Left Femur Research Articles

Hydrothermal extraction and physicochemical characterization of biogenic hydroxyapatite nanoparticles from buffalo waste bones for in vivo xenograft in experimental rats

Hydroxyapatite (HA) can be used in odontology and orthopedic grafts to restore damaged bone due to its stable chemical characteristics, composition, and crystal structural affinity for human bone. A three-step hydrothermal method was used for the extraction of biogenic calcined HA from the buffalo waste bones at 700 °C (HA-700) and 1000 °C (HA-1000). Extracts were analyzed by thermogravimetric analysis, differential scanning calorimetry, X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and in vivo examination of HA xenografts for femoral lesions in experimental rats. Crystallinity, purity, and morphology patterns showed that the HA main phase purity was 84.68% for HA-700 and 88.99% for HA-1000. Spherical HA nanoparticles were present for calcined HA-700 samples in the range 57–423 nm. Rats with critical bone lesions of 3 mm in diameter in the left femur treated with calcined HA-700 nanoparticles healed significantly (p < 0.001) faster than rats treated with HA-1000 or negative controls. These findings showed that spherical biogenic HA-700 NPs with a bud-like structure have the potential to stimulate both osteoconduction and bone remodeling, leading to greater bone formation potential in vivo. Thus, the calcined biogenic HA generated from buffalo waste bones may be a practical tool for biomedical applications.

SAT262 Bilateral Stress Fractures Of The Femur In A Patient With HIV On Long-term Tenofovir Disoproxil Fumarate And Short-term Alendronate

Abstract Disclosure: R.J. Mahatme: None. A.D. Lindsay: None. F.S. Mirza: None. Background: Tenofovir disoproxil fumarate (TDF) is a reverse transcriptase inhibitor used for HIV treatment, which has been documented to reduce bone mineral density through enhanced osteoclastic activity, reduced osteoblastic activity, disrupted calcium absorption and renal phosphate wasting. Prolonged use of TDF increases the risk of osteoporosis and fractures. Bisphosphonates (BP) are typically used to prevent osteoporotic fractures by inhibiting bone resorption. However, BP use for more than five years, and concomitant suppression of bone remodeling may be associated with an increased risk of subtrochanteric fractures. We report a case of unusual bilateral subtrochanteric stress fractures of the femur in a patient on long term TDF for HIV, who had taken alendronate for a very short duration. Clinical Case: A 56-year-old woman presented to orthopedics in 2017 with complaint of bilateral leg/hip pain associated with weight bearing. Past medical history was significant for HIV diagnosed in 1995, osteopenia diagnosed in 2015 and fibromyalgia. The patient had been taking TDF as part of HIV therapy since 1995 and had been started on alendronate 15 months prior for osteopenia. X-ray of the hips revealed diffuse osteopenia with areas of possible stress reaction/stress fracture at the proximal third of the right femur and in the subtrochanteric left femur. Nuclear medicine bone scan showed faint foci of increased uptake in the lateral subtrochanteric regions of both proximal femora and midshaft of the right femur suggesting insufficiency fractures. The report noted that these areas were present and unchanged compared to a prior bone scan from 2011. In view of significant discomfort and risk of progression to full fracture, she underwent prophylactic intramedullary nailing of the right femur and was referred to endocrine for bone health evaluation. Endocrine evaluation showed vitamin D insufficiency and suboptimal calcium intake which were both corrected. A call to the pharmacy revealed that she had only filled 3 prescriptions of alendronate even though she was initially prescribed alendronate a year and a half prior to her presentation. Alendronate and TDF were discontinued and tenofovir alafenamide (TAF) was added to her HIV regimen due to its less deleterious effects on the skeletal system. Patient did not report significant improvement in her leg pain after the intramedullary nailing and decided to maintain a conservative approach without intervention for the left femur stress fractures. Conclusion: This is an unusual presentation of bilateral stress fractures of the femur likely related to long term TDF therapy in a relatively young postmenopausal female who had taken alendronate for less than a year of cumulative dose. This case highlights the need to use medications that have less harmful effects on the bone in adults with HIV who are also at an increased risk for low bone density and fractures. Presentation: Saturday, June 17, 2023

THU413 Does Continuous Positive Airway Pressure Affect Bone Loss Process In The Population Of Sleep Apnea?

