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Bone Health, Fractures, and Updates on Treatments for Bone Disorders: Grand Rounds Episode for MOC Credit! · Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner

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Welcome to Pediatrics Now, cases, updates, and discussions for the busy practitioner.
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I'm your host, Holly Wayment. I work for UT Health San Antonio's Department of Pediatrics.
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In this podcast, we explore how we can provide the best, most cutting-edge,
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compassionate care for children.
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We hope to give you a unique and behind-the-scenes edge from our expert guests.
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After listening, click on the link on this podcast for free credit.
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Music.
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It is my pleasure to introduce Dr. Nadia Merchant.
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Dr. Merchant is a pediatric endocrinologist and geneticist at Children's Health UT Southwestern.
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She attended medical school at Weill Cornell Medical College in Qatar and completed
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her pediatric residency at Wright State University.
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She completed her genetics and pediatric endocrine fellowship at Baylor College
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of Medicine, Texas Children's Hospital.
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She also has served as faculty at Children's National Hospital. Hospital.
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Her clinical and research interests include bone health and the intersection
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of genetics and endocrinology.
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She has specific interest in rickets, calcium disorders, osteoporosis in children,
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especially Duchenne's muscular dystrophy and skeletal dysplasia.
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Without further ado, please join me in welcoming Dr. Merchant.
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Hi, a little bit about me. I was born and grew up in Houston,
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so San Antonio has been some place that I've always come and been many times on vacation.
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I moved to Saudi when I was in eighth grade.
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And that really just led me to go to Cornell and Qatar and really gave me more
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of a global experience. And some of my interests really grew from there.
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And then I have had went to residency in Dayton.
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And so I had a lot of my colleagues come to do fellowship in San Antonio because of the base here.
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And then I went to Texas Children's. And recently, I just joined at UT Southwestern.
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And it's been great so far.
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So objectives today, to understand the basics of of bone health and distinguishing
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what traumatic and pathological factors could be and the clinical diagnosis
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to genetic diagnosis to now we're having rare disease treatments for bone disorders.
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And my main goal is really to inspire ways to maximize bone health in all children,
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especially those with disabilities and chronic health issues.
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And really why? It's because bone health, the bone bank is built really early.
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And so we can't wait. We need to start now. It starts from when a child's born.
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And it really, it's really the pediatricians and all of us who make an impact
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on how the quality of life these kids may live based on their bone health.
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And the reason for that is that children gain about 33% of their total bone
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mass just during puberty.
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And most of the other is built while right before they go go into puberty.
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So we need to think about how do we maximize their bone health and bone density.
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The way it works is that you as born as an infant, and then you your bones expand,
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and then you get endocortical like opposition, like to make it the peak bone mass.
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And then as adults, we lose it gradually. And based on our different risk factors,
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you will lose your bone density over time.
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And so you're mostly going through an anabolic or increasing your bone density
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as a child, and then it goes downhill from there.
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So I like to always draw this diagram when I'm talking to parents about bone
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density and the scale to risk factors, because some of these are things that
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we can address on a regular basis in clinic with our patients.
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So how do we, what do I do? For peak bone mass, how am I going to maximize it? I want a good history.
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What is their diet like, their activity? what medications they're on,
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have they had a history of fractures.
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And then on exam, like what's their growth, puberty, their spine,
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do they have back pain and their motor function overall.
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And then just getting sometimes we'll get labs depending on whether we need
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a vitamin D or not, that depends on some of the risks for the patient, and then puberty.
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And so first off, I'm going to start talking about nutrition and diet.
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So many of us know what Ricketts is, And it was called The Loss of Sunshine, the English Disease,
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because at one point it was estimated that 50 to 80 percent of children in industrialized
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like religion in northern Europe had rickets.
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But we have really clear descriptions of rickets from the 17th century and even before that.
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And it's also been noted if you
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think if you've tiny Tim and Charles Dickens novel has see it probably had rickets
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Maybe along with TV because he was described as short stature Asymmetric crippling
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and curious inman weakness that would lead to his death if untreated And so
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this is something that we always think of it.
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I for some reason like Oh rickets is something We've really managed in the US.
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We don't really see it well.
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I probably see a kid at least every month.
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And honestly, because I do bone health, I get they come to my clinic and I will
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see them. But this is a typical case.
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I have a two-year-old female who presents with history of walking without assistance, but limping.
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Extreme bowing since she started to walk at 13 months.
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And she was diagnosed by her PCP four months ago and was started on vitamin
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D 2000 international units.
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But then when I was seeing her in clinic, her diet history, she's still breastfeeding.
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There's no milk or cheese in mother's diet or the patient's diet, and she's a picky eater.
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And so this really, to me, was eye-opening because we were also getting admissions.
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During the pandemic, we saw quite a few kids coming in with severe hypocalcemia
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and vitamin D deficiency.
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So we did a small kind of inpatient admissions to see the severity of them just
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at Children's National.
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And we want to know how many cases were we getting and
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was this more getting more common and what
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was our breakdown of our population and so
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these are all kids that were admitted so they either came in with seizures or they
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had some abnormal movements so there was something that brought them to the
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hospital and that's when we got and we really our criteria was vitamin d less
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than 10 and calcium less than 8 so we did and we did a chart review from 2016
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to 2021 you can see that that there were increased number of cases that we saw
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in 2021. And this is just a retrospective chart review.
