Bone Health, Fractures, and Updates on Treatments for Bone Disorders
CME Link: https://cmetracker.net/UTHSCSA/Publisher?page=pubOpen#/getCertificate/10095736
In this episode of "Pediatrics Now", expert pediatric endocrinologist, Dr. Nadia Merchant from Children's Health UT Southwestern, embarks on an enlightening journey into the fascinating world of bone health in children. She delves into significant bone diseases like rickets, calcium disorders, osteoporosis, and skeletal dysplasia. The episode features a balanced mix of medical insights and practical tips on maintaining bone health, specifically for children with disabilities and other chronic issues.
Incorporating themes of nutrition, physical activity, and optimized genetics, the podcast also tackles the sensitive issue of child physical abuse, emphasizing the implications of bone fractures. We also explore therapeutic interventions for inherited bone disorders such as X-linked hypophosphatemia, and the role of physical activity in building stronger bones.
This episode further discusses management approaches for bone health and takes a deeper dive into skeletal disorders and the world of treatments for metabolic bone disorders. Dr. Merchant concludes the episode with a Q&A session answering listener queries about premature births, DEXA scans, toddler fractures, and much more.
Join host Holly Wayment for an enlightening discussion that intertwines medical knowledge with practical advice to increase awareness and improve bone health in children.
Bone Health, Fractures, and Updates on Treatments for Bone Disorders
FACULTY:
Nadia Merchant, MD is a pediatric endocrinologist and geneticist at Children’s Heath/UT Southwestern Medical Center.
OVERVIEW:
In this podcast episode, Host Holly Wayment brings a talk from Dr. Nadia Merchant about bone health, fractures, and updates on treatments for bone disorders.
DISCLOSURES:
Nadia Merchant, MD has disclosed she was a consultant/advisor for Pfizer, BioMarin, and Ascendis. The relevant financial relationships noted for Dr. Merchant have been mitigated.
The Pediatric Grand Rounds Planning Committee (Deepak Kamat, MD, PhD, Steven Seidner, MD, Daniel Ranch, MD and Elizabeth Hanson, MD) has no financial relationships with ineligible companies to disclose.
The UT Health Science Center San Antonio and Deepak Kamat, MD course director and content reviewer for the activity, have reviewed all financial disclosure information for all speakers, facilitators, and planning committee members; and determined and resolved all conflicts of interests.
CONTINUING MEDICAL EDUCATION STATEMENTS:
The UT Health Science Center San Antonio is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The UT Health Science Center San Antonio designates this live activity up to a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
CREDITS: AMA PRA Category 1 Credits™ (1.00) Non-Physician Participation Credit (1.00)
MOC 2 credit (1.00)
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Welcome to Pediatrics Now, cases, updates, and discussions for the busy practitioner.
I'm your host, Holly Wayment. I work for UT Health San Antonio's Department of Pediatrics.
In this podcast, we explore how we can provide the best, most cutting-edge,
compassionate care for children.
We hope to give you a unique and behind-the-scenes edge from our expert guests.
(00:21):
After listening, click on the link on this podcast for free credit.
Music.
It is my pleasure to introduce Dr. Nadia Merchant.
Dr. Merchant is a pediatric endocrinologist and geneticist at Children's Health UT Southwestern.
She attended medical school at Weill Cornell Medical College in Qatar and completed
(00:43):
her pediatric residency at Wright State University.
She completed her genetics and pediatric endocrine fellowship at Baylor College
of Medicine, Texas Children's Hospital.
She also has served as faculty at Children's National Hospital. Hospital.
Her clinical and research interests include bone health and the intersection
of genetics and endocrinology.
She has specific interest in rickets, calcium disorders, osteoporosis in children,
(01:06):
especially Duchenne's muscular dystrophy and skeletal dysplasia.
Without further ado, please join me in welcoming Dr. Merchant.
Hi, a little bit about me. I was born and grew up in Houston,
so San Antonio has been some place that I've always come and been many times on vacation.
I moved to Saudi when I was in eighth grade.
And that really just led me to go to Cornell and Qatar and really gave me more
(01:28):
of a global experience. And some of my interests really grew from there.
And then I have had went to residency in Dayton.
And so I had a lot of my colleagues come to do fellowship in San Antonio because of the base here.
And then I went to Texas Children's. And recently, I just joined at UT Southwestern.
And it's been great so far.
So objectives today, to understand the basics of of bone health and distinguishing
(01:50):
what traumatic and pathological factors could be and the clinical diagnosis
to genetic diagnosis to now we're having rare disease treatments for bone disorders.
And my main goal is really to inspire ways to maximize bone health in all children,
especially those with disabilities and chronic health issues.
And really why? It's because bone health, the bone bank is built really early.
(02:11):
And so we can't wait. We need to start now. It starts from when a child's born.
And it really, it's really the pediatricians and all of us who make an impact
on how the quality of life these kids may live based on their bone health.
And the reason for that is that children gain about 33% of their total bone
mass just during puberty.
And most of the other is built while right before they go go into puberty.
(02:35):
So we need to think about how do we maximize their bone health and bone density.
The way it works is that you as born as an infant, and then you your bones expand,
and then you get endocortical like opposition, like to make it the peak bone mass.
And then as adults, we lose it gradually. And based on our different risk factors,
(02:57):
you will lose your bone density over time.
And so you're mostly going through an anabolic or increasing your bone density
as a child, and then it goes downhill from there.
So I like to always draw this diagram when I'm talking to parents about bone
density and the scale to risk factors, because some of these are things that
(03:17):
we can address on a regular basis in clinic with our patients.
So how do we, what do I do? For peak bone mass, how am I going to maximize it? I want a good history.
What is their diet like, their activity? what medications they're on,
have they had a history of fractures.
And then on exam, like what's their growth, puberty, their spine,
(03:40):
do they have back pain and their motor function overall.
And then just getting sometimes we'll get labs depending on whether we need
a vitamin D or not, that depends on some of the risks for the patient, and then puberty.
And so first off, I'm going to start talking about nutrition and diet.
So many of us know what Ricketts is, And it was called The Loss of Sunshine, the English Disease,
(04:03):
because at one point it was estimated that 50 to 80 percent of children in industrialized
like religion in northern Europe had rickets.
But we have really clear descriptions of rickets from the 17th century and even before that.
And it's also been noted if you
think if you've tiny Tim and Charles Dickens novel has see it probably had rickets
(04:26):
Maybe along with TV because he was described as short stature Asymmetric crippling
and curious inman weakness that would lead to his death if untreated And so
this is something that we always think of it.
I for some reason like Oh rickets is something We've really managed in the US.
We don't really see it well.
I probably see a kid at least every month.
(04:48):
And honestly, because I do bone health, I get they come to my clinic and I will
see them. But this is a typical case.
I have a two-year-old female who presents with history of walking without assistance, but limping.
Extreme bowing since she started to walk at 13 months.
And she was diagnosed by her PCP four months ago and was started on vitamin
D 2000 international units.
(05:10):
But then when I was seeing her in clinic, her diet history, she's still breastfeeding.
There's no milk or cheese in mother's diet or the patient's diet, and she's a picky eater.
And so this really, to me, was eye-opening because we were also getting admissions.
During the pandemic, we saw quite a few kids coming in with severe hypocalcemia
(05:34):
and vitamin D deficiency.
So we did a small kind of inpatient admissions to see the severity of them just
at Children's National.
And we want to know how many cases were we getting and
was this more getting more common and what
was our breakdown of our population and so
these are all kids that were admitted so they either came in with seizures or they
(05:54):
had some abnormal movements so there was something that brought them to the
hospital and that's when we got and we really our criteria was vitamin d less
than 10 and calcium less than 8 so we did and we did a chart review from 2016
to 2021 you can see that that there were increased number of cases that we saw
in 2021. And this is just a retrospective chart review.
And what were some of the risk factors? We saw that dark skin pigmentation.
(06:17):
Dairy restriction, picky eaters, vegan diet.
Breastfeeding with most not being supplemented by vitamin D.
And so these were just some of the admissions, but the length of stay for these
hot patients was four and a half days.
And majority, if you look from zero to two years, were healthy children,
(06:38):
like with no known health issues.
The older kids, yes, they had neurological issues, some of them like autism and picky eaters.
And so some of that made sense, but it didn't make sense for something that's
completely preventable.
So this is just a little bit of like eye opening thinking about like,
what can we do to prevent that simple things is making sure that once the baby's
discharged from the nursery,
(06:58):
we make sure there's vitamin D supplementation that is recommended,
especially for breastfeeding mom and talking to the breastfeeding mother that
she's having enough high calcium foods.
