Left Femoral Neck Research Articles

Thoracic Vertebral Fracture in a Female Case of Ankylosing Spondylitis Complicated with Turner Syndrome and Insufficient Response to Adalimumab

Background: Ankylosing spondylitis (AS) is a chronic disease characterized by inflammatory back pain, with osteoporosis prevalence ranging from 18.7% to 62% 1. Vertebral fractures are four times more likely to occur 2. Turner syndrome (TS) is the most common sex chromosome abnormality in females, with a 1.4- to 2.2-fold increased likelihood of osteoporosis-related fractures 3. Seven cases of AS combined with TS with HLA-B27 positivity have been reported4. Methods: We report a case of a female patient with AS and TS who exhibited an inadequate response to adalimumab (ADA) and suffered a thoracic vertebral fracture. Results: A 41-year-old woman with HLA-B27 negative was diagnosed with AS in 2012 because of low back pain, and began ADA treatment in 2018. The patient had a past history of TS (45X/47XXX) with ultrasound revealing smaller than normal ovaries and uterus. Body weight was 54kg and height was 145cm (BMI25.68). She had primary amenorrhea, a wrist fracture at a young age, and a thoracic spine fracture in 2018. Bone mineral density (BMD) values for orthotopic lumbar vertebrae L1-L4 were 0.74 g/cm2, with Z-score of -2.7, and 0.564 g/cm2 at the left femoral neck with Z-score of -2.4. The FRAX tool predicted a 10-year fracture risk of 2.4% for the occurrence of major osteoporotic fracture (MOF), and a fracture risk of 0.9% for hip fracture. She initiated hormone replacement therapy (HRT). In November 2022, she discontinued ADA due to COVID-19 infection. Laboratory tests identified slightly elevated inflammatory markers (Fig. 1), low trough drug level of 0.31ug/ml and positive anti-drug antibody. In February 2023, she slipped in a snowdrift and experienced increased back pain. Spinal MRI revealed osteoporosis with a T7 compression fracture and a new T9 fracture (Figure 2 A,B). Sacroiliac (SI) joints MRI showed significant improvement of inflammation (Fig. 2 C,D). Spine surgery consultation suspected fracture attributed to obvious kyphosis deformity and stress concentration during falls, resulting in buckling compression. Repeated test determined a BMD value of 0.920 g/cm2 for orthotopic L3-L4 with a Z-score of -1.4, and a BMD value of 0.775 g/cm2 for the left total hip with a Z-score of -1.2, the 10-year probability of MOF was 3.2%, and that of hip fracture was 0.5%. She was diagnosed with severe osteoporosis due to recurrent fracture despite of BMD improvement and anti-osteoporosis medications were postponed. Conclusion: This case further proved the dominant role of disease co-morbidity and insufficient treatment in the unfavorable outcome regardless of genetic predisposition.

Osteoporosis and body composition in old patients with amputated lower limbs

The study aim was to investigate bone mineral density (BMD) and body composition in old patients with amputated lower limbs.Materials and methods. This work is a cross-sectional study, which enrolled 31 patients, who underwent amputation of one of the lower extremities. The mean age of the study patients was 73.4±9.0 years, ranging from 60 to 101 years. The majority of study patients were men (77.4%). 41.4% of patients underwent amputation of the left lower limb, 58.6% – right. The time from amputation to enrollment in the study ranged from 4 to 444 months, with a median of 30 months. Bone mineral density in the lumbar spine and proximal femurs was analyzed by dual energy x-ray absorptiometry.Results. Osteoporosis in the proximal part of the left femur was registered in 51.7% of patients, osteopenia – in 17.2%, normal BMD – in 31.1% of cases. Osteoporosis in the proximal part of the right femur was observed in 64.0% of patients. In the lumbar spine, osteoporosis was found only in 6.9% of patients. The mean T-score in the lumbar spine reached +0.38 SD, in the proximal left femur – -1.5 SD, in the left femur neck – -2.1 SD, in the proximal right femur – -2.0 SD, in the right femur neck – -2.1 SD. In the case of amputation of the left lower limb, the left femur BMD averaged 710.8±239 mg/cm3, the left femur T-score – -2.6±1.6SD, the T-score in the left femur neck – –3.0±1.3 SD, with the intact left leg – 980.1±194 mg/cm3,–0.8±1.5SD,–1.5±1.2SD, respectively (p=0.002, p=0.005 and p=0.006). In case of amputation of the right lower limb, the right femur BMD reached 743.8±268 mg/cm3, right femur T-score – -2.4±1.7SD, the T-score in the right femur neck – -2.4±1.7SD, with the intact right leg – 909.9±211.0 mg/cm3, -1.2±1.5SD, -1.5±1.5SD, respectively (p=0.09, p=0.06 and p=0.1). The likelihood of developing osteoporosis in the left femur with amputation of the left leg increased by 9.8 times, compared with patients who had a preserved left lower limb (odds ratio=9.8; 95% CI=1.1–93.5; p=0.02). In patients with amputation of the left leg, inverse correlation was registered between bone mineral density and the time from the moment of amputation to inclusion in the study (r= -0.65, p=0.03).Conclusion. Preliminary results of this study demonstrate a decrease in bone mineral density in the proximal femur of the amputated limb. Further studies are needed to study BMD in amputees and to elucidate the pathogenetic basis of the relationship between BMD and other clinical and laboratory parameters in this group of patients.

