and similar for vitamin D if people aren't taking any vitamin D, this usually if I do a straw poll of an audience, most people aren't taking vitamin D between October and May. Um, I can't see you all but, you know, it's often about 50% of people think, think it doesn't really apply to them and they'll be fine. Um But or maybe you're going on lovely skiing holidays with lots of sunshine after the Caribbean because your orthopedic surgeons, I don't know. But if you're not living these things, tablets, yeah, then yeah, then take the tablets between October and May. So next slide, um you know, we don't need to talk about this one because this is kind of really obvious. Um And the other thing I find that people don't always understand is Dexas in Children. So if you're um and you know, this is maybe not something that you'll be requesting, but it's worth understanding. Um So Dexas are slightly different in Children than adults. Um And I'll explain why and that's to do with the interpretation of them, they can only be done once you're five and over, that's because of normative data that exists. Um And they're not really worth doing more than once a year. So the next slide, please. So, um and the other thing that people often don't understand is how to interpret Dexter's or, you know, if you get the results back and your Dexter says your total bone density is minus three in an adult that would be clinically significant and you do something about it. But in Children, um although loan bone density is associated with frankness fracture risk because of the technical limitations, um and the kind of limitations of the data we've got in Children, it's not necessarily synonymous synonymous with fracture risk in Children. So we don't use it in the same way. So it just gives you an idea of where they sit on a scale um as opposed to something you directly act on. Do you go to the next slide? Um And the other thing that's really important about Children is they vary in size. Um And so your, you need to check that your local Dexa scan er is the results that come out are being adjusted for the size of the child. So when I arrived in Norwich, they weren't. And that means you really the results mean nothing, you can't interpret them at all because Dexa measures aerial, not volumetric bone density. So it will underestimate true volumetric bone density and small bones. So if you've got a child who's got short statue or delayed puberty, you're going to underestimate their true bone density and the opposite of your tool. Um and it's adjusted within the scan, er but that effectively needs to be switched on. Um And so the person who's analyzing that data needs to have thought about it. And you think that's really obvious. Um But it wasn't happening Addenbrooke's or Norwich five years ago, which are the kind of too big trusts in the east of England. So I wouldn't necessarily assume it's happening where you're working next slide now just um and this is just an image of how that works to show you the difference. I think from a time perspective, we'll just keep going and you can always have a look at that later because I think you'll get these slides, get to the next one. And, and again, that just gives you an example um of of how you can get completely wrong data. So by it, yeah, by adjusting it so effectively the child on the right has got growth hormone deficiency. So they're short to their height. Um but by adjusting for their height, their bone density becomes normal. So if you just interpreted their unadjusted said score, um both of them would appear to have low bone density. So low is anything below minus two. But in fact, once it's adjusted for the child on the rights height, um they have completely normal bone density as measured by Dexa as we go to the next slide. And I think the other thing that is helpful to be aware of is that we don't talk about osteopenia in Children, we talk about low bone density and that is divide um as per your dexa scan. But the most important thing to identify is osteoporosis because that from a metabolic bone perspective is going to make me do something. So if you've got any child who's got any vertebral fracture in the absence of trauma, that's osteo process. Um or if you've got a low bone density plus a clinically significant fracture history as we talked about earlier. So they're the kind of two things that it's really important to pick up on and refer on to go to the next slide. This slide just kind of re says that again, effectively. Okay. So you can go to the next slide because you've said that. Um again, my pediatric colleagues, I suspect less, you guys often will use plain x rays to identify Children with low bone density. Um So it's just to highlight that, I mean, you can, you can probably say that one of these children's very likely to have low bone density, but it's not on the basis of what their vertebrae look like because you can always obviously have completely different penetration. Um And it's not, it's not a measurement of bone density. So you go to the next slide. Um the child on the right, you can see he's got multiple vertebral fractures um and has actually receive treatment with bisphosphonates and that's the darkening of the lines. That's why you can see their vertebral in plates better. Um But the one where you can't see the vertebra at all has just been overexposed. Um And the child on the left has actually got the lowest bone density. So