Abstract Disclosure: Y. Chen: None. A. Suresh: None. S. Haile: None. Z. Perciuleac: None. B. Soni: None. A. Cuevas Velazquez: None. A. Amirian: None. C. Udeh: None. L. Sangha: None. B. Ravichander: None. K. Aljassani: None. R. Joshi: None. A. Atrash: None. N. Ramesh: None. J. Sta. Cruz: None. S. Al-saadi: None. Introduction: Patients with obstructive sleep apnea (OSA) were reported to have higher risk of developing osteoporosis or increased bone loss. One of the theories suggested nocturnal hypoxia led to imbalanced osteoclastic activity and contributed to bone loss. Continuous Positive Airway Pressure (CPAP) is the first-line treatment for OSA, which improves airway obstruction and limits hypoxia. This study attempts to evaluate if compliant with CPAP therapy reduces bone loss. Methods: This retrospective study included patients who visited UPMC Central Pa. sleep medicine clinic from January 2010 to October 2022 with diagnosis of OSA and have at least two dual-energy X-ray absorptiometry (DEXA) after the OSA diagnosis. Patients’ records of CPAP usage on two databases, Respironics and Resmed, were used to assess the compliance of the therapy. The definition of compliance is average usage of 4hrs/night; frequency of use being 70% or above. Patient demographics, CPAP compliance, bone mineral density (BMD) and T-scores of two DEXAs were obtained. All data after diagnosis of active malignancy, hyperparathyroidism, end stage renal disease, or after patient received osteoporosis pharmacological treatment are excluded. Annual change of BMD was calculated with the difference of BMD between the two DEXA scans divided by the study interval. Two-sample t-test and chi-square test were used for analysis. Results: 265 patients were included for analysis, with 254 female (95.8%), 92.1% Caucasian, mean age 68.3 years old, mean BMI 36.7kg/m2. 165 patients were compliant and 100 were non-compliant. The two groups were identical on demographic data including age, sex, ethnicities. The median of annual BMD changes at L-spine, left femur neck, left femur total, and left radius were 0.003, −0.003, −0.002, −0.002 g/cm2 respectively in compliant group and 0.003, 0, −0.006, −0.002 g/ cm2 in non-compliant group. The annual changes of T-scores were 0, −0.043, 0, −0.036 for the compliant group and 0, 0, −0.051, −0.034 for non-compliant group. No significant within-group or between-group difference in annual bone density reduction on BMD or T-score was noted in our analysis. Discussions: Our study did not reveal the benefit of treating OSA on bone loss. Small sample size could be the leading factor for the limited effect size. Retrospective study design also restricted our study population to predominantly postmenopausal Caucasian female. Further adjustments for possible confounding factors including BMI and age might be beneficial. Future study with prospective design, larger sample size, and diverse population is encouraged to discover the effect of CPAP therapy on BMD preservation. Presentation: Thursday, June 15, 2023

SAT249 Femur Lysis Calcium Crisis

Abstract Disclosure: G. Gupta: None. S. Idriss: None. N. Barua: None. J. Hodge: None. I. Jamal: None. Introduction: Primary hyperparathyroidism usually presents with symptoms of bone pain, fatigue, polyuria, constipation, and nephrolithiasis. Here we describe a 27-year-old female with a femoral neck fracture and found to have a parathyroid mass. Case: 27 y/o female with autism spectrum, presented to the ED for evaluation of a mechanical fall and was found to have a left femur and pubic ramus fracture. On arrival she was vitally stable, labs were significant for parathyroid hormone-related hypercalcemia corrected Ca 14.8 mg/dL, PTH 911 peaked to 2884 pg/mL, vit D level of 12.7 ng/mL, phosphorus of 2.3 mg/dL. Trauma workup revealed numerous osseous lytic lesions lower extremities. Review of system was negative except for localized pain at fracture site. Family history negative for hypercalcemia or hyperparathyroidism. She was managed with IV fluids, IV Zoledronic Acid 4 mg, SC calcitonin 240 units, and 50K IU D3. During hospitalization, she needed re-dozing with Zoledronic acid and Cinacalcet due to recurrence of significant hypercalcemia, warranting further imaging. CT neck showed mandibular and maxillary bone lesions raising suspicion of hyperparathyroidism jaw tumor syndrome (HPT-JT) vs brown tumors, 3.1 cm lobular mass inferior to the right thyroid lobe suspicious for large parathyroid adenoma vs carcinoma, and other multiple enlarged parathyroids. She underwent left femur cephalomedullary nailing and prophylactic nailing for the impending right femur fracture. Bone pathology showed fragmented bone, adipose, and skeletal muscle with fibrinous debris. She underwent subtotal parathyroidectomy (4-1/2 glands) and intraoperative PTH level declined from 1537 to 75 pg/mL 15 minutes after removal. Pathology showed tissue consistent with multi glandular parathyroid disease without evidence of malignancy. Postop her course was complicated with hungry bone syndrome requiring a few weeks on IV calcium. Discussion: Pathologic conditions in primary hyperparathyroidism include single adenomas (80-90% of the time), multiglandular hyperplasia multiple-gland (three or more glands) accounting for approximately 6%, and parathyroid carcinomas account for 1-2% of cases. Other conditions as with primary hyperparathyroidism include Familial hyperparathyroidism such as MEN 1 &amp; 2A, Familial isolated hyperparathyroidism, and Familial HPT-JT syndrome, previously termed familial cystic parathyroid adenomatosis. Interestingly our pt had multiglandular hyperplasia which is a less common cause, she also demonstrated jaw lesions but didn’t fulfill the criteria for HPT-JT. Conclusion: Our patient had an unusual presentation of large bone fracture and multiple lytic lesions likely representing a brown tumor of the bone due to primary hyperparathyroidism. Most patients with lytic lesions have malignancy, however, endocrine pathologies should also be considered. Presentation: Saturday, June 17, 2023

THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome

Abstract Disclosure: E. Milazzo: None. K.L. Hermayer: None. Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases. Presentation: Thursday, June 15, 2023

THU469 Inhalant Use Resulting In Diffuse Osteosclerosis: Case Report And Review Of The Literature