So just a little bit on the recommendations of daily intake, vitamin D.
So for 400 IU is what we do for the vitamin D supplementation for breastfeeding,
(07:21):
or even breastfeeding children, mostly babies, because formula is often has
enough vitamin D in there.
And then there are some patients that I would say, do I need to get a vitamin D level or not?
I think that there's always been this debate whether vitamin D level is helpful.
But if a patient's not getting enough enough vitamin D, you're just going to keep chasing after it.
And so that's where I say, unless there's a really risky population,
(07:43):
it makes sense maybe to get a vitamin D level.
But otherwise, I would just recommend looking into their diet and see,
are they getting enough?
And this is just a few foods that are high in vitamin D that you want to be thinking about.
And if you notice, majority of them are fortified.
So milk has been fortified with vitamin D. And so cod liver oil is one of those
(08:05):
that, but I mean, how many of us are walking around having cod liver oil every day?
But the majority of them don't have much vitamin D.
And, you know, the one thing about calcium intake and vitamin D,
I think the Got Milk campaign to me is a little bit eye-opening because they
noticed that in the 1990s, Americans were drinking about 0.78 cups of milk per
(08:28):
day. and they want to really boost their sales.
So they started doing a lot of the Got Milk campaign, which eventually changed
to the campaign of including like oat and other types of milk.
But what happened, if you think back historically in the 1940s,
we were fortifying milk, assuming in like juice, orange juice,
because assuming that all Americans would be drinking milk and orange juice,
(08:49):
but that trend had been gradually decreasing.
And so some of the maybe reasons we may be seeing rickets is because of that.
And I don't know, like, there's not a lot of data of how much rickets we're seeing now.
But I think the main thing is our diets have changed a little bit in what we
thought Americans were eating.
And we really need to be thinking about what the kids are having to make sure
(09:12):
they're getting enough calcium and vitamin D in their diet.
Drink your milk, kids. I don't want milk. Milk's for babies.
Yeah, babies. Oh, yeah? Well, I happen to know that milk helps build strong bones. So drink up.
Well, Mr. Miller told me he never drinks milk. Look at him. Yeah.
(09:35):
Oh, that's not good.
So that's just a little bit of... The Got Milk campaign is always a little eye-opening
for me, especially because of the data they showed.
So how do we get milk and calcium in our diet?
The recommended calcium intake is about, I always say, if you say around 1000
milligrams, but there's a little bit more needs when you're during pubertal age.
(09:59):
But if you can do about three servings of high calcium foods,
you probably will be getting enough in your diet.
And so how do we work on optimizing it? Nutrition is preferred.
And so you want to really try to get it in their diet compared to giving it
as supplementation, unless really needed.
(10:19):
And so I sometimes will find I have kids who are picky eaters,
I'll say, well, you're getting a calcium supplement for those who are higher
risk, and then gradually try to get it in your diet.
And so only take it at the end of the day, if you didn't get enough during the
day. So these are just things to think about.
And then there's some adult studies that were done on adverse cardiovascular
effects of calcium supplements.
So that's why I really try to prefer
(10:40):
doing supplementation, not supplementation, but doing it in the diet.
So now when we're talking about
rickets, we do have to always think about beyond nutritional rickets.
There are genetic forms of rickets, but what we most commonly see is the nutritional
rickets, but then there's the vitamin D dependent and vitamin D resistant rickets.
And one of the ones that I'm going to kind of go through is XLH,
(11:02):
which is X-linked hypophosphatemia, because that is one of the more common,
it's the most common form of inherited phosphate wasting and inherited form of rickets.
And so you can have short stature, lower extremity, deformity, nostril malacia.
And then the rickets, it's more severe in males as it's X-linked.
And there's other findings like you can have tooth abscesses that they may have.
(11:25):
And so one of the things that have come out is the conventional treatment was
giving phosphate multiple times a day, calcitriol and vitamin D.
And then in 2018, barazumab was approved by the FDA.
And it's a fully human monoclonal IgG1 antibody that neutralizes FGF23 and really
helps keep the phosphate levels under better control.
(11:47):
And it's really has shown to be really promising and doing well.
For my patients, especially the conventional treatment, it's phosphate several
times a day, and it's really hard to keep up.
And so some of the side effects that we were seeing, we see less of and the
the complications for those who have more severe XLH.
Otherwise, the conventional treatment does work for patients that are less severe.
(12:09):
And this is just something from one of the newer treatments out there that are available.
Obviously, it's expensive, but it is really been life-changing for some of these families.
So now I'm going to talk about the skeletal risk factors more physical activity.
And the way I always say is like, we need our mechanosensors to tell our bones
build bone and so your bone density is really built by the response to kind
(12:37):
of activity so if you have high impact weight bearing the other day because
of this you know you ever yeah.
So dose response to activity is like you have, just depending on where you are
in mobility and how much you're walking, you are going to build stronger bones.
And some of this has been seen in our cerebral palsy population.
(12:59):
If you have controls in cerebral palsy, they have narrower, thinner cortex.
And there's no difference in the length of their bones and their vertebral body,
but it's really that they have a thinner cortex and that probably has to do with less activity.
And they we see that
there is if you look at in this population you have
the fractures that they're having is a lot
(13:22):
higher compared to what you have in the general population and a lot of it has
has to do with the bone density and so this in cp patients are a much higher
risk for fractures the fractures for them occur disproportionately risk is more
of the lower lower extremities,
maybe with distal femur being the most common site.
(13:42):
And it can happen with just minimal traumatic fractures. So like you're with
transfers from falls from wheelchairs and standers.
And so that's some, so those are like patient populations that we think about
where we have higher risk for fractures and we need to think about how to help them.
In general, my prescription, I say for activity is really, you need to try to reach the individual.
(14:04):
So if you you have a patient who has CP, you could try to get them safely to
help ambulate a little bit with a stand or even it can help build stronger bones.
Some of the data may not be, it's not exactly being shown that it's improving
bone density everywhere.
But I think the kids who do standards for at least anecdotally,
who will not fracture or fall,
(14:26):
if we can decrease their risk, they tend to have stronger bones and less likely
to fracture than the kids who've not been on a, doing any kind of standing at all.
So we need to really recognize the risk of fractures and make sure that we're
not putting them at risk for fracturing by falling and avoid immobilization or overuse too.
And so those are some things that I think about. So pediatric osteoporosis,
(14:50):
so how do we even define it?
Because it's different than in the adult world.
In PEDS, we think about if you have one or more vertebral compression fractures
without high energy trauma or a local disease, irrespective of your BMD DEXA.
So it doesn't matter what density your bones are.
If you have achievable compression fractures, you have osteoporosis.
That's one definition. The other, you could have low bone mineral density on
(15:13):
a DEXA scan, and you have to have at least two long bone fractures by age 10 or three by the age of 19.
That means that if you've fractured in your fingers or your toes,
that does not include it.
It has to be a long bone fracture. And that's the definition for pediatric osteoporosis.
And so it's important to know that definition because that helps us to decide
(15:36):
whether we're going to do anything for these patients or not.
But fractures, what do we need to consider on our differential?
The one that you have to always think about is child physical abuse,
like abuse of any sort, because the fractures are the second most common injury
from child physical abuse. Well, first is bruising.
(15:56):
In a child that's young, an infant or less than three years of age,
20% of the fractures caused by abuse may be misdiagnosed initially as accidental
or attribute to another cause.
And about a quarter of the fractures in children younger than one are caused by child abuse.
So it's important that we don't miss those cases.
(16:17):
We don't miss child abuse in general.
So how do you evaluate a fracture? If you want to think about for all fractures,
is it accidental or is it non-accidental?
If it's, and does the patient, could they have OI, obstetrician's imperfecta?
And do we need to further investigate that because depending on how the fall
happened does it make sense that they should fracture like that and then if
(16:41):
it's not accidental you need to be thinking about whether or not is there any
reasoning behind could it be some other genetic form but also child abuse is
always on there and so just want to be thinking about that.
And then when we're there's all there's no really distinguishing guidelines
that can help us distinguish traumatic versus pathologic fracture.
(17:01):
But in general, long bone fractures are the most common in children,
and then low trauma non-vertebral fractures.
And if you have a hip fracture, that's really, really rare. And you should always
be thinking of some underlying disease in that child.
But what do children fracture? They fracture the distal forearm,
their fingers, their clavicle, their ankle, toes, metatarsal and distal humerus,
(17:24):
but less likely are going to be like vertebral fractures, ribs, the skull.
