Teriparatide and stress fracture healing in young adults (RETURN – Research on Efficacy of Teriparatide Use in the Return of recruits to Normal duty): study protocol for a randomised controlled trial

Background Stress fractures are a common and potentially debilitating overuse injury to bone and occur frequently among military recruits and athletes. Recovery from a lower body stress fracture typically requires several weeks of physical rehabilitation. Teriparatide, a recombinant form of the bioactive portion of parathyroid hormone (1–34 amino acids), is used to treat osteoporosis, prevent osteoporotic fractures, and enhance fracture healing due to its net anabolic effect on bone. The study aim is to investigate the effect of teriparatide on stress fracture healing in young, otherwise healthy adults undergoing military training. Methods In a two-arm, parallel, prospective, randomised controlled, intention-to-treat trial, Army recruits (n = 136 men and women, 18–40 years) with a magnetic resonance imaging (MRI) diagnosed lower body stress fracture (pelvic girdle, sacrum, coccyx, or lower limb) will be randomised to receive either usual Army standard care, or teriparatide and usual Army standard care. Teriparatide will be self-administered by subcutaneous injections (20 μg/day) for 16 weeks, continuing to 24 weeks where a fracture remains unhealed at week 16. The primary outcome will be the improvement in radiological healing by two grades or more, or reduction to grade zero, 8 weeks after randomisation, assessed using Fredericson grading of MRI by radiologists blind to the randomisation. Secondary outcomes will be time to radiological healing, assessed by MRI at 8, 10, 12, 14, 16, 20 and 24 weeks, until healed; time to clinical healing, assessed using a clinical severity score of injury signs and symptoms; time to discharge from Army physical rehabilitation; pain, assessed by visual analogue scale; health-related quality of life, using the Short Form (36) Health Survey; and adverse events. Exploratory outcomes will include blood and urine biochemistry; bone density and morphology assessed using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography (pQCT), and high-resolution pQCT; physical activity measured using accelerometers; and long-term future fracture rate. Discussion This study will evaluate whether teriparatide, in addition to standard care, is more effective for stress fracture healing than standard care alone in Army recruits who have sustained a lower body stress fracture. Trial registration ClinicalTrials.govNCT04196855. Registered on 12 December 2019.

Low Dose Depot Oral Vitamin D3 Versus Daily Oral Vitamin D3 for Treating Nutritional Rickets: A Randomized Clinical Trial

Objective: To compare the efficacy of daily versus low dose depot oral vitamin D3 for treating nutritional rickets. Design: Randomized Controlled Trial Setting: Paediatrics department of a tertiary care hospital catering to semi-urban and rural population in Delhi, India Methods: We randomized 66 children aged 3 months to 5 years with nutritional rickets to receive either daily oral vitamin D3 drops (3-12 months: 2000 IU; >12 months-5y: 4000 IU; n=33) for 12 weeks duration, or a single oral depot dose of vitamin D3 granules (3-12 months: 60,000 IU; >12 months-5y: 150,000 IU; n=33). Results: Participants in both groups had comparable demographic characteristics, laboratory features and radiological severity of rickets. 33 participants in each group received the assigned intervention and all were followed up till 12 weeks. At 12 weeks follow up, children in both groups showed a significant improvement in all biochemical parameters [serum calcium, phosphorus, alkaline phosphatase, parathormone and 25(OH) vitamin D levels] as well as radiological healing. At 12 weeks, the mean (SD) serum 25(OH) vitamin D levels (nmol/L) were statistically comparable in both groups [daily: 120.2 (83.2), depot: 108 (74), P=0.43] and 31 (94%) children in each group had radiological healing (Thacher score <1.5). Two children in each group persisted to have raised alkaline phosphatase and one child each in the daily group continued to have hypocalcemia and hypophosphatemia at 12 weeks. Conclusion: Low dose oral depot vitamin D3 is an effective alternative to daily oral vitamin D3 for nutritional rickets.

Comparison of two methods in the treatment of congenital pseudarthrosis of clavicle: multicenter experience

Background Congenital pseudoarthrosis of the clavicle (CPC) is an uncommon entity. Owing to its scarce presentation, treatment of this disorder has not been well established. This study aimed (1) to compare surgical treatment methods that included excision of pseudoarthrosis and iliac crest bone graft and fixate with either the elastic stable intramedullary nail (ESIN) or K-wires or plate and screws, and (2) to assess the clinical outcomes of two different surgical methods. Methods A multi-central retrospective study was performed between 2013 and 2017 in four tertiary teaching hospitals. Fifteen clavicles of 11 children were identified as CPC. All patients underwent pseudarthrosis resection and iliac crest bone autograft. They were divided into two groups as per the surgical treatment they underwent—plate stabilization as group A and elastic stable intramedullary nailing (ESIN) or K-wires as group B. Nine clavicles in 6 patients in group A and 6 clavicles in 5 patients in group B, were included. The Quick Disabilities of the Arm and Shoulder (QuickDASH) score was used to assess patients’ satisfaction and function following treatment at each follow-up. Results There were eight boys and three girls, with an average age of 4.7 years. All patients, except one with intellectual impairments, had radiological healing. Implant removal time was significantly shorter in group B compared to group A. No statistically significant differences existed in terms of age at surgery, time of radiological healing, complication, and clinical outcome between different groups. Conclusion Surgical resection of pseudoarthrosis with an iliac crest bone graft was an effective means of surgical treatment in CPC. However, ESIN or K-wires can achieve shorter union time compared to the plate. Hence, surgical treatment is recommended for congenital pseudarthrosis of clavicular in pediatric patients. Level of evidence Retrospective comparative study; Level III