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And what were some of the risk factors? We saw that dark skin pigmentation.
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Dairy restriction, picky eaters, vegan diet.
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Breastfeeding with most not being supplemented by vitamin D.
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And so these were just some of the admissions, but the length of stay for these
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hot patients was four and a half days.
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And majority, if you look from zero to two years, were healthy children,
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like with no known health issues.
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The older kids, yes, they had neurological issues, some of them like autism and picky eaters.
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And so some of that made sense, but it didn't make sense for something that's
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completely preventable.
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So this is just a little bit of like eye opening thinking about like,
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what can we do to prevent that simple things is making sure that once the baby's
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discharged from the nursery,
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we make sure there's vitamin D supplementation that is recommended,
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especially for breastfeeding mom and talking to the breastfeeding mother that
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she's having enough high calcium foods.
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So just a little bit on the recommendations of daily intake, vitamin D.
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So for 400 IU is what we do for the vitamin D supplementation for breastfeeding,
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or even breastfeeding children, mostly babies, because formula is often has
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enough vitamin D in there.
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And then there are some patients that I would say, do I need to get a vitamin D level or not?
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I think that there's always been this debate whether vitamin D level is helpful.
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But if a patient's not getting enough enough vitamin D, you're just going to keep chasing after it.
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And so that's where I say, unless there's a really risky population,
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it makes sense maybe to get a vitamin D level.
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But otherwise, I would just recommend looking into their diet and see,
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are they getting enough?
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And this is just a few foods that are high in vitamin D that you want to be thinking about.
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And if you notice, majority of them are fortified.
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So milk has been fortified with vitamin D. And so cod liver oil is one of those
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that, but I mean, how many of us are walking around having cod liver oil every day?
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But the majority of them don't have much vitamin D.
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And, you know, the one thing about calcium intake and vitamin D,
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I think the Got Milk campaign to me is a little bit eye-opening because they
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noticed that in the 1990s, Americans were drinking about 0.78 cups of milk per
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day. and they want to really boost their sales.
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So they started doing a lot of the Got Milk campaign, which eventually changed
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to the campaign of including like oat and other types of milk.
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But what happened, if you think back historically in the 1940s,
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we were fortifying milk, assuming in like juice, orange juice,
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because assuming that all Americans would be drinking milk and orange juice,
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but that trend had been gradually decreasing.
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And so some of the maybe reasons we may be seeing rickets is because of that.
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And I don't know, like, there's not a lot of data of how much rickets we're seeing now.
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But I think the main thing is our diets have changed a little bit in what we
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thought Americans were eating.
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And we really need to be thinking about what the kids are having to make sure
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they're getting enough calcium and vitamin D in their diet.
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Drink your milk, kids. I don't want milk. Milk's for babies.
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Yeah, babies. Oh, yeah? Well, I happen to know that milk helps build strong bones. So drink up.
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Well, Mr. Miller told me he never drinks milk. Look at him. Yeah.
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Oh, that's not good.
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So that's just a little bit of... The Got Milk campaign is always a little eye-opening
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for me, especially because of the data they showed.
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So how do we get milk and calcium in our diet?
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The recommended calcium intake is about, I always say, if you say around 1000
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milligrams, but there's a little bit more needs when you're during pubertal age.
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But if you can do about three servings of high calcium foods,
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you probably will be getting enough in your diet.
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And so how do we work on optimizing it? Nutrition is preferred.
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And so you want to really try to get it in their diet compared to giving it
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as supplementation, unless really needed.
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And so I sometimes will find I have kids who are picky eaters,
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I'll say, well, you're getting a calcium supplement for those who are higher
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risk, and then gradually try to get it in your diet.
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And so only take it at the end of the day, if you didn't get enough during the
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day. So these are just things to think about.
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And then there's some adult studies that were done on adverse cardiovascular
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effects of calcium supplements.
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So that's why I really try to prefer
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doing supplementation, not supplementation, but doing it in the diet.
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So now when we're talking about
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rickets, we do have to always think about beyond nutritional rickets.
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There are genetic forms of rickets, but what we most commonly see is the nutritional
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rickets, but then there's the vitamin D dependent and vitamin D resistant rickets.
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And one of the ones that I'm going to kind of go through is XLH,
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which is X-linked hypophosphatemia, because that is one of the more common,
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it's the most common form of inherited phosphate wasting and inherited form of rickets.
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And so you can have short stature, lower extremity, deformity, nostril malacia.
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And then the rickets, it's more severe in males as it's X-linked.
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And there's other findings like you can have tooth abscesses that they may have.
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And so one of the things that have come out is the conventional treatment was
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giving phosphate multiple times a day, calcitriol and vitamin D.
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And then in 2018, barazumab was approved by the FDA.
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And it's a fully human monoclonal IgG1 antibody that neutralizes FGF23 and really
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helps keep the phosphate levels under better control.
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And it's really has shown to be really promising and doing well.
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For my patients, especially the conventional treatment, it's phosphate several
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times a day, and it's really hard to keep up.
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And so some of the side effects that we were seeing, we see less of and the
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the complications for those who have more severe XLH.
