\documentclass[twocolumn,twoside]{article}
\makeatletter\if@twocolumn\PassOptionsToPackage{switch}{lineno}\else\fi\makeatother

\usepackage{amsfonts,amssymb,amsbsy,latexsym,amsmath,tabulary,graphicx,times,xcolor}

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Following additional macros are required to function some 
% functions which are not available in the class used.
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
\usepackage{url,multirow,morefloats,floatflt,cancel,tfrupee}
\makeatletter


\AtBeginDocument{\@ifpackageloaded{textcomp}{}{\usepackage{textcomp}}}
\makeatother
\usepackage{colortbl}
\usepackage{xcolor}
\usepackage{pifont}
\usepackage[nointegrals]{wasysym}
\urlstyle{rm}
\makeatletter

%%%For Table column width calculation.
\def\mcWidth#1{\csname TY@F#1\endcsname+\tabcolsep}

%%Hacking center and right align for table
\def\cAlignHack{\rightskip\@flushglue\leftskip\@flushglue\parindent\z@\parfillskip\z@skip}
\def\rAlignHack{\rightskip\z@skip\leftskip\@flushglue \parindent\z@\parfillskip\z@skip}

%Etal definition in references
\@ifundefined{etal}{\def\etal{\textit{et~al}}}{}


%\if@twocolumn\usepackage{dblfloatfix}\fi
\usepackage{ifxetex}
\ifxetex\else\if@twocolumn\@ifpackageloaded{stfloats}{}{\usepackage{dblfloatfix}}\fi\fi

\AtBeginDocument{
\expandafter\ifx\csname eqalign\endcsname\relax
\def\eqalign#1{\null\vcenter{\def\\{\cr}\openup\jot\m@th
  \ialign{\strut$\displaystyle{##}$\hfil&$\displaystyle{{}##}$\hfil
      \crcr#1\crcr}}\,}
\fi
}

%For fixing hardfail when unicode letters appear inside table with endfloat
\AtBeginDocument{%
  \@ifpackageloaded{endfloat}%
   {\renewcommand\efloat@iwrite[1]{\immediate\expandafter\protected@write\csname efloat@post#1\endcsname{}}}{\newif\ifefloat@tables}%
}%

\def\BreakURLText#1{\@tfor\brk@tempa:=#1\do{\brk@tempa\hskip0pt}}
\let\lt=<
\let\gt=>
\def\processVert{\ifmmode|\else\textbar\fi}
\let\processvert\processVert

\@ifundefined{subparagraph}{
\def\subparagraph{\@startsection{paragraph}{5}{2\parindent}{0ex plus 0.1ex minus 0.1ex}%
{0ex}{\normalfont\small\itshape}}%
}{}

% These are now gobbled, so won't appear in the PDF.
\newcommand\role[1]{\unskip}
\newcommand\aucollab[1]{\unskip}
  
\@ifundefined{tsGraphicsScaleX}{\gdef\tsGraphicsScaleX{1}}{}
\@ifundefined{tsGraphicsScaleY}{\gdef\tsGraphicsScaleY{.9}}{}
% To automatically resize figures to fit inside the text area
\def\checkGraphicsWidth{\ifdim\Gin@nat@width>\linewidth
	\tsGraphicsScaleX\linewidth\else\Gin@nat@width\fi}

\def\checkGraphicsHeight{\ifdim\Gin@nat@height>.9\textheight
	\tsGraphicsScaleY\textheight\else\Gin@nat@height\fi}

\def\fixFloatSize#1{}%\@ifundefined{processdelayedfloats}{\setbox0=\hbox{\includegraphics{#1}}\ifnum\wd0<\columnwidth\relax\renewenvironment{figure*}{\begin{figure}}{\end{figure}}\fi}{}}
\let\ts@includegraphics\includegraphics

\def\inlinegraphic[#1]#2{{\edef\@tempa{#1}\edef\baseline@shift{\ifx\@tempa\@empty0\else#1\fi}\edef\tempZ{\the\numexpr(\numexpr(\baseline@shift*\f@size/100))}\protect\raisebox{\tempZ pt}{\ts@includegraphics{#2}}}}

%\renewcommand{\includegraphics}[1]{\ts@includegraphics[width=\checkGraphicsWidth]{#1}}
\AtBeginDocument{\def\includegraphics{\@ifnextchar[{\ts@includegraphics}{\ts@includegraphics[width=\checkGraphicsWidth,height=\checkGraphicsHeight,keepaspectratio]}}}

