Wing-Hoi Cheung

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.

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.

Age-associated decrease of type IIA/B human skeletal muscle fibers

Elderly individuals often fall because of poor muscle strength and reduced balancing ability related to muscle aging. However, it is unclear whether changes in muscle fiber types contribute to poor strength or imbalance. We studied age- associated changes in human skeletal muscle fibers using muscle biopsy specimens taken from 65 male and female Chinese patients aged 17-96 years. The muscle specimens were cryosectioned with alkaline triphosphatase staining at pH 4.4, followed by image analysis. We analyzed morphologic observations and performed quantitative analyses of the number, size, and area percentage of different types of skeletal muscle fibers and connective tissues. Types IIA and IIB muscle fibers decreased with age in the area percentage, fiber number percentage, and mean fiber area, whereas Type I fibers increased in area and number but not in size. Morphologically, Type II fibers appeared smaller and flatter. Our findings suggest deterioration in muscle quality and balancing coordination in elderly patients. We provide data to help determine treatments for reversing muscle fiber changes and reducing the number of falls and related fractures in patients.

Low-Intensity Pulsed Ultrasound Accelerates Bone-Tendon Junction Healing A Partial Patellectomy Model in Rabbits

Background Low-intensity pulsed ultrasound has been demonstrated to be beneficial for accelerating fracture healing, delayed union, nonunion, and soft tissue repair. Hypothesis Low-intensity pulsed ultrasound accelerates healing of bone-to-tendon junction repair by promoting osteogenesis and tissue remodeling at the healing junction. Study Design Controlled laboratory study. Methods Standard partial patellectomy was conducted in forty-eight 18-week-old rabbits divided into an ultrasound treatment and control group. Daily ultrasound was delivered 3 days after surgery onto the patellar tendon–patella healing junction and continuously up to weeks 2, 4, 8, and 16 postoperatively, when the patella–patellar tendon complexes were harvested for radiographic, histologic, and biomechanical evaluations. Results Radiographic measurements showed significantly more newly formed bone at the patellar tendon–patella healing junction in the ultrasound group compared with the controls at week 8 (4.91 ± 2.74 mm2 vs 2.50 ± 1.83 mm2, P < .05) and week 16 (7.22 ± 2.34 mm2 vs 4.61 ± 2.22 mm2, P < .05) after partial patellectomy. Histologically, the ultrasound group at weeks 8 and 16 showed improved tissue integration, characterized by trabecular bone expansion from the remaining patella and regeneration of fibrocartilage layer at the patellar tendon–patella healing junction. Fluorescence microscopy revealed earlier bone formation in the ultrasound group when compared with the controls at week 8 (1.78 ± 0.32 vs 1.23 ± 0.43, P < .01) and week 16 (2.10 ± 0.67 vs 1.29 ± 0.35, P < .01). Mechanical testing showed significantly higher failure load and ultimate strength in the ultrasound group (300.2 ± 61.7 N and 7.10 ± 1.29 MPa, respectively) as compared with controls (222.3 ± 65.1 N and 5.26 ± 1.36 MPa, respectively) at week 16 (P < .05 for both). Conclusion Low-intensity pulsed ultrasound was able to accelerate bone-to-tendon junction repair. Clinical Relevance These results may help establish treatment efficacy for accelerating bone-to-tendon junction repair and facilitating earlier rehabilitation.

Low-Intensity Pulsed Ultrasound Accelerated Bone-Tendon Junction Healing Through Regulation of Vascular Endothelial Growth Factor Expression and Cartilage Formation

The purpose of this study was to use our established partial patellectomy rabbit model to study the effects of low-intensity pulsed ultrasound (LIPUS) on patella-patellar tendon (PPT) junction repair through hypothesized pathways including regulation of vascular endothelial growth factor (VEGF) and chondrogenesis. Standard partial patellectomy was conducted in sixty-four 18 wk-old rabbits that were subsequently divided into LIPUS and control group. The PPT complex was harvested at week 2, 4, 8 and 16 postoperatively (n = 8 for each time point) for preparation of sagittal sections that were evaluated for angiogenesis by analyzing VEGF expression and chondrogenesis. Results showed differences in the pattern of VEGF expression between LIPUS and control groups during the entire healing process, i.e., significant differences in the average percentage of VEGF expression found in between the LIPUS and the control groups. At postoperative week 4, the chondrocytes and osteoblasts in woven bone expressed significantly more VEGF in the LIPUS group than that in the control group (35.6% +/- 7.0% versus 28.0% +/- 4.6%, p < 0.05). Compared with the control group, the development of cartilaginous metaplasia was found more advanced in the scar tissue next to the articular cartilage of the remaining patella in the LIPUS group that was expressed with VEGF in the chondrocytes (38.8% +/- 12.3%). However, the specimens in the control group just showed the similar cartilaginous metaplasia region until postoperative week 8. Histomorphometry revealed thicker fibrocartilage zone and larger cartilaginous metaplasia field at PPT healing interface in LIPUS group compared with those of the control group at week 8 and 16. In conclusion, this was the first quantitative study to demonstrate that LIPUS improved B-T junction healing through regulation of VEGF expression in early healing phase and subsequent chondrogenesis.