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Otherwise, the conventional treatment does work for patients that are less severe.
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And this is just something from one of the newer treatments out there that are available.
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Obviously, it's expensive, but it is really been life-changing for some of these families.
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So now I'm going to talk about the skeletal risk factors more physical activity.
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And the way I always say is like, we need our mechanosensors to tell our bones
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build bone and so your bone density is really built by the response to kind
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of activity so if you have high impact weight bearing the other day because
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of this you know you ever yeah.
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So dose response to activity is like you have, just depending on where you are
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in mobility and how much you're walking, you are going to build stronger bones.
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And some of this has been seen in our cerebral palsy population.
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If you have controls in cerebral palsy, they have narrower, thinner cortex.
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And there's no difference in the length of their bones and their vertebral body,
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but it's really that they have a thinner cortex and that probably has to do with less activity.
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And they we see that
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there is if you look at in this population you have
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the fractures that they're having is a lot
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higher compared to what you have in the general population and a lot of it has
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has to do with the bone density and so this in cp patients are a much higher
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risk for fractures the fractures for them occur disproportionately risk is more
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of the lower lower extremities,
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maybe with distal femur being the most common site.
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And it can happen with just minimal traumatic fractures. So like you're with
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transfers from falls from wheelchairs and standers.
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And so that's some, so those are like patient populations that we think about
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where we have higher risk for fractures and we need to think about how to help them.
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In general, my prescription, I say for activity is really, you need to try to reach the individual.
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So if you you have a patient who has CP, you could try to get them safely to
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help ambulate a little bit with a stand or even it can help build stronger bones.
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Some of the data may not be, it's not exactly being shown that it's improving
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bone density everywhere.
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But I think the kids who do standards for at least anecdotally,
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who will not fracture or fall,
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if we can decrease their risk, they tend to have stronger bones and less likely
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to fracture than the kids who've not been on a, doing any kind of standing at all.
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So we need to really recognize the risk of fractures and make sure that we're
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not putting them at risk for fracturing by falling and avoid immobilization or overuse too.
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And so those are some things that I think about. So pediatric osteoporosis,
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so how do we even define it?
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Because it's different than in the adult world.
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In PEDS, we think about if you have one or more vertebral compression fractures
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without high energy trauma or a local disease, irrespective of your BMD DEXA.
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So it doesn't matter what density your bones are.
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If you have achievable compression fractures, you have osteoporosis.
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That's one definition. The other, you could have low bone mineral density on
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a DEXA scan, and you have to have at least two long bone fractures by age 10 or three by the age of 19.
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That means that if you've fractured in your fingers or your toes,
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that does not include it.
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It has to be a long bone fracture. And that's the definition for pediatric osteoporosis.
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And so it's important to know that definition because that helps us to decide
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whether we're going to do anything for these patients or not.
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But fractures, what do we need to consider on our differential?
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The one that you have to always think about is child physical abuse,
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like abuse of any sort, because the fractures are the second most common injury
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from child physical abuse. Well, first is bruising.
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In a child that's young, an infant or less than three years of age,
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20% of the fractures caused by abuse may be misdiagnosed initially as accidental
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or attribute to another cause.
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And about a quarter of the fractures in children younger than one are caused by child abuse.
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So it's important that we don't miss those cases.
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We don't miss child abuse in general.
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So how do you evaluate a fracture? If you want to think about for all fractures,
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is it accidental or is it non-accidental?
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If it's, and does the patient, could they have OI, obstetrician's imperfecta?
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And do we need to further investigate that because depending on how the fall
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happened does it make sense that they should fracture like that and then if
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it's not accidental you need to be thinking about whether or not is there any
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reasoning behind could it be some other genetic form but also child abuse is
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always on there and so just want to be thinking about that.
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And then when we're there's all there's no really distinguishing guidelines
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that can help us distinguish traumatic versus pathologic fracture.
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But in general, long bone fractures are the most common in children,
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and then low trauma non-vertebral fractures.
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And if you have a hip fracture, that's really, really rare. And you should always
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be thinking of some underlying disease in that child.
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But what do children fracture? They fracture the distal forearm,
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their fingers, their clavicle, their ankle, toes, metatarsal and distal humerus,
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but less likely are going to be like vertebral fractures, ribs, the skull.
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And so some of these sometimes can help you decide whether or not you think
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it's a child abuse or not, or other risks that you like other types of things that might be going on.
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In specifically child abuse, one of the common fractures we may see are the
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classic metaphysial lesions of the distal tibia.
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So which you only can see them for a few days and because they heal pretty fast often.
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So if you don't get that x-ray, you may miss it if you do it two weeks later.
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And these fractures are thought to occur because of the torsional,
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like, tractional shearing strains that are applied across the metaphysis.
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And so that pulling and twisting of the infant's extremities,
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that's how these fractures tend to occur.
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The other fractures that we think about in child abuse are the posterior rib
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fractures that occur from like the way that are found with the way they hold the child itself.
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And those will not initially appear right away on the x-rays.
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And then if you do an x-ray two
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weeks later, you will see those fractures appear and be much more clear.
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So you have to know when you're looking for x-rays and what the timeline and
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getting a a good history from the family of like when the child,
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what injury happened and how it happened.