in terms of what who needs further management when Children are likely to remodel their own vertebra, it's best that they do that without any treatment. Um That's never happens in Duchennes, but it does happen if you've got really good linear growth and you've suffered an acute insult. So for example, Children who present with leukemia um often will have a vertebral fracture at presentation because they're really, really unwell. Um And their bodies been focusing other thing on other things rather than laying down healthy bone. But once they start treatment, their growth improves the nutrition improves and those vertebral bodies improve as well, you get a similar thing in Children with JIA who start treatment. Um So that's what I'm talking about here to go to the next slide and the next one, please. Um So I think Anish got a referral this week to ask him to consider starting someone on treatment for osteoporosis stabilisation. Um So I don't know if you guys get those kind of referrals as well, but they would generally come um to pediatric endocrine um team and there's not huge numbers of options available at the moment and the mainstay of treatment is bisphosphonate about which there's not huge evidence. Um I'll talk through that a little bit. Um Sorry, just go up a little bit. So what bisphosphonate's do is they slow bone turnover um and effectively, therefore thicken the cortex and reduce fracture risk. That's the idea get to the next night. Um There are lots of studies in diverse conditions which show some benefit and bone density, but they're mainly short term, they use different agents. So historically, we use pamidronate. Now it's more siladryl a chronic acid adults use oral bisphosphonates. We use intravenous in pediatrics and then the regime the dose um follow up time is already variable. We know that the greatest improvements in bone density in the first two years. But the efficacy for fracture reduction is less clear, partly because of all of the above. Next slide, please. Um They, I've been used for quite a long time and so long term safety appears to be quite good in Children. But the acute complications are definitely there and I talked about them before I give Children bisphosphonates and they're particularly around low calcium having a flu like illness when you first get the dose and you are at risk of acute kidney injury if you're not well hydrated, um they're more problematic in Children with Duchennes that if you've got osteogenesis imperfecta. Um but we give them quite often. Um and they're really fairly well tolerated particularly after the first dose. So the second time you get exposed to the medicine, really, the side effects are very minimal. Second, next slide, please. Um I haven't put written this down, but I think the biggest benefit of bisphosphonates for most Children is actually pain reduction. It's not just about fracture risk, but particularly kids with osteogenesis, imperfecta will often complain a lot about pain, pain with walking, um almost like aching in the, in the limbs. Um And that improved significantly with bisphosphonate. So there's not the data there about quality of life. Um but just in clinical experience, it really helps moving forward. Uh We hope that things like denosumab might potentially be helpful for the maintenance therapy, which we don't have at the moment. Um It's a potent anti resorptive agent. It's being used a lot in adults, cancers. Um and by decreasing differentiations of pre osteoclasts, um it reduces bone resort option and increases bone mass has quite a short term effects. You have to keep on the treatment but potentially something if it's not denosumab, but that kind of agent in the future might help not keep going. The big problem about these other agents that you could use recombinant P T H, which is being used a lot in adults um including in kids with do shins. Um is that it's country indicated in Children because of the risk of osteosarcoma in rodent models. But all of this is being used in adults. There is studies ongoing and hopefully we'll have other things that we can offer Children except this phosphinates in the future, keep going. So I'll get a talk. So I'll talk just, just either do the slide before quickly. So I think I've got time just to quickly talk through this case. Um This is the last one. Um This is a four year old boy who again presents with short stature, bowed legs, um, and difficulty with walking. Um So it's all the kind of things to measure people often think metabolic bone stuff is really complicated. But if you just start with these five things as a starter and in an ideal world, you'd also measure a urine calcium. Um Then you'll have a really good idea if there is anything going on from a metabolic bone perspective. So you go to the next slide. Um So the probably the commonest thing that would be abnormal when you do blood tests if you do blood tests, I don't know if you guys ever do but is a low vitamin D. Um And actually even that people aren't always sure what to do with it. So less than 25 is deficiency, 25 to 50 insufficiency and more than 50 sufficient. Um I would always treat less than 50 go to the next slide. Um And then the other thing, if you've got a low vitamin D is to say, is it just a biochemical abnormality of vitamin D or is there a biochemical evidence of rickets or ideological evidence of rickets because that would need different treatment? Um And you can find