\DeclareMathAlphabet{\mathpzc}{OT1}{pzc}{m}{it}

\def\URL#1#2{\@ifundefined{href}{#2}{\href{#1}{#2}}}

%%For url break
\def\UrlOrds{\do\*\do\-\do\~\do\'\do\"\do\-}%
\g@addto@macro{\UrlBreaks}{\UrlOrds}



\edef\fntEncoding{\f@encoding}
\def\EUoneEnc{EU1}
\makeatother
\def\floatpagefraction{0.8} 
\def\dblfloatpagefraction{0.8}
\def\style#1#2{#2}
\def\xxxguillemotleft{\fontencoding{T1}\selectfont\guillemotleft}
\def\xxxguillemotright{\fontencoding{T1}\selectfont\guillemotright}

\newif\ifmultipleabstract\multipleabstractfalse%
\newenvironment{typesetAbstractGroup}{}{}%

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

\usepackage[authoryear]{natbib}



\newif\ifnokeywords\nokeywordsfalse

\makeatletter\input{size10-pointfive.clo}\makeatother%
\definecolor{kwdboxcolor}{RGB}{242,242,242}
\usepackage[hidelinks,colorlinks=true,allcolors=blue]{hyperref}
\linespread{1}                 
\def\floatpagefraction{0.8}

\usepackage[paperheight=11.69in,paperwidth=8.26in,top=1in,bottom=1in,left=1in,right=.75in,headsep=24pt]{geometry}

\usepackage{multirow-custom}

\makeatletter

\def\hlinewd#1{%
  \noalign{\ifnum0=`}\fi\hrule \@height #1%
  \futurelet\reserved@a\@xhline}
\def\tbltoprule{\hlinewd{1pt}\\[-14pt]}
\def\tblbottomrule{\noalign{\vspace*{6pt}}\hline\noalign{\vspace*{2pt}}}
\def\tblmidrule{\hline\noalign{\vspace*{2pt}}}



\let\@articleType\@empty
\let\@journalDoi\@empty
\let\@journalVolume\@empty
\let\@journalIssue\@empty
\let\@crossMarkLink\@empty
\let\@receivedDate\@empty
\let\@acceptedDate\@empty
\let\@revisedDate\@empty
\let\@publishedDate\@empty
\let\@copyrightYear\@empty
\let\@firstPage\@empty
\def\articleType#1{\gdef\@articleType{#1}}
\def\journalDoi#1{\gdef\@journalDoi{#1}}
\def\crossMarkLink#1{\gdef\@crossMarkLink{#1}}
\def\receivedDate#1{\gdef\@receivedDate{#1}}
\def\acceptedDate#1{\gdef\@acceptedDate{#1}}
\def\revisedDate#1{\gdef\@revisedDate{#1}}
\def\publishedDate#1{\gdef\@publishedDate{#1}}
\def\copyrightYear#1{\gdef\@copyrightYear{#1}}
\def\journalVolume#1{\gdef\@journalVolume{#1}}
\def\journalIssue#1{\gdef\@journalIssue{#1}}
\def\firstPage#1{\gdef\@firstPage{#1}}
\let\@issuelogo\@empty%
\let\@issuelogoex\@empty%
\def\issuelogo#1{\gdef\@issuelogo{#1}}
\def\issuelogoex#1{\gdef\@issuelogoex{#1}}


\def\author#1{%
  \gdef\@author{%
    \hskip-\dimexpr(\tabcolsep)\hskip5pt%
    \parbox{\dimexpr\textwidth-1pt}%
    {\fontsize{11}{13}\selectfont\raggedright #1}%
  }%
}


\usepackage{pharmascope-abs}
\usepackage{caption}
\usepackage{lastpage}
\usepackage{fancyhdr}
\usepackage[noindentafter,explicit]{titlesec}
\usepackage{fontspec}

\setmainfont[%
BoldFont=cambriab.ttf,%
ItalicFont=CAMBRIAI.TTF,%
BoldItalicFont=CAMBRIAZ.TTF]{Cambria.ttf}
\lefthyphenmin = 3