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So these are just some of the specific radiologic findings in infants and toddlers for abuse.
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But it's sometimes really hard, depending on what type of fracture and how many
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they have, whether or not you can say this is abuse versus just a fracture from
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a fall or some other reason.
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And so I'm going to now move on to low bone marrow density and why do we develop
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it, especially in which conditions.
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So low BMD and chronic diseases, if you have chronic inflammation,
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any decreased weight-bearing activity, poor nutrition, delayed puberty,
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and then treatment related, they glue corticoids.
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One specific condition that's on long-term steroids is going to be Duchenne muscular dystrophy.
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And so we have a lot more, we understand kind of the risk for fractures for
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in general in DMD because they're on steroids and then they become non-ambulatory
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and we see them fracturing.
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So what does steroids do? It disrupts bone remodeling.
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So in the short term, you will have increased osteoclast survival.
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So you have increased bone breakdown.
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And then you get like long term,
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you get the osteoblasts where you have decreased osteoblast survival.
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So decreased bone formation. So the blue here is when the bones are forming
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and osteoclasts is when you're breaking down the bone.
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And remember, it's a dynamic process that's happening in children.
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And the goal is that we're supposed to be having more osteoblastic kind of bone
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formation and less of the breakdown.
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And then it also, steroids affect the calcium absorption you get.
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You get increased urine calcium excretion.
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And then it also can suppress puberty if you're on it for a prolonged period of time.
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And that's kind of one of the reasons we see a lot of side effects in children
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who are on steroids for a prolonged period of time.
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So the, and the bone loss occurs most rapidly in the first 12 months.
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And what the most, what you see often is vertebral compression fractures.
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And those are often going to be asymptomatic sometimes.
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And so the two populations that we think about are like the steroid treated
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leukemia patients and the Duchenne muscular dystrophy.
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And that's why they're trying to move away from in leukemia to do less steroid
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treatment if possible, because of the risk of fractures.
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And so how do we assess vertebral fractures?
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Because this is really good. If you have vertebral compression fractures, you have osteoporosis.
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So we really need to be able to know how do we assess it and what do we look for?
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There is a scoring that can be used to look at how much compression you're seeing
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and looking at whether the vertebrae has decreased.
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And so it's about like we have there's grade one, grade two,
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grade three. And it's helpful to have that because we see a domino effect in
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the vertebral compression fractures.
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So if you get one, you tend to get another one and another one.
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And so following those helps to see whether or not there is,
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if there really is a compression fracture and how severe it's getting.
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And then now at some places they're doing the DEXA scan, the bone density scan,
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can also do a vertebral fracture assessment using the dexilateral spine view. you.
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And so that is something that I think hopefully will be a lot more we can use.
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So we don't have to do to like do a vertebral film along with a DEXA and screening.
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But that is something that not all centers have been able to do.
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But it's where it is, it's been really helpful to have just because sometimes
22:12
we're doing DEXAs for other reasons, and then we see notice,
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and then you know, you can get a spine film.
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And so how you look at that is you really, you kind of measure the distance
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on both sides, and then you can see how much measurement loss that there has happened.
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And that gives you a little bit more quantitative information to go with in a way to look at it.
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So what about, what are DEXAs? It's widely available.
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It's highly reproducible. And there are many factors that affect the accuracy of BMD.
22:43
So you really need to make sure if you can't try to use the same place,
22:46
the same machine, because there are some differences in each machine.
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And it's so that's something that I think people don't really appreciate enough.
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But if you've got a deck set one place, you want to try to use the same deck
22:58
set can, it's really inexpensive, and it's really low radiation.
23:02
So it's and it's fast. And so that's why decks are really helpful.
23:06
It gives me more quantitative data.
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And the sites that we do depends on the child and the age.
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And if we can't do a full whole body, because they have any kind metal,
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then we can do certain sites.
23:18
And you can follow along, especially for those who are on some sort of treatment.
23:23
And what DEXA does is it uses, it's like, it uses x-ray at two photon densities
23:27
to distinguish between soft tissue and bone.
23:30
And it gives you like an estimated bone mineral density by outlining the bone itself.
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And then, but you want to make sure that you're using a pediatric algorithm
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and norms in the machine because the adults, they, it's a different algorithm
23:45
that's used differently compared to children.
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And you want to, and just remember, it's still a 2D. It's not a 3D measurement.
23:53
So it doesn't give you the bone depth.
23:55
Like it just gives you kind of a density similar to what you would get like an x-ray in a sense.
24:01
But what I want everybody to be careful is if you're ever getting a DEXA,
24:05
don't be using the T-score.
24:07
The T-score is what they use in adults.
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And it's a standard deviation compared to young adults at peak bone mass.
24:14
And so that's not helpful because obviously in kids, you're building more bone
24:18
density. So your T-score is going to be off.
24:21
Versus a z-score is your standard deviation score compared to age of and gender matched controls,
24:28
and so that's why you want to make sure you're using a z-score and
24:31
so if you send them to an adult facility to get a dexa they sometimes will
24:34
report a t-score and then you're like i what do i do with this and then you
24:37
have to figure out how to reread it and so the other thing is we do height correct
24:41
you can correct for height and then sometimes they look at the bone age and
24:44
see if they're if they have delayed puberty to just give you a rough idea whether
24:48
i should be worried how how worried should I be or not on their bone density?
