Publications by authors named "Wing-Hoi Cheung"

77 Publications

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

Ann Palliat Med 2021 Mar 1. Epub 2021 Mar 1.

Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures.

Methods: In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 μg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd month, the 6th months and 1 year after treatment.

Results: Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration.

Conclusions: In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.
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http://dx.doi.org/10.21037/apm-20-2333DOI Listing
March 2021

The role of gut microbiota in bone homeostasis.

Bone Joint Res 2021 Jan;10(1):51-59

Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Aims: The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Methods: Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.

Results: A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss.

Conclusion: Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article:  2021;10(1):51-59.
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http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0273.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845471PMC
January 2021

Fibrinolysis as a target to enhance osteoporotic fracture healing by vibration therapy in a metaphyseal fracture model.

Bone Joint Res 2021 Jan;10(1):41-50

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Aims: Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Methods: A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.

Results: All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively.

Conclusion: Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article:  2021;10(1):41-50.
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http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0185.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845465PMC
January 2021

AChRs Degeneration at NMJ in Aging-Associated Sarcopenia-A Systematic Review.

Front Aging Neurosci 2020 10;12:597811. Epub 2020 Dec 10.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in patients. The endplate, the post-synaptic part of the neuromuscular junction (NMJ), occupies 0.1% of the myofiber surface area only, but is composed of millions of acetylcholine receptors (AChRs) that are efficient in binding to acetylcholine (ACh) and triggering skeletal muscle contraction. This systematic review aims to examine aging-associated alterations of post-synaptic AChRs, including morphology, function and related gene expression. A systematic literature search was conducted in PubMed, Embase and Web of Science with relevant keywords by two independent reviewers. Original pre-clinical and clinical studies regarding AChRs changes during aging with available full text and written in English were included. Information was extracted from the included studies for further review. In total, 30 articles were included. Various parameters assessing AChRs alterations by radioassay, immunofluorescence, electrophysiology and mechanical test were reported. Endplate fragmentation and denervation were common in old skeletal muscles during aging. To ensure efficient NMJ transmission and force generation, type I or IIb muscle fibers tended to have increased ACh quanta releasing after electrical stimulations, while type IIa muscle fibers tended to have stronger binding between ACh and AChRs, but the overall function of AChRs was reduced during aging. Alterations of AChRs area depended on muscle type, species and the progress of muscle atrophy and type I muscles fibers tended to demonstrate enlarging AChRs areas. Myogenic regulator factors (MRFs) can regulate the expression of AChRs subunits, while decreased MRF4 may lead to expression changes of AChRs subunits during aging. Sarcoglycan-α can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.
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http://dx.doi.org/10.3389/fnagi.2020.597811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759742PMC
December 2020

Efficacy of low-magnitude high-frequency vibration (LMHFV) on musculoskeletal health of participants on wheelchair: a study protocol for a single-blinded randomised controlled study.

BMJ Open 2020 12 15;10(12):e038578. Epub 2020 Dec 15.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, New Territories, Hong Kong

Background: Osteoporosis is an age-related disease with progressive loss of bone, leading to fragile bone. It is one of the major health issues in older adults and causes medical, social and economic impacts globally. Patients with osteoporosis have high risk of osteoporotic fractures. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical intervention providing whole-body mechanical stimulation. Previous studies showed that LMHFV is beneficial to muscle strength, postural control, balancing ability, new bone formation, spinal bone mineral density (BMD) and blood circulation. During the LMHFV treatment, older adults need to stand upright on the platform for 20 min/day. However, some physically weak elderlies with poor musculoskeletal ability cannot stand for a long period. Therefore, the design of vibration platform is modified for the disabled patients to treat at sitting position and the efficacy of LMHFV on this group of elderlies will be verified. It is hypothesised that new design of LMHFV is beneficial to wheelchair users in terms of vertebral BMD, muscle health and musculoskeletal functions.

Methods: This study is a single-blinded randomised controlled trial to investigate the effect of LMHFV on vertebral BMD, muscle health, balancing ability and functional ability in wheelchair users (mainly on wheelchair for outdoor activities). Healthy elderlies aged 65 years or above with walking difficulties and using wheelchair are eligible. Exclusion criteria are those: (1) who cannot stand and walk independently, (2) who have vibration treatment before, (3) with malignancy, (4) with acute fractures or severe osteoarthritis, (5) with cardiovascular concern such as with pacemaker in situ, (6) with chronic inflammatory conditions known to affect muscle metabolism such as rheumatoid arthritis and (7) with high frequency of physical activities, such as participants who participated in regular exercise five times a week or more. Recruited participants will be randomised to either LMHFV or control group. Participant assigned to LMHFV group will receive LMHFV (35 Hz, 0.3g (g=gravitational acceleration), 20 min/day, at least three times/week) for 6 months. The primary outcome is BMD at the lumbar spine to be assessed by dual-energy X-ray absorptiometry that is clinically recommended for the diagnosis of osteoporosis. All primary and secondary outcome assessments for all groups will be performed in the investigators' institute at baseline and 6 months post treatment.

Discussion: This study aims to investigate the effects of LMHFV on wheelchair users. The findings of this study will help to confirm the efficacy of LMHFV on vertebral BMD, muscle health, balancing ability and functional outcomes in wheelchair using elderlies. LMHFV therapy is an intervention strategy that is easy to implement at the community healthcare level or individually at home that has previously been proven to reduce fall risk and muscle strength at the lower limb. The ultimate goal is to improve their bone and muscle quality of wheelchair users, as well as enhancing their quality of life.

