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Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="37156007">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1097/CORR.0000000000002672"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3159&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=37156007&amp;db=pubmed&amp;nlmid=0075674"
title="See full text options at Wolters Kluwer"
data-ga-category="full_text"
data-ga-action="Wolters Kluwer"
data-ga-label="37156007"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg" alt="Wolters Kluwer full text link"><span class="text">
Wolters Kluwer
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/37156007/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=37156007&amp;db=pubmed&amp;nlmid=0075674"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="37156007"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/37156007/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/37156007/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="37156007" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F37156007%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="8RF6uyvcnLJ1CaVcf81RIbkQAYSYgMsGpEpb7oYyXmwvwB12SrETcjQu82Aa9n00"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
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<h1 class="heading-title">
Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Center for Research in FOP and Related Disorders, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff">
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2
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3
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Département de Genetique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France." href="#full-view-affiliation-4" ref="linksrc=author_aff">
4
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea." href="#full-view-affiliation-5" ref="linksrc=author_aff">
5
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina." href="#full-view-affiliation-6" ref="linksrc=author_aff">
6
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo, Brazil." href="#full-view-affiliation-7" ref="linksrc=author_aff">
7
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA." href="#full-view-affiliation-10" ref="linksrc=author_aff">
10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany." href="#full-view-affiliation-11" ref="linksrc=author_aff">
11
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa." href="#full-view-affiliation-12" ref="linksrc=author_aff">
12
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#full-view-affiliation-14" ref="linksrc=author_aff">
14
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#full-view-affiliation-15" ref="linksrc=author_aff">
15
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea." href="#full-view-affiliation-5" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina." href="#full-view-affiliation-6" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo, Brazil." href="#full-view-affiliation-7" ref="linksrc=author_aff">
7
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Internal Medicine, Division of Endocrinology, Amsterdam University Medical Center, VU University Medical Center, Amsterdam, the Netherlands." href="#full-view-affiliation-8" ref="linksrc=author_aff">
8
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Rehabilitation Services Bureau, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan." href="#full-view-affiliation-9" ref="linksrc=author_aff">
9
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA." href="#full-view-affiliation-10" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany." href="#full-view-affiliation-11" ref="linksrc=author_aff">
11
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa." href="#full-view-affiliation-12" ref="linksrc=author_aff">
12
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany." href="#full-view-affiliation-13" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#full-view-affiliation-14" ref="linksrc=author_aff">
14
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#full-view-affiliation-15" ref="linksrc=author_aff">
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA." href="#full-view-affiliation-16" ref="linksrc=author_aff">
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><sup class="key">4</sup> Département de Genetique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France.</li>
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><sup class="key">5</sup> Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea.</li>
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><sup class="key">6</sup> Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.</li>
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><sup class="key">10</sup> Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA.</li>
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><sup class="key">11</sup> Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany.</li>
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><sup class="key">12</sup> Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa.</li>
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><sup class="key">13</sup> Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany.</li>
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><sup class="key">14</sup> Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland.</li>
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<h1 class="heading-title">
Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility
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<span class="authors-list-item "><span class="full-name">Carter M Lindborg</span><span class="citation-separator">&nbsp;et al.</span></span>
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<span class="authors-list-item "><a class="full-name"
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data-ga-label="Carter M Lindborg">Carter M Lindborg</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Center for Research in FOP and Related Disorders, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Mona Al Mukaddam">Mona Al Mukaddam</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Center for Research in FOP and Related Disorders, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Département de Genetique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea." href="#short-view-affiliation-5" ref="linksrc=author_aff">
5
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina." href="#short-view-affiliation-6" ref="linksrc=author_aff">
6
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo, Brazil." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Internal Medicine, Division of Endocrinology, Amsterdam University Medical Center, VU University Medical Center, Amsterdam, the Netherlands." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Rehabilitation Services Bureau, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa." href="#short-view-affiliation-12" ref="linksrc=author_aff">