Abstract Disclosure: C. Hung: None. M. Jesse: None. D. Saxon: None. Osteosclerosis of the bone can develop from excessive fluoride intake. Fluoride sources range from oral intake of fluorinated water, ingestion of toothpaste, to fluorocarbon inhalation. Skeletal fluorosis can manifest with bony changes ranging from increased striation/granulation to thickened trabeculae, and ligaments and tendons can ossify (1). In the literature patients have presented after noticing joint enlargement, worsening chronic joint pains, immobility, and stiffness. Workup generally includes radiographs and dual x-ray absorptiometry (DXA) can reveal increased bone density (2). We describe a patient with osteosclerosis and the workup for this condition. We review the existing literature on fluorinated inhalant use as a cause of osteosclerosis. The patient is a 49-year-old man with type 2 diabetes, chronic pain in multiple joints, hypogonadism, and osteomyelitis status post right above knee amputation was referred to Endocrinology after he was found to have sclerotic bone lesions while undergoing workup for poor mobility. X-ray, CT and MRI scans over the past 7 years showed diffuse bone sclerosis in the spine, pelvis, knee, tibia, and foot. Labs demonstrated normal calcium, albumin, and alkaline phosphatase. DXA confirmed elevated T-scores of +6.8 (1.985 g/cm2) at left femoral neck, +8.6 (2.097 g/cm2) at left proximal femur and +9.8 (2.406 g/cm2) at lumbar spine. The patient confirmed “huffing” computer cleaner for 1 year while having severe depression and had stopped inhalant use 7 years prior to presentation. On literature review we identified case reports of bone sclerosis related to inhalant use. Long-term outcomes and optimal management were described only in case reports. Osteosclerosis from fluorosis should be considered in patients with diffusely increased bone density at multiple sites. 1. Wang Y, Yin Y, Gilula LA, Wilson AJ. Endemic fluorosis of the skeleton: radiographic features in 127 patients. AJR Am J Roentgenol. 1994;162(1):93-8. Epub 1994/01/01. doi: 10.2214/ajr.162.1.8273699. PubMed PMID: 8273699.2.Tucci JR, Whitford GM, McAlister WH, Novack DV, Mumm S, Keaveny TM, et al. Skeletal Fluorosis Due To Inhalation Abuse of a Difluoroethane-Containing Computer Cleaner. J Bone Miner Res. 2017;32(1):188-95. Epub 2016/07/28. doi: 10.1002/jbmr.2923. PubMed PMID: 27449958; PubMed Central PMCID: PMCPMC5977397. Presentation: Thursday, June 15, 2023

SAT537 Thyroid Cancer Mimicking Acute Coronary Syndrome

Abstract Disclosure: N.M. Rodrigues: None. B. Alexander: None. J. Palacios Merchan: None. Background: The use of thyrotropin –alpha for preparation of remnant ablation is associated with superior short-term quality of life and similar rates of remnant ablation as thyroid hormone withdrawal. Usually treatment with thyrotropin-alpha is well tolerated, but we need to be aware of the potential side effects. Clinical case: 61-year-old Hispanic female with multinodular goiter, underwent total thyroidectomy for compressive symptoms. The pathology report showed 4 cm invasive papillary carcinoma, well-differentiated follicular variant, with invasion of an adjacent parathyroid gland. The margins were negative, and no nodal involvement was noted. Due to the extra thyroidal extension, the plan was to undergo radioactive iodine ablation. She received two doses of thyrotropin-alpha. On the following day, 24 hours after the second thyrotropin-alpha, she complained of severe left sided chest pain and went to the emergency room. Initial workup for acute coronary syndrome was negative. CT angiography done to rule out aortic dissection showed diffuse multifocal bilateral pulmonary nodules and a 2.4 cm lytic lesion on the superior aspect of the manubrium suggesting osseous metastasis. She had severe tenderness to palpation of her chest - mostly of the sternum. We decided to perform a whole-body scan to determine if the lesions were iodine avid. Due to down trending TSH at 25 microIU/mL, she received another dose of thyrotropin-alpha. Her TSH subsequently increased to 209.4 microIU/mL with a thyroglobulin level of 2250 ng/mL. Whole body scan showed evidence of metastatic disease to the lungs bilaterally and bone metastatic lesions in the manubrium and left proximal femur. . The pain did not improve with morphine but responded well to oral diclofenac. One week later, she again received two doses of thyrotropin-alpha in preparation for radioactive iodine ablation with 200 mCi of I-131 due to the metastatic lesions. She started taking prednisone 50 mg daily for 1 week before the thyrotropin- alpha injection and continued prednisone 25 mg for five additional days. She remained asymptomatic during the radioactive iodine treatment. Conclusion: Thyrotropin-alfa has a manufacturer warning that it can lead to an increase in tumor burden resulting in severe pain and inflammation, especially at the metastatic sites. Even though imaging to look for metastasis is usually not part of the protocol before radioactive iodine ablation, it could be considered in patients with high-risk features on the surgical pathology report. This could prevent possible complications related to thyrotropin-alpha by identifying patients at risk. It is recommended that patients with cancer near their trachea, in their central nervous system, or in their lungs receive treatment with glucocorticoids to reduce inflammation. This pretreatment is shown to be very effective in preventing these complications. Presentation Date: Saturday, June 17, 2023