Femoral neck fracture after femoral head necrosis: a case report and review of the literature

IntroductionPathological fractures of the femoral neck caused by necrosis of the femoral head are extremely rare. Here, we report a rare case of bilateral femoral head osteonecrosis extending to the femoral neck, with bilateral pathological fractures of the femoral neck occurring within a short period of time.Case reportA 65-year-old male with a 25-year history of daily consumption of 750 ml of liquor, presented with right hip pain after labor for 1 month. He subsequently sustained a right femoral neck fracture without trauma and underwent a right total hip arthroplasty. Two months later, he suffered a non-traumatic left femoral neck fracture and underwent a left total hip arthroplasty. Histopathological examination revealed osteonecrosis of the femoral head and neck, along with the presence of osteoclasts and granulomatous inflammation. Bone mineral density testing also showed osteoporosis. The bilateral femoral neck fractures were ruled out to be caused by any other pathological factors.DiscussionThis is the first report of pathological fractures of the bilateral femoral neck caused by femoral head necrosis. During the literature review process, we found that this case conforms to the histological characteristics of rapidly destructive hip disease and analyzed the etiology of femoral head necrosis and the pathogenesis of femoral neck fractures.

Link between depression and bone mineral density in Cooper Center Longitudinal Study: Indirect effects of vitamin D, inflammation, and physical activity

BackgroundTo examine the effect of depressive symptom severity on bone mineral density (BMD) and the potential mediators of the relationship. MethodThis study used data from n = 7273 participants in the Cooper Center Longitudinal Study at the Cooper Clinic in Dallas. Participants were included if they had data for all study variables, including left and right femoral neck (BMD), age, sex, body mass index, smoking status, antidepressant (SSRI/SNRI) use, standard alcoholic drinks consumed per week, and depressive symptom severity as measured with the Center for Epidemiological Studies-Depression (CESD)-10. To evaluate the effect of depressive symptoms on both L/R femur BMD, two multiple linear regression analyses were conducted. To examine effects of vitamin D, high sensitivity C-reactive protein (hs-CRP), and physical activity (MET units) on the relationship between depressive symptom severity and BMD, parallel mediation analyses were conducted. ResultsDepressive symptom severity (CES-D 10 score) significantly predicted both L/R BMD (L: β = −0.048, R: β = −0.047, both p ≤ .001). Only physical activity significantly mediated the relationship between depressive symptom severity and L/R BMD (L: β = −0.008, 95 % CI [−0.011, −0.005]; R: β = −0.007, 95 % CI [−0.010, −0.005]). LimitationsThe sample may not be generalizable to all patient populations. ConclusionDepressive symptom severity was inversely related to both L/R femur BMD in a large cohort of relatively healthy adults. Physical activity, but not vitamin D or hs-CRP, mediated this relationship. Future research might examine the effect of physical activity interventions both on depression and BMD. Impact statementWe certify that this work is both novel and confirmatory of recent clinical research (Lee et al., 2015; Amsterdam and Hooper, 1998; Hlis et al., 2018; Wainstein et al., 2016; Blair et al., 1989; Farrell et al., 2022; Ainsworth et al., 2011). We demonstrated a negative relationship between depression and BMD in a large cohort of adults and expanded on previous findings by demonstrating that physical activity acts as a mediator of this relationship. Physical activity is known to stimulate osteogenesis in osteoporotic patients, and this study further expands on its role in depressive symptoms in this population. Key points•This study of a large cohort of adults adds to the growing body of evidence associating depression severity with low bone mineral density.•Physical activity acts as a mediator on the negative relationship between bone mineral density and depression.