12
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-14" ref="linksrc=author_aff">
14
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-15" ref="linksrc=author_aff">
15
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA." href="#short-view-affiliation-16" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Nobuhiko Haga">Nobuhiko Haga</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Rehabilitation Services Bureau, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan." href="#short-view-affiliation-9" ref="linksrc=author_aff">
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data-ga-label="Edward C Hsiao">Edward C Hsiao</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
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11
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8
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Seemann+P&amp;cauthor_id=37156007"
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data-ga-label="Petra Seemann">Petra Seemann</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Szczepanek+M&amp;cauthor_id=37156007"
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data-ga-label="Małgorzata Szczepanek">Małgorzata Szczepanek</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-14" ref="linksrc=author_aff">
14
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Tabarkiewicz+J&amp;cauthor_id=37156007"
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data-ga-label="Jacek Tabarkiewicz">Jacek Tabarkiewicz</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-15" ref="linksrc=author_aff">
15
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Pignolo+RJ&amp;cauthor_id=37156007"
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data-ga-label="Robert J Pignolo">Robert J Pignolo</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA." href="#short-view-affiliation-16" ref="linksrc=author_aff">
16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Kaplan+FS&amp;cauthor_id=37156007"
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data-ga-label="Frederick S Kaplan">Frederick S Kaplan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Center for Research in FOP and Related Disorders, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Département de Genetique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea." href="#short-view-affiliation-5" ref="linksrc=author_aff">
5
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina." href="#short-view-affiliation-6" ref="linksrc=author_aff">
6
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo, Brazil." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Internal Medicine, Division of Endocrinology, Amsterdam University Medical Center, VU University Medical Center, Amsterdam, the Netherlands." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Rehabilitation Services Bureau, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa." href="#short-view-affiliation-12" ref="linksrc=author_aff">
12
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-14" ref="linksrc=author_aff">
14
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland." href="#short-view-affiliation-15" ref="linksrc=author_aff">
15
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA." href="#short-view-affiliation-16" ref="linksrc=author_aff">
16
</a></sup></span>
</div>
</div>
<div class="affiliations">
<h3 class="title">
Affiliations
</h3>
<ul class="item-list">
<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> Department of Orthopaedic Surgery, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> The Center for Research in FOP and Related Disorders, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Department of Medicine, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Département de Genetique, Institut IMAGINE and Hôpital Universitaire Necker-Enfants Malades, Paris, France.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Division of Pediatric Orthopaedics, Seoul National University Children&#x27;s Hospital, Seoul, Republic of Korea.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Pediatrics, Pediatric Rheumatology Section, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo, Brazil.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Department of Internal Medicine, Division of Endocrinology, Amsterdam University Medical Center, VU University Medical Center, Amsterdam, the Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Rehabilitation Services Bureau, National Rehabilitation Center for Persons with Disabilities, Tokorozawa City, Japan.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Division of Endocrinology, Diabetes, and Metabolism, the Institute for Human Genetics, the Ely and Edythe Broad Institute for Regeneration Medicine, the Program in Craniofacial Biology and the Department of Medicine, University of California, San Francisco, CA, USA.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Department of Pediatrics, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Department of Orthopaedic Surgery, the University of Cape Town, Cape Town, South Africa and Department of Rheumatology, Red Cross Children&#x27;s Hospital, Cape Town, South Africa.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Institute for Experimental Endocrinology, Charite University Hospital, Berlin, Germany.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Department of Pediatrics, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland.</li>
<li data-affiliation-id="short-view-affiliation-15"
id="short-view-affiliation-15"
><sup class="key">15</sup> Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszow University, University of Rzeszow, Rzeszow, Poland.</li>
<li data-affiliation-id="short-view-affiliation-16"
id="short-view-affiliation-16"
><sup class="key">16</sup> Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.</li>
</ul>
</div>
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<strong class="current-id" title="PubMed ID">37156007</strong>
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<h2 class="title">
Abstract
</h2>
<div class="abstract-content selected"
id="eng-abstract">
<p>
<strong class="sub-title">
Background:
</strong>
Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder with episodic and progressive heterotopic ossification. Tissue trauma is a major risk factor for flareups, heterotopic ossification (HO), and loss of mobility in patients with FOP. The International Clinical Council on FOP generally recommends avoiding surgery in patients with FOP unless the situation is life-threatening, because soft tissue injury can trigger an FOP flareup. Surprisingly little is known about flareups, HO formation, and loss of mobility after fractures of the normotopic (occurring in the normal place, distinct from heterotopic) skeleton when treated nonoperatively in patients with FOP.