\def\title#1{%
  \gdef\@title{%
      \vspace*{-40pt}%
       \ifx\@articleType\@empty\else{\fontsize{10}{12}\scshape\selectfont\hspace{8pt}\@articleType\hfill\mbox{}\par\vspace{2pt}}\fi%
       \minipage{\linewidth}
         \hrulefill\\[-0.7pt]%%{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}\hfill
         \mbox{~}\hspace{5pt}\parbox{.1\linewidth}{\IfFileExists{images/\@issuelogo.\@issuelogoex}{\includegraphics[width=79pt,height=61pt]{images/\@issuelogo.\@issuelogoex}}{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}}\hfill
         \fcolorbox{kwdboxcolor}{kwdboxcolor}{\parbox{.792\linewidth}{%
          \begin{center}\fontsize{17}{17}\selectfont\scshape\vskip-7pt International Journal of Research in Pharmaceutical Sciences\hfill\end{center}%
          \vspace*{-10pt}\hspace*{4pt}{\fontsize{8}{9}\selectfont Published by JK Welfare \& Pharmascope Foundation\hfill  Journal Home Page: \href{www.ijrps.com}{\color{blue}\underline{\smash{www.ijrps.com}}}}\hspace*{4pt}\mbox{}}}%
       \par\vspace*{-1pt}\rule{\linewidth}{1.3pt}%
       \endminipage%
    \par\vspace*{9.2pt}\parbox{.98\linewidth}{\linespread{.9}\raggedright\fontsize{14}{17}\selectfont #1}%
    \vspace*{-8pt}%
  }
}


\setlength{\parindent}{0pt}
\setlength{\parskip}{0.4pc plus 1pt minus 1pt}

\def\abbrvJournalTitle{Int. J. Res. Pharm. Sci.}

\fancypagestyle{headings}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
}\pagestyle{headings}

                                                         
\fancypagestyle{plain}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}%
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
  \ifx\@firstPage\@empty\else\setcounter{page}{\@firstPage}\fi
}


\def\NormalBaseline{\def\baselinestretch{1.1}}
\usepackage{textcase}
\setcounter{secnumdepth}{0}

\titleformat{\section}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{13}\selectfont}
{\thesection}
{6pt}
{\MakeTextUppercase{#1}}
[]
\titleformat{\subsection}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsection}
{6pt}
{#1}
[]
\titleformat{\subsubsection}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsubsection}
{6pt}
{#1}
[]
\titleformat{\paragraph}[block]{\NormalBaseline\filright\fontsize{10.5}{10}\selectfont}
{\theparagraph}
{6pt}
{#1}
[]
\titleformat{\subparagraph}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubparagraph}
{6pt}
{#1}
[]

\titlespacing{\section}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsubsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\paragraph}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subparagraph}{0pt}{.5\baselineskip}{.5\baselineskip}

\captionsetup[figure]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}
\captionsetup[table]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}

\def\bibyear#1{#1}
%\def\bibjtitle#1{#1}   %%Publisher request
\def\bibauand{}
\setlength\bibsep{3pt}
\setlength\bibhang{8pt}

\makeatother
\date{}


\begin{document}


\def\RunningAuthor{Abeeshna Ashok and Dhanesh Kumar K U}
\firstPage{951}
\articleType{Review Article}
\receivedDate{11 Aug 2020}
\acceptedDate{11 Sep 2020}
\revisedDate{09 Sep 2020}
\journalVolume{2020, 11 (SPL)}
\journalIssue{1}
\journalDoi{ijrps.v11iSPL1.3243}
\copyrightYear{2020}
\def\authorCount{2}
\def\affCount{1}

\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{Osteogenesis imperfecta and physical therapy: A review of recent trends during the COVID-19 pandemic}
\author{Abeeshna~Ashok\textsuperscript{*}, 
            Dhanesh~Kumar~K~U~\\[5pt]{Nitte Institute of Physiotherapy, Nitte (Deemed to be University), Mangalore-570018, Karnataka, India}}