And so some of these sometimes can help you decide whether or not you think
it's a child abuse or not, or other risks that you like other types of things that might be going on.
In specifically child abuse, one of the common fractures we may see are the
classic metaphysial lesions of the distal tibia.
(17:46):
So which you only can see them for a few days and because they heal pretty fast often.
So if you don't get that x-ray, you may miss it if you do it two weeks later.
And these fractures are thought to occur because of the torsional,
like, tractional shearing strains that are applied across the metaphysis.
And so that pulling and twisting of the infant's extremities,
(18:06):
that's how these fractures tend to occur.
The other fractures that we think about in child abuse are the posterior rib
fractures that occur from like the way that are found with the way they hold the child itself.
And those will not initially appear right away on the x-rays.
(18:27):
And then if you do an x-ray two
weeks later, you will see those fractures appear and be much more clear.
So you have to know when you're looking for x-rays and what the timeline and
getting a a good history from the family of like when the child,
what injury happened and how it happened.
So these are just some of the specific radiologic findings in infants and toddlers for abuse.
(18:47):
But it's sometimes really hard, depending on what type of fracture and how many
they have, whether or not you can say this is abuse versus just a fracture from
a fall or some other reason.
And so I'm going to now move on to low bone marrow density and why do we develop
it, especially in which conditions.
(19:07):
So low BMD and chronic diseases, if you have chronic inflammation,
any decreased weight-bearing activity, poor nutrition, delayed puberty,
and then treatment related, they glue corticoids.
One specific condition that's on long-term steroids is going to be Duchenne muscular dystrophy.
And so we have a lot more, we understand kind of the risk for fractures for
(19:29):
in general in DMD because they're on steroids and then they become non-ambulatory
and we see them fracturing.
So what does steroids do? It disrupts bone remodeling.
So in the short term, you will have increased osteoclast survival.
So you have increased bone breakdown.
And then you get like long term,
(19:51):
you get the osteoblasts where you have decreased osteoblast survival.
So decreased bone formation. So the blue here is when the bones are forming
and osteoclasts is when you're breaking down the bone.
And remember, it's a dynamic process that's happening in children.
And the goal is that we're supposed to be having more osteoblastic kind of bone
formation and less of the breakdown.
(20:12):
And then it also, steroids affect the calcium absorption you get.
You get increased urine calcium excretion.
And then it also can suppress puberty if you're on it for a prolonged period of time.
And that's kind of one of the reasons we see a lot of side effects in children
who are on steroids for a prolonged period of time.
So the, and the bone loss occurs most rapidly in the first 12 months.
(20:36):
And what the most, what you see often is vertebral compression fractures.
And those are often going to be asymptomatic sometimes.
And so the two populations that we think about are like the steroid treated
leukemia patients and the Duchenne muscular dystrophy.
And that's why they're trying to move away from in leukemia to do less steroid
(20:57):
treatment if possible, because of the risk of fractures.
And so how do we assess vertebral fractures?
Because this is really good. If you have vertebral compression fractures, you have osteoporosis.
So we really need to be able to know how do we assess it and what do we look for?
There is a scoring that can be used to look at how much compression you're seeing
(21:21):
and looking at whether the vertebrae has decreased.
And so it's about like we have there's grade one, grade two,
grade three. And it's helpful to have that because we see a domino effect in
the vertebral compression fractures.
So if you get one, you tend to get another one and another one.
And so following those helps to see whether or not there is,
(21:42):
if there really is a compression fracture and how severe it's getting.
And then now at some places they're doing the DEXA scan, the bone density scan,
can also do a vertebral fracture assessment using the dexilateral spine view. you.
And so that is something that I think hopefully will be a lot more we can use.
So we don't have to do to like do a vertebral film along with a DEXA and screening.
(22:05):
But that is something that not all centers have been able to do.
But it's where it is, it's been really helpful to have just because sometimes
we're doing DEXAs for other reasons, and then we see notice,
and then you know, you can get a spine film.
And so how you look at that is you really, you kind of measure the distance
on both sides, and then you can see how much measurement loss that there has happened.
(22:27):
And that gives you a little bit more quantitative information to go with in a way to look at it.
So what about, what are DEXAs? It's widely available.
It's highly reproducible. And there are many factors that affect the accuracy of BMD.
So you really need to make sure if you can't try to use the same place,
the same machine, because there are some differences in each machine.
(22:50):
And it's so that's something that I think people don't really appreciate enough.
But if you've got a deck set one place, you want to try to use the same deck
set can, it's really inexpensive, and it's really low radiation.
So it's and it's fast. And so that's why decks are really helpful.
It gives me more quantitative data.
And the sites that we do depends on the child and the age.
(23:12):
And if we can't do a full whole body, because they have any kind metal,
then we can do certain sites.
And you can follow along, especially for those who are on some sort of treatment.
And what DEXA does is it uses, it's like, it uses x-ray at two photon densities
to distinguish between soft tissue and bone.
And it gives you like an estimated bone mineral density by outlining the bone itself.
(23:35):
And then, but you want to make sure that you're using a pediatric algorithm
and norms in the machine because the adults, they, it's a different algorithm
that's used differently compared to children.
And you want to, and just remember, it's still a 2D. It's not a 3D measurement.
So it doesn't give you the bone depth.
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,
don't be using the T-score.
The T-score is what they use in adults.
And it's a standard deviation compared to young adults at peak bone mass.
And so that's not helpful because obviously in kids, you're building more bone
density. So your T-score is going to be off.
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
so if you send them to an adult facility to get a dexa they sometimes will
report a t-score and then you're like i what do i do with this and then you
have to figure out how to reread it and so the other thing is we do height correct
you can correct for height and then sometimes they look at the bone age and
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?
So those are other things that we can look at.
And remember, it's really a helpful tool to add on to your evaluation.
It's not used as a diagnostic tool.
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
to have a BMDZ score that is normal.
And so that's why we don't really use it always to just say this patient has osteoporosis or not.
It really just gives you a rough idea of like what is going on and whether it's
getting worse or better.
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.
And that's because obviously, I said, it's misapplication of T-scores.
But then there's inattention to the need to correct for height.
And bone age are two things that we do.
Height, because if you think about it, it gives you a BMD number.
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,
you're going to get a higher BMD.
But when you correct it for height, it's going to be a it's going to be showing that it's worse.
So it's really important that you take the height into consideration when you're
looking at the bone marrow density for these kids, because you don't want to
(26:13):
misinterpret and give them the wrong information.
So overall, in management, we have to address all the factors, right?
And how do we minimize anything we can?
So for example, especially in chronic diseases like Crohn's,
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,
well, how do we manage your underlying condition as much as we can to be able
to improve your bone density?
And then nutrition is something we can always work on in physical activity.
But that's why I say it's everybody's role in bone health.
It's not just seeing an endocrinologist or somebody who's specifically bone
health related, but it's everybody who can play a factor in making sure they
(26:56):
have built strong bones.
And then the other thing is we have really few treatments, especially in kids.
The anabolic agents really don't work. So we have like we can give estrogen
and testosterone if they have to like delay puberty to help build their bones.
And then there is bisphosphonates, which we also use in osteoporosis.
(27:17):
And bisphosphonates is a synthetic analog of pyrophosphate, and it incorporates
into the skeletal matrix.
What it does is it inhibits the osteoclastic bone resorption,
so it helps keep the bone density.
It's almost like the way I think of it is kind of like you're putting a layer
of cement on the bone so you don't keep losing that bone that you already have.
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.
There's not as many randomized control studies. there's little
a lot of anecdotal i mean a lot of like case retrospective studies
that have been done but there's some there's evidence that it is used
really for well for oi cerebral palsy to shade
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
anorexia nervosa like that is some it will not work for that so you have to
think about who you're using it for and what and And how are we using it?
Because the other thing you don't want to do is give too much bisphosphonates.
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.
And so when you have some patient who got bisphosphonates, if you look at their
x-ray, they'll have lines of each treatment that they basically receive.
And so really want to be thinking about before you just prescribe bisphosphonates,
what the long-term implications are.
It's a pretty safe drug. like the first time they get it, they can have like
(28:44):
an acute phase reaction.
They'll have fever and they may feel achy for like a day or two.
And then their calcium can kind of drop a little bit. So you want to make sure
you're monitoring them carefully.
What we do is outpatient and just make sure that their vitamin D level is good,
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
know what you're doing and you're treating, it's really helps,
especially for some of the higher risk patients.
And for OI, Osteogenesis Imperfecta will give it to like babies,
those who have severe OI. So it's done in all age groups.
