The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit.

BACKGROUND: Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination. RESULTS: Based on the x-rays and CT scans, fracture healing or bone formation was observed to be faster in the control group. From the x-ray findings, 80 % of the fracture united and by CT scan, 60 % of the fracture united in the control group at the end of the six-week study. None of the fractures united in the test group. However, the histopathology report showed that a callus of different stages was being formed in both groups, consisting of 80 % of bone. The serum levels of osteocalcin and alkaline phosphatase initially remained similar up to three weeks and changed slightly at the end of six weeks. CONCLUSIONS: We conclude that the strontium effect begins slowly, and while it may not interfere with bone cell proliferation it may interfere in the mineralization and delay the acute stage of fracture healing. We recommend that a larger sample size and a longer duration of the study period be implemented to confirm our finding.

Cytokine release by human bone marrow stromal cells isolated from osteoarthritic and diabetic osteoarthritic patients in vitro.

OBJECTIVES: Primary Osteoarthritis (OA) is a disease of progressive joints degeneration due to idiopathic causes. Recent evidence showed a positive relationship between OA and metabolic syndrome. This pilot study aimed to assess the baseline level of pro and anti-inflammatory cytokines in OA patients with or without Diabetic Mellitus (DM) and assess the effect of hydrogen peroxide (H2O2) in cytokine production. METHODS: Patients with primary hip and knee OA were recruited, and 3 mL of bone marrow was harvested during joint replacement surgery. Bone marrow stromal cells (BMSC) was isolated and cultured in a culture flask for three passages. Later experiment was then sub-cultured in a well plate labeled as the control group and H2O2 (0.1 mM) treated group. ProcartaPlex® Multiplex Immunoassay was performed to measure cytokine levels produced by the BMSC at 0 h, as well as 72 h. RESULTS: Cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-1ß generally exhibited higher cytokine levels in subjects with DM than in nonDM subjects at 0 and 72 h. For IL-17, its expression was similar in nonDM and DM groups at 0 and 72 h. Cytokine IL-10 showed no significant difference in both the groups while DM and nonDM groups treated with H2O2 showed decreased IL-4 levels compared to control groups at 72 h. Bone marrow cells from DM-OA are more vulnerable to chemical insult and are associated with higher levels of proinflammatory cytokines production and lower IL-4 level production. CONCLUSIONS: This study provides a clue that management of OA with co-morbidity like DM needs future studies.

Fragility fracture care gap at a tertiary teaching hospital in Malaysia.

Fracture begets fracture, pharmacological treatment is needed to prevent secondary fractures. This study found that there was a fragility fracture care gap where both bone health investigations and treatment initiation rates were low. Strategies such as Fracture Liaison Service is needed to address the care gap. PURPOSE: This study aimed to investigate the clinical burden and secondary fracture prevention of fragility fractures at a tertiary teaching hospital in Malaysia. METHODS: Electronic medical records of all patients admitted with fragility fractures between 1 January 2017-31 December 2018 were reviewed. Patients < 50 years old, with non-fragility fractures, restricted access to medical records, transferred to another hospital or who passed away during admission were excluded. Descriptive statistics were used to summarise patients' characteristics, frequency of fragility fractures, and secondary fracture prevention details. Binomial logistic regression was performed to analyse predictive factors for post-fracture bone health assessments and treatment initiation. RESULTS: 1030 patients [female (767/1030, 74.5%)] presented with 1071 fractures [hip fractures (378/1071, 35.3%)]. 170/993 (17.1%) patients were initiated on anti-osteoporosis medications (AOMs) and 148/984 (15.0%) had bone mineral density (BMD) performed within 1-year post-fracture. Less than half (42.4%) of the patients remained on treatment at 1-year post-fracture. Older patients [65-74 years old: odds ratio (OR) = 2.18, 95%CI 1.05-4.52, p = 0.04; ≥ 75 years: OR = 3.06, 95%CI 1.54-6.07, p < 0.01], hip fractures (OR = 1.95, 95%CI 1.23-3.11, p < 0.01), Chinese ethnicity (OR = 1.90, 95%CI 1.07-3.35, p = 0.03),previously diagnosed with osteoporosis (OR = 2.65, 95%CI:1.32-5.31, p < 0.01) and a BMD test performed (OR = 12.48, 95%CI 8.04-19.37, p < 0.01) were found to have higher AOM initiation. Patients with past diagnosis of osteoporosis (OR = 4.45, 95%CI 2.25-8.81, p < 0.01) and initiated on AOM (OR = 11.34, 95%CI 7.57-16.97, p < 0.01) had a higher likelihood to undergo BMD testing. CONCLUSION: The AOM initiation and BMD testing rates were low. There is a need to address the fragility fracture care gap with strategies such as Fracture Liaison Service.