\begin{abstract}
Osteogenesis Imperfecta (OI) is a genetic disease affecting the bones. The main feature of the disease is bone fragility and low bone density. Between 6 and 7 in 100,000 people are affected by the disease. The clinical features are painful bones, bowlegs, short stature, enlarged head, bone fractures, hearing loss, and scoliosis. It is classified into four types: I~to IV. Subgroups have been identified, whereby types V, VI, and VII are not associated with collagen mutation. Many patients experience deformities resulting in reduced mobility and difficulty to carry out daily activities. COVID-19 is defined as "a mild to severe respiratory illness that is caused by a coronavirus, is transmitted chiefly by contact with infectious material (such as respiratory droplets) or with objects or surfaces contaminated by the causative virus, and is characterized especially by fever, cough and shortness of breath and may progress to pneumonia and respiratory failure". During the lock down, OI patients suffer from reduced physical activity. Home exercise programmes/physical therapy and the number of clinical visits is also reduced. Rehabilitation sessions should include strengthening, developmental exercises, positioning, standing, and walking, whole-body vibration exercises, and aerobic exercise. Continuous physiotherapy is recognized as one of the essential conservative treatment options. A search was carried out of databases, including CINHAL, Embase, Cochrane, Pubmed, and Google Scholar. This was used to answer the following research questions: What is OI? How is it being treated? How did rehabilitation change during the COVID-19 pandemic? This is the first extensive review of research on the topic.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Congenital Bone Deformity,\newline Physical Rehabilitation,\newline Whole-Body Vibration,\newline COVID-19,\newline Physical Therapy
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Abeeshna~Ashok~\\ Phone:\ -~\\  Email:\ abeeshnaashok@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
        \vspace*{-11pt}\rule{\linewidth}{1.2pt}
        \makeatother
        
    
\section{Introduction}
Osteogenesis Imperfecta (OI) is a hereditary disorder affecting osteoblast activity of the bone. The main feature of the disease is the fragility of the bones due to low bone mass. Hence, it is also termed as `'brittle bone disease'' \unskip~\citep{881340:20288453,881340:20297485}. A large proportion of the patient population, around 15\% of the cases, has a mutation in a gene affecting bone modeling and resorption. Immobilization can reduce muscle mass and thereby, bone mass and cause low energy factors \unskip~\citep{881340:20288455}. Based on clinical criteria, there are four types of OI: I~to IV. Subgroups within the population of OI have been further identified based on the existence of collagen mutation. These patients are classified into OI types V, VI, and VII \unskip~\citep{881340:20288456}.

The disease is common in community patients and affects the strength, walking, running, and daily activities. The main treatment goals are improving the range of motion of the joints as well as increasing the strength of the muscles \unskip~\citep{881340:20288459}. Along with medical and surgical treatment, functional training of the muscle and self-care management is beneficial to provide independence and to improve quality of life. There is a need for a standardized protocol for the treatment of OI patients \unskip~\citep{881340:20288464}. ''Osteogenesis imperfecta'' means imperfect bone formation. Fractures are common and in severe cases, occur \textit{in utero}. In some individuals, the chances of fractures are minimal.

Coronavirus disease 2019 (COVID-19), primarily affecting the respiratory system, has become a threat to human health. The disease is caused by the novel coronavirus, which leads to severe acute respiratory syndrome (SARS-CoV-2). The disease was first identified in the city of Wuhan, China, and started spreading all over the world. Children are thought to be less likely to be infected, and some children show less severe symptoms. However, the death rate may be higher than expected in children as they are prone to infection due to low immunity \unskip~\citep{881340:20288460}. The best treatment practice is multi-disciplinary approach \unskip~\citep{881340:20288462,881340:20288470}. This review aims to identify the potential effects of the multi-disciplinary approach in patients with orthopaedic conditions. 

\textbf{Pathogenesis}

The pathophysiological mechanism behind OI is mutations in the genetic programming of type I~collagen. Type I~collagen the essential structural protein of the skin, bone, dentin, tendons, and sclera. Collagen is a long triple-helical molecule consisting of two \ensuremath{\alpha }1 chains and one \ensuremath{\alpha }2 chain, each possessing a different amino acid chain. The chain contains the amino acid triplet GXY, where G is glycine, X is proline and Y is hydroxyproline. The presence of glycine, a vital amino acid, is critical for the formation of the helix. Substitution of other amino acids instead of glycine disrupts the structure of the helix. This change happens in the collagen. I~chain of patients with types II, III, and IV OI. Based on the nature and location of the phenotype, symptoms can vary from mild to very severe \unskip~\citep{881340:20288458}.

\textbf{Classification}

In 1979, before molecular studies of the underlying collagen disorder, Silence and Rimoin developed the classification of the disease that is used commonly to date. This classification was based on clinical and radiologic findings and has been updated to reflect the current pathogenic understanding \unskip~\citep{881340:20288461}.