Trial Registration Number: ClinicalTrials.gov (NCT04180267).
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http://dx.doi.org/10.1136/bmjopen-2020-038578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745337PMC
December 2020

Inflammatory response in postmenopausal osteoporotic fracture healing.

Bone Joint Res 2020 Jul 31;9(7):368-385. Epub 2020 Jul 31.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: 2020;9(7):368-385.
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http://dx.doi.org/10.1302/2046-3758.97.BJR-2019-0300.R2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393186PMC
July 2020

Salviae miltiorrhizae radix and puerariae lobatae radix herbal formula improves circulation, vascularization and gait function in a peripheral arterial disease rat model.

J Ethnopharmacol 2021 Jan 7;264:113235. Epub 2020 Aug 7.

Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Ethnopharmacological Relevance: DG is a herbal formula, containing the root of Salvia miltiorrhiza Bunge (Danshen) and the root of Pueraria lobate (Willd.) Ohwi (Gegen), has a history of usage in China for cardiovascular protection and anti-atherosclerosis.

Aim Of The Study: The present study aims to determine the beneficial effect of DG on the hind-limb ischemia rat model which mimics peripheral arterial disease (PAD) and its vasodilative effect on isolated femoral artery.

Materials And Methods: The vasodilatory effects were assessed by contractile responses to DG in the isolated femoral artery and its underlying mechanisms were evaluated by the involvement of endothelium, potassium channel and calcium channel. For hind-limb ischemia study, treatment outcomes were assessed by evaluating hind-limb blood flow, functional limb recovery, muscle histology and angiogenesis.

Results: Our results demonstrated positive dose-dependent vasodilatory response to DG via an endothelium-independent mechanism that involved inwardly rectifying K channels and Ca channels. We also demonstrated significant improvement in blood perfusion and micro-vessel density in the ischemic limb and positive effects in functional limb recovery.

Conclusion: In conclusion, our study supported the potential use of DG as a novel treatment for symptomatic PAD.
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http://dx.doi.org/10.1016/j.jep.2020.113235DOI Listing
January 2021

Enhancement of osteoporotic fracture healing by vibration treatment: The role of osteocytes.

Injury 2020 May 21. Epub 2020 May 21.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.

The prevalence of osteoporotic fracture is high due to global aging problem. Delayed and impaired healing in osteoporotic fractures increase the socioeconomic burden significantly. Through intensive animal and clinical research in recent years, the pathogenesis of osteoporotic fracture healing is unveiled, including decreased inflammatory response, reduced mesenchymal stem cells and deteriorated angiogenesis, etc. The enhancement of osteoporotic fracture healing is important in shortening hospitalization, thus reducing related complications. Mechanical stimulation is currently the most well-accepted approach for rehabilitation of osteoporotic fracture patients. Some new interventions providing mechanical signals were explored extensively in recent years, including vibration treatment, and osteoporotic fracture healing was found to respond very well to these signals. Vibration treatment could accelerate osteoporotic fracture healing with improved callus formation, mineralization and remodeling. However, the mechanism of how osteoporotic fracture bones sense mechanical signals and relay to bone formation remains unanswered. Osteocytes are the most abundant cells in bone tissues. Cumulative evidence confirm that osteocyte is a type of mechanosensory cell and shows altered morphology and reduced cell density during aging. Meanwhile, osteocytes serve as endocrine cells to regulate bone and mineral homeostasis. However, the contribution of osteocytes in osteoporotic fracture healing is largely unknown. A recent in vivo study was conducted to examine the morphological and functional changes of osteocytes after vibration treatment in an osteoporotic metaphyseal fracture rat model. The findings demonstrated that vibration treatment induced significant outgrowth of canaliculi and altered expression of various proteins (E11, DMP1, FGF23 and sclerostin), particularly osteocyte-specific dentin matrix protein 1 (DMP1) which was greatly increased. DMP1 may play a major role in relaying mechanical signals to bone formation, which may require further experiments to consolidate. Most importantly, vibration treatment significantly increased the mineralization and accelerated the osteoporotic fracture healing in metaphyseal fracture model. In summary, osteocyte is the major cell type to sense mechanical signals and facilitate downstream healing in osteoporotic fracture bone. Vibration treatment has good potential to be translated for clinical application to benefit osteoporotic fracture patients, while randomized controlled trials are required to validate its efficacy.
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http://dx.doi.org/10.1016/j.injury.2020.05.020DOI Listing
May 2020

Elastic-band resistance exercise or vibration treatment in combination with hydroxymethylbutyrate (HMB) supplement for management of sarcopenia in older people: a study protocol for a single-blinded randomised controlled trial in Hong Kong.

BMJ Open 2020 06 30;10(6):e034921. Epub 2020 Jun 30.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Introduction: Sarcopenia is a geriatric syndrome characterised by progressive loss of skeletal muscle mass and function with risks of adverse outcomes and becomes more prevalent due to ageing population. Elastic-band exercise, vibration treatment and hydroxymethylbutyrate (HMB) supplementation were previously proven to have positive effects on the control of sarcopenia. The purpose of this study is to evaluate the effectiveness of elastic-band exercise or vibration treatment with HMB supplementation in managing sarcopenia. Our findings will provide a safe and efficient strategy to mitigate the progression of sarcopenia in older people and contribute to higher quality of life as well as improved long-term health outcomes of elderly people.