24:51
So those are other things that we can look at.
24:54
And remember, it's really a helpful tool to add on to your evaluation.
25:00
It's not used as a diagnostic tool.
25:03
Because even when we said for osteoporosis definition is vertebral compression fractures.
25:09
And so when you could have vertebral compression fractures, and you could going
25:14
to have a BMDZ score that is normal.
25:16
And so that's why we don't really use it always to just say this patient has osteoporosis or not.
25:21
It really just gives you a rough idea of like what is going on and whether it's
25:25
getting worse or better.
25:26
So you can kind of compare it to themselves to see how they're making improvement or not.
25:31
Especially when they're recovering. And then there's overdiagnosis of low BMD in kids.
25:36
And that's because obviously, I said, it's misapplication of T-scores.
25:41
But then there's inattention to the need to correct for height.
25:44
And bone age are two things that we do.
25:46
Height, because if you think about it, it gives you a BMD number.
25:49
And if the kid's shorter, their bone density is going to be smaller.
25:52
So you have to relate to their adult height. If you're tall,
25:57
you're going to get a higher BMD.
25:59
But when you correct it for height, it's going to be a it's going to be showing that it's worse.
26:03
So it's really important that you take the height into consideration when you're
26:07
looking at the bone marrow density for these kids, because you don't want to
26:13
misinterpret and give them the wrong information.
26:17
So overall, in management, we have to address all the factors, right?
26:22
And how do we minimize anything we can?
26:26
So for example, especially in chronic diseases like Crohn's,
26:28
if we do manage their Crohn's really well, and then their bones will be healthier in a sense.
26:34
And that's one of the things I'll always talk to them. I'm like,
26:37
well, how do we manage your underlying condition as much as we can to be able
26:40
to improve your bone density?
26:42
And then nutrition is something we can always work on in physical activity.
26:45
But that's why I say it's everybody's role in bone health.
26:49
It's not just seeing an endocrinologist or somebody who's specifically bone
26:53
health related, but it's everybody who can play a factor in making sure they
26:56
have built strong bones.
26:58
And then the other thing is we have really few treatments, especially in kids.
27:03
The anabolic agents really don't work. So we have like we can give estrogen
27:07
and testosterone if they have to like delay puberty to help build their bones.
27:12
And then there is bisphosphonates, which we also use in osteoporosis.
27:17
And bisphosphonates is a synthetic analog of pyrophosphate, and it incorporates
27:22
into the skeletal matrix.
27:23
What it does is it inhibits the osteoclastic bone resorption,
27:27
so it helps keep the bone density.
27:29
It's almost like the way I think of it is kind of like you're putting a layer
27:32
of cement on the bone so you don't keep losing that bone that you already have.
27:35
You're not helping build more bone. You're helping maintain what you may have.
27:39
It's used in the pediatric population for several different conditions.
27:44
There's not as many randomized control studies. there's little
27:47
a lot of anecdotal i mean a lot of like case retrospective studies
27:50
that have been done but there's some there's evidence that it is used
27:53
really for well for oi cerebral palsy to shade
27:55
muscular dystrophy crone cf and for some of these you'll use them depending
28:00
on the situation it does not work for us like secondary osteoporosis in like
28:06
anorexia nervosa like that is some it will not work for that so you have to
28:10
think about who you're using it for and what and And how are we using it?
28:15
Because the other thing you don't want to do is give too much bisphosphonates.
28:19
And then you fracture because your bones are too dense.
28:22
And so you really want to monitor them because their half-life is greater than 10 years.
28:26
And so when you have some patient who got bisphosphonates, if you look at their
28:29
x-ray, they'll have lines of each treatment that they basically receive.
28:34
And so really want to be thinking about before you just prescribe bisphosphonates,
28:38
what the long-term implications are.
28:39
It's a pretty safe drug. like the first time they get it, they can have like
28:44
an acute phase reaction.
28:45
They'll have fever and they may feel achy for like a day or two.
28:49
And then their calcium can kind of drop a little bit. So you want to make sure
28:53
you're monitoring them carefully.
28:55
What we do is outpatient and just make sure that their vitamin D level is good,
28:59
their calcium supplements, their zinc calcium supplementation in their first and second infusion.
29:04
And then after that, they generally do well. So I think that if as long as you
29:09
know what you're doing and you're treating, it's really helps,
29:12
especially for some of the higher risk patients.
29:14
And for OI, Osteogenesis Imperfecta will give it to like babies,
29:18
those who have severe OI. So it's done in all age groups.
29:22
Okay, now I'm going to move on to skeletal disorders specifically and the question
29:26
of, because we're talking about fractures, do they fracture?
29:29
So there are about 425 skeletal dysplasias that have a known molecular and etiology,
29:35
and there are 461 described.
29:38
So dysplasia is, there's like, we kind of split into three.