\textbf{Clinical Features}

\textbf{Facial features}

The shape of the face is triangular due to the presence of a large skull (compared to the body size), and frontal bossing is evident. A developmental deformity of the base of the skull where the upper cervical spine pushes the lower occiput into the cranial fossa is commonly connected with the basilar impression known as platybasia, which is a cardinal feature in the face. 11\% of individuals with types III and IV OI have platybasia. The teeth of the OI patient is translucent, discolored and frail. 

\textbf{Skin}

Bruising is a common symptom of connective tissue fragility.

\textbf{Hearing}

Mixed conductive and sensorineural hearing loss is a common sign. This hearing loss is prevalent among 7\% of affected children and can be seen between the ages of 5 and 9. It can progress after puberty. The cause of the initial conductive hearing loss is the fractures of the bones in the middle ear. And can be further exacerbated later by contractures and scarring of the incus. 

\textbf{Cardio-pulmonary}

The common cause of death in type II and severe type III OI is pulmonary insufficiency. Chet wall pathology and kyphoscoliosis leads to vertebral compression and causes restrictive lung disease.  Coronary artery dissection or cerebral aneurysm and valvular regurgitation have also been reported in patients with OI but are also relatively common in the general population \unskip~\citep{881340:20288461}. Patients may show a reduction in exercise tolerance and muscle strength. Patients often experience fatigue because of proximal muscle weakness and reduced peak oxygen consumption \unskip~\citep{881340:20288454,881340:20297487}.

\textbf{Musculoskeletal}

Patients with type I~OI have weakness of the ankle plantar flexors \unskip~\citep{881340:20288464}. Short stature is common in all types of OI \unskip~\citep{881340:20288461}. Mild to moderate cases are associated with scoliosis, pain, and contractures; trouble running/walking fast, and difficulty lifting heavy objects. Pain limits functional activity and thereby reduces the quality of life. Patients may also develop thoracic deformities, kyphoscoliosis or scoliosis \unskip~\citep{881340:20288463}.

\textbf{Presentation}

Symptoms can develop at any stage of life.

\textbf{Antenatally}

Ultrasound shows asymmetrical skeletal findings by 13 to 14 weeks of gestation. The diagnosis can be made based on clinical, radio logical, and DNA or protein testing. Type III is detected from 16 to 20 weeks' gestational age, and rarely type IV is detected at the 20-week scan.

\textbf{Perinatally}

Breech presentations are shared at birth due to reduced mobility or large head and small, deformed long bones. Chest complications in neonates require the assistance of ventilators. During birth, babies with OI types II and III have dark blue sclerae, triangular faces, and bowlegs. Skull radiography shows Wormian bones.

\textbf{Infancy}

Blue sclerae is the most common symptom. A detailed history, examination, and long-term follow up can help in the prognosis. 

\textbf{Early childhood}

Activity often causes long bone fractures due to deformities of the lower limbs atypical strain on the bones at this age.

\textbf{Mid-childhood to early teens}

The growth of the child is rapid. During this period, vertebral compression fractures and scoliosis are common. The surgical complications are coxa vara, basilar invagination, and protrusion acetabuli.

\textbf{Adulthood}

The chances of fractures become less as the skeletal system achieves maturity. The underlying collagen disorder and severe scoliosis lead to lung complications; one of the leading causes of mortality in OI type III. 

\textbf{Investigations}

\textbf{Genetic Testing}

There are two main types of genetic testing, namely DNA testing and protein testing. Protein analysis includes skin biopsy, and fibroblast culture helps in identifying OI type.



\begin{itemize}
  \item \relax The specimen can take from blood or screen the mutations.
\end{itemize}
  \textbf{Radiologic features}

The major radiographic features are osteopenia, bone deformities and bone fractures \unskip~\citep{881340:20288463,881340:20288457}.

\textbf{Management}

Multi-disciplinary management is most effective in OI. The multi-disciplinary team includes medical, orthopaedic, physiotherapy, and rehabilitation experts.

\textbf{Medical management}

Bisphosphonates are commonly used. These drugs 189 have anti-resorptive properties which inhibit the function of osteoclasts\unskip~\citep{881340:20288470}. Treatment with cyclical intravenous pamidronate, a second-generation bisphosphonate, has shown better results in children. Pamidronate increases the cortical thickness and bones become stronger, reducing the chances of fracture. The dosage of pamidronate is in cycles of 3 days. It is repeated every 2 to 4 months, depending on the age of the child. Pamidronate should be started in early life to help in improving ambulation \unskip~\citep{881340:20288456}.