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?
So there are about 425 skeletal dysplasias that have a known molecular and etiology,
and there are 461 described.
So dysplasia is, there's like, we kind of split into three.
If you look at the way they've split them up,
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
and then you have metabolic so that's when it's more
the hypophosphatemia rickets the storage disorders hypophosphatasia
those are more metabolic and then you have the ones that don't change so basically
you're born with it it stays the same dysostosis which is like cleft lip palate
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
small number of them of the total predisposed to fractures.
And so, and the reason I bring this up, because when you come think about like,
people say, oh, could it be a skill disorder?
And could they have for child abuse, for example, and majority of them don't
fracture, there's only a few that are known to cause fractures,
(30:33):
and specifically like hypophosphatasia.
So you could check some labs and see whether the outpost is low,
and then OI, and then the other ones that we have, they all of them have very
very significant clinical findings that are pretty straightforward to be able to diagnose them.
And so the majority of the skeletal dysplasia themselves don't have a higher
(30:53):
risk of fracturing itself.
So this is something to think about when we're talking about skeletal dysplasias,
and especially when it comes up with like child abuse or any other form,
but also audio differential when you're having a kid who has been fracturing a lot.
I'm going to move a little bit now to some updates on treatments,
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.
So with XLH, verazimab has helped with the, for a lot of our patients,
instead of having to do the conventional treatment, which was really having
multiple medications a day.
And then hypophosphatasia is when you have like low ALKBOS level,
you have like kind of softer bones.
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
not for every patient who has hypoplasmatasia it's more
used in the ones that have more moderate to severe
forms and depending on but it's been
really helpful and done great for patients for that but then and then the other
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
some targeted treatments that that are being studied right now.
Vazirotide is the only one that's been currently FDA approved.
There's clinical trials currently on CMP at Transcon-CMP, which is basically
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.
And that's the most common form of skeletal dysplasia.
And so what they're doing is they're working, it's kind of working in the down
signaling, a kind of, if you give CMP, P, you're inhibiting kind of the increased
chondrocyte hypertrophy and differentiation from happening.
(32:42):
And so you would hope that then the growth and everything, a lot of some of
the other complications may be less.
So this is one that's currently been FDA approved, but there are a few other
drugs that are being tried and targets.
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.
So I'm going to go through a little bit on CMP analog. So Vazirotide is the
one that's once daily. It's been approved in children.
And they use the end goal for the FDA approval, really the growth.
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,
five, six inches of growth, maybe.
And honestly, it will be only time will tell us because the FDA only approved it in 2021.
And recently in 2023
it got approved starting at birth but there's
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
that they did did show sustained improvement at least for a couple years so
far for mesuritide but the question a lot of patients will say is is only height
important in achondroplasia is that that really what we care for?
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.
But what about them needing the, they have spinal stenosis, they can have sepharomycinosis
in a sense, and then they need, and then they can also have spinal stenosis.
So those, they need surgery. And there's like, some of the achondroplasia patients
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.
And so the question is, will this decrease change the outcome of that?
And different families will have different perspective. There are generations
of like of a chondroplasia family and they might be saying, well,
height's not the most important thing to us.
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
and other complications?
And so versus the family that has a newborn who has no experience with achondroplasia,
for them, sometimes they're coming
in with just wanting to get like any medication and to help in growth.
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
the other medical management. Remember that some of the kids,
there's a higher incidence of what we call SIDS, which is like sudden infant death syndrome.
But really, we know it happens in the babies with achondroplasia because of
the fibromyalgia stenosis.
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,
they get their sleep studies, and not just focus on the treatment.
And I just remind everybody because a lot of the families are just looking at
treatment, treatment, treatment. And then they're forgetting the regular routine
management for these kids.
And we just don't want to lose a child because we didn't do what was the routine
standard of care for achondroplasia also.
(35:58):
So this is just something to think about as new treatments emerge.
We also have to make sure that we're still doing what's important for their
routine management. And the other thing is that's really nice for some of these
conditions is now they're seeing their doctors more often.
So I think we're going to learn so much more about these conditions as we see
these kids more often because they're coming in for treatments possibly or for
(36:21):
newer drugs that may be coming.
But then we also have to help the families decide which treatment.
Do they want to be part of a clinical trial because there's several trials going
on and drugs available versus do they want to take the one that's FDA approved
so far? And so there's a lot to come.
And I think it's an exciting field, but it's also really challenging when you're
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
in maximizing bone health and quality of life.
We really need, there's so much that goes into nutrition and diet.
The cases that I've seen with, you know, parents like deciding to do vegan diet,
which is great if that's what you want to do, but making sure that they're still
getting high calcium foods with that.
(37:07):
And then the vitamin D, I know one of the things kind of thinking back,
I remember when when I was in my in Ohio, and I was in nursery,
every baby left home with vitamin D supplementation.
In DC, I don't know if that was really hot. That wasn't happening.
The nurseries weren't discharging them.
And I don't know if the lactation consultant was meeting with them before discharge
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
having newborns, whether your pediatrician asked you if you were on vitamin
D supplements while they're breastfeeding.
And I think sometimes that those are simple things. But a lot of people said
their pediatrician even asked them about did you like whether they started vitamin
D supplements, or have they were, if they were breastfeeding,
(37:49):
and if the breastfeeding mother was having enough calcium in her diet.
So like, we would I really hope that we could prevent rickets,
especially in the US where we know we have the food that and hopefully accessibility
to it with something we can do and then physical activity, right?
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
can help increase your bone density.
And then the other things, well, that's something we can have as doctors have
to decide what we're doing and how we're going to manage to optimize treatment.
But in conclusion, fractures are common in childhood and they are a major cause
of morbidity and chronic illnesses and their therapies are risk factors for osteoporosis.
(38:32):
Osteoporosis so a thorough history and physical can often
elucidate diagnosis and it starts with all of us and assessing
the assessment of osteoporosis in childhood is a
functional approach with a goal of early identification of those who are at
increased risk and there are now new emerging treatments for cell disorders
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.
So for hypophosphatasia, for example, it may be the dentist who identifies it
because the kid's losing their teeth.
And so we all play a role in making sure that we improve the skeletal health in general.
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,
as treatments improve, they're living into their 30s and 40s and 50s, maybe.
And if we don't take care of their bones, their quality of life will be affected
with that bone pain as they become adults.
So we really have to be thinking about maximizing their bone health and really
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
fractures and earlier risk of fractures in general?
And thank you. And I just wanted to give a note to Dr. Lynch,
who's been really a great mentor to me over the years and has given me a lot of opportunities.
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
a DEXA scan gives reliable results?
So I think we can do it as early as three.
Now we're doing a lot of the DEXAs. and I a
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
changes or improvement but remember DEXA is not a diagnostic tool it's just
used as an adjuvant right so it's you using it to give you more data to help
interpret what's going on.
The second question is is there information about the extreme premature population
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
in the NICU and that suddenly they fractured while they were in the NICU.
So in that, I think we have to be thinking about, are we optimizing their bone health in general?
But then there is some data about the fractures, but I think it's just variable
(41:02):
on what they have, right?
Did they have neck? Were they on TPN and other risks?
And so I think optimizing whatever we can after they get out out of the NICU
also is really, really important.
And then the ones that did not fracture in the NICU, I don't know.
I honestly don't know what data that's there.
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?
So toddlers who fracture without like any risk factors should not be hypocalcemic.
So if they are hypocalcemic, I would definitely really check a vitamin D level
and then to see why they did become hypocalcemic because they shouldn't have
(41:47):
a low calcium just because they fractured.
So there must be something underlying. So is there a vitamin D deficiency?
Rickets along with them having had a fracture itself. And then if you treat
their vitamin D deficiency, then it's also going to, it doesn't improve.
Then you want to be thinking of genetic forms because sometimes the genetic
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
still not improving and they kind of reveal themselves at that point.
Thank you. Any other questions, comments, Dr. Merchant? Okay,
there's a question by Dr. Asanasan.
Has the STOP trial looked at the difference between collaborative group protocols?
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.
The other reality is a lot of the bisphosphonate data, everybody's doing different protocols.
And even the treatments, like some people are using Zometa, some are using permidronate,
some people, when they decide to give treatments or not, there is right now,
at least in the Duchenne muscular dystrophy, there's been discussion whether
(42:56):
or not we should start treatment earlier and earlier,
because those kids are on chronic steroids and also on,
they're also on, become non-ambulatory.
And so there's discussion on whether we should give them bisphosphonates before they fracture.
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
these kids will often, you know, they don't, they're on steroids for a shorter period of time.