P399 Higher anti-tumour necrosis factor-alpha drug levels are associated with improved radiological outcomes in patients with perianal fistulising Crohn’s disease: A retrospective multi-centre study

Background Higher anti-tumour necrosis factor-α (TNF) drug levels are associated with improved clinical fistula healing and closure in perianal fistulising Crohn’s disease (pfCD). It is hypothesised that higher drug levels will lead to improved healing on magnetic resonance imaging (MRI); but this is yet to be established. This study evaluated the association between anti-TNF drug levels and radiological outcomes in pfCD. Methods A multi-centre retrospective study (FISCAL), across 10 ANZ Inflammatory Bowel Disease Consortium sites. Patients with pfCD on stable maintenance dosing of infliximab or adalimumab, with drug levels within 6-months of a pelvic MRI from 2010 to 2020 were included. Patients receiving perianal fistula surgery between drug level and MRI were excluded. MRI disease activity was scored using the Van Assche Index (VAI), with an inflammatory sub-score (VAIinfl) derived from the VAI indices: hyperintensity on T2-weighted images, collections &gt;3mm diameter, and rectal wall involvement. Primary endpoint was radiological healing (VAIinfl≤6). Secondary endpoint was radiological remission (VAIinfl=0). Drug level tertiles were correlated to changes in VAIinfl scores. ROC analyses were used to identify optimal target drug levels. Results Of 193 patients (infliximab, n=117; adalimumab, n=76), radiological healing was achieved in 47.0 and 44.7% and radiological remission in 17.1 and 15.8% of patients receiving infliximab and adalimumab, respectively. Patients with radiological healing had higher median drug levels compared to those with radiologically active disease (infliximab 6.0 vs 3.9µg/mL, P=0.03; adalimumab 9.1 vs 6.2µg/mL, P=0.02). Patients with radiological remission had higher median drug levels compared to those with radiologically active disease (infliximab 7.4 vs 3.9µg/mL, P&lt;0.01; adalimumab 9.8 vs 6.2µg/mL, P=0.07). There was a significant incremental reduction in median VAIinfl with higher anti-TNF drug level tertiles, shown in Figure 1. By ROC analyses, the optimal trough infliximab levels for radiological healing and remission were 4.0µg/mL (sensitivity 69.1%, specificity 45.2%, AUC 0.62, P=0.03) and 6.5µg/mL (sensitivity 60.0%, specificity 72.2%, AUC 0.67, P=0.02), respectively. The optimal adalimumab levels for radiological healing and remission were 7.2µg/mL (sensitivity 67.6%, specificity 59.5%, AUC 0.65, P=0.03) and 9.7µg/mL (sensitivity 58.0%, specificity 70.0%, AUC 0.62, P=0.20), respectively. Conclusion In the largest study of its kind, higher anti-TNF drug levels were associated with improved MRI parameters as per the VAI in patients with pfCD; with an incremental improvement in MRI outcomes at higher anti-TNF drug level tertiles for both infliximab and adalimumab. Replication in prospective studies are awaited.

Hyperbaric oxygen treatment for late low colorectal anastomosis ischaemia: Case report

Introduction: This report describes the use of hyperbaric oxygen treatment (HBOT) to treat a case of colorectal anastomosis ischaemia following colorectal surgery. Case report: A 47-year-old man developed post-operative colorectal anastomosis ischaemia with leak after laparoscopic low anterior resection for T3N0 adenocarcinoma of the rectum. The leak with concomitant ischaemia presented 17 days after surgery. HBOT was administrated in 11 sessions over three weeks and the patient followed endoscopically and radiologically for two months. At two months the anastomosis showed both endoscopic and radiological healing; therefore the ileostomy was closed. Anal function was satisfactory with no incontinence or evidence of sepsis. Conclusions: Intra-operative or late leak with concomitant ischaemia of a colorectal anastomosis is a challenging event in colorectal surgery. HBOT may be beneficial in promoting healing in selected patients. Further studies are needed to evaluate conservative treatments and the role of HBOT.

Rosai-Dorfman Disease of the Talus in a Child: A Case Report

Background Primary Rosai-Dorfman disease of bone is a rare disorder. Radiologic and clinical evaluation is insufficient in differentiating malignancy from these lesions. Methods We present a talar lesion in a 17-month-old boy who presented with deterioration in gait pattern, limping, pain, and swelling of the left ankle of 4-months' duration. Curettage and demineralized bone matrix grafting were performed. Results At 1 year after surgery, complete clinical and radiological healing was obtained. Conclusions Primary RDD of bone may present a diagnostic challenge. The condition must be included in the differential diagnosis of lytic or lucent lesions of the skeleton. Curettage and grafting provide satisfactory outcomes in talar RDD lesion in the pediatric age group.

