Osteoarthritis (OA) is a common degenerative disease that is ranked as the 10th largest
contributor to disabilities that has a link to higher comorbidity and excess mortality.
One of most common degenerative diseases is knee osteoarthritis (KOA). KOA is a
progressive, chronic degenerative condition that places a heavy socioeconomic burden on
healthcare systems and society. The prevalence of knee OA has sharply increased to more
than the double in the last 10 years as result of steady state in life expectancy.
KOA is a well-known as a cartilage disease that involves degradation and loss of
articular cartilage. However, OA is usually accompanied by changes in the subchondral
bone, with sclerosis, bone cyst, and osteophyte formation.
Recent studies reported that subchondral bone remodeling plays a very important role in
KOA, mediating and preceding cartilage damage. The increase in subchondral bone stiffness
decreases the ability to scatter the loading forces within the knee joint, which then
increases the force loaded on articular cartilage. Therefore, the cartilage damage and
progress of OA accelerated over time. The focus of treatment in early KOA have shifted
from the articular cartilage to the subchondral bone and become a potential therapeutic
target of various therapeutic methods.
Regarding KOA pain, accumulating evidence suggests that bottom-up vascularization from
subchondral bone plays a larger role than top-down vessel invasion originating from
synovial tissue or synovium during cartilage erosion in OA. As a result, it is a common
complaint of orthopedists that osteoarthritis pain is not associated with the
radiographic presentation. Recent work revealed a relatively weak relationship between
cartilage loss and OA joint pain.
As different approaches aimed at articular cartilage or synovial components had
inefficient results and the mechanism of bone cartilage crosstalk is gradually becoming
clear, this study will try to confirm the critical role of subchondral bone in knee
osteoarthritis and that subchondral bone could be an ideal outcome measure of
osteoarthritis treatment.
Low-intensity pulsed ultrasound (LIPUS) and extracorporeal shockwave therapy (ECSWT) are
effective as a non-invasive method in histopathological recovery with more intense sight,
ECSWT has shown effectiveness in the regression of early KOA associated with improving
the subchondral bone remodeling, decrease the number of osteophytes and it can also
increase osteocytes activity. Besides, ECSWT could alleviate chronic inflammatory
activities in the whole joint through down-regulating inflammatory cytokines.
Additionally, it was reported that application of ESWT to the subchondral bone of the
knee significantly increased bone volume and trabecular number and reduced bone porosity.
Overall, ESWT could reverse the pathology of OA progression to some extent.
Low-intensity US might influence the subchondral bone unit under joint disuse. LIUS with
its associated acoustic radiation force can alleviate subchondral bone sclerosis during
OA progression under normal joint use. In addition, if US technology combined with
bioactive compounds materials as chitosan (CS), could improve the encapsulation
efficiency of bioactive compounds whereas not only reduced the nanoparticle size but also
narrowed their size distribution, this makes US as an effective delivery of biomaterials
such as chitosan. In this context, inclusion of mixed interventions with US could improve
its effect. Therefore, this study will couple the use of US therapy with a new green
environmentally friendly material called chitosan in the form of a topical gel.
Chitosan appears as proteoglycan in the extracellular matrix (shells) of some species of
cephalopods. Chitosan's biocompatibility, gradual degradability, non-toxicity, biological
activity, anti-inflammatory properties, and antibacterial action, makes chitosan regarded
as the best material for hydrogel. Some studies used CS as intra-articular injection for
KOA and concluded that CS can promote chondrocyte proliferation, block inflammatory and
catabolic mediators. Therefore, Phonophoresis using chitosan could reduce inflammation,
limit cartilage degeneration and improve subchondral bone remodeling process.
Additionally, it is well known that confirming diagnosis of KOA is based on assessing
joint space width and this is carried out through radiography which depends on the
Kellgren-Lawrence grade (K-LG) scale. Despite K-LG scale is considered the most used
classical diagnostic tool for KO, it has several drawbacks, including its application to
the progression of diseases, its insensitivity to change, or inconsistencies in the
authors' initial descriptions. Furthermore, it is limited in how it evaluates treatment
efficacy because it mostly uses pain scores.
By looking to the adverse effects of conventional radiology, many studies had reported
the possibility of an allergic reaction, expensive costs, lengthy inspection times, and
difficulties in scanning patients with specific conditions.
Taking this into account, artificial intelligence (AI)-based approaches are starting to
be used to solve these issues as image identification, pre-operative risk assessment,
clinical decision- making, and analysis of large data sets, diagnosis, monitor, prognosis
of rheumatological diseases, identifying risk factors for complications and has the
unique ability to anticipate outcomes using patient-specific algorithms. AI plays a vital
role in the appraisal of treatment, in which key progress in the clinical practice of
rheumatology is the innovation of advanced imaging modalities.
The use of AI in orthopedics has mostly concentrated on the development of Machine
learning (ML) and deep learning (DL) on these pictures. Deep learning, which is a subset
of ML, can assist in automatic interpretation of medical images, which may increase
diagnostic accuracy and speed, flag the most urgent and critical patients for immediate
attention, reduce the amount of human error caused by fatigue and/or inexperience, lessen
the strain on medical professionals by reducing their workload, and, in general, improve
orthopedic care.
Subchondral bone-remodeling process was reported previously as an important
pathophysiology of KO whereas subchondral bone sclerosis is widely considered to be the
hallmark of OA. Texture analysis (TA) algorithm is used to detect changes in the
subchondral bone density during remodeling process. It was demonstrated encouraging
findings and the potential of automated texture analysis employing an AI algorithm as a
diagnostic tool for OA in comparison to traditional TA techniques. Bone structure value
(BSV) is considered as a maximum-likelihood estimator of OA as automated TA depends on it
in the analysis and assessment process that measures the micro-structure of the tibial
subchondral bone depends on area of interest (ROI). Consequently, the purpose of this
study is to explore the difference between ECSWT, LIUS and traditional exercises
regarding the pain reduction, functional improvement (self-reported and physical
function) and anatomical improvement of subchondral bone (trabecular tibial bone)
micro-structural changes.