THU434 A Case Of An Atypical Femur Fracture Managed Medically With Teriparatide

Abstract Disclosure: S.V. Rupani: None. A. Kotwal: None. L. Graeff-Armas: None. Atypical femur fractures (AFFs) are atraumatic or low-trauma femur fractures located in the sub-trochanteric region or femoral shaft. AFFs represent around 0.5% of all femur fractures. The increased use of bisphosphonates has led to a rise in the incidence of AFFs as it has emerged as a potential complication. While the mechanism of bisphosphonate-related AFFs has yet to be elucidated, one proposed mechanism is that bisphosphonates can cause over-suppression of bone turnover. If over-suppression is a contributing factor, then hypothetically, anabolic therapy can help heal existing fractures and prevent impending fractures by reversing over-suppression. Numerous animal models have demonstrated that parathyroid hormone and teriparatide enhance fracture healing. However, clinical trials and meta-analyses on the effects of teriparatide in fracture healing have been equivocal. There have been both retrospective and prospective studies, along with anecdotal reports demonstrating the benefits of teriparatide in healing in AFFs. However, there have been no randomized controlled trials assessing the efficacy of teriparatide in AFFs. Based on this limited evidence, the American Society for Bone and Mineral Research recommends considering teriparatide in patients who have failed conservative therapy. We present a case of an incomplete AFF in the setting of short-term bisphosphonate use that was managed with teriparatide in addition to conservative measures. Our patient presented with a complete right AFF treated surgically and an incomplete left AFF that we managed medically with teriparatide. Repeat left femur imaging six months after starting teriparatide therapy showed interval callus formation consistent with a healed fracture. Right femur imaging also showed a healing proximal femoral shaft fracture status post intramedullary fixation. She completed twenty-five months of teriparatide therapy and did not sustain any interval fractures. Repeat imaging one year after completion of teriparatide therapy continued to show a stable healed left AFF, along with a healed right AFF. She is currently more than two years post-completion of teriparatide and has remained fracture free. This case highlights the role that teriparatide may have as an option for medical management in incomplete AFFs and to accelerate healing in complete AFFs that have been managed surgically. Furthermore, with therapeutic options for osteoporosis management limited in the post-AFF setting, teriparatide helps increase bone mineral density and reduce future fracture risk. Randomized controlled trials are needed to draw definite conclusions on the efficacy of teriparatide in managing AFFs. However, this is difficult given the rare occurrence of AFFs. Therefore, case reports like ours offer insight into when teriparatide may be helpful in managing AFFs. Presentation: Thursday, June 15, 2023

Clinical Evaluation of Deep Learning-Based Auto-Segmentation toward MRI-Only Prostate Radiotherapy.

Due to its superior soft-tissue contrast, MRI is the imaging modality of choice for target and organs-at-risk delineation in prostate radiotherapy. A recent advanced MR scanner allows for an MRI-only workflow owing to its ability to generate synthetic CT (MRCAT) that enables accurate dose calculation and treatment planning. While auto-segmentation algorithms for CT images are increasingly being adopted in clinical practice, there are fewer such algorithms for MRI images. The purpose of this study was to evaluate a deep learning-based auto-segmentation tool (from MVision AI) for both MRI and MRCAT images. We hypothesize that such algorithms could produce accurate contours that require little manual editing, resulting in significant time saving and workflow efficiency in MRI-only treatment planning. T2 MRI and MRCAT image pairs (acquired on a Philips Ingenia 1.5T MRI Scanner) for 10 prostate patients treated in an MRI-only workflow at our institution were retrospectively collected with IRB approval. These image volumes were then segmented using deep learning-based auto-segmentation models trained for MRI and CT images, respectively. The structures were manually edited by an experienced physician in a commercial imaging informatics system (Velocity). Finally, the auto-segmented and the post-edit structures were compared using Dice Similarity Coefficient (DSC) and 95% Hausdorff Distance (HD95). Excellent agreement was found between the auto-segmented and post-edit structures. For MRCAT, the average DSC was 0.92±0.03, 0.99±0.00, 0.90±0.06, 0.89±0.07, 0.89±0.06, 0.95±0.04, and 0.96±0.03 for prostate, bladder, rectum, penile bulb, seminal vesicles, left femur, and right femur, respectively. The average HD95 for these structures were 0.65±0.51mm, 0.01±0.01mm, 2.07±1.68mm, 1.10±0.91mm, 1.67±1.81mm, 0.86±1.24mm, and 0.67±1.49mm, respectively. For MRI, the average DSC was 0.96±0.02, 0.99 ±0.00, 0.96±0.03, 0.87±0.03, 0.94±0.06, and 0.89±0.11 for prostate, bladder, rectum, penile bulb, seminal vesicles, and Barrigel spacer, respectively. The average HD95 was 0.25±0.21mm, 0.00±0.00mm, 1.60±1.87mm, 1.43±0.98mm, 0.50±0.86mm, and 1.56±2.26mm, respectively. We evaluated the clinical acceptability of deep learning-based auto-segmentation models for prostate radiotherapy, one for MRI and one for MRCAT delineation. Both models demonstrated superior accuracy, and a high degree of consistency, offering the potential for significant time saving in treatment planning and improved workflow efficiency.