29:43
If you look at the way they've split them up,
29:46
this dysplasia is going to be like the OI, and then you have like the chondroplasia,
29:50
then that's the other type of like skeletal dysplasias
29:53
and then you have metabolic so that's when it's more
29:55
the hypophosphatemia rickets the storage disorders hypophosphatasia
30:00
those are more metabolic and then you have the ones that don't change so basically
30:04
you're born with it it stays the same dysostosis which is like cleft lip palate
30:08
craniosynostosis those like once it happens it happens when you're born and
30:10
then it kind of stays the same but the question do they really fracture really
30:15
small number of them of the total predisposed to fractures.
30:19
And so, and the reason I bring this up, because when you come think about like,
30:22
people say, oh, could it be a skill disorder?
30:24
And could they have for child abuse, for example, and majority of them don't
30:29
fracture, there's only a few that are known to cause fractures,
30:33
and specifically like hypophosphatasia.
30:35
So you could check some labs and see whether the outpost is low,
30:39
and then OI, and then the other ones that we have, they all of them have very
30:43
very significant clinical findings that are pretty straightforward to be able to diagnose them.
30:49
And so the majority of the skeletal dysplasia themselves don't have a higher
30:53
risk of fracturing itself.
30:55
So this is something to think about when we're talking about skeletal dysplasias,
31:00
and especially when it comes up with like child abuse or any other form,
31:03
but also audio differential when you're having a kid who has been fracturing a lot.
31:08
I'm going to move a little bit now to some updates on treatments,
31:11
because I think there's some, it's been an interesting landscape in the last
31:14
few years, really, since I've been in training.
31:16
So with XLH, verazimab has helped with the, for a lot of our patients,
31:21
instead of having to do the conventional treatment, which was really having
31:25
multiple medications a day.
31:26
And then hypophosphatasia is when you have like low ALKBOS level,
31:30
you have like kind of softer bones.
31:31
And giving asphatase alpha, it's an innovative enzyme replacement for the patients.
31:37
And so it and they really it's it's
31:41
not for every patient who has hypoplasmatasia it's more
31:44
used in the ones that have more moderate to severe
31:47
forms and depending on but it's been
31:50
really helpful and done great for patients for that but then and then the other
31:55
one I'm going to bring up is achondroplasia because that's it's a lot of different
31:58
drugs currently being studied to see if we can help in any way so these are
32:03
some targeted treatments that that are being studied right now.
32:08
Vazirotide is the only one that's been currently FDA approved.
32:10
There's clinical trials currently on CMP at Transcon-CMP, which is basically
32:16
a once a week instead of giving it daily, which is Vazirotide.
32:20
And in achondroplasia, it's FGFR3, which is the mutation variant that happens.
32:26
And that's the most common form of skeletal dysplasia.
32:29
And so what they're doing is they're working, it's kind of working in the down
32:32
signaling, a kind of, if you give CMP, P, you're inhibiting kind of the increased
32:38
chondrocyte hypertrophy and differentiation from happening.
32:42
And so you would hope that then the growth and everything, a lot of some of
32:46
the other complications may be less.
32:48
So this is one that's currently been FDA approved, but there are a few other
32:52
drugs that are being tried and targets.
32:55
Currently, there is to try to work exactly on the FGFR3, that's being done.
33:02
And so there's looking at whether other medications may help.
33:07
So I'm going to go through a little bit on CMP analog. So Vazirotide is the
33:11
one that's once daily. It's been approved in children.
33:14
And they use the end goal for the FDA approval, really the growth.
33:19
And it showed about 1.57 centimeters per year in favor for Vazirotide,
33:25
which comes out to be like maybe if kids were started really early,
33:28
five, six inches of growth, maybe.
33:30
And honestly, it will be only time will tell us because the FDA only approved it in 2021.
33:36
And recently in 2023
33:39
it got approved starting at birth but there's
33:42
so much data we don't really know that what
33:46
the long-term implications of it are and how they're going to do but the studies
33:50
that they did did show sustained improvement at least for a couple years so
33:55
far for mesuritide but the question a lot of patients will say is is only height
34:02
important in achondroplasia is that that really what we care for?
34:06
I mean, there are a lot of the medical complications that are associated with achondroplasia.
34:10
So yes, the height can help maybe some of the functional outcomes and the quality of life.
34:15
But what about them needing the, they have spinal stenosis, they can have sepharomycinosis
34:21
in a sense, and then they need, and then they can also have spinal stenosis.
34:25
So those, they need surgery. And there's like, some of the achondroplasia patients
34:29
will, their quality of life is affected because of the pain that they may have
34:33
as later as an an adult and need to go through major spine surgery.
34:36
And so the question is, will this decrease change the outcome of that?
34:40
And different families will have different perspective. There are generations
34:44
of like of a chondroplasia family and they might be saying, well,
34:48
height's not the most important thing to us.
34:50
Please tell us whether or not, if we're gonna take a drug every single day,
34:54
is it going to improve our outcomes and improve our quality of life from a surgical
34:59
and other complications?
35:01
And so versus the family that has a newborn who has no experience with achondroplasia,
35:06
for them, sometimes they're coming
35:07
in with just wanting to get like any medication and to help in growth.
35:13
And I think that it's important that we, for those families that are new,
35:17
especially because now that it's been approved at birth, that we don't forget
35:20
the other medical management. Remember that some of the kids,
35:23
there's a higher incidence of what we call SIDS, which is like sudden infant death syndrome.