And so do we treat all of them or not is a different question to give them bisphosphonates or not.
I see a hand raised. Can you ask your question?
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,
you could get a vitamin D level at some point and see what it looks like and
make sure that it's above 30.
And so you may, and so it depends on, so remember, when you're getting breast,
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
just check a vitamin D level just to make sure that you're not undertreating.
Any other questions? I see a hand raised and I don't know who it is.
Can you ask your question? If you have a question.
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.
I just had an interesting case years ago.
Pre-teenage little girl with localized lumbar vertical pain.
It's just one of her lumbar vertebrae. And actually, I was a lab tech before
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
in just one of her spines.
So that's just something to consider.
The other interesting thing, I used to do physicals at Crest Haven Children's
Home, which was a residential place for mostly children with cerebral palsy
(45:18):
and severe retardation.
They all had extremely high urine-specific gravities, 1030 or more.
And what I finally found out is all these children were in diapers and they
were voluntarily restricting their P.O.
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.
And also, I did see one case with Munchausen's by proxy, which usually isn't
bone fractures, but it could be, I suppose. Thank you. Thank you.
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.
And it's happened to me more than once. I get called up for a consult on a child
with a vertebral compression fracture.
And I'm like, and if the kid's healthy, otherwise has no other health issues.
And then they find out in the end it is cancer.
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.
Welcome to Pediatrics Now, cases, updates, and discussions for the busy practitioner.
I'm your host, Holly Wayment. I work for UT Health San Antonio's Department of Pediatrics.
In this podcast, we explore how we can provide the best, most cutting-edge,
compassionate care for children.
We hope to give you a unique and behind-the-scenes edge from our expert guests.
(00:21):
After listening, click on the link on this podcast for free credit.
Music.
It is my pleasure to introduce Dr. Nadia Merchant.
Dr. Merchant is a pediatric endocrinologist and geneticist at Children's Health UT Southwestern.
She attended medical school at Weill Cornell Medical College in Qatar and completed
(00:43):
her pediatric residency at Wright State University.
She completed her genetics and pediatric endocrine fellowship at Baylor College
of Medicine, Texas Children's Hospital.
She also has served as faculty at Children's National Hospital. Hospital.
Her clinical and research interests include bone health and the intersection
of genetics and endocrinology.
She has specific interest in rickets, calcium disorders, osteoporosis in children,
(01:06):
especially Duchenne's muscular dystrophy and skeletal dysplasia.
Without further ado, please join me in welcoming Dr. Merchant.
Hi, a little bit about me. I was born and grew up in Houston,
so San Antonio has been some place that I've always come and been many times on vacation.
I moved to Saudi when I was in eighth grade.
And that really just led me to go to Cornell and Qatar and really gave me more
(01:28):
of a global experience. And some of my interests really grew from there.
And then I have had went to residency in Dayton.
And so I had a lot of my colleagues come to do fellowship in San Antonio because of the base here.
And then I went to Texas Children's. And recently, I just joined at UT Southwestern.
And it's been great so far.
So objectives today, to understand the basics of of bone health and distinguishing
(01:50):
what traumatic and pathological factors could be and the clinical diagnosis
to genetic diagnosis to now we're having rare disease treatments for bone disorders.
And my main goal is really to inspire ways to maximize bone health in all children,
especially those with disabilities and chronic health issues.
And really why? It's because bone health, the bone bank is built really early.
(02:11):
And so we can't wait. We need to start now. It starts from when a child's born.
And it really, it's really the pediatricians and all of us who make an impact
on how the quality of life these kids may live based on their bone health.
And the reason for that is that children gain about 33% of their total bone
mass just during puberty.
And most of the other is built while right before they go go into puberty.
(02:35):
So we need to think about how do we maximize their bone health and bone density.
The way it works is that you as born as an infant, and then you your bones expand,
and then you get endocortical like opposition, like to make it the peak bone mass.
And then as adults, we lose it gradually. And based on our different risk factors,
(02:57):
you will lose your bone density over time.
And so you're mostly going through an anabolic or increasing your bone density
as a child, and then it goes downhill from there.
So I like to always draw this diagram when I'm talking to parents about bone
density and the scale to risk factors, because some of these are things that
(03:17):
we can address on a regular basis in clinic with our patients.
So how do we, what do I do? For peak bone mass, how am I going to maximize it? I want a good history.
What is their diet like, their activity? what medications they're on,
have they had a history of fractures.
And then on exam, like what's their growth, puberty, their spine,
(03:40):
do they have back pain and their motor function overall.
And then just getting sometimes we'll get labs depending on whether we need
a vitamin D or not, that depends on some of the risks for the patient, and then puberty.
And so first off, I'm going to start talking about nutrition and diet.
So many of us know what Ricketts is, And it was called The Loss of Sunshine, the English Disease,
(04:03):
because at one point it was estimated that 50 to 80 percent of children in industrialized
like religion in northern Europe had rickets.
But we have really clear descriptions of rickets from the 17th century and even before that.
And it's also been noted if you
think if you've tiny Tim and Charles Dickens novel has see it probably had rickets
(04:26):
Maybe along with TV because he was described as short stature Asymmetric crippling
and curious inman weakness that would lead to his death if untreated And so
this is something that we always think of it.
I for some reason like Oh rickets is something We've really managed in the US.
We don't really see it well.
I probably see a kid at least every month.
(04:48):
And honestly, because I do bone health, I get they come to my clinic and I will
see them. But this is a typical case.
I have a two-year-old female who presents with history of walking without assistance, but limping.
Extreme bowing since she started to walk at 13 months.
And she was diagnosed by her PCP four months ago and was started on vitamin
D 2000 international units.
(05:10):
But then when I was seeing her in clinic, her diet history, she's still breastfeeding.
There's no milk or cheese in mother's diet or the patient's diet, and she's a picky eater.
And so this really, to me, was eye-opening because we were also getting admissions.
During the pandemic, we saw quite a few kids coming in with severe hypocalcemia
(05:34):
and vitamin D deficiency.
So we did a small kind of inpatient admissions to see the severity of them just
at Children's National.
And we want to know how many cases were we getting and
was this more getting more common and what
was our breakdown of our population and so
these are all kids that were admitted so they either came in with seizures or they
(05:54):
had some abnormal movements so there was something that brought them to the
hospital and that's when we got and we really our criteria was vitamin d less
than 10 and calcium less than 8 so we did and we did a chart review from 2016
to 2021 you can see that that there were increased number of cases that we saw
in 2021. And this is just a retrospective chart review.
And what were some of the risk factors? We saw that dark skin pigmentation.
(06:17):
Dairy restriction, picky eaters, vegan diet.
Breastfeeding with most not being supplemented by vitamin D.
And so these were just some of the admissions, but the length of stay for these
hot patients was four and a half days.
And majority, if you look from zero to two years, were healthy children,
(06:38):
like with no known health issues.
The older kids, yes, they had neurological issues, some of them like autism and picky eaters.
And so some of that made sense, but it didn't make sense for something that's
completely preventable.
So this is just a little bit of like eye opening thinking about like,
what can we do to prevent that simple things is making sure that once the baby's
discharged from the nursery,
(06:58):
we make sure there's vitamin D supplementation that is recommended,
especially for breastfeeding mom and talking to the breastfeeding mother that
she's having enough high calcium foods.
So just a little bit on the recommendations of daily intake, vitamin D.
So for 400 IU is what we do for the vitamin D supplementation for breastfeeding,
(07:21):
or even breastfeeding children, mostly babies, because formula is often has
enough vitamin D in there.
And then there are some patients that I would say, do I need to get a vitamin D level or not?
I think that there's always been this debate whether vitamin D level is helpful.
But if a patient's not getting enough enough vitamin D, you're just going to keep chasing after it.
And so that's where I say, unless there's a really risky population,
(07:43):
it makes sense maybe to get a vitamin D level.
But otherwise, I would just recommend looking into their diet and see,
are they getting enough?
And this is just a few foods that are high in vitamin D that you want to be thinking about.
And if you notice, majority of them are fortified.
So milk has been fortified with vitamin D. And so cod liver oil is one of those
(08:05):
that, but I mean, how many of us are walking around having cod liver oil every day?
But the majority of them don't have much vitamin D.
And, you know, the one thing about calcium intake and vitamin D,
I think the Got Milk campaign to me is a little bit eye-opening because they
noticed that in the 1990s, Americans were drinking about 0.78 cups of milk per
(08:28):
day. and they want to really boost their sales.
So they started doing a lot of the Got Milk campaign, which eventually changed
to the campaign of including like oat and other types of milk.