</p>
<p>
<strong class="sub-title">
Questions/purposes:
</strong>
(1) What proportion of fractures had radiographic evidence of union (defined as radiographic evidence of healing at 6 weeks) or nonunion (defined as the radiographic absence of a bridging callus at 3 years after the fracture)? (2) What proportion of patients had clinical symptoms of an FOP flareup because of the fracture (defined by increased pain or swelling at the fracture site within several days after closed immobilization)? (3) What proportion of patients with fractures had radiographic evidence of HO? (4) What proportion of patients lost movement after a fracture?
</p>
<p>
<strong class="sub-title">
Methods:
</strong>
We retrospectively identified 36 patients with FOP from five continents who sustained 48 fractures of the normotopic skeleton from January 2001 to February 2021, who were treated nonoperatively, and who were followed for a minimum of 18 months after the fracture and for as long as 20 years, depending on when they sustained their fracture during the study period. Five patients (seven fractures) were excluded from the analysis to minimize cotreatment bias because these patients were enrolled in palovarotene clinical trials (<a href="http://clinicaltrials.gov/show/NCT02190747" title="See in ClinicalTrials.gov">NCT02190747</a> and <a href="http://clinicaltrials.gov/show/NCT03312634" title="See in ClinicalTrials.gov">NCT03312634</a>) at the time of their fractures. Thus, we analyzed 31 patients (13 male, 18 female, median age 22 years, range 5 to 57 years) who sustained 41 fractures of the normotopic skeleton that were treated nonoperatively. Patients were analyzed at a median follow-up of 6 years (range 18 months to 20 years), and none was lost to follow-up. Clinical records for each patient were reviewed by the referring physician-author and the following data for each fracture were recorded: biological sex, ACVR1 gene pathogenic variant, age at the time of fracture, fracture mechanism, fracture location, initial treatment modality, prednisone use at the time of the fracture as indicated in the FOP Treatment Guidelines for flare prevention (2 mg/kg once daily for 4 days), patient-reported flareups (episodic inflammatory lesions of muscle and deep soft connective tissue characterized variably by swelling, escalating pain, stiffness, and immobility) after the fracture, follow-up radiographs of the fracture if available, HO formation (yes or no) as a result of the fracture determined at a minimum of 6 weeks after the fracture, and patient-reported loss of motion at least 6 months after and as long as 20 years after the fracture. Postfracture radiographs were available in 76% (31 of 41) of fractures in 25 patients and were independently reviewed by the referring physician-author and senior author for radiographic criteria of fracture healing and HO.
</p>
<p>
<strong class="sub-title">
Results:
</strong>
Radiographic healing was noted in 97% (30 of 31) of fractures at 6 weeks after the incident fracture. Painless nonunion was noted in one patient who sustained a displaced patellar fracture and HO. In seven percent (three of 41) of fractures, patients reported increased pain or swelling at or near the fracture site within several days after fracture immobilization that likely indicated a site-specific FOP flareup. The same three patients reported a residual loss of motion 1 year after the fracture compared with their prefracture status. HO developed in 10% (three of 31) of the fractures for which follow-up radiographs were available. Patient-reported loss of motion occurred in 10% (four of 41) of fractures. Two of the four patients reported noticeable loss of motion and the other two patients reported that the joint was completely immobile (ankylosis).
</p>
<p>
<strong class="sub-title">
Conclusion:
</strong>
Most fractures treated nonoperatively in individuals with FOP healed with few flareups, little or no HO, and preservation of mobility, suggesting an uncoupling of fracture repair and HO, which are two inflammation-induced processes of endochondral ossification. These findings underscore the importance of considering nonoperative treatment for fractures in individuals with FOP. Physicians who treat fractures in patients with FOP should consult with a member of the International Clinical Council listed in the FOP Treatment Guidelines ( https://www.iccfop.org ).
</p>
<p>
<strong class="sub-title">
Level of evidence:
</strong>
Level IV, therapeutic study.
</p>
</div>
</div>
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Copyright © 2023 by the Association of Bone and Joint Surgeons.