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

THU459 Hypophosphatasia With Normal ALPL Gene Test; A Case Report

Abstract Disclosure: K. Alkwatli: None. L.Z. Khan: None. Introduction: Hypophosphatasia is a rare hereditary disorder caused by loss of tissue nonspecific alkaline phosphatase activity, an essential enzyme in phosphate metabolism. Severe cases present perinatally and in early childhood. Mild cases can present in adulthood and can be misdiagnosed. We present an interesting patient who was clinically diagnosed with hypophosphatasia despite negative molecular genetic testing. Case presentation: 40 years-old female with a history of fibromyalgia and multiple bone fractures presented to the clinic with a long-standing history of multiple cavities, severe fatigue, headaches, muscle cramps, and arthralgia. The patient had numerous fractures throughout her life that started at age five without significant trauma, including wrist, forearm, and metatarsal bones. Her family history was negative. Laboratory testing showed low alkaline phosphatase levels on multiple occasions, 28,29,30 U/L (reference range 34-123). Her vitamin B6 was elevated at 309 nmol/L (20-125). Her zinc, calcium, vitamin D, and liver function tests were all within normal limits. Bone density scan showed a Z score of -1.0 at the lumbar spine and a Z score of -0.3 at the left femoral neck. Molecular genetic testing of the ALPL gene was negative. Hypophosphatasia was diagnosed based on her clinical and lab assessments, and she is being treated with Asfotase alfa. Her clinical course is yet to be determined. Discussion: ALPL gene is responsible for encoding the tissue nonspecific alkaline phosphatase (TNALP), the main enzyme affected in patients with hypophosphatasia. TNALP degrades inorganic pyrophosphate (PPi) to inorganic phosphate (Pi), an essential element for bone mineralization. It also facilitates vitamin B6 to cross the cell membranes. Therefore, loss of function mutations of the ALPL gene cause accumulation of PPi, which impairs the calcium-phosphate hemostasis and causes damage to multiple organs. In addition, the accumulation of the active form of vitamin B6 extracellularly can result in neurological damage.Patients present with a broad spectrum of musculoskeletal, renal, dental, and neurological symptoms. The variability of the phenotypic magnitudes is thought to be due to heterogeneity in the ALPL gene mutations. Over 400s of ALPL gene mutations have been identified in patients with hypophosphatasia. Novel variants are increasingly being reported.Negative genetic testing of the ALPL gene can still be seen in patients with hypophosphatasia due to either a variant that is undetectable by current testing methodology or if the causative gene/s are not on the ALPL gene panel. Conclusion: Genetic testing is helpful in confirming the disease and providing genetic counseling; however, treatment should still be considered if patients have sufficient clinical and laboratory findings. Presentation: Thursday, June 15, 2023

SAT339 Osteopenia In The Setting of Mild Autonomous Cortisol Secretion

Abstract Disclosure: J.J. Mao: None. K.C. McCowen: None. C. Choe: None. Jimmy J. Mao, MD (1); Karen C. McCowen (1); Charles H. Choe (1)(1) Division of Endocrinology, Diabetes, and Metabolism, University of California San Diego, La Jolla, CA. Background: Over 80% of adrenal incidentalomas are benign adrenal cortical adenomas, of which 30-50% are found to have mild autonomous cortisol secretion (MACS). Bone fragility is a known complication of MACS. Clinical Case: A 57-year-old postmenopausal female with no prior history of fracture, venous thromboembolism, and atherosclerotic cardiovascular disease, was referred for incidental bilateral adrenal nodules. Body mass index was normal at 21 kg/m2, and no clinical stigmata of Cushing syndrome were noted on physical exam. Unenhanced computed tomography scan revealed a 4.6 cm right adrenal nodule and a 3.3 cm left adrenal nodule; both nodules measured less than -18 Hounsfield Units. Biochemical work-up for pheochromocytoma, primary aldosteronism, and non-classical congenital adrenal hyperplasia was negative. Evaluation for hypercortisolism revealed a morning cortisol of 20.3 mcg/dL (ref. 4-22 mcg/dL) with concurrent adrenocorticotropic hormone of <5 pg/mL (ref. 6-50 pg/mL), 24-hour urine free cortisol of 16.9 mcg (ref. 4-50 mcg), and midnight salivary cortisol of 0.07 mcg/dL (ref. <0.09 mcg/dL). A 1 mg dexamethasone suppression test measured on two separate occasions was elevated at 6.3 mcg/dL and 7.9 mcg/dL (ref. <1.8 mcg/dL). A subsequent 8 mg dexamethasone suppression test was also elevated at 6.1 mcg/dL (ref. <1.8 mcg/dL). The diagnosis of MACS was made. A bone mineral density (BMD) scan revealed T-scores at the right femoral neck, left femoral neck, and lumbar spine at -1.6, -1.3, and -0.8, respectively. Ten-year probability of major osteoporotic fracture and hip fracture were 8.3% and 1.0%, respectively. To reduce the risk for future fractures, the decision was made to proceed with adrenal vein sampling (AVS) in preparation for potential adrenalectomy. Conclusion: MACS is the most frequent hormonal abnormality in adrenal incidentalomas, with an estimated prevalence of 0.8-2 cases per 1000 persons. A previous prospective study found that surgical cure of unilateral MACS may lead to a substantial risk reduction (up to 15-fold) of future incident asymptomatic vertebral fractures. Additionally, the highest risk for clinical fracture in those with adrenal adenomas (either nonfunctional or with cortisol hypersecretion) appears to occur at 7-10 years after initial diagnosis. BMD does not perfectly correlate with fracture risk, so unilateral adrenalectomy (if lateralization is observed on AVS) and/or pharmacotherapy should be strongly considered in patients with an expected longevity of >10 years even with mild osteopenia and low fracture risk assessment tool scores. Presentation: Saturday, June 17, 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