But what happened, if you think back historically in the 1940s,
we were fortifying milk, assuming in like juice, orange juice,
because assuming that all Americans would be drinking milk and orange juice,
(08:49):
but that trend had been gradually decreasing.
And so some of the maybe reasons we may be seeing rickets is because of that.
And I don't know, like, there's not a lot of data of how much rickets we're seeing now.
But I think the main thing is our diets have changed a little bit in what we
thought Americans were eating.
And we really need to be thinking about what the kids are having to make sure
(09:12):
they're getting enough calcium and vitamin D in their diet.
Drink your milk, kids. I don't want milk. Milk's for babies.
Yeah, babies. Oh, yeah? Well, I happen to know that milk helps build strong bones. So drink up.
Well, Mr. Miller told me he never drinks milk. Look at him. Yeah.
(09:35):
Oh, that's not good.
So that's just a little bit of... The Got Milk campaign is always a little eye-opening
for me, especially because of the data they showed.
So how do we get milk and calcium in our diet?
The recommended calcium intake is about, I always say, if you say around 1000
milligrams, but there's a little bit more needs when you're during pubertal age.
(09:59):
But if you can do about three servings of high calcium foods,
you probably will be getting enough in your diet.
And so how do we work on optimizing it? Nutrition is preferred.
And so you want to really try to get it in their diet compared to giving it
as supplementation, unless really needed.
(10:19):
And so I sometimes will find I have kids who are picky eaters,
I'll say, well, you're getting a calcium supplement for those who are higher
risk, and then gradually try to get it in your diet.
And so only take it at the end of the day, if you didn't get enough during the
day. So these are just things to think about.
And then there's some adult studies that were done on adverse cardiovascular
effects of calcium supplements.
So that's why I really try to prefer
(10:40):
doing supplementation, not supplementation, but doing it in the diet.
So now when we're talking about
rickets, we do have to always think about beyond nutritional rickets.
There are genetic forms of rickets, but what we most commonly see is the nutritional
rickets, but then there's the vitamin D dependent and vitamin D resistant rickets.
And one of the ones that I'm going to kind of go through is XLH,
(11:02):
which is X-linked hypophosphatemia, because that is one of the more common,
it's the most common form of inherited phosphate wasting and inherited form of rickets.
And so you can have short stature, lower extremity, deformity, nostril malacia.
And then the rickets, it's more severe in males as it's X-linked.
And there's other findings like you can have tooth abscesses that they may have.
(11:25):
And so one of the things that have come out is the conventional treatment was
giving phosphate multiple times a day, calcitriol and vitamin D.
And then in 2018, barazumab was approved by the FDA.
And it's a fully human monoclonal IgG1 antibody that neutralizes FGF23 and really
helps keep the phosphate levels under better control.
(11:47):
And it's really has shown to be really promising and doing well.
For my patients, especially the conventional treatment, it's phosphate several
times a day, and it's really hard to keep up.
And so some of the side effects that we were seeing, we see less of and the
the complications for those who have more severe XLH.
Otherwise, the conventional treatment does work for patients that are less severe.
(12:09):
And this is just something from one of the newer treatments out there that are available.
Obviously, it's expensive, but it is really been life-changing for some of these families.
So now I'm going to talk about the skeletal risk factors more physical activity.
And the way I always say is like, we need our mechanosensors to tell our bones
build bone and so your bone density is really built by the response to kind
(12:37):
of activity so if you have high impact weight bearing the other day because
of this you know you ever yeah.
So dose response to activity is like you have, just depending on where you are
in mobility and how much you're walking, you are going to build stronger bones.
And some of this has been seen in our cerebral palsy population.
(12:59):
If you have controls in cerebral palsy, they have narrower, thinner cortex.
And there's no difference in the length of their bones and their vertebral body,
but it's really that they have a thinner cortex and that probably has to do with less activity.
And they we see that
there is if you look at in this population you have
the fractures that they're having is a lot
(13:22):
higher compared to what you have in the general population and a lot of it has
has to do with the bone density and so this in cp patients are a much higher
risk for fractures the fractures for them occur disproportionately risk is more
of the lower lower extremities,
maybe with distal femur being the most common site.
(13:42):
And it can happen with just minimal traumatic fractures. So like you're with
transfers from falls from wheelchairs and standers.
And so that's some, so those are like patient populations that we think about
where we have higher risk for fractures and we need to think about how to help them.
In general, my prescription, I say for activity is really, you need to try to reach the individual.
(14:04):
So if you you have a patient who has CP, you could try to get them safely to
help ambulate a little bit with a stand or even it can help build stronger bones.
Some of the data may not be, it's not exactly being shown that it's improving
bone density everywhere.
But I think the kids who do standards for at least anecdotally,
who will not fracture or fall,
(14:26):
if we can decrease their risk, they tend to have stronger bones and less likely
to fracture than the kids who've not been on a, doing any kind of standing at all.
So we need to really recognize the risk of fractures and make sure that we're
not putting them at risk for fracturing by falling and avoid immobilization or overuse too.
And so those are some things that I think about. So pediatric osteoporosis,
(14:50):
so how do we even define it?
Because it's different than in the adult world.
In PEDS, we think about if you have one or more vertebral compression fractures
without high energy trauma or a local disease, irrespective of your BMD DEXA.
So it doesn't matter what density your bones are.
If you have achievable compression fractures, you have osteoporosis.
That's one definition. The other, you could have low bone mineral density on
(15:13):
a DEXA scan, and you have to have at least two long bone fractures by age 10 or three by the age of 19.
That means that if you've fractured in your fingers or your toes,
that does not include it.
It has to be a long bone fracture. And that's the definition for pediatric osteoporosis.
And so it's important to know that definition because that helps us to decide
(15:36):
whether we're going to do anything for these patients or not.
But fractures, what do we need to consider on our differential?
The one that you have to always think about is child physical abuse,
like abuse of any sort, because the fractures are the second most common injury
from child physical abuse. Well, first is bruising.
(15:56):
In a child that's young, an infant or less than three years of age,
20% of the fractures caused by abuse may be misdiagnosed initially as accidental
or attribute to another cause.
And about a quarter of the fractures in children younger than one are caused by child abuse.
So it's important that we don't miss those cases.
(16:17):
We don't miss child abuse in general.
So how do you evaluate a fracture? If you want to think about for all fractures,
is it accidental or is it non-accidental?
If it's, and does the patient, could they have OI, obstetrician's imperfecta?
And do we need to further investigate that because depending on how the fall
happened does it make sense that they should fracture like that and then if
(16:41):
it's not accidental you need to be thinking about whether or not is there any
reasoning behind could it be some other genetic form but also child abuse is
always on there and so just want to be thinking about that.
And then when we're there's all there's no really distinguishing guidelines
that can help us distinguish traumatic versus pathologic fracture.
(17:01):
But in general, long bone fractures are the most common in children,
and then low trauma non-vertebral fractures.
And if you have a hip fracture, that's really, really rare. And you should always
be thinking of some underlying disease in that child.
But what do children fracture? They fracture the distal forearm,
their fingers, their clavicle, their ankle, toes, metatarsal and distal humerus,
(17:24):
but less likely are going to be like vertebral fractures, ribs, the skull.
And so some of these sometimes can help you decide whether or not you think
it's a child abuse or not, or other risks that you like other types of things that might be going on.
In specifically child abuse, one of the common fractures we may see are the
classic metaphysial lesions of the distal tibia.
(17:46):
So which you only can see them for a few days and because they heal pretty fast often.
So if you don't get that x-ray, you may miss it if you do it two weeks later.
And these fractures are thought to occur because of the torsional,
like, tractional shearing strains that are applied across the metaphysis.
And so that pulling and twisting of the infant's extremities,
(18:06):
that's how these fractures tend to occur.
The other fractures that we think about in child abuse are the posterior rib
fractures that occur from like the way that are found with the way they hold the child itself.
And those will not initially appear right away on the x-rays.
(18:27):
And then if you do an x-ray two
weeks later, you will see those fractures appear and be much more clear.
So you have to know when you're looking for x-rays and what the timeline and
getting a a good history from the family of like when the child,
what injury happened and how it happened.
So these are just some of the specific radiologic findings in infants and toddlers for abuse.
(18:47):
But it's sometimes really hard, depending on what type of fracture and how many
they have, whether or not you can say this is abuse versus just a fracture from
a fall or some other reason.
And so I'm going to now move on to low bone marrow density and why do we develop
it, especially in which conditions.