Growth Arrest in Type IV Osteogenesis Imperfecta After Fassier-Duval Rod Insertion Treated by a Lengthening Magnetic Intramedullary Nail: A Case Report.

A child with Type IV Osteogenesis Imperfecta (OI) sustained a growth arrest of the distal femur after fixation of a left femur fracture with a Fassier-Duval expanding rod at 3 years old. Despite bar resection with fat interposition, the discrepancy progressed to 7.5 cm at maturity. Because the femur had grown to a sufficient diameter, he underwent successful lengthening with a magnetic intramedullary rod. Although it is a potential complication, growth arrest has not been reported in association with placement of an expanding nail in a child with osteogenesis imperfecta. This case illustrates this rare complication and treatment using a magnetic intramedullary rod.

Comparison of AI-Based Auto-Segmentation Quality with Different Daily IGRT Imaging Modalities for Adaptive Radiotherapy Treatment Planning

Modern AI-based auto-segmentation tools may be applied on daily computed tomography (CT) images in an image-guided radiotherapy course to facilitate evaluation of anatomical variations and adaptive treatment planning. However, most AI auto-segmentation models are trained with high-quality diagnostic or planning CT image data. This study aims to evaluate and compare auto-segmentation quality by an AI-based auto-segmentation system with different daily CT imaging modalities. We retrospectively retrieved daily IGRT images for sixty patients. Among them, twenty patients were treated on helical tomotherapy with daily megavoltage CT (MVCT) scans, twenty patients were treated on conventional Linacs with daily cone-beam CT (CBCT) scans, and twenty patients were treated on a biology-guided radiotherapy (BgRT)-capable machine with daily fan-beam kilovoltage CT (kVCT) scans. With each treatment modality, ten patients received daily CT scans in the pelvic region while the other ten received daily CT scans in the thoracic region. An auto-segmentation system using a convolutional neural network algorithm was trained in-house with historical treatment planning CT and contouring data to generate auto-segmentation models for the pelvic and thoracic regions, respectively. Normal organs were first delineated the auto-segmentation system on the daily CT images and then drawn by an experienced planner. A set of metrics including the dice similarity coefficient (DSC), Jaccard similarity index, and Hausdorff distance were used to evaluate the quality of the auto segmentation results compared with manual contours. The auto-segmentation contours on the kVCT images showed higher average DSC compared to those on the MVCT and CBCT images for all the major organs in both the pelvic and thoracic regions including the bladder, rectum, bowel, left and right femurs, esophagus, heart, left and right lung, and spinal cord. With the kVCT images, the average DSC ranged from 0.52±0.22 to 0.996±0.005. In the pelvic region, the largest absolute difference in DSC was observed for the bowel volume with an average DSC of 0.69±0.16, 0.49±0.27, and 0.32±0.25 for the kVCT, MVCT, and CBCT images, respectively (p-value < 0.05 with unpaired t-tests between kVCT and the other two imaging modalities); in the thoracic region, the largest absolute difference in DSC was observed for the esophagus with an average DSC of 0.63±0.16, 0.22±0.08, and 0.15±0.18 for the kVCT, MVCT, and CBCT images, respectively (p-value < 0.05 with unpaired t-tests between kVCT and the other two imaging modalities). Similar results were observed with other metrics. The AI-based auto segmentation system showed improved agreement with manual contouring when using kVCT images from the BgRT capable machine compared to MVCT or CBCT images. However, manual correction is necessary on auto-segmentation results from all imaging modalities especially for organs with limited contrast from surrounding tissues.

OA08 Atypical femoral fracture secondary to long term bisphosphonate use; are we doing enough to prevent it?