Impact of Prior Radiation Therapy on Bone Mineral Density Change Over Time: Secondary Analysis of the Control Arm of a Phase III Randomized Trial

Retrospective studies have demonstrated that pelvic radiation therapy (RT) can lead to decreased bone mineral density (BMD) and increased risk of fracture. This is more relevant for men with prostate cancer (PCa) who often receive androgen deprivation therapy (ADT) in conjunction with RT. We performed a post-hoc secondary analysis of publicly available data of the control arm of a phase III randomized controlled study (NCT00089674) to determine if history of prior pelvic RT affects change in BMD over time in non-metastatic PCa patients treated with ADT. In this study, PCa patients with age ≥70 years or <70 years with low BMD (T-score <-1) or history of osteoporotic fracture, on ADT for at least 12 months were randomized to receive densoumab vs. placebo every 6 months for 3 years. Additionally, all patients received daily vitamin D and calcium supplementation. Randomization was stratified by duration of prior ADT (≤6 months vs >6 months) and age (<70 vs ≥70 years). BMD was measured at baseline, and at months 1, 3, 6, 12, 24, and 36 with blind reading by central reviewer. To model the effect of prior pelvic RT on dynamic change in BMD in the hip, lumbar spine, and femoral neck, we applied separate multivariate linear mixed effect models for each site. Age, ECOG performance score, history and number of prior fractures, smoking history, and years from initial cancer diagnosis were included as fixed covariates while patients were included as random intercepts. Among 734 patients who were randomized to the control arm, 563 participants with baseline and at least one post baseline assessment of BMD were eligible for this analysis. Overall, 34.4% (n = 194) received prior RT. We did not find any significant association of dynamic change in BMD with receipt of prior pelvic RT for left femoral neck (p = 0.7), total hip (p = 0.8), and lumbar spine (p = 0.5), respectively. At 36 months, there was no significant association of prior RT with percent change in BMD in femoral neck (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.30-2.41), total hip (OR: 0.96; 95% CI: 0.43-2.15), and lumbar spine (OR: 2.01; 95% CI: 0.63-6.45). However, note should be made of the opposite direction of association of prior RT with percent BMD change at 36 months for femoral neck and hip versus lumbar spine. In this exploratory analysis of the control arm of a phase III randomized trial, we did not find sufficient evidence of an association between prior pelvic RT and dynamic changes in BMD in femoral neck, hip, and lumbar spine over time in men with non-metastatic PCa and low BMD at baseline. This analysis should be interpreted cautiously considering its post-hoc nature with likely inadequate power, the possibility of selection bias, lack of information on receipt of prior ADT, and missing data in longitudinal assessments.

P01 An unusual case of pregnancy associated osteoporosis presenting with bilateral neck of femur fractures

P01 An unusual case of pregnancy associated osteoporosis presenting with bilateral neck of femur fractures

P02 When should we stop the antiresorptive medications in patients with osteoporosis?