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<div class="conflict-of-interest" id="conflict-of-interest">
<h2 class="title">
Conflict of interest statement
</h2>
<div class="statement">
<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.</p>
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<div class="figures" id="figures">
<h2 class="title">
Figures
</h2>
<div class="figures-list" id="slides-container"
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<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/c1ed49cf3e04/abjs-481-2447-g001.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="624"
data-image-height="354"
data-image-alt="Fig. 1"
data-pmc-id="PMC10642855"
data-figure-id="F1">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/0a27582a6990/abjs-481-2447-g001.gif"
alt="Fig. 1" />
</a>
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<strong class="figure-label">
<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> This flow diagram shows the… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 1 </p>
</strong>
<div class="figure-caption-contents"><p> This flow diagram shows the study allocation and analysis. </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 1
</strong>
<div class="figure-caption-contents">This flow diagram shows the study allocation and analysis.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="1"
data-label-slug="fig-2">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/ec10c744e710/abjs-481-2447-g002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="620"
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data-image-alt="Fig. 2"
data-pmc-id="PMC10642855"
data-figure-id="F2">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/9cb0647cce9e/abjs-481-2447-g002.gif"
alt="Fig. 2" />
</a>
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<div class="caption-wrap">
<strong class="figure-label">
<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> These illustrative acute and postfracture… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 2 </p>
</strong>
<div class="figure-caption-contents"><p> These illustrative acute and postfracture radiographs are from two patients with FOP in… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 2
</strong>
<div class="figure-caption-contents">These illustrative acute and postfracture radiographs are from two patients with FOP in whom HO formed after nonoperative treatment of fractures of the normotopic skeleton. (<b>A</b>) A lateral radiograph of the knee of one patient shows an acute fracture of the patella (arrow) with preexisting HO anteriorly (star). (<b>B</b>) This postfracture radiograph shows nonunion of the patellar fracture (arrow), osteopenia of the preexisting HO (star), and new HO posteriorly (arrowhead). (<b>C</b>) This lateral radiograph shows the knee of a patient with open growth plates of the distal femur and proximal tibia and acute nondisplaced fracture of the proximal tibia (arrow). (<b>D</b>) Postfracture radiographs show obliteration of the previous fracture site, fracture callus (star), and abundant HO posteriorly (arrowhead).</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/41191363342b/abjs-481-2447-g003.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="672"
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data-image-alt="Fig. 3"
data-pmc-id="PMC10642855"
data-figure-id="F3">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8963/10642855/6971d6e24739/abjs-481-2447-g003.gif"
alt="Fig. 3" />
</a>
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<div class="caption-wrap">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> These illustrative acute and postfracture… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Fig. 3 </p>
</strong>
<div class="figure-caption-contents"><p> These illustrative acute and postfracture radiographs were taken in seven patients with FOP… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Fig. 3
</strong>
<div class="figure-caption-contents">These illustrative acute and postfracture radiographs were taken in seven patients with FOP in whom HO did not form after nonoperative treatment of fractures of the normotopic skeleton. (<b>A</b>) A CT image of the cervical spine in one patient shows an acute fracture (arrowhead) of the spinous process of C6 with adjacent preexisting HO (arrow). A 1-year postfracture CT image shows the fracture of the spinous process healed without additional HO. (<b>B</b>) An AP radiograph of the shoulder in another patient shows an acute fracture (arrow) of the proximal humerus with preexisting HO of the chest wall (star). A 3-month postfracture radiograph shows a fracture callus (arrowhead) without any additional HO. (<b>C</b>) An AP shoulder radiograph in another patient reveals a spiral fracture of the humeral diaphysis (arrow) with preexisting HO (star) bridging the proximal humerus to the chest wall. A 6-week postfracture radiograph reveals a bridging callus at the fracture site (arrowhead) without additional HO. (<b>D</b>) An AP radiograph of the elbow in one patient reveals a transverse fracture of the midshaft of the ulna (arrow) with preexisting ankylosis of the elbow and a screw transfixing the proximal ulna in a previously undisclosed fracture of the proximal ulna. A 6-week postfracture radiograph reveals a fracture callus bridging the ulnar fracture (arrowhead), with no new HO. (<b>E</b>) An AP radiograph of the wrist in one patient reveals torus fractures of the distal radius and ulna (arrows) with open growth plates. A postfracture radiograph reveals well-healed fractures of the radius and ulna with no new HO. (<b>F</b>) An AP radiograph reveals a spiral fracture of the tibia (arrow) and fibula (star) in one patient. A 5-month postfracture radiograph reveals an abundant fracture callus of the tibia (arrowhead) and fibula (star). (<b>G</b>) AP and lateral 5-month postfracture radiographs of the leg in another patient reveal a well-healed tibia fracture (arrow and arrowhead). The distal tibial growth plate is patent. There is incidental proximal medial osteochondroma of the tibia (star). There is no evidence of HO. No acute fracture radiographs are available.</div>
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