Kwok-Sui Leung

Gamma nails and dynamic hip screws for peritrochanteric fractures. A randomised prospective study in elderly patients

The Gamma nail was introduced for the treatment of peritrochanteric fractures with the theoretical advantage of a load-sharing femoral component which could be implanted by a closed procedure. We report a randomised prospective study of 186 fractures treated by either the Gamma nail or a dynamic hip screw. Gamma nails were implanted with significantly shorter screening times, smaller incisions, and less intraoperative bleeding. The Gamma nail group had a shorter convalescence and earlier full weight-bearing, but there was no significant difference in mortality within six months, postoperative mobility, or hip function at review. More intra-operative complications were recorded in the Gamma nail group, mainly due to the mismatching of the femoral component of the nail to the small femurs of Chinese people. Use of a smaller modified nail reduced these complications. We conclude that with careful surgical technique and the modified femoral component, the Gamma nail is an advance in the treatment of peritrochanteric fractures.

A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy

Metabolic skeletal disorders associated with impaired bone formation are a major clinical challenge. One approach to treat these defects is to silence bone-formation–inhibitory genes by small interference RNAs (siRNAs) in osteogenic-lineage cells that occupy the niche surrounding the bone-formation surfaces. We developed a targeting system involving dioleoyl trimethylammonium propane (DOTAP)-based cationic liposomes attached to six repetitive sequences of aspartate, serine, serine ((AspSerSer)6) for delivering siRNAs specifically to bone-formation surfaces. Using this system, we encapsulated an osteogenic siRNA that targets casein kinase-2 interacting protein-1 (encoded by Plekho1, also known as Plekho1). In vivo systemic delivery of Plekho1 siRNA in rats using our system resulted in the selective enrichment of the siRNAs in osteogenic cells and the subsequent depletion of Plekho1. A bioimaging analysis further showed that this approach markedly promoted bone formation, enhanced the bone micro-architecture and increased the bone mass in both healthy and osteoporotic rats. These results indicate (AspSerSer)6-liposome as a promising targeted delivery system for RNA interference–based bone anabolic therapy.

Low intensity pulsed ultrasound stimulates osteogenic activity of human periosteal cells

The effect of low intensity pulsed ultrasound on human periosteal cells was investigated. Normal human periosteum was obtained to culture the periosteal cells. After characterization, cultures of periosteal cells at Days 2 and 4 were treated with ultrasound for 5, 10, and 20 minutes respectively. Assessments were done to assess total number of viable cells, cell proliferation, alkaline phosphatase activity, osteocalcin secretion, vascular endothelial growth factor expression, and calcium nodule formation. With the cells not treated with ultrasound as the control, the results showed that ultrasound did not affect the total number of viable cells. It stimulated cell proliferation at the early phase of cell culture. The activity of alkaline phosphatase was increased significantly in the culture at Day 4. A similar effect was seen with osteocalcin secretion and the responses were dose-dependent. The vascular endothelial growth factor secretion increased in Day 2 and Day 4 cultures with the dose-dependent effect. Formation of calcium nodules was significantly higher with ultrasound treatment. We think that low intensity pulsed ultrasound stimulated periosteal cell proliferation and differentiation toward osteogenic lineage. The dose-dependent effect on osteogenic activities may modify the existing treatment regimen. Ultrasound treatment should be started from the beginning of fracture healing.

Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model

OBJECTIVE To establish a drill-hole defect model in osteoporotic mouse femur by comparing temporal cortical bone healing pattern between OVX-induced osteoporotic bone and sham-operated bone. METHODS 3-month-old female C57BL/6 mice were randomly divided into an ovariectomy group (OVX) and a sham-operated group (Sham). At 6 weeks post-surgery, 7 mice from each group were sacrificed to examine the distal femur and femoral shaft by both micro-CT and mechanical testing for confirming established osteoporosis induced by OVX. In the remaining mice, a cortical bone defect 0.8mm in diameter was created on the mid-diaphysis of the right femur. The local repair process at days 0, 3, 7, 10, 14 and 21 after creation of the drill-hole was in vivo monitored by high-resolution micro-CT scanning. At each time point, each animal was scanned four times and was removed from the scanner between scans to determine reproducibility. Mice were sacrificed at each time point (n=12 at days 0, 3, 7, 10 and 14; n=20 at day 21). Before sacrifice, sera were collected to examine expression of bone formation marker P1NP (procollagen type I N-terminal propeptide) and bone resorption marker CTX (C-terminal telopeptide of type I collagen). After sacrifice, callus samples were collected and subjected to the following analyses: micro-CT-based angiography; histological examination; immunohistochemical staining to determine estrogen receptor expression; quantitative real-time PCR analysis of collagen type I, collagen type II, collagen type X, osteocalcin, tartrate-resistant acid phosphatase, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) gene expression; and three-point mechanical testing. RESULTS At 6 weeks post-surgery, OVX mice had significantly lower bone mass, impaired bone micro architecture and compromised mechanical properties compared to the Sham mice. In vivo micro-CT analysis revealed that the bone volume fraction in the defect region was significantly lower in the OVX group from day 10 to day 21 post-injury as compared to the Sham group, and was significantly lower in the intra-medulla region in the OVX group from day 7 to day 14 as compared to the Sham group, consistent with the histological data. Analysis of bone biochemical markers indicated that circulating P1NP levels normalized by baseline in the OVX mice were significantly lower than in the Sham mice from day 7 to day 10, and that temporal expression of circulating CTX levels normalized by baseline was also lower in the OVX mice as compared to the Sham mice. These results were consistent with quantitative real-time PCR analysis. ER alpha mRNA expression was significantly lower in the OVX mice, whereas ER beta mRNA expression was significantly higher in the OVX mice as compared to the Sham mice at all time points examined, consistent with immunohistochemical staining. The restoration of femoral mechanical property, determined based on ultimate load and energy-to-failure, was significantly lower in the OVX mice than in the Sham mice. In addition, in vivo micro-CT scanning for quantifying new bone formation in the defect site was highly reproducible in this model. CONCLUSION The bone healing of the drill-hole defect was impaired in mice with OVX-induced osteoporosis. The present study provides a model to investigate the functional role of specific gene in osteoporotic bone healing and may facilitate development of novel therapeutic strategies for promoting osteoporotic bone healing.

Implant-Derived Magnesium Induces Local Neuronal Production of CGRP to Improve Bone-Fracture Healing in Rats

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

Beneficial effects of regular Tai Chi exercise on musculoskeletal system

This study was performed to evaluate the potential benefits of regular Tai Chi Chun (TCC) exercise on bone mineral density (BMD) and neuromuscular function in postmenopausal women. In this cross-sectional study, 99 healthy postmenopausal women, with a mean age of 55.9 ± 3.1 years and within 10 years after the menopause, were recruited; including 48 subjects who had been regularly practicing TCC exercise for more than 3 h/week and 51 age- and sex-matched sedentary controls (CON). BMD was measured in the lumbar spine and proximal femur of the non-dominant leg (femoral neck, greater trochanter, and Ward’s triangle), using dual-energy X-ray absorptiometry (DXA). Neuromuscular function was evaluated, including magnitude of trunk bend-and-reach, quadriceps muscle strength, and single-stance time on the nondominant leg. The TCC group showed overall higher BMD at all measurement sites, with a significant difference found at the spine (7.1%), greater trochanter (7.2%), and Ward’s triangle (7.1%) of the proximal femur (all; P < 0.05). Functional tests revealed an average 43.3% significantly greater quadriceps strength (P < 0.01), and 67.8% significantly longer single-stance time in the TCC group as compared with the CON group (P < 0.05), as well as a greater magnitude of trunk bend-and-reach in the TCC group (P = 0.08). Bivariate linear correlation analysis showed that quadriceps muscle strength was significantly correlated with the single-stance time (r = 0.41; P < 0.01). This study revealed that regular TCC exercise may have an association with higher BMD and better neuromuscular function in early postmenopausal women.

Low-magnitude high-frequency vibration treatment augments fracture healing in ovariectomy-induced osteoporotic bone.