\textbf{Surgical management}

Realignment osteotomy with rod fixation comprises the internal fixation of metal rods in severe cases, which can be performed before walking, to correct deformities. The Dubow{\textendash}Bailey telescopic rod has been the standard for several decades. Plastic braces can be used as an alternative for children with fragile bones if the bone diameter prohibits rodding. 

\textbf{Correction of spinal deformities}

From 7 years of age, scoliosis more significant than 30\ensuremath{^\circ} is present in every child with type III OI. The use of a brace is contraindicated for the correction of scoliosis, as the rib cage fails to effectively transfer the pressure of the brace to the vertebral column. This weak force transfer may worsen the existing chest deformities. Surgical correction is indicated for the treatment of curvatures of more than 45\ensuremath{^\circ}, and more than 30 {\textemdash} 35\ensuremath{^\circ} in severe forms if the bone quality allows the procedure. Posterior vertebral arthrodesis is an alternative treatment for patients. 

\textbf{Multi-disciplinary management}

OI can be managed through a multi-disciplinary approach. The team should include a physician, orthopaedic surgeon, neurosurgeon, physical therapist, occupational therapist, psychologist, speech and language therapist, dietician, and social worker. The combined approach of all these aspects gives a better result. In infants, concentrating on the positioning will minimize the risk of fracture and give good alignment and reduce the development of deformities. Handling babies in a supine position is advised. Prolonged time in a supine position can cause complications such as brachycephaly and plagiocephaly, which can be reduced by frequent head turns. The baby should be placed on their side, and when appropriate, prone. Placing the baby in these positions should be taught to the parents. Parents also should lift their baby for transportation, nappy changing, bathing, and dressing according to the therapist's instructions.

In children, aids and adaptations at home can help children achieve independence. Muscle weakness can be developed because of a sedentary lifestyle and can increase the severity of the disease. The symptoms can affect the mental status and social well-being during adolescence and increase the severity of the condition. A balanced diet and psychological support have also been shown to be beneficial \unskip~\citep{881340:20288468}.

\textbf{Physiotherapy Interventions}

The physiotherapist should follow the developmental sequence with head and trunk control first, then sitting balance and ending with ambulation. A child with good head control achieves trunk control fast and can sit independently. Following which, supported standing and ambulation with braces are achieved. Aquatic exercise should be encouraged, which is easy to perform and valuable. Long-sleeved clothing should be encouraged in the pool to add resistance to movement.

Therapists should avoid diagonal or rotational movements to avoid fractures. Neck flexion, extension, and rotation are performed in anti-gravity positions to aid head control. Trunk control can be achieved by strengthening the spinal extensors, abdominal, and lateral trunk muscles. The exercises should start in the prone position and then progress to sitting. Strengthening of the upper limbs can be achieved with push-ups on the elbow or extended arms and wheeling of the wheelchair if a manual wheelchair is tolerated. In the wheelchair, the armrests should be removed so that the arms are straight to avoid bowing of the forearm \unskip~\citep{881340:20288468}. Physiotherapy interventions for OI consist of:



\begin{itemize}
  \item \relax Development/strengthening exercises
  \item \relax Positioning
  \item \relax Standing and walking
  \item \relax Whole-body vibration
  \item \relax Exercise training program
\end{itemize}
  \textbf{Development/ strengthening exercises}

Active movement using hydrotherapy is used to assist brittle bones. When the child follows commands at the age of 2 years, proper strengthening can start with the movement against gravity. Movements should start by using straight planes, then progress to resistive exercises with weights. Shoulder flexion contractures are common in children caused by bony deformities, resulting in a limited range of motion. Dislocation of the radial heads leads to limited supination of the forearm. Some children develop Meta Carpo Phalangeal (MCP) joint contractures, perhaps to have a more extended reach. Hence, the upper-extremity range of motion, strengthening, and functional exercises play a significant role in rehabilitation.