Methods And Analysis: In this single-blinded, randomised controlled trial (RCT), subjects will be screened for sarcopenia based on the Asian Working Group for Sarcopenia (AWGS) definition and 144 sarcopenic subjects aged 65 or above will be recruited. This RCT will have three groups evaluated at two time points to measure changes over 3 months-the control and the groups with combined HMB supplement and elastic-band resistance exercise or vibration treatment. Changes in muscle strength in lower extremity will be the primary outcome. Muscle strength in the upper extremity, gait speed, muscle mass (based on AWGS definition), functional performance in terms of balancing ability and time-up-and-go test and quality of life will be taken as secondary outcomes. In addition, each participant's daily activity will be monitored by a wrist-worn activity tracker. Repeated-measures analysis of variance will be performed to compare within-subject changes between control and treatment groups at two time points of pretreatments and post-treatments.

Ethics And Dissemination: The procedures have been approved by the Joint CUHK-NTEC Clinical Research Management Office (Ref. CREC 2018.602) and conformed to the Declaration of Helsinki. Results will be disseminated through peer-reviewed publications, conferences and workshops.

Trial Registration Number: NCT04028206.
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http://dx.doi.org/10.1136/bmjopen-2019-034921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328808PMC
June 2020

The Predictive Value of Sarcopenia and Falls for 2-Year Major Osteoporotic Fractures in Community-Dwelling Older Adults.

Calcif Tissue Int 2020 08 30;107(2):151-159. Epub 2020 May 30.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

To evaluate the associations of sarcopenia and previous falls with 2-year major osteoporotic fractures (MOFs) in community-dwelling older adults. Four thousand Chinese men and women ≥ 65 years recruited from Hong Kong communities were prospectively followed up. Measures of muscle mass, grip strength, gait speed and falls in the previous year were recorded at baseline, the 2nd year and the 4th year visit for each subject. The associations of fall history, sarcopenia and its components with 2-year MOFs were evaluated using generalized linear mixed models. Poor grip strength and poor gait speed were significantly associated with a higher 2-year MOFs risk, with an adjusted OR (95% CI) per one SD decrease of 1.48 (1.17, 1.87) and 1.17 (1.00, 1.36), respectively. Falls in the previous year was a significant predictor for 2-year MOFs risk, with an adjusted OR (95% CI) per one added fall of 1.85 (1.40, 2.44) in men and 1.26 (1.01, 1.58) in women. The adjusted OR (95% CI) of height adjusted appendicular lean muscle mass (ALM/height) per one SD decrease and sarcopenia for 2-year MOFs risk were 1.34 (0.87, 2.06) and 1.72 (0.92, 3.21) in men, and were 0.73 (0.57, 0.93) and 0.76 (0.39, 1.47) in women, respectively (P for interaction by gender = 0.012 and 0.017, respectively). Poor sarcopenia-related physical performance and falls in the previous year were significant predictors for 2-year MOFs in community-dwelling older adults. The predictive value of ALM by DXA for near-term fracture risk is limited and different across genders.
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http://dx.doi.org/10.1007/s00223-020-00709-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382674PMC
August 2020

A systematic review on current osteosynthesis-associated infection animal fracture models.

J Orthop Translat 2020 Jul 30;23:8-20. Epub 2020 Mar 30.

Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

Objective: Osteosynthesis-associated infection is a challenging complication post fracture fixation, burdening the patients and the orthopaedic surgeons alike. A clinically relevant animal model is critical in devising new therapeutic strategies. Our aim was to perform a systematic review to evaluate existing preclinical models and identify their applications in aspects of animal selection, bacterial induction, fracture fixation and complications.

Methods: A systematic literature research was conducted in PubMed and Embase up to February 2020. A total of 31 studies were included. Information on the animal, bacterial induction, fracture fixation, healing result and complications were extracted.

Results: Animals selected included murine (23), rabbit (6), ewe (1) and goat (1). Larger animals had enabled the use of human-sized implant, however small animals were more economical and easier in handling. was the most frequently chosen bacteria for induction. Bacterial inoculation dose ranged from 10 ​CFU. Consistent and replicable infections were observed from 10 ​CFU in general. Methods of inoculation included injections of bacterial suspension (20), placement of foreign objects (8) and pretreatment of implants with established biofilm (3). Intramedullary implants (13), plates and screws (18) were used in most models. Radiological (29) and histological evaluations (24) in osseous healing were performed. Complications such as instability of fracture fixation (7), unexpected surgical death (5), sepsis (1) and persistent lameness (1) were encountered.

Conclusion: The most common animal model is the infected open fracture internally fixated. Replicable infections were mainly from 10 ​CFU of bacteria. However, with the increase in antibiotic resistance, future directions should explore polymicrobial and antibiotic resistant strains, as these will no doubt play a major role in bone infection. Currently, there is also a lack of osteoporotic bone infection models and the pathophysiology is unexplored, which would be important with our aging population.

The Translational Potential Of This Article: This systematic review provides an updated overview and compares the currently available animal models of osteosynthesis-associated infections. A discussion on future research directions and suggestion of animal model settings were made, which is expected to advance the research in this field.
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http://dx.doi.org/10.1016/j.jot.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231979PMC
July 2020

Vibration and β-hydroxy-β-methylbutyrate treatment suppresses intramuscular fat infiltration and adipogenic differentiation in sarcopenic mice.

J Cachexia Sarcopenia Muscle 2020 04 28;11(2):564-577. Epub 2020 Jan 28.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China.

Background: Sarcopenia is an aging-induced deterioration of skeletal muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to improve muscle functions and β-hydroxy-β-methylbutyrate (HMB) to increase muscle mass and strength. Muscle-derived stem cells (MDSCs) are progenitor cells important for muscle regeneration. We hypothesized that LMHFV and HMB could retard sarcopenia by reducing fat infiltration through inhibiting adipogenesis in MDSCs.