(19:07):
So low BMD and chronic diseases, if you have chronic inflammation,
any decreased weight-bearing activity, poor nutrition, delayed puberty,
and then treatment related, they glue corticoids.
One specific condition that's on long-term steroids is going to be Duchenne muscular dystrophy.
And so we have a lot more, we understand kind of the risk for fractures for
(19:29):
in general in DMD because they're on steroids and then they become non-ambulatory
and we see them fracturing.
So what does steroids do? It disrupts bone remodeling.
So in the short term, you will have increased osteoclast survival.
So you have increased bone breakdown.
And then you get like long term,
(19:51):
you get the osteoblasts where you have decreased osteoblast survival.
So decreased bone formation. So the blue here is when the bones are forming
and osteoclasts is when you're breaking down the bone.
And remember, it's a dynamic process that's happening in children.
And the goal is that we're supposed to be having more osteoblastic kind of bone
formation and less of the breakdown.
(20:12):
And then it also, steroids affect the calcium absorption you get.
You get increased urine calcium excretion.
And then it also can suppress puberty if you're on it for a prolonged period of time.
And that's kind of one of the reasons we see a lot of side effects in children
who are on steroids for a prolonged period of time.
So the, and the bone loss occurs most rapidly in the first 12 months.
(20:36):
And what the most, what you see often is vertebral compression fractures.
And those are often going to be asymptomatic sometimes.
And so the two populations that we think about are like the steroid treated
leukemia patients and the Duchenne muscular dystrophy.
And that's why they're trying to move away from in leukemia to do less steroid
(20:57):
treatment if possible, because of the risk of fractures.
And so how do we assess vertebral fractures?
Because this is really good. If you have vertebral compression fractures, you have osteoporosis.
So we really need to be able to know how do we assess it and what do we look for?
There is a scoring that can be used to look at how much compression you're seeing
(21:21):
and looking at whether the vertebrae has decreased.
And so it's about like we have there's grade one, grade two,
grade three. And it's helpful to have that because we see a domino effect in
the vertebral compression fractures.
So if you get one, you tend to get another one and another one.
And so following those helps to see whether or not there is,
(21:42):
if there really is a compression fracture and how severe it's getting.
And then now at some places they're doing the DEXA scan, the bone density scan,
can also do a vertebral fracture assessment using the dexilateral spine view. you.
And so that is something that I think hopefully will be a lot more we can use.
So we don't have to do to like do a vertebral film along with a DEXA and screening.
(22:05):
But that is something that not all centers have been able to do.
But it's where it is, it's been really helpful to have just because sometimes
we're doing DEXAs for other reasons, and then we see notice,
and then you know, you can get a spine film.
And so how you look at that is you really, you kind of measure the distance
on both sides, and then you can see how much measurement loss that there has happened.
(22:27):
And that gives you a little bit more quantitative information to go with in a way to look at it.
So what about, what are DEXAs? It's widely available.
It's highly reproducible. And there are many factors that affect the accuracy of BMD.
So you really need to make sure if you can't try to use the same place,
the same machine, because there are some differences in each machine.
(22:50):
And it's so that's something that I think people don't really appreciate enough.
But if you've got a deck set one place, you want to try to use the same deck
set can, it's really inexpensive, and it's really low radiation.
So it's and it's fast. And so that's why decks are really helpful.
It gives me more quantitative data.
And the sites that we do depends on the child and the age.
(23:12):
And if we can't do a full whole body, because they have any kind metal,
then we can do certain sites.
And you can follow along, especially for those who are on some sort of treatment.
And what DEXA does is it uses, it's like, it uses x-ray at two photon densities
to distinguish between soft tissue and bone.
And it gives you like an estimated bone mineral density by outlining the bone itself.
(23:35):
And then, but you want to make sure that you're using a pediatric algorithm
and norms in the machine because the adults, they, it's a different algorithm
that's used differently compared to children.
And you want to, and just remember, it's still a 2D. It's not a 3D measurement.
So it doesn't give you the bone depth.
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,
don't be using the T-score.
The T-score is what they use in adults.
And it's a standard deviation compared to young adults at peak bone mass.
And so that's not helpful because obviously in kids, you're building more bone
density. So your T-score is going to be off.
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
so if you send them to an adult facility to get a dexa they sometimes will
report a t-score and then you're like i what do i do with this and then you
have to figure out how to reread it and so the other thing is we do height correct
you can correct for height and then sometimes they look at the bone age and
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?
So those are other things that we can look at.
And remember, it's really a helpful tool to add on to your evaluation.
It's not used as a diagnostic tool.
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
to have a BMDZ score that is normal.
And so that's why we don't really use it always to just say this patient has osteoporosis or not.
It really just gives you a rough idea of like what is going on and whether it's
getting worse or better.
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.
And that's because obviously, I said, it's misapplication of T-scores.
But then there's inattention to the need to correct for height.
And bone age are two things that we do.
Height, because if you think about it, it gives you a BMD number.
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,
you're going to get a higher BMD.
But when you correct it for height, it's going to be a it's going to be showing that it's worse.
So it's really important that you take the height into consideration when you're
looking at the bone marrow density for these kids, because you don't want to
(26:13):
misinterpret and give them the wrong information.
So overall, in management, we have to address all the factors, right?
And how do we minimize anything we can?
So for example, especially in chronic diseases like Crohn's,
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,
well, how do we manage your underlying condition as much as we can to be able
to improve your bone density?
And then nutrition is something we can always work on in physical activity.
But that's why I say it's everybody's role in bone health.
It's not just seeing an endocrinologist or somebody who's specifically bone
health related, but it's everybody who can play a factor in making sure they
(26:56):
have built strong bones.
And then the other thing is we have really few treatments, especially in kids.
The anabolic agents really don't work. So we have like we can give estrogen
and testosterone if they have to like delay puberty to help build their bones.
And then there is bisphosphonates, which we also use in osteoporosis.
(27:17):
And bisphosphonates is a synthetic analog of pyrophosphate, and it incorporates
into the skeletal matrix.
What it does is it inhibits the osteoclastic bone resorption,
so it helps keep the bone density.
It's almost like the way I think of it is kind of like you're putting a layer
of cement on the bone so you don't keep losing that bone that you already have.
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.
There's not as many randomized control studies. there's little
a lot of anecdotal i mean a lot of like case retrospective studies
that have been done but there's some there's evidence that it is used
really for well for oi cerebral palsy to shade
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
anorexia nervosa like that is some it will not work for that so you have to
think about who you're using it for and what and And how are we using it?
Because the other thing you don't want to do is give too much bisphosphonates.
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.
And so when you have some patient who got bisphosphonates, if you look at their
x-ray, they'll have lines of each treatment that they basically receive.
And so really want to be thinking about before you just prescribe bisphosphonates,
what the long-term implications are.
It's a pretty safe drug. like the first time they get it, they can have like
(28:44):
an acute phase reaction.
They'll have fever and they may feel achy for like a day or two.
And then their calcium can kind of drop a little bit. So you want to make sure
you're monitoring them carefully.
What we do is outpatient and just make sure that their vitamin D level is good,
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
know what you're doing and you're treating, it's really helps,
especially for some of the higher risk patients.
And for OI, Osteogenesis Imperfecta will give it to like babies,
those who have severe OI. So it's done in all age groups.
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?
So there are about 425 skeletal dysplasias that have a known molecular and etiology,
and there are 461 described.
So dysplasia is, there's like, we kind of split into three.
If you look at the way they've split them up,
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
and then you have metabolic so that's when it's more
the hypophosphatemia rickets the storage disorders hypophosphatasia
those are more metabolic and then you have the ones that don't change so basically
you're born with it it stays the same dysostosis which is like cleft lip palate
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
small number of them of the total predisposed to fractures.
And so, and the reason I bring this up, because when you come think about like,
people say, oh, could it be a skill disorder?
And could they have for child abuse, for example, and majority of them don't
fracture, there's only a few that are known to cause fractures,
(30:33):
and specifically like hypophosphatasia.
So you could check some labs and see whether the outpost is low,
and then OI, and then the other ones that we have, they all of them have very
very significant clinical findings that are pretty straightforward to be able to diagnose them.
And so the majority of the skeletal dysplasia themselves don't have a higher
(30:53):
risk of fracturing itself.
So this is something to think about when we're talking about skeletal dysplasias,
and especially when it comes up with like child abuse or any other form,
but also audio differential when you're having a kid who has been fracturing a lot.
I'm going to move a little bit now to some updates on treatments,
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.
So with XLH, verazimab has helped with the, for a lot of our patients,
instead of having to do the conventional treatment, which was really having
multiple medications a day.