that out by looking at P T H and alkaline phosphatase, which should both increase if you've got rickets, um you might have deficiency and calcium and you can look at the X ray to see if there's any radiological evidence of rickets the next slide. Um So when you have a low vitamin D um with a normal calcium intake, you shouldn't ever get ricket. But if you have a normal calcium, low calcium plus low vitamin D um urine saying that risk group and, and that risk group would be someone who's, you know, inside all the time, very covered up with dark skin. Um then you might get biochemical signs which would be a raised P T H A low urine calcium creatinine ratio. So low calcium because you're trying to hold on to all the calcium, keep it in your bones. The next thing you get is evidence of pre rickets or early osteo Malaysia. And if you did an X ray at this point, it would be okay. But in your serum, you'd now have a raised alkaline phosphatase and P T H and you might have a low phosphate and a low calcium and again, low calcium in your urine. And then eventually, if you have a persistently low calcium and low vitamin D intake, you'll get radiological signs as well. Um But just to say, I suppose if you haven't got the radiological signed, it doesn't mean that you're not on the pathway to getting them next slide. And the next bit um, it's super common vitamin D deficiency. Um, I don't think the message really gets out there still. This is at the end of summer. Okay. It was quite a long time ago, but the data from recently hasn't really improved. So, right at the end of the summer, um, 65% of adults have low vitamin D concentrations and it's more common if you're African Caribbean or Asian, but it's also very common in Caucasian populations. So we're great on Suntan lotion. Um So you can go to the next light. Um So what the treatment of Ricketts, I unless you've got biochemical abnormalities or radiological abnormalities that I tend to tell people to take between 4, 400,000 units a day and guidelines vary, depend where you're looking from and to just make sure you're getting enough calcium as well next slide. Um And then finally, so if your alkaline phosphatase is low, this is worth looking out for again because not all labs will highlight a low alkaline phosphate tires. Some, some will only highlight it if it's high. So check that wherever you're working has a bottom end of the range and if they haven't asked you by chemist about it. Um First of all, make sure that the sample wasn't contaminated. Just look at, look at your other um other things in the blood sample, potassium calcium magnesium. So we just click through them. It's fine. Um It the most common cause of a low alkaline phosphatase is actually fasting being chronically unwell, having a low copper zinc. Um And then very rarely you can get Children with hypophosphatasia. They will often have associated high calcium and phosphate. Be short, have increased fractures, bone pain, and then have this kind of really classical history of the teeth falling out with the root intact that you can see on right on the right there. Um So next slide um and if you did X rays in the boy that you, we started with, um you might get these radiographic focal defects. Um the project from the growth plates into the meta facist, so their tongues of radio lucency. Um Again, that is a clue that there might be hypophosphatasia. Next slide. Uh Next one. Um So H P P is caused by mutations in the gene which encodes um alkaline phosphatase is um and you get deficient alkaline phosphatase activity. Um And then you get substrate to the precursors accumulates, you can measure them as part of the diagnosis if you want to or you can look at it by doing the genetic analysis next slide. Um And there's various different sorts. Um it can present in the perinatal period. That's his previously was completely fatal um infantile, which again, really not great for you. Um mortality, 50% or like this child bit later on in childhood. So, next slide, amazingly in this um as part of the rare drugs program, there is actually hormone replacement. Now for Children with this condition and particularly in the perinatal and infantile group, it's resulted in Children who couldn't walk, walking. Um and just huge, massive changes in, you know, they now survive where they weren't surviving. Um And in pain and things like that. So, really exciting things happening here just like in achondroplasia. So I think I'm going to have to stop because I do need to go and find my Children. But thank you. And if you've got any really quick questions, I'm happy to answer them. Yeah, that was brilliant. Emma, thank you very much. Any questions guys? Would you expect us to have done blood tests if we find somebody with a fracture? No, I'm not. No, I've talked about it because the brief was metabolic bone disease, which is hard to talk about without blood tests. And I think it's nice for you to have an understanding of what sort of things we're looking at. And that actually it's not that complicated for a lot of Children, I suppose. But no, I don't expect you to um if you want to when you're doing an operation great. But I think it's just thinking about it because this is really, really good at thinking about it, but not everybody is um and just having that awareness of what you might be looking for and why you might be looking for it and what other clues might be there. Can I ask you, is it?