Closed reduction techniques in acute anterior shoulder dislocation: modified Milch technique compared with traction-countertraction technique.

BACKGROUND: To perform closed manual reduction of acute anterior shoulder dislocation using the traction-countertraction technique requires sedation (TCTS) and the participation of 2 people. We studied the modified Milch (MM) technique, a positional reductive maneuver that requires 1 operator, without patient sedation or analgesia. MATERIALS AND METHODS: The study comprised 56 prospective nonrandomized consecutive patients, of whom 31 were in group A (MM, nonsedated) and 25 in group B (TCTS). RESULTS: The success rate of MM technique was 83.9% (26 of 31), which increased to 96.3% (26 of 27) when 4 patients with associated greater tuberosity fractures were excluded. The success rate was 100% in the TCTS group, with 5 patients with associated greater tuberosity fractures. The reduction in pain from the preprocedural to intraprocedural phases in MM group was significant (P < .001), at a reduction rate of 2.07 (29%) on the numeric rating scale pain score. There was a greater pain reduction rate of 2.43 (34%) on the numeric rating scale when patients with greater tuberosity fractures were excluded. The MM group had a significantly shorter hospital stay (mean, 35 minutes) than the TCTS group (mean, 4 hours). No postreduction neurovascular or fracture complications occurred in either group. CONCLUSIONS: The results showed that the Milch technique was effective, safe, shortened hospital stay, and was well tolerated. We recommend the modified Milch technique as a first-line maneuver for acute anterior shoulder dislocations without associated fractures.

Hip fracture management in the emergency department and its impact on hospital outcomes: a retrospective cross-sectional analysis.

PURPOSE: The emergency department (ED) plays an important role in initiating early treatment for hip fractures and ensuring prompt transfer to orthopaedic wards. This study reported on the care delivered in a tertiary centre ED in Malaysia and the association between time spent in ED with hospital outcomes. METHODS: Patients aged ≥ 65 years with fragility hip fractures and seen by the geriatric team were recruited. Data were collected on patient characteristics, key time points for treatment and hospital outcomes. Median time in ED was used to dichotomise long and short waiting time. RESULTS: 447 patients were recruited. The mean (SD) age was 80.5 (7.0) years and 69.8% were women. 74.9% were prescribed analgesia within 30 min. Median (Q1,Q3) time to diagnostic imaging was 27.0 (24.0-43.0) minutes, clinician confirmation of fracture was 83.0 (49.0-129.0) minutes, and time in ED was 4.8 (3.5-6.9) h. A weekday, weekend, in-hour or out-of-hour admission did not demonstrate a difference in the time important care was delivered. Patients who spent ≥ 5 h in ED had more cardiac events (4.6 vs 10.1%, p = 0.023) and more spent ≥ 14 days in hospital (17.5 vs 29.0%, p = 0.004) compared to those < 5 h. No significant increase in inpatient complications (43.5 vs 34.6%, p = 0.054), length of stay (median, 8 vs 7 days, p = 0.119), care home discharge (5.3 vs 4.6%, p = 0.772), or in-hospital death (6.3 vs 4.2%, p = 0.313) were observed. CONCLUSION: Time to early hip fracture pain relief and diagnosis was adequate in this ED. Time ≥ 5 h in ED was associated with cardiac events and 2 weeks or more inpatient stay.

Mobility and mortality outcomes among older individuals with hip fractures at a teaching hospital in Malaysia.

