Sarcopenia is an age-related geriatric syndrome which is associated with subsequent disability and morbidity. Currently there is no promising therapy approved for the treatment of sarcopenia. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK) are expressed in bone and skeletal muscle. Activation of the NF-κB pathway mainly inhibits myogenic differentiation, which leads to skeletal muscle dysfunction and loss. LYVE1 and CD206 positive macrophage has been reported to be associated with progressive impairment of skeletal muscle function with aging. The study aims to investigate the effects of an anti-RANKL treatment on sarcopenic skeletal muscle and explore the related mechanisms on muscle inflammation and the polarization status of macrophages.

Sarcopenic senescence-accelerated mouse P8 (SAMP8) mice at month 8 were treated intraperitoneally with 5mg/kg anti-RANKL (IK22/5) or isotype control (2A3; Bio X Cell) antibody every 4 weeks and harvested at month 10. Senescence accelerated mouse resistant-1 (SAMR1) were collected at month 10 as the age-matched non-sarcopenic group. Ex-vivo functional assessment, grip strength and immunostaining of C/EBPa, CD206, F4/80, LYVE1 and PAX7 were performed. Data analysis was done with one-way ANOVA, and the significant level was set at p≤0.05.

At month 10, tetanic force/specific tetanic force, twitch force/specific twitch force in anti-RANKL group were significantly higher than control group (all p<0.01). The mice in the anti-RANKL treatment group also showed significantly higher grip strength than Con group (p<0.001). The SAMP8 mice at month 10 expressed significantly more C/EBPa, CD206 and LYVE1 positive area than in SAMR1, while anti-RANKL treatment significantly decreased C/EBPa, CD206 and LYVE1 positive area.

The anti-RANKL treatment protected against skeletal muscle dysfunctions through suppressing muscle inflammation and modulating M2 macrophages, which may represent a novel therapeutic approach for sarcopenia.

Acknowledgment: Collaborative Research Fund (CRF, Ref: C4032-21GF)

Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation.

Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin.

DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 & 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process.

The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing.

Acknowledgment: General Research Fund (Ref: 14113018)

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.

Of 37 consecutive patients suffering from tuberculosis of the lumbosacral spine, 26 were reviewed after an average follow-up of 20 years. Those presenting at under 10 years of age usually had a discharging sinus or a pointing abscess and a visible kyphosis. In older patients, low back pain was the predominant presenting symptom. Neurological involvement was uncommon. Both operative and conservative treatment had resulted in fusion but all patients treated conservatively ended up with a kyphosis associated with trunk shortening. They had a higher incidence of back pain and more complications in pregnancy. Anterior debridement and fusion with a strut graft can reduce the incidence and size of kyphosis, but is technically demanding. Treatment remains difficult and requires individual consideration.

We have reviewed 16 patients with avulsion fractures of the tibial tubercle, mostly boys who sustained left-sided injuries during sport. Two-thirds had type I or II injuries and were treated conservatively. Fractures involving the knee joint (type III) had internal fixation. The final results were good except for minor complications such as a prominent and uncomfortable tibial tubercle.

We reviewed 40 extensive destructive vertebral lesions in 35 patients with established ankylosing spondylitis. Of these, 31 had presented with localised pain while three had a neurological deficit. The radiographs suggested ununited fractures through either ankylosed discs (37) or vertebral bodies (3). Corresponding fractures were seen in the posterior column in 34 cases. Sixteen patients with 18 lesions underwent anterior spinal fusion, and pseudarthrosis was consistently proven by histopathology. Two pseudarthroses healed in conservatively treated patients. Thirteen of the operated patients were followed for an average of 7 years 7 months. There were two cases of non-union and one required an additional posterior fusion; in the remainder fusion was sound.

Crushing of the radial side of the hand results in a wide spectrum of injuries varying from contusion of muscles to total loss. The main problem concerns the function of the thumb. The results of such injuries in 161 hands were reviewed. Those with mild injuries treated conservatively or by debridement alone had good results. When skin flaps were required for wound coverage, the results were still satisfactory. However, when bones and joints were injured, the results were poor. In certain patients opponensplasty through scarred tissue proved to be a good procedure to improve the function of the thumb.