Abstract Introduction Bisphosphonates are first line and denosumab is the latest antiresorptive agent approved for osteoporosis treatment. Those drugs showed a reduction in vertebral fracture risk and other non-vertebral by 35-70%. One of the rare adverse events with antiresorptive treatment is medicine-related osteonecrosis of jaw (MONJ) which mainly occur in individuals receiving high doses for the treatment of cancer. Recent research found true incidence of MONJ is very low despite public perception. Studies indicate that 50% of women and 20% of men aged over 50 years will experience an osteoporosis-related fracture which have significant associated morbidity and mortality. Case description We report a case of an osteoporosis patient who was treated with alendronate followed by denosumab and presented with suspicion of MONJ. In 2014, a 77-year-old female was referred following right neck of fragility femur fracture. DXA showed osteoporosis (T- score of the spine −3.2, T- score total hip −2.4 and T- score of left neck of femur −2.1). She was initially treated with four years of alendronate (70 mg once weekly) but sustained a pubic rami fracture. Hence, she was then treated with six monthly injections of denosumab (60 mg subcutaneously). After three injections, she developed jaw pain. She was reviewed by her dentist who advised her to stop the denosumab for suspected MONJ. She was then seen by the oral surgeon who confirmed that there was a piece of bone in UR6 socket but with no bone sequestrum and this piece of bone was removed under local anaesthesia with good healing. She was advised to restart denosumab. The patient was extremely worried and anxious about denosumab recommencement and teriparatide was considered. After completion of teriparatide treatment her DXA still showed osteoporosis (T- score of the spine −2.1, T- score of total hip −2.2 and T- score of left neck of femur −2.6) with stable changes in the hip and improvement in the spine. On review, she continued to have concerns about antiresorptive treatment. Further oral surgeon review stated low grade infection around UL7 with poor gum condition around UR6 and LR6 with some bleeding points but no definite diagnosis of MRONJ. It was advised that any further manoeuvre involving tooth extraction will be conducted by the oral surgeon. Following this, the patient was happy to consider zoledronic acid infusions. She is due for her 3rd zoledronate infusion and is undergoing regular dental checks. Discussion The incidence of MONJ in patients taking oral bisphosphonates for osteoporosis is relatively low, estimated to be less than 1% (0.001% to 0.01%). However, the risk is higher for individuals receiving higher doses of intravenous bisphosphonates for the treatment of cancer or bone-related complications of cancer. The incidence of MONJ in cancer patients receiving intravenous bisphosphonates ranges from 1% to 15%. More clinical studies have been published that describe the relation between MONJ and denosumab in cancer patients with the risk of MONJ varying between 0.7 to 1.9% (70 to 90 cases per 10,000 patients). However, in patients with osteoporosis treated with denosumab, the incidence of MONJ is lower, resulting in an even lower frequency of 0.04% (4 cases per 10,000 patients). It is understandable that there is a significant concern amongst dentists about MONJ risk with antiresorptive treatment, but it is paramount that the patients are made aware of the fracture risk and its significant effect on quality of life. Many patients are not aware that more than 20% of patients die in the first year after a hip fracture from complications surrounding the fracture and a significant number of patients lose their long-term ability to live independently. Vertebral fractures have significant morbidity and the mortality rate of 72% at 5 years and 90% at 7 years. Key learning points Most dentists are often reluctant to treat patients on anti-resorptive medications due to the risk of MONJ which results in patient’s concerns about treatment and subsequent stoppage of osteoporosis treatment leading to fracture risks. Thus, it is imperative to assure the patients of benefits of the anti-resorptive medications versus the MONJ risks. This calls for increased awareness and national guidelines for the prevention and management of ONJ in osteoporosis patients treated with antiresorptive.

261 Bilateral Femoral Neck Stress Fractures in an Active Adolescent Female: A Case Report

Abstract Bilateral femoral neck stress fractures are uncommon injuries in adolescents. We present such a case in a 15-year-old athletic female with no preceding trauma or underlying metabolic bone abnormality. The patient presented to Accident and Emergency with a three-week history of left buttock and lateral thigh pain and one-week history of right lateral thigh pain. The pain developed during physical activity and was relieved upon rest. Activities included running, dancing, and attendance at a six-week cadet marching course. Simple analgesia did not alleviate the pain. History revealed low caloric intake and previous secondary amenorrhea. The patient was previously managed by the General Practitioner and physiotherapist for suspected atypical sciatica. Physical examination showed a minimally antalgic gait and pain on palpation of the left groin. Both hips had full range of motion. Bone profile was normal. Radiographic films were initially interpreted as normal, however, formal reporting revealed sclerotic appearances to both femoral necks and a subtle break in the left femoral neck cortex. MRI confirmed the diagnosis of a complete displaced left femoral neck fracture and incomplete right inferomedial femoral neck fracture. Trace bilateral hip joint effusions were noted. The patient underwent bilateral fixation with cannulated screws. One-month post-operative, she engaged in walking and swimming without pain. Radiographic appearances were satisfactory. Early radiographic changes associated with stress fractures are subtle. This case highlights the importance of prompt formal radiological reporting and the early use of MRI as a diagnostic tool, particularly in patients with risk factors.