Methods: Senescence-accelerated mouse P8 male mice were randomized into control (CTL), HMB, LMHFV (VIB), and combined (COM) groups. Interventions started at age of month 7 and assessed at 1, 2, and 3 months post-intervention by densitometry, histology, and functional tests. In vitro, MDSCs isolated from gastrocnemius of senescence-accelerated mouse P8 mice were characterized, randomized into CTL, VIB, HMB, and COM groups, and assessed by oil red O staining, mRNA, and protein expression.

Results: At 2 months post-intervention, percentage lean mass of HMB, VIB, and COM groups were significantly higher than CTL group. Twitch, tetanic, and specific tetanic forces of COM group were higher, while specific twitch force of both VIB and COM groups were higher. Grip strength of HMB, VIB, and COM groups were higher. Histologically, both VIB and COM groups presented lower oil red O area than CTL group. Type I muscle fibre in CTL group was higher than HMB, VIB, and COM groups. MDSC were detected in situ by immunofluorescence stain with stem cell antigen-1 signals confirmed with higher β-catenin expression in the COM group. The observations were also confirmed in vitro, MDSCs in the HMB, VIB, and COM groups presented lower adipogenesis vs. the CTL group. β-Catenin mRNA and protein expressions were lower in the CTL group while their relationship was further validated through β-catenin knock-down approach.

Conclusions: Our results showed that combined LMHFV and HMB interventions enhanced muscle strength and decreased percentage fat mass and intramuscular fat infiltration as compared with either treatment alone. Additive effect of LMHFV and HMB was demonstrated in β-catenin expression than either treatment in MDSCs and altered cell fate from adipogenesis to myogenesis, leading to inhibition of intramuscular lipid accumulation. Wnt/β-catenin signalling pathway was found to be the predominant regulatory mechanism through which LMHFV and HMB combined treatment suppressed MDSCs adipogenesis.
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http://dx.doi.org/10.1002/jcsm.12535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113529PMC
April 2020

Can we enhance osteoporotic metaphyseal fracture healing through enhancing ultrastructural and functional changes of osteocytes in cortical bone with low-magnitude high-frequency vibration?

FASEB J 2020 03 21;34(3):4234-4252. Epub 2020 Jan 21.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Fragility fractures are related to the loss of bone integrity and deteriorated morphology of osteocytes. Our previous studies have reported that low-magnitude high-frequency vibration (LMHFV) promoted osteoporotic fracture healing. As osteocytes are known for mechanosensing and initiating bone repair, we hypothesized that LMHFV could enhance osteoporotic fracture healing through enhancing morphological changes in the osteocyte lacuna-canalicular network (LCN) and mineralization. A metaphyseal fracture model was established in female Sprague-Dawley rats to investigate changes in osteocytes and healing outcomes from early to late phase post-fracture. Our results showed that the LCN exhibited an exuberant outgrowth of canaliculi in the osteoporotic fractured bone at day 14 after LMHFV. LMHFV upregulated the E11, dentin matrix protein 1 (DMP1), and fibroblast growth factor 23 (FGF23), but downregulated sclerostin (Sost) in osteocytes. Moreover, LMHFV promoted mineralization with significant enhancements of Ca/P ratio, mineral apposition rate (MAR), mineralizing surface (MS/BS), and bone mineral density (BMD) in the osteoporotic group. Consistently, better healing was confirmed by microarchitecture and mechanical properties, whereas the enhancement in osteoporotic group was comparable or even greater than the normal group. This is the first report to reveal the enhancement effect of LMHFV on the osteocytes' morphology and functions in osteoporotic fracture healing.
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http://dx.doi.org/10.1096/fj.201901595RDOI Listing
March 2020

A study protocol for a randomized controlled trial evaluating vibration therapy as an intervention for postural training and fall prevention after distal radius fracture in elderly patients.

Trials 2020 Jan 16;21(1):95. Epub 2020 Jan 16.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.

Background: Fractures of the distal radius are one of the most common osteoporotic fractures in elderly men and women. These fractures are a particular health concern amongst the elderly, who are at risk of fragility fractures, and are associated with long-term functional impairment, pain and a variety of complications. This is a sentinel event, as these fractures are associated with a two to four times increased risk of subsequent hip fractures in elderly patients. This is an important concept, as it is well established that these patients have an increased risk of falling. Fall prevention is therefore crucial to decrease further morbidity and mortality. The purpose of this study is to investigate the effect of low-magnitude high-frequency vibration (LMHFV) on postural stability and prevention of falls in elderly patients post distal radius fracture.

Methods: This is a prospective single-blinded randomized controlled trial. Two hundred patients will be recruited consecutively with consent, and randomized to either LMHFV (n = 100) or a control group (n = 100). The primary outcome is postural stability measured by the static and dynamic ability of patients to maintain centre of balance on the Biodex Balance System SD. Secondary outcomes are the occurrence of fall(s), the health-related quality of life 36-item short form instrument, the Timed Up and Go test for basic mobility skills, compliance and adverse events. Outcome assessments for both groups will be performed at baseline (0 month) and at 6 weeks, 3 months and 6 months time points.

Discussion: Previous studies have stressed the importance of reducing falls after distal radius fracture has occurred in elderly patients, and an effective intervention is crucial. Numerous studies have proven vibration therapy to be effective in improving balancing ability in normal patients; However, no previous study has applied the device for patients with fractures. Our study will attempt to translate LMHFV to patients with fractures to improve postural stability and prevent recurrent falls. Positive results would provide a large impact on the prevention of secondary fractures and save healthcare costs.