And then hypophosphatasia is when you have like low ALKBOS level,
you have like kind of softer bones.
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
not for every patient who has hypoplasmatasia it's more
used in the ones that have more moderate to severe
forms and depending on but it's been
really helpful and done great for patients for that but then and then the other
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
some targeted treatments that that are being studied right now.
Vazirotide is the only one that's been currently FDA approved.
There's clinical trials currently on CMP at Transcon-CMP, which is basically
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.
And that's the most common form of skeletal dysplasia.
And so what they're doing is they're working, it's kind of working in the down
signaling, a kind of, if you give CMP, P, you're inhibiting kind of the increased
chondrocyte hypertrophy and differentiation from happening.
(32:42):
And so you would hope that then the growth and everything, a lot of some of
the other complications may be less.
So this is one that's currently been FDA approved, but there are a few other
drugs that are being tried and targets.
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.
So I'm going to go through a little bit on CMP analog. So Vazirotide is the
one that's once daily. It's been approved in children.
And they use the end goal for the FDA approval, really the growth.
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,
five, six inches of growth, maybe.
And honestly, it will be only time will tell us because the FDA only approved it in 2021.
And recently in 2023
it got approved starting at birth but there's
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
that they did did show sustained improvement at least for a couple years so
far for mesuritide but the question a lot of patients will say is is only height
important in achondroplasia is that that really what we care for?
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.
But what about them needing the, they have spinal stenosis, they can have sepharomycinosis
in a sense, and then they need, and then they can also have spinal stenosis.
So those, they need surgery. And there's like, some of the achondroplasia patients
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.
And so the question is, will this decrease change the outcome of that?
And different families will have different perspective. There are generations
of like of a chondroplasia family and they might be saying, well,
height's not the most important thing to us.
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
and other complications?
And so versus the family that has a newborn who has no experience with achondroplasia,
for them, sometimes they're coming
in with just wanting to get like any medication and to help in growth.
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
the other medical management. Remember that some of the kids,
there's a higher incidence of what we call SIDS, which is like sudden infant death syndrome.
But really, we know it happens in the babies with achondroplasia because of
the fibromyalgia stenosis.
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,
they get their sleep studies, and not just focus on the treatment.
And I just remind everybody because a lot of the families are just looking at
treatment, treatment, treatment. And then they're forgetting the regular routine
management for these kids.
And we just don't want to lose a child because we didn't do what was the routine
standard of care for achondroplasia also.
(35:58):
So this is just something to think about as new treatments emerge.
We also have to make sure that we're still doing what's important for their
routine management. And the other thing is that's really nice for some of these
conditions is now they're seeing their doctors more often.
So I think we're going to learn so much more about these conditions as we see
these kids more often because they're coming in for treatments possibly or for
(36:21):
newer drugs that may be coming.
But then we also have to help the families decide which treatment.
Do they want to be part of a clinical trial because there's several trials going
on and drugs available versus do they want to take the one that's FDA approved
so far? And so there's a lot to come.
And I think it's an exciting field, but it's also really challenging when you're
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
in maximizing bone health and quality of life.
We really need, there's so much that goes into nutrition and diet.
The cases that I've seen with, you know, parents like deciding to do vegan diet,
which is great if that's what you want to do, but making sure that they're still
getting high calcium foods with that.
(37:07):
And then the vitamin D, I know one of the things kind of thinking back,
I remember when when I was in my in Ohio, and I was in nursery,
every baby left home with vitamin D supplementation.
In DC, I don't know if that was really hot. That wasn't happening.
The nurseries weren't discharging them.
And I don't know if the lactation consultant was meeting with them before discharge
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
having newborns, whether your pediatrician asked you if you were on vitamin
D supplements while they're breastfeeding.
And I think sometimes that those are simple things. But a lot of people said
their pediatrician even asked them about did you like whether they started vitamin
D supplements, or have they were, if they were breastfeeding,
(37:49):
and if the breastfeeding mother was having enough calcium in her diet.
So like, we would I really hope that we could prevent rickets,
especially in the US where we know we have the food that and hopefully accessibility
to it with something we can do and then physical activity, right?
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
can help increase your bone density.
And then the other things, well, that's something we can have as doctors have
to decide what we're doing and how we're going to manage to optimize treatment.
But in conclusion, fractures are common in childhood and they are a major cause
of morbidity and chronic illnesses and their therapies are risk factors for osteoporosis.
(38:32):
Osteoporosis so a thorough history and physical can often
elucidate diagnosis and it starts with all of us and assessing
the assessment of osteoporosis in childhood is a
functional approach with a goal of early identification of those who are at
increased risk and there are now new emerging treatments for cell disorders
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.
So for hypophosphatasia, for example, it may be the dentist who identifies it
because the kid's losing their teeth.
And so we all play a role in making sure that we improve the skeletal health in general.
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,
as treatments improve, they're living into their 30s and 40s and 50s, maybe.
And if we don't take care of their bones, their quality of life will be affected
with that bone pain as they become adults.
So we really have to be thinking about maximizing their bone health and really
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
fractures and earlier risk of fractures in general?
And thank you. And I just wanted to give a note to Dr. Lynch,
who's been really a great mentor to me over the years and has given me a lot of opportunities.
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
a DEXA scan gives reliable results?
So I think we can do it as early as three.
Now we're doing a lot of the DEXAs. and I a
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
changes or improvement but remember DEXA is not a diagnostic tool it's just
used as an adjuvant right so it's you using it to give you more data to help
interpret what's going on.
The second question is is there information about the extreme premature population
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
in the NICU and that suddenly they fractured while they were in the NICU.
So in that, I think we have to be thinking about, are we optimizing their bone health in general?
But then there is some data about the fractures, but I think it's just variable
(41:02):
on what they have, right?
Did they have neck? Were they on TPN and other risks?
And so I think optimizing whatever we can after they get out out of the NICU
also is really, really important.
And then the ones that did not fracture in the NICU, I don't know.
I honestly don't know what data that's there.
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?
So toddlers who fracture without like any risk factors should not be hypocalcemic.
So if they are hypocalcemic, I would definitely really check a vitamin D level
and then to see why they did become hypocalcemic because they shouldn't have
(41:47):
a low calcium just because they fractured.
So there must be something underlying. So is there a vitamin D deficiency?
Rickets along with them having had a fracture itself. And then if you treat
their vitamin D deficiency, then it's also going to, it doesn't improve.
Then you want to be thinking of genetic forms because sometimes the genetic
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
still not improving and they kind of reveal themselves at that point.
Thank you. Any other questions, comments, Dr. Merchant? Okay,
there's a question by Dr. Asanasan.
Has the STOP trial looked at the difference between collaborative group protocols?
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.
The other reality is a lot of the bisphosphonate data, everybody's doing different protocols.
And even the treatments, like some people are using Zometa, some are using permidronate,
some people, when they decide to give treatments or not, there is right now,
at least in the Duchenne muscular dystrophy, there's been discussion whether
(42:56):
or not we should start treatment earlier and earlier,
because those kids are on chronic steroids and also on,
they're also on, become non-ambulatory.
And so there's discussion on whether we should give them bisphosphonates before they fracture.
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
these kids will often, you know, they don't, they're on steroids for a shorter period of time.
And so do we treat all of them or not is a different question to give them bisphosphonates or not.
I see a hand raised. Can you ask your question?
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,
you could get a vitamin D level at some point and see what it looks like and
make sure that it's above 30.
And so you may, and so it depends on, so remember, when you're getting breast,
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
just check a vitamin D level just to make sure that you're not undertreating.
Any other questions? I see a hand raised and I don't know who it is.
Can you ask your question? If you have a question.
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.
I just had an interesting case years ago.
Pre-teenage little girl with localized lumbar vertical pain.
It's just one of her lumbar vertebrae. And actually, I was a lab tech before
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
in just one of her spines.
So that's just something to consider.
The other interesting thing, I used to do physicals at Crest Haven Children's
Home, which was a residential place for mostly children with cerebral palsy
(45:18):
and severe retardation.
They all had extremely high urine-specific gravities, 1030 or more.
And what I finally found out is all these children were in diapers and they
were voluntarily restricting their P.O.
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.
And also, I did see one case with Munchausen's by proxy, which usually isn't
bone fractures, but it could be, I suppose. Thank you. Thank you.
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.
And it's happened to me more than once. I get called up for a consult on a child
with a vertebral compression fracture.
And I'm like, and if the kid's healthy, otherwise has no other health issues.
And then they find out in the end it is cancer.
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):
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