Musculoskeletal Development, Health and Ageing Research (MDHAR)

Prof. LAW Sheung-wai	Prof. LAM Tsz-ping (ORCID)	Prof. CHEUNG Wing-hoi, Louis (ORCID)
Prof. WANG Huating (ORCID)	Dr. TANG Ning	Dr. HUNG Lik-hang, Alec
Prof. WONG Man-yeung, Ronald (ORCID)	Prof. LEE Yuk-wai, Wayne (ORCID)	Prof. CHOW Kwoon-ho, Simon (ORCID)
Prof. CHENG Chun-yiu, Jack (ORCID)	Prof. LEUNG Kwok-sui

Children Bone Health and Musculoskeletal Disorders During Growth

Clinical Research

Adolescent idiopathic scoliosis (AIS) is a prevalent three-dimensional spinal deformity mainly affecting adolescents during growth. Our research team is internationally recognized for defining the association between low bone mineral density (BMD) and AIS. We found that low bone mass was an important prognostic factor for curve progression to the surgical threshold and it does persist across maturity in AIS girls. In addition, we investigated bone qualities with advanced in vivo imaging and micro-imaging technologies including dual energy x-ray absorptiometry, quantitative ultrasound, quantitative computed tomography (QCT) as well as high resolution pQCT (HR-pQCT or XtremeCT). All these have significantly contributed to our understanding of the etiopathogenesis of AIS.

1)   Anthropometric, Skeletal Growth and Bone Mineral Study in AIS Girls

2)   Whole-body Sagittal Alignment

In spine surgery, it is necessary to understand the age- and gender-related reference values of whole-body sagittal alignment with the use of EOS imaging system, which serve as an important reference for spine surgeons planning deformity correction. The prevalence of adult spinal deformity (ASD) has been reported to be as high as 60 % in the elderly population. Sagittal alignment among patients with ASD plays a critical role in pain and disability, and a primary determinant on the health-related quality of life assessment. In age-related decompensated sagittal balance, the trunk often shows increased forward leaning, retroverted pelvis, extended hip and flexed knee, which suggest the activation of adaptive whole-body compensatory mechanism to maintain an economic balanced erect posture.

3)   Neuro-anatomy, Otoneurology and Radiological Advanced Computational Imaging Studies for AIS

4)   Non-ionizing Radiation Ultrasound Assessment

5)   Health-related Quality of Life (HR-QOL) Studies in AIS

HR-QOL is an important consideration when treating AIS both with braces and with surgery. Our centre is equipped with a web-based platform for self-administration of the AIS HR-QOL questionnaire, SRS-22 and SAQ, before and after operative procedures to monitor any changes in HR-QOL with surgery. HR-QOL designed for various domains of health are translated and subjected to validity and reliability testing. They relate to more specific domains which are of particular relevance when spinal appearance or other aspects of quality of life are being considered.

Basic Research

1)   Vitamin D Insufficiency in Adolescents

Adolescence is the critical period for bone mineral accretion and deserves our attention and focus as an important area for research. We are active throughout these years in carrying out researches on children bone health, calcium absorption and calcium dietary supplementation for children. Our recent studies were evaluating the Vit-D status and knowledge on Vit-D among adolescents in Hong Kong. We noted gross deficiency in knowledge on Vit-D among our adolescents and a high prevalence of Vit-D insufficiency and its association with bone parameters which are physiologic surrogates for bone health status. These will be followed by further in-depth studies into Vit-D physiology and preventive measures and therapeutic intervention for Vit-D insufficiency for the young population.

Image adopted from Cheung et al., Osteoporosis International, 2016.

2)   Bone Qualities in Normal Adolescents During Pubertal Growth

By HR-pQCT, we found that, after adjustment of age, bone area, lifestyle parameters, there is a transient phase of higher porosity at distal radius due to longer delay in trabecular bone formation and coalescence may contribute to lower bone mechanical properties and higher distal radial bone fragility in Chinese boys than girls.

Adjusted mean of porosity of total cortex and bone mechanical property at distal radius of boys (solid line) and girls (dotted line) by Tanner stage. *: p<0.05 in sex difference at that Tanner stage by ANCOVA.

Result adopted from Cheuk et al., Journal of Bone and Mineral Research, 2018.

3)   Genome-Wide Association Study and Heritability of AIS

AIS is regarded as a multi-factorial disorder with significant genetic predisposition. Genetic association study is therefore one of the principal approaches in etiology studies in AIS.

Like many common diseases such as diabetes mellitus, myocardial infarction and cancers, a proportion of AIS appears to run in families. Through a familial study in AIS, we reported the overall heritability of AIS was estimated to be 87.5±11.1%.