Trial Registration: ClinicalTrials.gov, NCT03380884. Registered on 21 December 2017.
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http://dx.doi.org/10.1186/s13063-019-4013-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966815PMC
January 2020

2020 Young Investigator Award Winner: Age- and Sex-related Normative Value of Whole-body Sagittal Alignment Based on 584 Asymptomatic Chinese Adult Population From Age 20 to 89.

Spine (Phila Pa 1976) 2020 Jan;45(2):79-87

SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Study Design: A cross-sectional radiographic study.

Objective: The aim of this study was to establish the age- and sex-related normative values of whole-body sagittal alignment in asymptomatic Chinese adult population, and to investigate the changes and possible associated compensation mechanisms across age groups.

Summary Of Background Data: Previous studies have reported normative data for sagittal spinal alignment in asymptomatic adults. However, there was a lack of comprehensive investigation on age- and sex-related normative values of whole-body sagittal alignment.

Methods: A total of 584 asymptomatic Chinese adults aged 20 to 89 years were recruited. Subjects were grouped according to age and sex. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Comparisons of sagittal parameters between sex in different age groups were performed by independent t test. Pearson correlation analysis was used to determine relationships between each parameter.

Results: Mean values of each sagittal parameter were presented based on age and sex. Thoracic kyphosis showed steady increasing trend while lumbar lordosis gradual decrease in both sexes. Pelvic tilt (PT) in males is greater than in females across all age groups with age-related gradual increase. There were significant differences between males and females from 20 to 60 years in terms of KneeFlex angle (KA) and AnkleFlex angle, but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK.

Conclusion: This study presented a comprehensive study of whole-body sagittal alignment based on a large asymptomatic population, which could serve as an age- and sex-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involves more pelvic and lower limb mechanisms for elderly people.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003187DOI Listing
January 2020

Abnormal Osteoblastic Response to Leptin in Patients with Adolescent Idiopathic Scoliosis.

Sci Rep 2019 11 20;9(1):17128. Epub 2019 Nov 20.

SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong, SAR, China.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.
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http://dx.doi.org/10.1038/s41598-019-53757-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868007PMC
November 2019

Fragility fractures and imminent fracture risk in Hong Kong: one of the cities with longest life expectancies.

Arch Osteoporos 2019 10 29;14(1):104. Epub 2019 Oct 29.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, 5/F, Lui Che Woo Clinical Sciences Building, Shatin, New Territories, Hong Kong SAR, China.

Introduction: Imminent fracture risk, or fractures within 2 years of an initial fracture, is a pressing issue worldwide. Hong Kong is a city with one of the longest life expectancies. The concern of fragility fractures and the imminent risk of a subsequent fracture is becoming a top priority. The objective of this study was to present the epidemiology of incident fragility fractures of all public acute hospitals and the imminent risk of a subsequent fracture in Hong Kong.

Methodology: This was a retrospective population-based analysis. Patient records from all acute hospitals in Hong Kong from 1 January 2004 to 31 December 2018 were retrieved for patients ≥ 50 years of age with hip, distal radius, or proximal humerus fractures. Secondary fractures and falls were identified in the subsequent 5 years. Post hoc analysis in recent 2013-2018 period was performed. Overall survival (re-fracture incidence) on age subgroups using Kaplan survival analysis and variables was compared using the log-rank test. Cox proportional hazard regressions, obtaining the hazard ratios (HR) and their respective 95% confidence intervals (CI), were used.

Results: There is an overall increasing trend of fragility fractures (hip, distal radius, proximal humerus) from 5596 in 2004 to 8465 in 2018. The average cumulative imminent risk of fractures from recent 5 years is 3.87% at 1 year and 6.50% at 2 years. 49.5% of the patients with a secondary fracture occurred within 2 years since the initial major fragility fracture. Post hoc analysis in recent 2013-2018 period (N = 7039) showed male patients were 1.21 times more likely to have further fractures with time (HR = 1.21 (1.02, 1.45), p = 0.03) compared with female patients. Patients over age 95 were 2.01 times higher than patients of age under 75 to have further fracture over time.

Conclusions: Following an initial fracture, prompt treatment strategies should be adopted to avoid imminent risk of fractures. This window of opportunity in the first 2 years is a golden period to treat osteoporosis and prevent falls. Our post hoc analysis has shown that male patients and patients older than 95 are at even higher risk. Clinicians and allied healthcare professionals should be alert on these patients.
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http://dx.doi.org/10.1007/s11657-019-0648-4DOI Listing
October 2019

Impaired Fracture Healing in Sarco-Osteoporotic Mice Can Be Rescued by Vibration Treatment Through Myostatin Suppression.

J Orthop Res 2020 02 3;38(2):277-287. Epub 2019 Oct 3.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, 5/F Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China.