Extracorporeal Shock Wave Therapy in Treatment of Delayed Bone-Tendon Healing

Background Extracorporeal shock wave therapy is indicated for treatment of chronic injuries of soft tissues and delayed fracture healing and nonunion. No investigation has been conducted to study the effect of shock wave on delayed healing at the bone-tendon junction. Hypothesis Shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling of healing tissue in delayed healing of bone-tendon junction surgical repair. Study Design Controlled laboratory study. Methods Twenty-eight mature rabbits were used for establishing a delayed healing model at the patella–patellar tendon complex after partial patellectomy and then divided into control and shock wave groups. In the shock wave group, a single shock wave treatment was given at week 6 postoperatively to the patella–patellar tendon healing complex. Seven samples were harvested at week 8 and 7 samples at week 12 for radiologic, densitometric, histologic, and mechanical evaluations. Results Radiographic measurements showed 293.4% and 185.8% more new bone formation at the patella–patellar tendon healing junction in the shock wave group at weeks 8 and 12, respectively. Significantly better bone mineral status was found in the week 12 shock wave group. Histologically, the shock wave group showed more advanced remodeling in terms of better alignment of collagen fibers and thicker and more mature regenerated fibrocartilage zone at both weeks 8 and 12. Mechanical testing showed 167.7% and 145.1% higher tensile load and strength in the shock wave group at week 8 and week 12, respectively, compared with controls. Conclusion Extracorporeal shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling in the delayed bone-to-tendon healing junction in rabbits. Clinical Relevance These results provide a foundation for future clinical studies toward establishment of clinical indication for treatment of delayed bone-to-tendon junction healing.

Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

BackgroundIncreased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development.ObjectiveThe present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development.MethodsON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON+ (with at least one ON lesion) group and ON- (without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON+ rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion).ResultsLocal intra-osseous perfusion index was found lower in either ON+ or MON group when compared to either ON- or SON group, whereas the marrow fat cells number and area were much larger in either ON+ or MON group as compared with ON- and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON+ or MON group were elevated significantly as compared with either ON- or SON group.ConclusionThese findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.

An orthogeriatric collaborative intervention program for fragility fractures: a retrospective cohort study.

BACKGROUND This retrospective cohort study aims to investigate the impact of regular pre- and postoperative geriatric input into the management of geriatric patients with hip fracture, with specific interests in morbidity and mortality. METHODS Patients with hip fracture (n = 548) older than 60 years were identified within a 2-year period. In the first year, the patients (n = 270) were managed mainly by orthopedics and this group constituted the control group. In the second year, this group of patients (orthogeriatric group, n = 278) had reviews by orthopedic surgeons and geriatricians (physicians specializing in medicine for the elderly), within 48 hours of admission and regularly thereafter. The main outcomes measured included demographics, length of hospital stay, postoperative complications, mortality, and functional outcomes. Data were collected from records of acute and rehabilitation admissions, and outpatient consultations. RESULTS The admission to operation time for those in the orthogeriatric group was shorter by 17% (p = 0.02). The percentage of patients deceased at 12 months postoperative was 11.5% for the orthogeriatric group and 20.4% for the conventional group (p = 0.02). A higher percentage of patients in the orthogeriatric group remained independent for daily living activities (24.5%) when compared with the conventional group (23.7%; p = 0.02). CONCLUSION In addition to existing evidence that postoperative orthogeriatric collaboration improves mortality and functional outcomes in older patients with hip fractures, this study suggests that allowing preoperative geriatric input in this model of care can produce even more superior results.

Low-magnitude high-frequency vibration (LMHFV) enhances bone remodeling in osteoporotic rat femoral fracture healing.

Low‐magnitude high‐frequency vibration (LMHFV) (35 Hz, 0.3 g) accelerates fracture healing by enhancing callus formation and mineralization for both normal and osteoporotic rats in our previous studies. 1,2 We hypothesized that LMHFV enhances fracture healing through bone remodeling. Ibandronate was used to suppress LMHFV‐stimulated bone remodeling and changes in remodeling were investigated to verify our hypothesis. Closed femoral fractures were created in 80 osteoporotic female Sprague–Dawley rats. The rats were randomly assigned into control (CG), LMHFV (VG) (20 min/day, 5 days/week), ibandronate (BG) (7 µg/kg/week), or LMHFV + ibandronate (VBG) for a treatment duration of 2, 4, 6, or 8 weeks. Blood was taken and the femora were harvested for histological and radiological analyses. VG had the fastest drop in callus area (CA) and width (CW), and bone volume to tissue volume ratio (BV/TV); whereas, a plateaued trend in BG and VBG was observed. The fastest callus reduction, highest mineral apposition rate at week 6, and increased serum concentration of osteocalcin and TRAP5b in VG suggested enhanced remodeling. LMHFV partially reversed the inhibition of bone remodeling by ibandronate suggested LMHFV had an opposite effect on bone remodeling to ibandronate. In conclusion, LMHFV accelerated fracture healing by enhancing bone remodeling and the administration of ibandronate can impair this enhancement. LMHFV has great potential in improving fracture outcome clinically.