Migration of a Kirschner Wire Into the Urinary Bladder: A Case Report

Background. Migration of Kirschner wires is a dangerous complication of osteosynthesis, especially when they displace into adjacent anatomical areas. Preventive measures do not eliminate the possibility of this complication.&#x0D; Aim of the study to draw physicians attention to the possibility of asymptomatic migration of a Kirschner wire into the bladder after osteosynthesis of a femoral neck fracture with a bundle of wires&#x0D; Case presentation. We present a case report of a 70-year-old patient with asymptomatic migration of Kirschner wires into the bladder and hip joint cavity, which occurred 5 years after the primary surgery for the fracture of the left femoral neck. To manage the complication, a combination of endoscopic removal of the foreign body from the bladder and open removal from the hip joint followed by total hip replacement were used simultaneously. The surgical intervention was performed without any complications. The patient began rehabilitation the next day after the surgery.&#x0D; Conclusion. Osteosynthesis should be supplemented with preventive measures against the fracture of fixator and its migration. The patient must be dynamically followed up during the treatment period with all necessary monitoring methods (X-ray, CT scan, ultrasound, etc.). In case of wire fracture and/or migration, it must be removed immediately. Once the fracture has healed or the period of fixation of the dislocation is over, the wires should also be removed. Preventive measures can avoid the migration of Kirschner wires and related complications.

Correlation of Bone Textural Parameters with Age in the Context of Orthopedic X-ray Studies

The aim of this study was to establish a relationship between the textural parameters observed in X-ray images of bones and the age of the individual. The study utilized a meticulous visual analysis of the images to identify significant correlations between textural features and age. Five distinct regions of interest, namely the Wing of the Ilium, Neck of the Femur, Greater Trochanter, Ischium, and Shaft of the Femur, were identified on both sides of the body. Textural parameters were then measured for each of these regions. The left femoral neck showed the most noteworthy associations, with the textures generated from the histogram of oriented gradients and gray-level co-occurrence matrix exhibiting the strongest correlations (ρ −0.52, p-value 4.95 × 10−14). The main finding of the current study is that correlation of age-dependent bone structure differences in the femoral neck area is higher than in other structures of the femur. This proposed methodology has the potential to aid in the early detection of osteoporosis, which is crucial for devising treatment plans and identifying potential risks associated with bone fragility.

Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors – results from a randomized double-blind trial

Background Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. Methodology In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). Results After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. Conclusion 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.

Abstract #1400160: Early Onset Osteoporosis Associated with Novel Mutation of WNT1 Gene

Canonical WNT signaling plays a significant role in bone development and maintenance of bone mass. WNT1 gene mutations have been associated with osteogenesis imperfecta type XV in homozygotes and early onset osteoporosis in heterozygotes. We present a case of early onset osteoporosis associated with a novel mutation of the WNT1 gene. A 56-year-old female presented for evaluation of early onset osteoporosis. History was significant for hypothyroidism as well as chronic inflammatory demyelinating polyneuropathy on IVIG infusions. She was diagnosed with low bone density in the setting of a vertebral compression fracture from a diving accident when she was 24. She had mild scoliosis, brittle teeth and 10 fractures as a child and young adult including rib fractures, pelvic fracture and compression fracture of the spine, some of which occurred in the setting of low impact trauma. Her family history was notable for possible osteoporosis in her grandmother. Initial evaluation demonstrated PTH 75 (18 - 80 PG/ML), Calcium 9.5 (8.5 - 10.5 MG/DL ), Albumin 4.1 (3.5 - 5.0 G/DL ), 25-hydroxy vitamin D 44.6 (30.0-100.0 ng/mL), Phosphorus 3.6 (2.4 - 4.8 MG/DL), creatinine 0.59 (0.44 - 1.03 MG/DL), TSH 1.24 (0.350 - 5.500 uIU/ML ), 24-hour urine calcium 133 (50 - 300 MG/24H), late night salivary cortisol 0.066 (less than 0.112 ug/dL), tryptase 6.1 (< 11.0 mcg/L), tissue transglutaminase IgA antibody 2.5 (0-20 units), hemoglobin A1c 4.1 (4.3 - 5.6 % ), IGF-1 112 (50 - 317 ng/mL), Alkaline Phosphorus 62 (34 - 104 IU/L). Dual-energy X-ray absorptiometry (DEXA) scan at the age of 50 showed bone mineral density (BMD) 0.828 g/cm2 with T score of -2.0 at lumbar spine, BMD of 0.593 g/cm2 with T score of -2.3 at left femoral neck and BMD of 0.707 g/cm2 with T score of -1.9. She sustained a low trauma spine fracture at L1 at the age of 55. Subsequent DEXA scan at age 55 showed significant decline of BMD with T score of -3.3 at lumbar spine and T score of -3.0 at the left femoral neck. Due to suspicion for osteogenesis imperfecta, a genetic panel was sent which showed a heterozygous variant in WNT1 gene, c.581T >G (p.L194R). She was treated with oral alendronate 70 mg once weekly for less than one year which was stopped due to gastrointestinal side effects. Follow-up is planned for discussion of additional therapeutic options. Heterozygous mutations in WNT1 have been described in the literature as a cause of early onset osteoporosis. The currently described variant mutation in the WNT1 gene has not been previously reported in literature. In silico analysis using SIFT and PolyPhen2 predict this variant to be deleterious/possibly damaging. Genetic testing and evaluation of bone density in other family members may help further support the clinical importance of this mutation.