Sarcopenia is highly prevalent in fragility fracture patients and is associated with delayed healing. In this study, we investigated the effect of low-magnitude high-frequency vibration (LMHFV) on osteoporotic fracture with sarcopenia and the potential role of myostatin. Osteoporotic fractures created in sarcopenic SAMP8, non-sarcopenic SAMR1 were randomized to control or LMHFV (SAMP8, SAMR1, SAMP8-V, or SAMR1-V) groups. Healing and myostatin expression were evaluated at 2, 4, and 6 weeks post-fracture. In vitro, conditioned-media were collected from myofibers isolated from aged and young SAMP8 or C2C12 myoblasts with or without LMHFV. Osteoblastic MC3T3-E1 under osteogenic differentiation were treated with plain or conditioned-medium (±myostatin propeptide). LMHFV significantly enhanced callus formation was in non-sarcopenic SAMR1 mice; but the enhancement effect was not significant in SAMP8 mice at week 2. Myostatin expressions in callus and biceps femoris of SAMP8 group were significantly higher all groups with significant negative correlation with callus size (R  = 0.7256; p = 0.0004). Mechanical properties (week 4) and callus remodeling (week 6) were inferior in SAMP8 versus SAMR1 and were significantly enhanced by LMHFV. Alkaline Phosphatase (ALP) and Runx2 expression of MC3T3-E1 was lower in aged myofiber compared with young, but upregulated by LMHFV or myostatin inhibition; also confirmed with C2C12. LMHFV enhanced early callus formation, microarchitecture, callus remodeling and mechanical properties of fracture healing in both SAMP8 and SAMR1; however, more effective in non-sarcopenic SAMR1 mice. Impaired fracture healing in sarcopenic SAMP8 mice is attributed by elevated myostatin expression in callus and muscle, which correlated negatively with callus formation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:277-287, 2020.
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http://dx.doi.org/10.1002/jor.24477DOI Listing
February 2020

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility.

Sci Signal 2019 08 13;12(594). Epub 2019 Aug 13.

School of Biological Sciences, The University of Hong Kong, 6N01 Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong.

The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance.
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http://dx.doi.org/10.1126/scisignal.aau1468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219567PMC
August 2019

One-year mortality in displaced intracapsular hip fractures and associated risk: a report of Chinese-based fragility fracture registry.

J Orthop Surg Res 2018 Sep 14;13(1):235. Epub 2018 Sep 14.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, 5/F, Clinical Sciences Building, Shatin, New Territories, Hong Kong, SAR, China.

Background: The purpose of this registry-based retrospective study was to investigate the risk factors related to one-year mortality in displaced intracapsular fragility hip fracture patients.

Methods: Patients were screened from the Fragility Fracture Registry. Inclusion criterion was displaced intracapsular hip fracture patients with atypical or pathological fractures excluded. One-year mortality was investigated against risk factors including age, gender, past medical history, pre-fracture mobility (PFM), pre-operation ASA grade, delayed surgery over 48 h, post-surgical complications, and length of stay at acute orthopedic ward (LOS).

Results: A total of 1050 patients were included for further analysis. Gross one-year mortality was 14.9%. One-year mortality was significantly higher in patients who received non-operative treatment and those who received surgery but delayed over 48 h after admission (both p <  0.001). Male gender (OR = 2.708), advanced age (OR = 1.359), higher risk ASA grades (III to V) (OR = 1.990), past history of gastrointestinal disease (OR = 1.671), and renal impairment (OR = 1.984) were related to higher one-year mortality. The mortality of patients in PFM grade 3 and LOS group 3 was significantly higher (OR = 2.240 and 1.722, respectively).

Conclusions: Higher age, male gender, past gastrointestinal disease and renal impairment, ASA grade over 3, indoor confined pre-fracture ambulatory, and stay at hospital over 15 days were risk factors related to higher one-year mortality in surgically treated displaced intracapsular hip fracture patients. A multi-disciplinary approach is advised to patients identified with these risks factors and co-managed by orthopedic surgeons, geriatricians, and fracture liaison nurses.
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http://dx.doi.org/10.1186/s13018-018-0936-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137732PMC
September 2018

Global sagittal alignment in elderly patients with osteoporosis and its relationship with severity of vertebral fracture and quality of life.

Arch Osteoporos 2018 09 7;13(1):95. Epub 2018 Sep 7.

Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.

We compared global sagittal alignment and quality of life in osteoporotic patients with and without vertebral compression fracture (VCF) and determined its relationship with VCF severity. The findings revealed osteoporotic patients with VCF showed decreased quality of life and worse global sagittal alignment, which was significantly associated with VCF severity.

Introduction: The aim of this study was to compare the global sagittal alignment and quality of life in elderly osteoporotic patients with and without vertebral compression fracture (VCF), and to investigate the relationship between global sagittal alignment and severity of VCF.

Methods: A consecutive series of 72 female patients with osteoporosis aged over 60 years and 31 age-matched females without osteoporosis were prospectively enrolled. The patients were divided into VCF and non-VCF group. Patient's clinical demography, nature of VCF, and bone mineral density (BMD) were also recorded. Spinal deformity index was used to evaluate severity of VCF. EOS® biplanar imaging system was then used to evaluate global sagittal parameters: T1 pelvic angle (TPA) and global sagittal angle (GSA). In addition, quality of life was assessed with self-reported questionnaires: the Oswestry Disability Index (ODI) and Short-form 12 (SF-12).

Results: Osteoporotic patients and controls were found to be significantly different in terms of TPA, GSA, and BMD. And in patients with VCF, they were found to have significantly higher TPA and GSA. TPA and GSA were significantly correlated with SF-12 and ODI. The number of VCF and SDI significantly correlated with global sagittal alignment. Using regression analysis, parameters significantly associated with abnormal global alignment were the number of VCF (OR = 1.13) and SDI (OR = 1.84).

Conclusion: Osteoporotic patients with VCF showed worse global sagittal alignment and decreased quality of life. The number and severity of VCF had a negative influence on global sagittal balance, which indicates that poorer sagittal global alignment may imply worse quality of life and more severe VCF.
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http://dx.doi.org/10.1007/s11657-018-0512-yDOI Listing
September 2018

Ultrasound as a stimulus for musculoskeletal disorders.