4)   Bone Cell Morphometric and Functional Analysis

Systemic osteopenia, defined as Z-score of BMD ≤ -1 with reference to age and gender-matched controls, was found in over 30% of AIS patients. Our clinical findings have shown that osteopenia in AIS is an important prognostic factor for curve progression. These abnormal profiles in bone density and quality are associated with a number of genetic and endocrine factors. We have previously identified that low bone mineral density in AIS was partially attributed to aberrant melatonin receptor 1B and soluble leptin receptor. Recently, our research focus is on the roles and interactions of osteocytes, osteoblasts and osteoclasts in osteopenic AIS. We examined osteocytes in AIS biopsies Vs control with state-of-art techniques, and investigate the cellular functions and genetic profiles of primary osteoblasts and osteoclasts.

Service

1)   School Screening Program for AIS in Hong Kong

Program conducted by Department of Health since 1995, our center is one of the two quaternary referral centers for treating scoliosis in Hong Kong. The prevalence of scoliosis in Hong Kong is about 2.8%.

Adopted from Luk et al., Spine, 2010.

2)   Multimedia Scoliosis Clinical Management System

A web-based Multimedia Scoliosis Clinical Management System has been developed to meet the need of handling 800 new referrals annually from screening program. More than 17,000 patient records are now recorded in the system which supports concomitant access of 100 users from various workstations linked to the network in different locations within the hospital.

3)   Bracing Treatment

We are active in providing bracing treatment for our patients including application of CAD CAM system in brace manufacturing and fitting; 3D ultrasound monitoring of brace fitting; temperature sensor to monitor the bracing compliance; and mindfulness program. The Brace Clinic is recently established for cross-disciplinary collaborative clinical research related to braces and other non-operative treatment for AIS.

4)   Surgical Treatment

Major surgery for curve correction and instrumentation in severe scoliosis patients are performed in our center. Related research on instrumentation techniques, fusion strategy, SSEP monitoring and treatment outcome are actively being carried out. We went through various stages of development in surgical strategies and instrumentation from the posterior Harrington rod, ISOLA system, CD to the latest third and fourth generation posterior pedicle screw system and anterior surgery from Zielke instrumentation, Halms-Zielke system to the recent VATS procedures (video assisted thoracoscopic surgery). Our centre also pioneered the field of computer assisted surgical modelling and navigation surgery in improving the accuracy and safety of multiple pedicle screw application in major scoliosis corrections.

5)   Health Promotion (Educational Talks, Exhibition Booth and Pamphlet)

Educational talks related to vitamin D and bone health were conducted in many primary and secondary school to increase the awareness on Vit-D and bone health through knowledge transfer and promoting healthy lifestyles to optimize Vit-D and bone health status through behavioral modification. Up to the end of 2017, more than 80,000 students, scoliotic patients and their parents have listened to our talks or video. We set up a booth to promote bone health through mini game in "Healthy Lifestyle Festival" funfair organized by The Boys' & Girls' Clubs Association of Hong Kong on 20 May 2017.

6)   Web-based Bone Health Educational Platform

It is called "健骼知多D" (http://bonehealth.ort.cuhk.edu.hk) available both in English and Chinese. It was launched available for public viewing in May-2016. The interactive website has attracted more than 6,500 visiting count.

7)   Mobile Application in Both Android and iOS System

It is available for free public download in Jun-2016 with narration in both English and Chinese languages on resource videos. About 600 downloads of mobile application was recorded.

Android version: https://play.google.com/store/apps/details?id=com.cuhk.vdp&hl=zh-TW
iOS version: https://itunes.apple.com/WebObjects/MZStore.woa/wa/viewSoftware?id=1153485574

Musculoskeletal Aging Research

Sarcopenia Research

Sarcopenia is an age-related systemic syndrome with a progressive loss of skeletal muscle mass and muscle force combined with poor physical performance. Our research team utilizes the SAMP8 animal model to investigate the changes of functional outcomes of muscle, muscle fiber cross-sectional area and myofiber type and various treatment effects. According to our report (Wong et al, Osteoporosis International, 2019, 30(3), pp. 541–553), sarcopenia is a major risk factor for osteoporotic fracture. Our mission is to utilize this accelerated ageing animal model to investigate the pathology of the disease including denervation, intramuscular fat infiltration (myosteatosis), mitochondrial dysfunction, and more. Ultimately, we target to understand the disease, to make better our strategy to tackle sarcopenia for the ultimate goal to reduce fall and fracture.

Fig.1 Muscle typing by myosin heavy chain (MHC) staining. Fiber type I (blue), fiber type IIa (green), fiber type IIb (red), fiber type IIX (black).

Fig.2 in vitro muscle physiology testing of SAMP8 mice.

Fig.3 Morphological changes of the neuromuscular junction (NMJ) in SAMP8 mice demonstrated with increased fragmentation as compared to its control strain of SAMR1.

