History Of Fragility Fracture Research Articles

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

#2775 ERCOS multicenter Spanish study: clinical profile of patients with chronic kidney disease G3a-G5D and osteoporosis

Abstract Background and Aims Fracture risk evaluation has recently been integrated into the 2017 KDIGO CKD-MBD (Chronic Kidney Disease- Mineral and Bone Disorder) guideline and its 2021 Spanish endorsement. It is now suggested to test bone mineral density (BMD) to assess fracture risk “if results will impact treatment decisions”. In fact, multiple new prospective studies have now documented that lower BMD predicts incident fractures in patients with CKD G3a–G5D. However, we scarcely know current real clinical practice in this population. Thus, the aim of the ERCOS (“Enfermedad Renal Crónica OSteoporosis”) study was to describe the clinical profile of patients with CKD who had been diagnosed of osteoporosis in outpatient Nephrology and Rheumatology clinics in Spain. Method ERCOS is a descriptive, observational, and multicenter Spanish study. Patients were recruited by consecutive sampling from 15 different Spanish hospitals. Osteoporosis characteristics (history of fragility fracture, BMD and other fracture risk factors), associated comorbidities, biochemical parameters and treatment were analyzed. Results A total of 163 patients (median age 77 years old) were included. Most were women (71.2%) and 98.3% of them were postmenopausal. Hypertension was the most frequent comorbidity (87.1%) and “attributed” cause of CKD (43.2%). Diabetes mellitus and cardiovascular disease were present in 35.6% and 29.4% of patients, respectively. Median estimated glomerular filtration rate was 36 ml/min/1.73 m2 [creatinine 1.48 mg/dl (95% CI 1,2-2)]. 38% of patients were G5D CKD patients (95.2% undergoing hemodialysis). 37.7% of patients had had a fragility fracture after the diagnosis of CKD (vertebral 52.5%, hip 24.6%, wrist 21.3%, humerus 16.4%, among others). Importantly, despite the diagnosis of osteoporosis, only 60.1% of the patients received specific treatment (mainly bisphosphonates or denosumab). Moreover, antiosteoporotic treatment was much more frequently prescribed by rheumatologists (46.9%), internal medicine physicians (23.5%), and only 13.3% was prescribed by nephrologists. 19.4% of patients suffered from fragility fractures even after initiating specific treatment. Conclusion Most patients with moderate and severe CKD with osteoporosis were old postmenopausal women with a high prevalence of diabetes or cardiovascular disease. Although about 40% had even suffered a fragility fracture, there is a high treatment gap, especially relevant among nephrologists. A call to action and to avoid existing therapeutic nihilism seems necessary, expanding the knowledge of the new more proactive guidelines and homogenizing the care and therapeutic approach in these patients.

History of fragility fracture is associated with cardiovascular mortality in hemodialysis patients: the Q-Cohort study.

In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. In total, 3499 patients undergoing hemodialysis were analyzed for 10years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16-1.85). In the Fine-Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07-1.72). In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.

The experience of feeling old after a fragility fracture

BackgroundThere has been little exploration of the effect of fragility fractures on patient perceptions of their age. The common assumption is that fractures “happen to old people”. In individuals with a fragility fracture, our objective was to explore the experience of feeling old after sustaining a fragility fracture.MethodsA secondary analysis of data from 145 community-dwelling women and men participating in six qualitative primary studies was conducted relying on a phenomenological approach. Participants were English-speaking, 45 years and older, who had sustained a recent fragility fracture or reported a history of previous fragility fractures. Data for the analysis included direct statements about feeling old as well any discussions relevant to age post-fracture.ResultsWe highlight two interpretations based on how individuals with a history of fragility fracture talked about age: (1) Participants described feeling old post-fracture. Several participants made explicit statements about being “old”. However, the majority of participants discussed experiences post-fracture that implied that they felt old and had resigned themselves to being old. This appeared to entail a shift in thinking and perception of self that was permanent and had become a part of their identity; and (2) Perceptions of increasing age after sustaining a fracture were reinforced by health care providers, family, and friends.ConclusionsOur findings challenge the notion that fractures “happen to old people” and suggest that fractures can make people feel old. Careful consideration of how bone health messages are communicated to patients post-fracture by health care providers is warranted. (Word Count: 248)

Unveiling the Burden of Osteoporosis: Exploring the Prevalence and Risk Factors among Postmenopausal Women in North Central Bangladesh.