J Orthop Translat 2017 Apr 5;9:52-59. Epub 2017 Apr 5.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Ultrasound is an inaudible form of acoustic sound wave at 20 kHz or above that is widely used in the medical field with applications including medical imaging and therapeutic stimulation. In therapeutic ultrasound, low-intensity pulsed ultrasound (LIPUS) is the most widely used and studied form that generally uses acoustic waves at an intensity of 30 mW/cm, with 200 ms pulses and 1.5 MHz. In orthopaedic applications, it is used as a biophysical stimulus for musculoskeletal tissue repair to enhance tissue regeneration. LIPUS has been shown to enhance fracture healing by shortening the time to heal and reestablishment of mechanical properties through enhancing different phases of the healing process, including the inflammatory phase, callus formation, and callus remodelling phase. Reports from studies reveal insights in the mechanism through which acoustic stimulations activate cell surface integrins that, in turn, activate various mechanical transduction pathways including FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), PI3K, and Akt. It is then followed by the production of cyclooxygenase 2 and prostaglandin E2 to stimulate further downstream angiogenic, osteogenic, and chondrogenic cytokines, explaining the different enhancements observed in animal and clinical studies. Furthermore, LIPUS has also been shown to have remarkable effects on mesenchymal stem cells (MSCs) in musculoskeletal injuries and tissue regeneration. The recruitment of MSCs to injury sites by LIPUS requires the SDF-1 (stromal cell derived factor-1)/CXCR-4 signalling axis. MSCs would then differentiate differently, and this is regulated by the presence of different cytokines, which determines their fates. Other musculoskeletal applications including bone-tendon junction healing, and distraction osteogenesis are also explored, and the results are promising. However, the use of LIPUS is controversial in treating osteoporosis, with negative findings in clinical settings, which may be attributable to the absence of an injury entry point for the acoustic signal to propagate, strong attenuation effect of cortical bone and the insufficient intensity for penetration, whereas in some animal studies it has proven effective.
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http://dx.doi.org/10.1016/j.jot.2017.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822964PMC
April 2017

Inflammation and age-associated skeletal muscle deterioration (sarcopaenia).

J Orthop Translat 2017 Jul 3;10:94-101. Epub 2017 Jun 3.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Ageing is accompanied by chronic inflammatory responses due to elevated circulatory inflammatory cytokine production. Several inflammatory cytokines have been shown to be responsible for a decrease in muscle mass. However, little is known about the possible relationship between inflammation and sarcopaenia. This review aims to summarise the existing evidence about inflammation and sarcopaenia. Sarcopaenia is defined as an age-related decrease of muscle mass and/or muscle strength; it is caused by multiple factors, such as skeletal muscle atrophy, neuromuscular junction degeneration, hormone imbalance, cytokine imbalance, protein synthesis and proteolysis. Several inflammatory cytokines have been considered to promote muscle loss; C-reactive protein levels are significantly upregulated in sarcopaenia and sarcopenic obesity, and high levels of interleukin-6 are associated with reduced muscle mass and muscle strength (the administration of interleukin-6 could lead to a reduction in muscle mass). Up-regulation of tumour necrosis factor-α expression is also related to the development of sarcopaenia. Signalling pathways, such as protein kinase B/mammalian target of rapamycin, Janus kinase/signal transducer and activator of transcription-5 and signal transducer and activator of transcription 3 signalling, involved in muscle metabolism are regulated by insulin-like growth factor-1, tumour necrosis factor-α and interleukin-6 respectively. In conclusion, the inflammatory cytokines produced during chronic inflammation due to ageing, may influence their respective related pathways, thus leading to age-related muscle deterioration.

The Translational Potential Of This Article: This review can provide more information for sarcopaenia medicine research in terms of anti-inflammation therapy.
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http://dx.doi.org/10.1016/j.jot.2017.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822997PMC
July 2017

Evaluation of a multidisciplinary rehabilitation programme for elderly patients with hip fracture: A prospective cohort study.

J Rehabil Med 2018 Feb;50(3):285-291

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, N/A Hong Kong, Hong Kong.

Objective: To investigate the effectiveness and cost of an 18-month multi-disciplinary Comprehensive Fragility Fracture Management Program (CFFMP) for fragility hip fracture patients.

Design: Prospective cohort study.

Patients: Elderly patients with hip fracture were recruited at their first postoperative follow-up in 2 district hospitals. The intervention group comprised patients from the hospital undergoing CFFMP, and the control group comprised patients from another hospital undergoing conventional care. CFFMP provided geri-orthopaedic co-management, physician consultations, group-exercise and vibration-therapy. Timed-up-and-go test (TUG), Elderly Mobility Scale (EMS), Berg Balance Scale (BBS) and fall risk screening (FS) were used to assess functional performance. Incidences of falls and secondary fractures, the cost of the programme and related healthcare resources were recorded.

Results: A total of 76 patients were included in the intervention group (mean age 77.9 years ((standard deviation; SD) 6.1) ) and 77 in the control group (79.9 (SD 7.2)), respectively. The re-fracture rate in the control group (10.39%) was significantly higher than in the intervention group (1.32%) (p = 0.034). The intervention group improved significantly in TUG, EMS and FS after a 1-year programme. The overall healthcare costs per patient in the intervention and control groups were US$22,450 and US$25,313, respectively.