Fig.4 Evaluation of intramuscular fat content using high-resolution peripheral micro-computed tomography (HR-pQCT, XtremeCT 1, Scanco Medical, Swiss) in skeletal muscles.

Fig.5 Evaluation of body composition, skeletal muscle mass and screening of sarcopenia in community centres to understand more of our local prevalence of sarcopenia.

Osteoporotic Fracture Healing

Osteoporotic or fragility fracture is a global health problem due to the escalating ageing population. We are interested in how fracture healing is impaired in osteoporosis, and the mechanism involved in the enhancement of its healing. Our comprehensive research program of osteoporotic fracture include in vitro cellular studies, in vivo animal studies, and clinical research projects.

Fig.1 Osteoporotic fracture rat model at the diaphyseal and metaphyseal region suitable for mechanistic studies.

Fig.2 Morphological deterioration of osteocytes and their network in osteoporotic bone may play an important role in impaired fracture healing.

Biophysical Intervention

As the ageing population in Hong Kong continues to rise, the purpose of utilizing a non-pharmaceutical biophysical intervention is to reintroduce weight-bearing exercise to physically inactive senior citizens to reduce fall risks leading to possible fractures, as well as to accelerate the healing process if a fracture really does occur.

Fig.1 Self-developed and patented technology in Low Magnitude High Frequency Vibration Therapy (LMHFV).

Fig.2 Clinical application of LMHFV platform.

Fig.3 Laboratory application of LMHFV platform.

Translational Research

As the ageing population in Hong Kong continues to rise, the purpose of utilizing a non-pharmaceutical biophysical intervention is to reintroduce weight-bearing exercise to physically inactive senior citizens to reduce fall risks leading to possible fractures, as well as to accelerate the healing process if a fracture really does occur.

Fig.1 Research subject receiving LMHFV treatment in a elderly community center.

Fig.2 Patent related to the method to produce and transmit the vibration treatment was granted, successfully licensed and commercialized for application in the over 300 community centres in Hong Kong. Its impact has been proven beyond academia!

Personalized Orthopaedics Prosthesis and Implants

Personalized Orthopaedics Prosthesis and Implants are one of the most critical breakthroughs in orthopaedics and traumatology. They can be designed with the input data of a particular skeleton contour of the patient. Personalised orthopaedic prosthesis and implants designed in the preoperative planning procedure can enhance smooth and accurate intraoperative execution.

Fig.1 Personalised prosthesis for pelvic fracture.

Fig.2 Personalised prosthesis for acetabular fracture.

Fig.3 Personalised implant for pelvic fracture.

Fig.4 Personalised implant for acetabular fracture.

Personalized Surgical Instrument

Implementation of personalized surgical instrument in orthopaedic surgeries with careful preoperative study of the fracture configuration, deformity and pathology, analysis of the surgical approach, trial reduction or osteotomy will facilitate precise intraoperative execution with satisfactory clinical outcome. Since 2013, with the establishment of the Computer Aided Surgical Modeling Laboratory (CASMLab), we have started the computer aided surgical planning and modeling service.

Fig.1 Preoperative analysis.

Fig.2 Personalised surgical instrument for corrective osteotomy.

Fig.3 Personalised surgical instrument for femoral fracture.

Fig.4 Personalised surgical instruments and bone models.

Fig.5 Patent granted for the invention of a method to manufacturing of personalized prosthesis using computer aided strategies.

Robotic Arm Assisted Surgery

Implementation of surgical robot with superior precision, rigidity and stability can minimize intraoperative surgical error to avoid unnecessary surgical accidents. We are actively participate in the research and development of surgical robot systems. We have developed two generations of surgical robots and completed more than 50 robot assisted clinical cases.

Fig.1 The 1st generation of our developed robot.

Fig.3 Surgical robot with passive-active design.

Fig.2 The 2nd generation of our developed robot.

Community Fall Prevention Campaign

http://www.no-fall.hk

Primary prevention of fragility fracture is the next upcoming challenge of our ageing society. The most effective way to reduce fracture is to reduce the risk of those who are most prone to fall and get a fracture. We have over a decade of experience in educating older people and community workers to reduce fall-risks. Working with the community is an indispensable component of our knowledge transfer effort.

Fig.1 Fall prevention talk to participating elderly volunteers.

Fig.2 Workshop on home-based muscle strengthening exercise delivered to fragility fracture patients and their carer.

Fig.3 Elastic-band exercise is an effective home-based resistance exercise for the primary prevention of sarcopenia and fall-related fractures.

Fig.4 Fall prevention talk in the community with specific focus on home risks, diet recommendations and physical activities.

Fig.5 Community older people participating at elastic-band exercise workshop delivered by the fall prevention team.

Fig.6 Fall prevention talk in the community with specific focus on home risks, diet recommendations and physical activities.