Abstract #1408105: Treatment of Bisphosphonate Associated Atypical Femur Fracture with a Combination of Teriparatide and a Novel Surgical Technique

Atypical femur fractures (AFF) caused by long term Bisphosphonate use are associated with high rates of delayed healing and non-union, posing a significant challenge in the management of these patients. We describe the case of a 64-year-old female with osteopenia on Bisphosphonate therapy for 15 years who sustained a displaced left AFF following a fall from standing height. She reported a 6-month history of antecedent left groin pain. Radiographs of the left femur showed an acute displaced transverse diaphyseal fracture with lateral cortical thickening and beaking. The right femur radiograph showed features of abnormal cortical remodeling with thickened, irregular cortices. DEXA showed T-scores of -2.1 at the left femoral neck, -1.4 at the left total hip, and -1.4 at the lumbar spine. She underwent an open reduction and internal fixation with insertion of a cephalomedullary nail placed in compression mode. A novel technique of intraoperative removal of the endosteal hypertrophied cortical bone at the fracture with a Midas rex cutting burr was used and there was excellent cortical contact after reduction. She had immediate relief of her pain and was permitted to fully weight-bear postoperatively. Her bisphosphonate was stopped immediately and Teriparatide was initiated at 7 weeks post-operatively. Radiographs 8 weeks after initiation of Teriparatide showed evidence of normal fracture union with mature callus formation. AFF caused by prolonged Bisphosphonate use have a high rate of delayed healing and non-union due to abnormal bone remodeling. Use of Teriparatide post-operatively has been shown to reduce healing time in recent small studies in surgically treated patients. Our case demonstrates expedited healing time when Teriparatide was combined with a novel surgical technique involving removal of a portion of the abnormal fracture end and placement of an intramedullary nail in compression mode. Furthermore, the patient had radiographic evidence of cortical thickening on her right femur, increasing her risk for contralateral AFF. Prophylactic surgical stabilization was recommended but the patient has deferred this. She remains fracture-free and pain-free on the right side, suggesting a possible benefit of Teriparatide use in patients at risk for impending AFF. Our case demonstrates an expedited healing time (3.5 months) relative to previously reported average healing times for AFF (10.7 months), supporting the use of the combination of Teriparatide and a novel surgical technique.

Abstract #1377932: An Inherited Metabolic Disorder That Masquerades as Osteoporosis

Hypophosphatasia is a rare genetic disorder caused by loss-of-function mutations in the ALPL gene, which encodes tissue non-specific alkaline phosphatase. The enzyme defect results in the accumulation of substrates like inorganic pyrophosphate, thereby inhibiting mineralization of bones and teeth. Clinical features include premature loss of deciduous teeth, bowed legs, lower extremity stress fractures, bone pain and impaired mobility. Serum alkaline phosphatase (ALP) is a marker of bone turnover. Low ALP, high serum vitamin B6 and high urine phosphoethanolamine are diagnostic hallmarks of hypophosphatasia. A 54-year-old lady was referred to the endocrinology clinic for severe osteoporosis, characterized by an olecranon fracture and low bone mineral density (T score -3.0 at the left femoral neck). Bone disease risk factors included premature menopause at age 38 years and maternal history of hip fracture. There was no personal or family history of recurrent fractures, impaired mobility, or unexplained tooth loss. Despite treatment with ibandronate, zoledronic acid and teriparatide, her bone mineral density declined over the course of a decade. Physical examination revealed low BMI (18.07 kg/m2), normal gait and intact muscle strength. Lab testing disclosed low serum alkaline phosphatase (ALP) 18 units/L [reference 45 to 117 units/L], high serum vitamin B6 131.8 nmol/L [reference 20.0 to 125.0 nmol/L] and high urine phosphoethanolamine 104 nmol/mg Cr [reference < 48]. ALP results prior to bisphosphonate exposure were unavailable. Vitamin D status, thyroid function, parathyroid hormone, corrected serum calcium, ceruloplasmin and zinc levels were normal. Exome sequencing identified a pathogenic heterozygous nonsense ALPL gene mutation, c.1282C >T (p.Arg428X). She was counselled to avoid bisphosphonate therapy indefinitely. ALP measurement was advised for her blood relatives since hypophosphatasia is an autosomal recessive or dominant disorder. With asfotase alfa, the only FDA-approved therapy for juvenile-onset hypophosphatasia, there have been no further fractures to date, and her mobility remains unimpaired. Hypophosphatasia can be mistaken for osteoporosis since both conditions present with low bone mineral density on DEXA scan. Furthermore, bisphosphonate therapy and hypophosphatasia are mutually exclusive entities that can present with low ALP. Thus, bisphosphonate exposure may pose a diagnostic quandary when distinguishing between osteoporosis and hypophosphatasia. This case highlights the importance of assessing ALP when evaluating osteoporosis with atypical features such as age of onset under fifty years, remarkably low bone mineral density, fracture(s), and inadequate response to anti-osteoporosis agents. Moreover, if ALP is low, some index of suspicion for hypophosphatasia ought to be maintained, even if dental or lower extremity bone symptoms are absent. Genetic testing is confirmatory. Bisphosphonate therapy and parathyroid hormone analogs are not established treatment modalities for hypophosphatasia. Instead, enzyme replacement with asfotase alfa is recommended.