The therapist can incorporate play activities, reaching to stretch the soft tissue around the shoulders. MCP extension contractures can be achieved with squeezing of play dough or Theraputty. Functional use gives strength to the muscles, and progress can be made with small weights added proximally. Shoulder flexion contractures limit weight-bearing on the upper extremities, which can be countered through exercises such as a push-off against a reclined parent's shoulders and chest. Progression of the strengthening program is achieved with stair climbing, walking uphill on a treadmill or land, stationary cycling, Theraband exercises, and Biodex training. Regular exercise and regular clinic visits help to develop and maintain the integrity of muscles and bones in individuals with type I~OI. Involvement in other low impacts, non-contact, leisure activities may also improve the condition \unskip~\citep{881340:20288457}.

\textbf{Positioning}

The programme should be individually tailored. Children with OI tend to build up occipital flattening and positional torticollis as well as hip abduction contracture, making it challenging to keep the child on their back on a soft surface. This problem is addressed by advising the parents to use a regular mattress with a sheepskin mat or liner. If the child is unable to tolerate it, the parent can be educated in turning the child from side to side and a prone position. Children with respiratory problems, large head size, abnormal chest configuration or fractures/ contractures of the upper limbs will have difficulty lying prone. Therefore, sandbags or towel rolls can be used to adduct hips and to hold the child in position in supine and side-lying. Lying on a small foam rubber wedge or a mostly flatted beach ball can also be tried \unskip~\citep{881340:20288468}. 

\textbf{Standing and walking}

Neck control is the first component to be achieved before standing. The degree of lower limb bowing must be treated to allow bracing in patients who are unable to stand without support. Hip knee ankle-foot orthoses (HKAFO) with a pelvic band are used for external bracing. Strengthening exercises of the lower limb with small weights can be incorporated. Bicycling, tricycling, and swimming can help to improve aerobic fitness. A small percentage of children will advance to the use of indoor walkers or crutches. Children with ankle instability should wear ankle-foot orthoses (AFO). The benefits of braces are enhanced lower limb joint alignment, reduced pelvic rotation and femoral excursion and substitution for weak glutei{\textemdash}successful intervention results in a regular gait pattern and the ability to walk earlier. Braces give confidence to children and make them more active and able to engage in strenuous physical activity \unskip~\citep{881340:20288465}.

\textbf{Whole-body vibration training (WBVT)}

The principle of whole-body vibration training relies on reflex-induced muscle contractions. In children who have achieved standing without support, the side-alternating vibration platform is used without external support. In children who are unable to stand, a select platform can be used in combination with a tilt table. The tilt angle is adjusted according to the weight-bearing ability of the child. Flexor activation of the muscles and the low levels of force applied to the body are advantages of WBVT., to improve muscle function, the Cologne Standing-and-Walking-Trainer by Galileo is used. This is a tailored tilt table combined with Galileo's whole body system. During training, the patient lies on his/her back with the feet placed on the vibrating platform. The patient elevates one foot slightly while the other foot is lowered repeatedly during the treatment session. This utilizes musculo-spinal reflexes. Depending on the position of the patient's feet on the platform, the amplitude of the vibration will vary from 0 mm at the axis of the platform to 1 cm at the edge.\unskip~\citep{881340:20297553,881340:20297554}  The frequency of the vibration can be tailored based on the patient's functional status \unskip~\citep{881340:20288465}.

\textbf{Exercise training programme}

Start with 30 sessions aimed at improvement of exercise capacity and muscle force. A duration of 45 minutes for each session is recommended. Strength training is based on completing the maximum number of repetitions possible without heavyweights (i.e. a maximum of 1 kg) to begin with, low resistance training is recommended, depending on the patient's capacity and strength assessment. Later, resistance can be increased, but not too extensively, it helps in gaining endurance. Supervised training programs are recommended for children \unskip~\citep{881340:20288454}. Recent advances in the understanding of the structure and mechanical properties of bone in children with OI helps to develop finite element (FE) models that predict fracture risk during specific activities and help in the planning of physiotherapy \unskip~\citep{881340:20288469}. An integrated system can provide better results \unskip~\citep{881340:20288466}.
    
\section{Conclusion}
The SARS CoV-2 virus may not cause problems in the pediatric population; however, the lack of an integrated system can increase mortality rates in the pediatric population. A multi-disciplinary approach is essential in this situation and needs to be addressed during the COVID-19 pandemic, requiring extensive further study. Research findings may inform a multi-disciplinary approach during the pandemic, and thereby can reduce the morbidity and mortality of OI.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.
    

\bibliographystyle{pharmascope_apa-custom}

\bibliography{\jobname}
\end{document}