Fracture healing is impaired in osteoporotic bone. Low-magnitude high-frequency vibration (LMHFV) has recently been proven to be osteogenic in osteoporotic intact bone. Our previous study found that LMHFV significantly enhanced fracture healing in adult rats. This study was designed to explore whether LMHFV was able to promote fracture healing in osteoporotic bone by enhancing callus formation, remodeling, and mineralization and to compare with age-matched nonosteoporotic ones. Nine-month-old ovariectomy (OVX)-induced osteoporotic rats were randomized into control (OVX-C) or vibration group (OVX-V); age-matched sham-operated rats were assigned into control (Sham-C) or vibration group (Sham-V). LMHFV (35 Hz, 0.3 g) was given 20 min/day and 5days/week to the treatment groups, while sham treatment was given to the control groups. Weekly radiographs and endpoint micro-CT, histomorphometry, and mechanical properties were evaluated at 2, 4, and 8 weeks post-treatment. Results confirmed that the fracture healing in OVX-C was significantly inferior to that in Sham-C. LMHFV was shown to be effective in promoting the fracture healing in OVX group in all measured parameters, particularly in the early phases of healing, with the outcomes comparable to that of age-matched normal fracture healing. Callus formation, mineralization and remodeling were enhanced by 25-30%, with a 70% increase in energy to failure than OVX-C. However, Sham-V was found to have lesser fracture healing enhancement, with significant increase in callus area only on week 2 and 3 than Sham-C, suggesting non-OVX aged bones were less sensitive to mechanical loading. The findings of this study provide a good basis to suggest that proceeding to clinical trials is the next step to evaluate the efficacy of LMHFV on osteoporotic fracture healing.

Low-magnitude high-frequency vibration accelerates callus formation, mineralization, and fracture healing in rats.

Fracture healing is a biological regenerative process that follows a well‐orchestrated sequence. Most healing is uneventful and enhancement of normal fracture healing is not commonly done, although it is clinically important in the recovery and regain of functions after fracture. This study investigated the osteogenic effect of low‐magnitude high‐frequency vibration (LMHFV, 35 Hz, 0.3 g) on the enhancement of fracture healing in rats with closed femoral shaft fracture by comparing with sham‐treated control. Assessments with plain radiography, micro‐CT as well as histomorphometry showed that the amount of callus was significantly larger (p = 0.001 for callus area, 2 weeks posttreatment); the remodeling of the callus into mature bone was significantly faster (p = 0.039, 4 weeks posttreatment) in the treatment group. The mechanical strength of the healed fracture in the treatment group at 4 weeks was significantly greater (p < 0.001). The results showed the acceleration of callus formation, mineralization, and fracture healing in the treatment group. It is concluded that LMHFV enhances healing in the closed femoral shaft fracture in rats. The potential clinical advantages shall be confirmed in the subsequent clinical trials.

Ligamentotaxis and bone grafting for comminuted fractures of the distal radius

The conventional treatment of comminuted fractures in the distal radius has been unsatisfactory. We therefore made a prospective study using the principle of ligamentotoxis and primary cancellous bone grafting as the uniform method of treatment. Ligamentotaxis was maintained by using an external fixator for three weeks only, after which a carefully monitored programme of rehabilitation was given. We have reviewed 72 consecutive distal radial fractures after a follow-up of 7 to 40 months (average 11 months). Reduction had been maintained during healing and over 80% of patients regained full range of movement in hands, wrists and forearms with strong and pain-free wrist function. Complications were infrequent and gave no real problems. We conclude that distraction, external fixation and bone grafting appears to be an excellent method of treating comminuted fractures of the distal radius.

Mobile Human Airbag System for Fall Protection Using MEMS Sensors and Embedded SVM Classifier

This paper introduces a mobile human airbag system designed for fall protection for the elderly. A Micro Inertial Measurement Unit ( muIMU) of 56 mm times 23 mm times 15 mm in size is built. This unit consists of three dimensional MEMS accelerometers, gyroscopes, a Bluetooth module and a Micro Controller Unit (MCU). It records human motion information, and, through the analysis of falls using a high-speed camera, a lateral fall can be determined by gyro threshold. A human motion database that includes falls and other normal motions (walking, running, etc.) is set up. Using a support vector machine (SVM) training process, we can classify falls and other normal motions successfully with a SVM filter. Based on the SVM filter, an embedded digital signal processing (DSP) system is developed for real-time fall detection. In addition, a smart mechanical airbag deployment system is finalized. The response time for the mechanical trigger is 0.133 s, which allows enough time for compressed air to be released before a person falls to the ground. The integrated system is tested and the feasibility of the airbag system for real-time fall protection is demonstrated.