DENSIDAD MINERAL ÓSEA BAJA EN VARONES JÓVENES CON INFECCIÓN ASINTOMÁTICA POR EL VIRUS DE LA INMUNODEFICIENCIA HUMANA EN TRATAMIENTO ANTIRRETROVIRAL

The aim of this study was determine the frequency of low bone mineral density (BMD) in young men with asymptomatic Human Immunodeficiency Virus (HIV) infection on antiretroviral therapy for less than 2 years, as well as to compare the frequency of low and normal BMD according to antiretroviral treatment (ART) scheme and level of physical activity. 39 young men with asymptomatic HIV infection and ART less than 2 years were included. A bone densitometry was performed, and the following areas were evaluated: lumbar spine, left femoral neck and total left hip. 12 patients (31%) with low BMD and 27 patients (69%) with normal BMD were found. No differences were found between patients with normal and low BMD according to type of ART and level of physical activity. The frequency of low BMD is high in young men with asymptomatic HIV infection under antiretroviral treatment for less than 2 years.

A different indication of pisphosphonates: Bone marrow edema

Abstract Introduction Bone marrow edema (BME) is an uncommonly diagnosed, reversible condition most often affecting the hip of middle-aged men. BME is characterized clinically by the onset of disabling bone pain, usually at a single skeletal site, generally in the lower limbs and most often the hip. Diagnosis is often delayed. The increased bone turnover and low bone mineral density may indicate a potential role for bisphosphonate therapy in BME. There is some evidence of the successful use of intravenous bisphosphonates in the treatment of BME of the hip. We aimed to present two cases of BME that were successfully treated with bisphosphonates. Clinical Case 1: A 41-year-old male patient presented with left inguinal pain. His past medical history was unremarkable. The visual analog scale (VAS) was 8–9. On physical examination, there was a limited range of motion (ROM) on the left hip. Laboratory results were within normal limits. Non-contrast MRI revealed signal intensity changes consistent with BME in the left femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved one week after bisphosphonate infusion. Complete resolution of bone marrow edema was seen in the MRI taken 2 months later (Figure 1). Bisphosphonate treatment with alendronate was completed for one year. Clinical Case 2: A 59-year-old male patient presented with right hip pain that limits his walking. He was diagnosed with BME and avascular necrosis as a result of clinical and radiological evaluation in the center he applied and he underwent a right femoral core decompression operation. He was evaluated in our clinic due to ongoing pain and limitation of movement 5 months after the operation. On physical examination, there was limited ROM on right hip. All the results of laboratory tests were normal. MRI revealed signal changes consistent with bone marrow edema in the right femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved 10 days after bisphosphonate infusion, and he returned to working life 1 month later. Complete resolution of the BME was observed in MRI performed 10 weeks later. Completion of the bisphosphonate treatment with alendronate for 1 year was planned. Conclusion The hip is the most frequently involved joint, with diffuse BME pattern in the femoral head and intertrochanteric region observed on MRI. BME may be a precursor to avascular necrosis when the diagnosis is delayed or the treatment is not well managed. Therefore, optimal timing of medical intervention is very important. Treatment with bisphosphonates is an effective and safe treatment. Additionally, providing early mobilization may prevent the risk of avascular necrosis and the workforce loss.