Background: Osteoporosis affects 30% of women globally between the ages of 40 and 50. This disease is among the top causes of death and disability among the elderly. This study aimed to examine the prevalence of primary osteoporosis and poor bone density in postmenopausal women, as well as their socio demographic, obstetric, and lifestyle risk factors. Aim: The purpose of this study is to investigate at the prevalence of osteoporosis and the risk factors linked with it in postmenopausal women. Methods: The present prospective cross-sectional study was conducted on postmenopausal women who visited orthopedics, gynecology, and medicine outpatient departments between August 2022 and March 2023; 539 women aged 45 to 80 years with verified menopause were recruited. The final recommendation was for 539 women to have bone mineral density testing utilizing dual energy X-ray absorptiometry. Socio-individual, obstetric-medical, short-form physical activity, and anthropometric questionnaires were administered. Chi-square and Student's t-tests were applied to categorical and continuous data, respectively, to assess the differences between the groups. In SPSS 26, P<0.05 was regarded to indicate significant connections. Results: In our study, 38.0% of participants were between56 and 60 years of age. The majority of the individuals (51.9%) were illiterate. 37.7% of respondents reported having six or more children. 3.6% of the sample smoked or chewed tobacco. 61.0 percent of individuals had menopause after the age of 45, and 48.8% of subjects had experienced menopause for more than ten years at the time of enrollment in the research. 83.5% of postmenopausal women were affected by osteoporotic fractures (osteoporosis: 40.0% and osteopenia: 43.5%). The incidence of osteoporosis rose as parity and abortion rates increased. The prevalence of osteoporosis was greater (P< 0.05) among those with a familial history of osteoporosis-related symptoms and fragility fracture, as well as a personal history of fragility fracture. Conclusion: Given the significant prevalence of primary osteoporosis and poor bone density in postmenopausal women, health education is essential for minimizing modifiable risk factors and mitigating the disease's consequences. Central Medical College Journal Vol 7 No 1 January 2023 Page: 32-40

Position Statement: Postmenopausal Osteoporosis Treatment Strategies in Korea

Classifying patients with osteoporosis according to fracture risk and establishing adequate treatment strategies is crucial to effectively treat osteoporosis. The Korean Society for Bone and Mineral Research has issued a position statement regarding appropriate treatment strategies for postmenopausal osteoporosis. According to previous fragility fracture history, bone mineral density (BMD) test results, fracture risk assessment tool, and several clinical risk factors, fracture risk groups are classified into low, moderate, high, and very-high-risk groups. In high-risk groups, bisphosphonates (BPs) and denosumab are recommended as first-line therapies. Sequential BP treatment after denosumab discontinuation is required to prevent the rebound phenomenon. In the very high-risk group, anabolic drugs (teriparatide or romosozumab) are recommended as a first-line therapy; sequential therapy with antiresorptive agents is required to maintain BMD gain and reduce fracture risk. Fracture risk was reassessed annually, and the treatment plan was determined based on the results, according to the osteoporosis treatment algorithm for fracture risk.

Five-Year Outcomes of Continuous Treatment with Zoledronic Acid Versus Denosumab in Older Men with High Fracture Risk: Risk Factor Analysis of Bone Density Improvement and Incidence of New Fracture.

Denosumab and zoledronic acid are both effective and easily administrable injectable anti-osteoporotic medications for postmenopausal women. This study investigated the treatment efficacy of these agents in older male patients with low a bone mass and history of fragility fracture. A cohort of 175 male patients receiving continuous zoledronic acid treatment and a cohort of 366 male patients receiving continuous denosumab treatment at our medical center between 2015 and 2020 were included, and we analyzed the efficacy of treatment by the improvement in bone mineral density (BMD) and the new-onset low-energy fracture rate after 5years of continuous medication. BMD significantly improved after 5years of medication, and >90% of patients were satisfied with their treatment medication. BMD improved more with denosumab than with zoledronic acid, especially in patients with T-scores higher than -2.5. Smoking, alcohol abuse, diabetes, and inflammatory polyarthritis were associated with poor improvements in BMD. The incidence rate of new fragile fracture was 4.4% and old age was significantly associated with the incidence rate of new fracture. In summary, our study revealed that denosumab and zoledronic acid both significantly increased BMD among older male patients with high fragility fracture rates over a 5-year follow-up period. Early medical treatment and lifestyle adjustment were crucial for improving quality of life.

Gait characteristics in patients with distal radius fracture using an in-shoe inertial measurement system at various gait speeds

BackgroundDistal radius fractures (DRF) commonly occur in early postmenopausal females as the first fragility fracture. Although the incidence of DRF in this set of patients may be related to a lower ability to control their balance and gait, the detailed gait characteristics of DRF patients have not been examined. Research questionIs it possible to identify the physical and gait features of DRF patients using in-shoe inertial measurement unit (IMU) sensors at various gait speeds and to develop a machine learning (ML) algorithm to estimate patients with DRF using gait? MethodsIn this cross-sectional case control study, we recruited 28 postmenopausal females with DRF as their first fragility fracture and 32 age-matched females without a history of fragility fractures. The participants underwent several physical and gait tests. In the gait performance test, the participants walked 16 m with the in-shoe IMU sensor at slower, preferred, and faster speeds. The gait parameters were calculated by the IMU, and we applied the ML technique using the extreme gradient boosting (XGBoost) algorithm to predict the presence of DRF. ResultsThe fracture group showed lower hand grip strength and lower ability to change gait speed. The difference in gait parameters was mainly observed at faster speeds. The amplitude of the change in the parameters was small in the fracture group. The XGBoost model demonstrated reasonable accuracy in predicting DRFs (area under the curve: 0.740), and the most relevant variable was the stance time at a faster speed. SignificanceGait analysis using in-shoe IMU sensors at different speeds is useful for evaluating the characteristics of DRFs. The obtained gait parameters allow the prediction of fractures using the XGBoost algorithm.