Abstract Introduction Atypical femoral fractures (AFF) are low energy subtrochanteric or femoral shaft fracture associated with long term use of bisphosphonates (BP). Although the absolute risk of AFF is low and ranges between 3.2-50 cases/100,000 person-years, this risk is said to double with prolonged use (&amp;gt;5 years). ROS and American Society for Bone and Mineral Research (ASBMR) recommends regular review of patient at 5 years for oral BP and 3 years for intravenous BP. We would like to share our experience with two AFF which was seen in our bone clinic over the last one year resulting from prolonged bisphosphonates use. Case description Case 1 A 76-year-old Caucasian lady was reviewed for follow-up appointment in bone clinic for the management of steroid induced osteoporosis. She was on AA for 13 years for primary prophylaxis. It was noted that she was experiencing discomfort in her right thigh for the last 8 months. Her initial femoral X-ray showed incomplete AFF of the right femur and she was referred to orthopaedics who suggested conservative management. 6 months later, she unfortunately had a fall resulting in right femur fracture which required intramedullary nailing. X-ray of the contralateral side shows periosteal thickening and she is waiting for prophylactic nailing. Case 2 79 year old white Caucasian presented to the hospital with a fall. She has been on long term steroids for PMR and was on alendronate for 20 years for primary prophylaxis. X-ray showed complete AFF of proximal right femur shaft which required intramedullary nailing, subsequently developed pain in left hip during physiotherapy and X-ray showed incomplete AFF of mid left femur which needed prophylactic nailing. She was then referred to our clinic for further risk stratification. Both the patients had their bisphosphonates stopped and was advised reduced weight bearing along with calcium and vitamin D supplementation. The table summarises the background history and investigations post presentation with AFF: Discussion Bisphosphonates are one of the mainstays for managing steroid induced osteoporosis and for patients with high risk fragility fractures. Despite the increasing awareness of long term complication, we still see patients with AFF who have missed the opportunity for review in primary and secondary care particularly among patients with primary prophylaxis with satisfactory DEXA scan. ROS and ASBMR recommends review of patients who are on oral bisphosphonates at 5 years and for patients on intravenous bisphosphonates at 3 years for further risk stratification to reduce the incidence of AFFs. It also recommends close monitoring in patients with prodromal pain in the hip, groin or thigh especially in those who have high risk factors such as long term glucocorticoid use, Asian race and femoral bowing. Cessation of bisphosphonates can result in 70% reduction of developing AFF. Hence a break in the treatment for approximately 18-24 months needs to be considered for patients who are at lower levels of risk for fragility fracture such as age &amp;lt;75years, no previous history of fragility fracture, DEXA T score more than −2.5 and low FRAX score. Yet, this is not happening in routine clinical practice both in primary and secondary care and patients fall out of safety netting resulting in AFF. We need robust pathway and safety netting for patients who are on long term treatment. This situation could have also been exacerbated by the COVID pandemic which has increased the waiting lists and cancelled appointments. Resulting in many elderly patients having no follow ups and DEXA assessments for risk stratification. Key learning points Following the COVID pandemic there has been a huge impact on the waiting list, which has further pushed follow-up review for patients on long term bisphosphonates. This has resulted in a missed opportunity to identify patients with low risk to have a break in the BPs treatment. We feel that with appropriate treatment pathways needs to be set at primary care and secondary care level to capture these patients on long bisphosphonates after 3 to 5 years of BP use; especially patients who are at higher AFF risk, including patients on glucocorticoids and patients of Asian ancestry. Steps must be put in place to ensure counselling and education is given to patients about risk of AFF and prodromal symptoms such as thigh or groin pain which are initial symptoms, so that they can seek appropriate review at primary care level. ROS and ASBMR Task Force 2013 need to be implemented locally to capture patients with long term BPs treatment. Also, if patients has AFF fracture, imaging of the other leg has to be considered for further evaluation as more than one fourth of the cases have contralateral lesion.

P06 Think of hypophosphatasia if atypical fracture with persistent low ALP levels

Abstract Introduction Hypophosphatasia (HPP), a rare, underdiagnosed metabolic genetic bone disease caused by diminished or absent expression of the tissue non-specific alkaline phosphatase (TNSALP) enzyme. The mutation of alkaline phosphatase (ALPL) gene leads to wide-ranging clinical manifestations, broadly classified into six different types based on age of onset and severity of the disease. Fragility fractures are predominant characteristics of adult onset HPP and are often misdiagnosed as osteoporosis, stipulating antiresorptive treatment. However, bisphosphonates (BP) make HPP more susceptible to atypical fractures and thus are contraindicated. A recent study shows 1:4 atypical femoral fracture cases are linked with monogenic bone diseases including HPP. Case description A 63-year-old Caucasian female was referred to our osteoporosis clinic, at the age of 57 following an atypical right femur fracture while on bisphosphonate and steroids. Her past medical history includes multiple right thigh sarcoma at the age of 39, 45 and 49 years requiring multiple surgeries and localised radiotherapy. She was also diagnosed with ocular myasthenia gravis two years before the atypical fracture, requiring long term high dose steroids. Her other co-morbidities include type 2 diabetes and hypertension. Due to long term steroids, her primary care physician initiated weekly 70 mg oral alendronic acid. However, three months later she had a spontaneous right mid shaft femur fracture. The patient experienced one year of right thigh pain prior to fracture which was not brought to medical attention. She underwent intramedullary nailing and successful rehabilitation. A thorough assessment in fracture liaison service spotted the history of primary tooth loss with roots intact in childhood, and chronic dental problems crowning in adult life requiring many caps and crowns. Her mother has a history of “childhood onset rickets”, bowing of legs and complete loss of all her permanent teeth at the age of 30 years. A review of blood tests revealed normal calcium, vitamin D and parathyroid levels, multiple low alkaline phosphatase levels between 16 – 23 U/L(normal range 30-130 U/L) prior to bisphosphonates, vitamin B6 fasting blood test had shown raised result at 140 (normal range 40-100). Xray of the left femur was normal. The dual energy X-ray absorptiometry (DEXA) scan yielded normal T score. The genetic test confirmed heterozygous gene mutation in ALPL gene, confirming a diagnosis of hypophosphatasia. She recovered well from her fracture and manages to walk more than one mile unaided. She is currently under regular follow-up in our hypophosphatasia clinic and has stopped bisphosphonates indefinitely. Discussion The underlying cause for atypical femoral fracture (AFF) in this case is multifactorial; long-term steroids, radiotherapy, HPP and bisphosphonate usage. Regardless, there is a relationship between hypophosphatasia and AFF. Some studies have proved that more than 90% of the patients with AFF used long term BPs. The defective ALPL gene in HPP affects bone mineralisation, resulting in accumulation of inorganic pyrophosphate (PPi), which impairs hydroxyapatite crystal formation causing recurrent fractures, osteopenia, delayed wound healing, dental problems, atypical and pseudo fractures. Bisphosphonates are chemical derivates of PPi, and thus inversely affect bone mineralisation especially in cases of TNSALP mutations and thus are contraindicated in HPP. The atypical fractures often may remain undiagnosed for a long time despite often prolonged prodromal pain occurring before the actual fracture. Careful clinical evaluation and plain X-ray will help to make the diagnosis. Hypophosphatasia related fractures mostly occur laterally in the subtrochanteric diaphysis. AFF cases often require surgical repair with intramedullary nailing. If an imminent atypical fracture is diagnosed early, prophylactic surgery is sometimes recommended. After three months of alendronic acid, bone turnover markers are usually suppressed, therefore despite the short time of alendronate exposure, this is likely to have contributed to the atypical femur fracture. Also, genetic test revealed inherited autosomal dominant trait of HPP in this case, enabled family screening and prevention of potential use of future bisphosphonates in affected family members. Key learning points HPP presenting in adulthood may be more common than previously though with a recent study estimating prevalence of the mild HPP genotype to be 1:508, although not all cases will be symptomatic. A persistent low alkaline phosphatase together with a fragility or atypical fracture raises suspicion of hypophosphatasia. A thorough clinical evaluation, fasting vitamin B6 levels, urine phosphoethanol amine levels and ALPL genetic test will aid the diagnosis. Severe cases of hypophosphatasia are treated with asfotase alfa, enzyme replacement therapy, to prevent debilitating complications, while most mild and moderate cases are offered supportive management. Bisphosphonate treatment is contraindicated in hypophosphatasia. It is worth reviewing ALP levels prior to antiresorptive therapy in suspected cases, as bisphosphonates often reduce ALP levels, masking the diagnosis. High risk Osteoporosis cases should be discussed in a multidisciplinary setting with careful risk-benefit evaluation. Cases like this highlight the importance of early HPP diagnosis to avoid contraindicating treatments and their consequences.