35:28
But really, we know it happens in the babies with achondroplasia because of
35:32
the fibromyalgia stenosis.
35:34
And they have abnormal breathing that can happen. And so that is something we
35:38
still need to be monitoring for and making sure they get their MRIs,
35:41
they get their sleep studies, and not just focus on the treatment.
35:44
And I just remind everybody because a lot of the families are just looking at
35:48
treatment, treatment, treatment. And then they're forgetting the regular routine
35:51
management for these kids.
35:52
And we just don't want to lose a child because we didn't do what was the routine
35:56
standard of care for achondroplasia also.
35:58
So this is just something to think about as new treatments emerge.
36:01
We also have to make sure that we're still doing what's important for their
36:05
routine management. And the other thing is that's really nice for some of these
36:09
conditions is now they're seeing their doctors more often.
36:13
So I think we're going to learn so much more about these conditions as we see
36:17
these kids more often because they're coming in for treatments possibly or for
36:21
newer drugs that may be coming.
36:22
But then we also have to help the families decide which treatment.
36:25
Do they want to be part of a clinical trial because there's several trials going
36:30
on and drugs available versus do they want to take the one that's FDA approved
36:33
so far? And so there's a lot to come.
36:35
And I think it's an exciting field, but it's also really challenging when you're
36:39
working with these families and deciding what to advise the families with.
36:45
So in overall for like bone health and specific, I think we all play a role
36:50
in maximizing bone health and quality of life.
36:52
We really need, there's so much that goes into nutrition and diet.
36:56
The cases that I've seen with, you know, parents like deciding to do vegan diet,
37:01
which is great if that's what you want to do, but making sure that they're still
37:05
getting high calcium foods with that.
37:07
And then the vitamin D, I know one of the things kind of thinking back,
37:11
I remember when when I was in my in Ohio, and I was in nursery,
37:14
every baby left home with vitamin D supplementation.
37:17
In DC, I don't know if that was really hot. That wasn't happening.
37:20
The nurseries weren't discharging them.
37:22
And I don't know if the lactation consultant was meeting with them before discharge
37:26
to talk about like the diet and vitamin D supplements.
37:29
And so and then at the follow up visit, I was asking a lot of people who are
37:33
having newborns, whether your pediatrician asked you if you were on vitamin
37:36
D supplements while they're breastfeeding.
37:38
And I think sometimes that those are simple things. But a lot of people said
37:42
their pediatrician even asked them about did you like whether they started vitamin
37:47
D supplements, or have they were, if they were breastfeeding,
37:49
and if the breastfeeding mother was having enough calcium in her diet.
37:53
So like, we would I really hope that we could prevent rickets,
37:57
especially in the US where we know we have the food that and hopefully accessibility
38:02
to it with something we can do and then physical activity, right?
38:06
So So trying to make sure kids stay active, we can help them build stronger bones.
38:11
Doesn't have to be intense physical activity, but just having walking and stuff
38:14
can help increase your bone density.
38:16
And then the other things, well, that's something we can have as doctors have
38:19
to decide what we're doing and how we're going to manage to optimize treatment.
38:23
But in conclusion, fractures are common in childhood and they are a major cause
38:28
of morbidity and chronic illnesses and their therapies are risk factors for osteoporosis.
38:32
Osteoporosis so a thorough history and physical can often
38:35
elucidate diagnosis and it starts with all of us and assessing
38:38
the assessment of osteoporosis in childhood is a
38:41
functional approach with a goal of early identification of those who are at
38:46
increased risk and there are now new emerging treatments for cell disorders
38:50
but really everybody plays a role i don't think it's just one person that plays
38:54
a role and sometimes there are other specialties that identify a child with a skeletal disorder.
39:00
So for hypophosphatasia, for example, it may be the dentist who identifies it
39:04
because the kid's losing their teeth.
39:05
And so we all play a role in making sure that we improve the skeletal health in general.
39:11
And the field has a lot to learn, I think, as we think about this,
39:14
as kids are also living longer, our children that have chronic illnesses,
39:17
as treatments improve, they're living into their 30s and 40s and 50s, maybe.
39:22
And if we don't take care of their bones, their quality of life will be affected
39:26
with that bone pain as they become adults.
39:29
So we really have to be thinking about maximizing their bone health and really
39:34
the bone bank is built early.
39:36
So we have to, what is it we can do to make sure that they have less risk of
39:41
fractures and earlier risk of fractures in general?
39:45
And thank you. And I just wanted to give a note to Dr. Lynch,
39:48
who's been really a great mentor to me over the years and has given me a lot of opportunities.
39:54
Thank you, Dr. Merchant, for that wonderful presentation on fractures and related disorders.
39:59
I have two questions in the chat box at the moment. What is the youngest age
40:03
a DEXA scan gives reliable results?
40:06
So I think we can do it as early as three.
40:11
Now we're doing a lot of the DEXAs. and I a
40:14
lot of the time I like to use it and to compare it to the child so it gives
40:20
you an idea like if you're going to do it a year later and see whether there's
40:24
changes or improvement but remember DEXA is not a diagnostic tool it's just
40:28
used as an adjuvant right so it's you using it to give you more data to help
40:32
interpret what's going on.