The challenges of hip fracture care in Malaysia is scarcely discussed. This study evaluated the outcomes of older patients with hip fracture admitted to a teaching hospital in Malaysia. We found that one in five individuals was no longer alive at one year after surgery. Three out of five patients did not recover to their pre-fracture mobility status 6 months following hip fracture surgery. PURPOSE: With the rising number of older people in Malaysia, it is envisaged that the number of fragility hip fractures would also increase. The objective of this study was to determine patient characteristics and long-term outcomes of hip fracture in older individuals at a teaching hospital in Malaysia. METHODS: This was a prospective observational study which included consecutive patients aged ≥ 65 years old admitted to the orthopedic ward with acute hip fractures between March 2016 and August 2018. Patient socio-demographic details, comorbidities, pre-fracture mobility status, fracture type, operation and anesthesia procedure, and length of stay were recorded. Post-fracture mobility status was identified at 6 months. Cox proportional hazard analysis was used to assess the risk of death in all patients. RESULTS: 310 patients (70% women) with the mean age of 79.89 years (SD 7.24) were recruited during the study period. Of these, 284 patients (91.6%) underwent surgical intervention with a median time to surgery of 5 days (IQR 3-8) days. 60.4% of patients who underwent hip fracture surgery did not recover to their pre-fracture mobility status. One year mortality rate was 20.1% post hip fracture surgery. The independent predictor of mortality included advanced age (hazard ratio, HR = 1.05, 95% CI = 1.01-1.08; p = 0.01), dependency on activities of daily living (HR = 2.08, 95% CI = 1.26-3.45; p = 0.01), and longer length of hospitalization (HR = 1.02, 95% CI = 1.01-1.04; p < 0.01). CONCLUSION: One in 5 individuals who underwent hip fracture surgery at a teaching hospital in Kuala Lumpur was no longer alive at one year. A systematic approach to hip fracture management is crucial to improve outcomes and restore pre-fracture function of this vulnerable group of patients.

Calcium-Silicate-Incorporated Gellan-Chitosan Induced Osteogenic Differentiation in Mesenchymal Stromal Cells.

Gellan-chitosan (GC) incorporated with CS: 0% (GC-0 CS), 10% (GC-10 CS), 20% (GC-20 CS) or 40% (GC-40 CS) w/w was prepared using freeze-drying method to investigate its physicochemical, biocompatible, and osteoinductive properties in human bone-marrow mesenchymal stromal cells (hBMSCs). The composition of different groups was reflected in physicochemical analyses performed using BET, FTIR, and XRD. The SEM micrographs revealed excellent hBMSCs attachment in GC-40 CS. The Alamar Blue assay indicated an increased proliferation and viability of seeded hBMSCs in all groups on day 21 as compared with day 0. The hBMSCs seeded in GC-40 CS indicated osteogenic differentiation based on an amplified alkaline-phosphatase release on day 7 and 14 as compared with day 0. These cells supported bone mineralization on GC-40 CS based on Alizarin-Red assay on day 21 as compared with day 7 and increased their osteogenic gene expression (RUNX2, ALP, BGLAP, BMP, and Osteonectin) on day 21. The GC-40 CS-seeded hBMSCs initiated their osteogenic differentiation on day 7 as compared with counterparts based on an increased expression of type-1 collagen and BMP2 in immunocytochemistry analysis. In conclusion, the incorporation of 40% (w/w) calcium silicate in gellan-chitosan showed osteoinduction potential in hBMSCs, making it a potential biomaterial to treat critical bone defects.

Incorporation of Fucoidan in ß-Tricalcium phosphate-Chitosan scaffold prompts the differentiation of human bone marrow stromal cells into osteogenic lineage.

In our previous study, we reported the fabrication and characterization of a novel tricalcium phosphate-fucoidan-chitosan (TCP-Fu-Ch) biocomposite scaffold. However, the previous report did not show whether the biocomposite scaffold can exhibit osteogenic differentiation of human bone marrow stromal cells in osteogenic media and normal media supplemented with platelet-derived growth factor (PDGF-BB). On day 15, the release of osteocalcin, was significant in the TCP-Fu-Ch scaffold, when compared with that in the TCP-Ch scaffold, and the level of release was approximately 8 and 6 ng/ml in osteogenic and normal media supplemented with PDGF-BB, respectively. Scanning electron microscopy of the TCP-Fu-Ch scaffold demonstrated mineralization and apatite layer formation on day 14, while the addition of PDGF-BB also improved the osteogenic differentiation of the scaffold. An array of gene expression analysis demonstrated that TCP-Fu-Ch scaffold cultured in osteogenic and normal media supplemented with PDGF-BB showed significant improvement in the expression of collagen 1, Runt-related transcription factor 2, osteonectin, bone gamma-carboxyglutamate protein, alkaline phosphatase, and PPA2, but a decline in the expression of integrin. Altogether, the present study demonstrated that fucoidan-incorporated TCP-Ch scaffold could be used in the differentiation of bone marrow stromal cells and can be a potential candidate for the treatment of bone-related ailments through tissue engineering technology.