An in vivo study to investigate an original intramedullary bone graft harvesting technology

BackgroundHarvesting bone graft (BG) from the intramedullary canal to treat bone defects is largely conducted using the Reamer–Irrigator–Aspirator (RIA) system. The RIA system uses irrigation fluid during harvesting, which may result in washout of osteoinductive factors. Here, we propose a new harvesting technology dedicated to improving BG collection without the potential washout effect of osteoinductive factors associated with irrigation fluid. This novel technology involves the conceptual approach of first aspirating the bone marrow (BM) with a novel aspirator prototype, followed by reaming with standard reamers and collecting the bone chips with the aspirator (reaming–aspiration method, R–A method). The aim of this study was to assess the harvesting efficacy and osteoinductive profile of the BG harvested with RIA 2 system (RIA 2 group) compared to the novel harvesting concept (aspirator + R–A method, ARA group).MethodsPre-planning computed tomography (CT) imaging was conducted on 16 sheep to determine the femoral isthmus canal diameter. In this non-recovery study, sheep were divided into two groups: RIA 2 group (n = 8) and ARA group (n = 8). We measured BG weight collected from left femur and determined femoral cortical bone volume reduction in postoperative CT imaging. Growth factor and inflammatory cytokine amounts of the BGs were quantified using enzyme-linked immunosorbent assay (ELISA) methods.ResultsThe use of the stand-alone novel aspirator in BM collection, and in harvesting BG when the aspirator is used in conjunction with sequential reaming (R–A method) was proven feasible. ELISA results showed that the collected BG contained relevant amounts of growth factors and inflammatory cytokines in both the RIA 2 and the ARA group.ConclusionsHere, we present the first results of an innovative concept for harvesting intramedullary BG. It is a prototype of a novel aspirator technology that enables the stepwise harvesting of first BM and subsequent bone chips from the intramedullary canal of long bones. Both the BG collected with the RIA 2 system and the aspirator prototype had the capacity to preserve the BG’s osteoinductive microenvironment. Future in vivo studies are required to confirm the bone regenerative capacity of BG harvested with the innovative harvesting technology.

Plate-assisted bone-segment transport in the femur with 2 internal lengthening nails: a technical note and a case report.

A novel technique to resolve large bone defects, using 2 internal lengthening nails (ILNs), one antegrade and one retro-grade, aligned in a custom-made tube is presented. A 28-year-old, healthy, asymptomatic male presented with a slowly growing mass in the left femur.