Conclusion: Multi-disciplinary CFFMP is effective, with reduced overall cost, reduced length of hospital stay and reduced secondary fracture rate. The rehabilitation community service favours rehabilitation and improved quality of life of hip fracture patients.
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http://dx.doi.org/10.2340/16501977-2310DOI Listing
February 2018

Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation.

Sci Rep 2017 09 14;7(1):11631. Epub 2017 Sep 14.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.
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http://dx.doi.org/10.1038/s41598-017-11934-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599683PMC
September 2017

An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8).

Exp Gerontol 2017 10 12;97:1-8. Epub 2017 Jul 12.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People's Republic of China. Electronic address:

Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia.
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http://dx.doi.org/10.1016/j.exger.2017.07.008DOI Listing
October 2017

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

Exp Anim 2017 Aug 11;66(3):259-269. Epub 2017 Apr 11.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, P.R. China.

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.
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http://dx.doi.org/10.1538/expanim.17-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543247PMC
August 2017

Value of Measuring Bone Microarchitecture in Fracture Discrimination in Older Women with Recent Hip Fracture: A Case-control Study with HR-pQCT.

Sci Rep 2016 Sep 27;6:34185. Epub 2016 Sep 27.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.

We aimed to determine whether loss of volumetric bone mineral density (vBMD) and deterioration of microarchitecture imaged by high-resolution peripheral quantitative computed tomography at the distal radius/tibia provided additional information in fracture discrimination in postmenopausal women with recent hip fracture. This case-control study involved 24 postmenopausal Chinese women with unilateral femoral neck fracture (average [SD] age: 79.6[5.6]) and 24 age-matched women without any history of fracture. Each SD decrease in T-score at femoral neck (FN) was associated with a higher fracture risk (odds ratio: 6.905, p = 0.001). At the distal radius, fracture women had significantly lower total vBMD (-17.5%), fewer (-20.3%) and more unevenly spaced (81.4%) trabeculae, and thinner cortices (-14.0%) (all p < 0.05). At the distal tibia, vBMD was on average -4.7% (cortical) to -25.4% (total) lower, trabecular microarchitecture was on average -19.8% (number) to 102% (inhomogeneity) inferior, cortices were thinner (-21.1%) and more porous (18.2%) (all p < 0.05). Adding parameters of vBMD and microarchitecture in multivariate models did not offer additional discriminative capacity of fracture status compared with using T-score at FN. In old postmenopausal women with already excessive loss of bone mass, measuring bone microarchitecture may provide limited added value to improve identification of risk of femoral neck fracture.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037450PMC
http://dx.doi.org/10.1038/srep34185DOI Listing
September 2016

Bone formation and degradation behavior of nanocrystalline hydroxyapatite with or without collagen-type 1 in osteoporotic bone defects - an experimental study in osteoporotic goats.

Injury 2016 Jun;47 Suppl 2:S58-65

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.

The intention of the current work is to assess new bone formation and degradation behavior of nanocrystalline hydroxyapatite with (HA/col-1) or without collagen-type I (HA) in osteoporotic metaphyseal bone defects in goats. After ovariectomy and special low-calcium diet for three months, 3 drill hole defects in the vertebrae of L3, L4, L5, 4 drill hole defects in the right and left iliac crest and 1 drill hole defect at the distal femur were created in three Chinese mountain goats with a total of 24 defects. The defects were either filled with one of the biomaterials or left empty (empty defect control group). After 42 days, the animals were euthanized and the samples were assessed for new bone formation using high-resolution peripheral quantitative computed tomography (HR-pQCT) and histomorphometry with 2 regions of interest. Detail histology, enzymehistochemistry and immunohistochemistry as well as connexin-43 in situ hybridization and transmission electron microscopy were carried out for evaluation of degradation behavior of the materials and cellular responses of the surrounding tissue in respect to the implants. HR-pQCT showed the highest BV/TV ratio (p = 0.008) and smallest trabecular spacing (p = 0.005) for HA compared to the other groups in the region of interest at the interface with 1mm distance to the initially created defect. The HA/col-1 yielded the highest connectivity density (Conn.D) (p = 0.034) and the highest number of trabeculae (Tb.N) (p = 0.002) compared to the HA and the control group. Histomorphometric analysis for the core region of the initially created defect revealed a statistically higher new bone formation in the HA (p = 0.001) and HA/col-1 group (p = 0.001) compared to the empty defect group including all defect sites. This result was confirmed for site specific analysis with significant higher new bone formation for the HA group for vertebral defects compared to the empty defect group (p = 0.029). For the interface region, no statistically significant differences were found between the three groups (p = 0.08). Histology revealed a good biocompatibility without inflammatory reaction for the HA- and HA/col-1 implants with a higher fragmentation of the HA-implant compared to the HA/col-1 biomaterial and formation of new bone in the region between the biomaterial fragments by osteoblasts. Fragmentation was shown by transmission electron microscopy to be caused by multinuclear osteoclast-like cells with degradation of the implant via intracellular incorporation of degraded implant material particles. In conclusion, both nanoparticulate HA with and without collagen type-1 showed better new bone formation compared to untreated drill hole defects in metaphyseal regions of this osteoporotic Chinese mountain goat model with good biocompatibility.
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http://dx.doi.org/10.1016/S0020-1383(16)47010-5DOI Listing
June 2016

Fracture healing in osteoporotic bone.

Injury 2016 Jun;47 Suppl 2:S21-6

Department of Trauma Surgery, Giessen University Hospital, Giessen-Marburg, Germany.

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models.
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http://dx.doi.org/10.1016/S0020-1383(16)47004-XDOI Listing
June 2016