Zimmer Natural Nails in the Treatment of Unstable Intertrochanteric Fractures: A Longitudinal Study

Introduction:Cephalomedullary nails are preferred over intramedullary nails for internal fixation of unstable intertrochanteric fractures; however, they are associated with complications as they do not match the anatomy of the proximal femur to a great extent. Aim: To investigate functional and radiological results of Zimmer natural nails in the management of unstable intertrochanteric fractures. Materials and Methods: A longitudinal prospective study of 99 patients with unstable intertrochanteric fractures was carried out. All patients underwent closed reduction and internal fixation with 180 mm short Zimmer natural nails. Follow-up visits were scheduled for six weeks, three months, and six months for radiological healing and mobility measurements using RUSH and Parker scores, respectively. Statistical analysis was performed using Chi-square and ANOVA. Results: Mean age of patients was 69.77±11.47 years with a male to female ratio of 1:1. A majority of patients had co-morbidities like diabetes mellitus and hypertension. Average duration of surgery was 58.38 minutes with no statistically significant difference among the different categories of unstable intertrochanteric fractures. Fixation of fractures with Zimmer natural nails increased Parker score and RUSH score consistently with each follow-up visit (p<0.05). There were no postoperative complications in 93.94% cases. Conclusion: This study emphasised good functional and radiological results of Zimmer natural nails in the treatment of unstable intertrochanteric fractures.

Floor Level Activity as a Sign of Congruency and Containment in Perthes’ Disease

Background: This study aims to note the role of floor level activities like squatting and sitting cross-legged as the indicator of healing with good containment and congruency in Perthes’ disease in children below eight years of age. The research hypothesis of the study is that the functional outcome of the affected hip joint in the form of spontaneous, free and full painless floor level activity in day to day life of the child is a better indicator of outcome irrespective of the radiographic changes in the hip joint. Subjects and Methods: A retrospective observational study was conducted in a tertiary care university hospital. The study included all the patients diagnosed with Perthes’ disease whose last radiological assessment showed signs of healing. Patients above eight years and patients who had not started showing radiological healing were excluded. Parameters assessed were the presence of lurch, pain at the hip joint, limb length discrepancy, range of motion at the hip joint and ability to sit cross-legged and squat and epiphyseal extrusion index on radiographs. Results: Nineteen hips in 18 patients met criteria with a mean age of 7.1 1.5 years at presentation with a minimum follow-up of 30 (30 – 72) months. None of the patients had any residual lurch or tenderness at the hip joint at final follow up and all were able to sit cross-legged and squat symmetrically and comfortably with significant improvement of motion at the hip joint (p<0.05). No correlation was noted among the clinical and radiological features; except the internal rotation at healing with epiphyseal extrusion index at healing. Conclusion: Clinical function holds the key primarily in the course of treatment of Legg-Calve-Perthes’ disease. Conservative management in the form of bracing, floor level activities, and hip flexion and abduction exercises lead to congruency and containment in Legg-Calve-Perthes’ disease up to the age of eight years.

A Study Comparing the Outcomes of Transverse Ulnar Shortening Osteotomy Fixed with a DCP to Oblique Osteotomy Fixed with a Procedure Specific Plate

Background: Ulnar shortening osteotomy (USO) is a well-established procedure for ulnar impaction syndrome. Various types of osteotomies have been described. Methods: A retrospective cohort study was conducted to compare the results of transverse osteotomy (TO) fixed with a small fragment dynamic compression plate (Synthes, Pennsylvania, USA), to oblique osteotomy (OO) fixed with a procedure specific plate and instrumentation system (Acumed LLC, Oregon, USA). A total of 39 patients underwent TO and 62 patients underwent OO between 2007 and 2016. The main outcomes compared were rate of union, duration of radiological healing, implant removal rate and other complications. Results: The two groups were comparable with regards to demographics, side operated and smoking status (p > 0.05). Amongst the TO group; 36 out of 39 patients (92.3%) achieved union, 3 patients (7.7%) developed non-union. Six out of the 36 healed TO (16.6%) required removal of hardware due to implant-related pain. No other complications were recorded amongst TO group needing surgical intervention. Amongst the OO group, 2 of the early cohort of 62 patients (3.2%) sustained acute failure of the metalwork due to technical error. One of the remaining 60 patients (1.6%) developed non-union giving an overall union rate of 95.2%. Two patients out of 59 healed OO (3.3%) required removal of hardware. Conclusions: Although there were 2 early failures, there was a trend towards improved union rate with OO, but this did not reach statistical significance (p > 0.05). There was a significantly higher hardware removal rate recorded in TO group (p = 0.023). The OO showed shorter duration for radiological healing than TO (p < 0.05). USO performed with an OO and fixed with procedure specific plate has lower implant removal rate, a shorter duration for radiological healing and comparable union rate to TO fixed with DCP, but needs careful attention to detail.