Consequences of Proximal Femoral Focal Deficiency Case Report and Literature Review

Introduction: Proximal femoral focal deficit it is believe a congenital condition with phenomena known as dysplastic hip with shortening or absent femur. Proximal femoral focal deficit is relatively uncommon. Estimate of this infrequent anomaly on radiographs can aid treat these cases better as early treatment could help in achieving satisfactory growth of the femur. Importance: We report one of the rarest cases of patient underwent five different surgeries for correction of proximal femoral focal deficit starting from age of 11 years to 25 years of age and dealing with proximal femoral focal deficit complication. Case Presentation: 11 years with left lower limb shortening. The Patient was not following up with any clinic before. He was born via vaginal normal delivery as full-term baby with no postnatal complication. Upon examination, the patient had a shortening of the left lower limb of almost 6cm in comparison to the right side. x ray showed left hip proximal femur focal deficit. Our patient underwent 5 different surgical correction of proximal femoral focal deficit. Clinical Discussion: Proximal femoral focal deficit is an extremely rare congenital anomaly with few case reports in the literature. Therefore, for us to have one case with a long follow-up that includes five surgeries done to the same patient, which is not described in the existing literature, is exceptional. No literature describe how to deal with complication of Proximal femoral focal deficit. Conclusion: The discovery of one cases of proximal femoral focal deficiency, a rare entity. Moreover, dealing with such rare case with it is compilation consider a very rare entity

Does the type of medial plate fixation matter for supplemental fixation of distal femur fractures manage with a lateral pre-contoured locked plate? A Biomechanical study.

Fixation of distal femur fractures with a lateral pre-contoured locking plate provides stable fixation and is the standard treatment in most cases, allowing early range of motion with a high rate of union. However, in situations, the stability achieved with the lateral plate alone may be insufficient, predisposing to fixation failure. The objective of the study was to compare, in synthetic bone models, the biomechanical behaviour of the fixation with a distal femur lateral pre-contoured locking plate solely and associated with a 3.5mm proximal humeral locking plate applied upside down or a 4.5mm helical locking compression plate on the medial side. A total of 15 solid synthetic left femur samples were used. A metaphysical defect at the level of the medial cortex was simulated. The samples were randomly distributed into three groups equally. All groups received a 4.5/5.0mm single lateral 9-hole distal femur lateral pre-contoured locking plate. Group 1 had no supplementary plate. Group 2 received a supplementary 6-hole 3.5mm proximal humeral locking plate and Group 3 received a supplementary 4.5/5.0mm helical 14-hole narrow locking compression plate. Both supplementary plate types used in groups 2 and 3 contributed to increase the apparent stiffness of the construct, but pairwise comparison showed statically significant difference only between group 1 and 3. No significant difference was observed between groups 2 and 3. Both supplementary plates might be considered for improving the fixation in distal femur fracture in selected cases.

Abstract P180: Hypertension-linked Immune Activation Regulates Osteoclastogenesis

Osteoporosis is an age-related disease affecting 18% of adults. Hypertension is associated with increased risk for fragility fracture and accelerated bone loss in adults. We hypothesized that experimental hypertension would induce osteoporosis and examined the mechanisms involved. We used two preclinical models in 12-week-old male C57Bl/6J mice: angiotensin (ang) II infusion (490 ng/kg/min) and deoxycorticosterone acetate (DOCA)-salt. After 6 weeks of ang II or 3 weeks of DOCA-salt, the left femur and sixth lumbar vertebral body were studied. Mechanical testing showed that ang II reduced femoral ultimate strength (170.7±4.794 vs 157.3±3.670 MPa, p=0.0325; 154.1±7.403 vs. 119.9±4.375 MPa, p=0.0026) and peak moment (39.09±1.660 vs. 32.77±0.9380 Newton millimeters (Nmm), p=0.0018; 29.15±1.291 vs 19.58±1.308 Nmm, p=0.0004) with cortical and trabecular bone loss compared to controls. μCT showed that hypertension reduced vertebral body bone volume fraction (30.1±1.41 vs 25.1±0.992 %, p=0.0068; 25.9±2.03 vs 18.5±1.29 %, p=0.0119) and trabecular thickness (62±1.6 vs 57±1.4 μm, p=0.0105; 60±2.1 vs 51 ±1.6 μm, p=0.0069). Flow cytometry of bone marrow from ang II-treated mice revealed that CD4+ T cells and γδ T cells produce increased IL-17A which is known to induce osteoclastogenesis. Colony stimulating factor-1 (CSF1) is also known to stimulate osteoclast formation. Using in situ hybridization, we observed increased CSF1 mRNA in endothelial cells (ECs) of transcortical arterioles of hypertensive mice. Subsequent studies of cultured bone marrow derived ECs showed that CSF1 mRNA expression increased with 0% and 10% compared to 5% stretch. 5% stretch treated with endothelial nitric oxide synthase inhibitor, L-NAME, increased expression comparable to 0% and 10%, indicating that nitric oxide inhibits CSF1 production. Thus, T-cell activation and nitric oxide-dependent EC dysfunction in hypertension may skew the bone marrow to favor osteoclastogenesis, leading to bone loss. Understanding this mechanism will elucidate novel pharmacological targets to mitigate hypertension-induced bone loss.

Open Reduction of Pediatric Femur Fracture: A Technical Trick

Open Reduction of Pediatric Femur Fracture: A Technical Trick

Osteitis fibrosa cystica in primary hyperparathyroidism

A 29-year-old woman with no known medical history presented with a one-year-old pathological fracture of her left femur following a trivial fall at her residence. Initially treated with an intramedullary nail, she complained of difficulty in walking and multiple bony aches.