40:33
The second question is is there information about the extreme premature population
40:38
that continues to expand are there recommendations? recommendations?
40:42
So that's the population. So we have the extreme premature babies that we see
40:48
in the NICU and that suddenly they fractured while they were in the NICU.
40:51
So in that, I think we have to be thinking about, are we optimizing their bone health in general?
40:56
But then there is some data about the fractures, but I think it's just variable
41:02
on what they have, right?
41:03
Did they have neck? Were they on TPN and other risks?
41:07
And so I think optimizing whatever we can after they get out out of the NICU
41:11
also is really, really important.
41:14
And then the ones that did not fracture in the NICU, I don't know.
41:17
I honestly don't know what data that's there.
41:20
I'd have to look and see if there's anything on those patients.
41:24
Another question in chat, what is the incidence of toddler fracture and are they hypocalcemic?
41:30
So toddlers who fracture without like any risk factors should not be hypocalcemic.
41:38
So if they are hypocalcemic, I would definitely really check a vitamin D level
41:41
and then to see why they did become hypocalcemic because they shouldn't have
41:47
a low calcium just because they fractured.
41:49
So there must be something underlying. So is there a vitamin D deficiency?
41:53
Rickets along with them having had a fracture itself. And then if you treat
41:57
their vitamin D deficiency, then it's also going to, it doesn't improve.
42:04
Then you want to be thinking of genetic forms because sometimes the genetic
42:06
forms of rickets, they They can't be identified until you get the vitamin D
42:09
level up enough and you've given some calcium supplementation and then they're
42:12
still not improving and they kind of reveal themselves at that point.
42:15
Thank you. Any other questions, comments, Dr. Merchant? Okay,
42:19
there's a question by Dr. Asanasan.
42:22
Has the STOP trial looked at the difference between collaborative group protocols?
42:29
The STOP trial? Yeah, I can read that. I honestly don't know if the STOP trial
42:35
has looked at the different protocols.
42:37
The other reality is a lot of the bisphosphonate data, everybody's doing different protocols.
42:44
And even the treatments, like some people are using Zometa, some are using permidronate,
42:48
some people, when they decide to give treatments or not, there is right now,
42:53
at least in the Duchenne muscular dystrophy, there's been discussion whether
42:56
or not we should start treatment earlier and earlier,
42:59
because those kids are on chronic steroids and also on,
43:03
they're also on, become non-ambulatory.
43:05
And so there's discussion on whether we should give them bisphosphonates before they fracture.
43:12
So like, but that's not been completely like consensus on that either.
43:17
But with the oncology group, I mean, it's such a different population because
43:22
these kids will often, you know, they don't, they're on steroids for a shorter period of time.
43:27
And so do we treat all of them or not is a different question to give them bisphosphonates or not.
43:32
I see a hand raised. Can you ask your question?
43:36
This question in the chat box about Dr. Dharuparaman, is 400 IU enough if the baby has cannula TBs?
43:46
I don't know. I mean, I feel like you may want, that's one that I would probably,
43:51
you could get a vitamin D level at some point and see what it looks like and
43:57
make sure that it's above 30.
43:59
And so you may, and so it depends on, so remember, when you're getting breast,
44:04
400 IU is just a, you don't want to over-treat either.
44:07
But I think you could probably do 600 and it still would be safe but you could
44:11
just check a vitamin D level just to make sure that you're not undertreating.
44:16
Any other questions? I see a hand raised and I don't know who it is.
44:20
Can you ask your question? If you have a question.
44:24
I'm just going to say thank you, Nadia. This was a fabulous talk. It's Jane Lynch.
44:30
Can you hear me now? Yeah, we can hear you. Oh, yeah. This is Dr. Weimer.
44:34
I just had an interesting case years ago.
44:39
Pre-teenage little girl with localized lumbar vertical pain.
44:44
It's just one of her lumbar vertebrae. And actually, I was a lab tech before
44:49
I was a doctor. And so I did a white count.
44:53
And her white count was 30,000. In other words, she had a leukemic infiltrate
45:00
in just one of her spines.
45:03
So that's just something to consider.
45:06
The other interesting thing, I used to do physicals at Crest Haven Children's
45:12
Home, which was a residential place for mostly children with cerebral palsy
45:18
and severe retardation.
45:20
They all had extremely high urine-specific gravities, 1030 or more.
45:27
And what I finally found out is all these children were in diapers and they
45:34
were voluntarily restricting their P.O.
45:38
Intake, which probably included milk, in order to avoid the discomfort of a wet diaper.
45:46
So that is just an interesting thing to know about.
45:51
And also, I did see one case with Munchausen's by proxy, which usually isn't
45:59
bone fractures, but it could be, I suppose. Thank you. Thank you.
46:04
Yes. And I think that you brought up an important point. If you have a healthy
46:08
child who has any compression fracture, I always say it's cancer until proven otherwise.
46:13
And it's happened to me more than once. I get called up for a consult on a child
46:17
with a vertebral compression fracture.
46:20
And I'm like, and if the kid's healthy, otherwise has no other health issues.
46:23
And then they find out in the end it is cancer.
46:25
And so I think it's to me, that's one of the things that's always a challenge
46:28
because why did you get a compression fracture without any other risk factors.
46:51
Music.