The Use of Bone Density Scan in Monitoring Treatment Response in Patients Diagnosed with Osteoporosis: A Retrospective Cohort Study.

Osteoporosis is characterized as a metabolic bone disease defined by low bone mineral density (BMD) and bone tissue degeneration, particularly a reduction in the number of trabeculae and a drop in cortical bone thickness, and a rise in porosity, which is mainly due to an imbalance between bone resorption and formation. As a result, it increases bone fragility, and the susceptibility to fracture increases, especially among the elderly. The objective is to assess the effectiveness of dual-energy X-ray absorptiometry (DXA) scan in monitoring the response to osteoporosis treatment and compare the scan's response to different osteoporosis treatments. This retrospective cohort study included 51 adults selected from 300 patients diagnosed with osteoporosis based on World Health Organization (WHO) diagnostic criteria of a T-score of -2.5. Data were acquired from the electronic medical records between 2016 and 2019 from a private hospital in Dubai, United Arab Emirates (UAE). The study included sociodemographic characteristics, biomedical parameters, comorbidities, history of fracture, medications, laboratory, and DXA scan results. Ninety-four percent of the patients were females; the mean (±SD) age was 58.1 ± 11.5 years. Most patients were expatriates (84.3%), of which Asian ethnicity was 66.7%. The mean (±SD) duration of osteoporosis was 2.82 ± 1.8 years. Eleven (21.6%) patients had a history of fragility fracture. Ninety-six percent of the patients had vitamin D deficiency. One-third (29.4%) of the patients had hyperparathyroidism. Alendronate/cholecalciferol, received by nine patients (17.6%), showed a significant improvement (p = 0.018) in the BMD of the femoral neck among the study group. In conclusion, the DXA scan as a monitoring tool has shown a significant improvement in the BMD of the femoral neck among patients taking alendronate/cholecalciferol treatment compared to other medications.

SAT561 Pathogenic RET V804M Germline Variant Without Clinical Manifestations Of Multiple Endocrine Neoplasia Type 2 In An Elderly Male

Abstract Disclosure: R. Ghosh: None. G. Al-Naqeeb: None. P. Veeraraghavan: None. C. Craig: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Background: Germline pathogenic variants in the RET protooncogene give rise to multiple endocrine neoplasia (MEN) types 2A and 2B. MEN2A is mainly characterized by MTC (∼100%), pheochromocytoma (PHEO; 4% - 88%), and primary hyperparathyroidism (HPTH; 2% - 30%), while MEN2B predominantly manifests with MTC (100%), PHEO (50%), mucocutaneous neuromas, and marfanoid habitus. Both MEN2A and 2B follow an autosomal dominant mode of inheritance. While certain pathogenic RET variants (M918T, A883F, and C634X) have high penetrance and present with aggressive disease, other variants such as V804M are of low penetrance and manifest with clinically mild disease.Clinical case: A 75-year-old male was referred to our center for further evaluation of the finding of an abnormal RET gene that was identified on a peripheral blood whole-exome gene sequencing research panel performed at an outside center. The patient was noted to have a germline RET c.2410 G>A, p.V804M heterozygous pathogenic variant. The patient denied any history of lump in the neck, symptoms of hyper- or hypothyroidism, tremors, headaches, fatigue, facial flushing, palpitations, constipation, diarrhea, anxiety, depression, or history of fragility fractures. Medical history consisted of hypertension, nephrolithiasis, type 2 diabetes mellitus, obstructive sleep apnea, interstitial pulmonary fibrosis, and colonic diverticula and polyps. Family history was significant for leukemia, colon, and breast cancers, but none of the relatives had a history of MTC, PHEO, or MEN2, and his children, while healthy, had not undergone RET germline testing. Physical examination showed no evidence of hypothyroidism or hyperthyroidism. Neck examination showed no evidence of thyromegaly or cervical lymphadenopathy. Laboratory investigations were unremarkable [serum calcitonin: 7.9 pg/ml (NL: </=14.3), CEA 2.8 mcg/L (NL: 0.8-3.4), thyrotropin (TSH): 1.92 microIU/ml (NL: 0.35-4.94), free thyroxine: 0.9 ng/dl (NL: 0.7-1.5), plasma free normetanephrine: 0.31 nmol/L (NL: <0.9), plasma free metanephrines 0.24 nmol/L (NL: <0.5), parathyroid hormone: 28.2 pg/ml (NL: 15-65), and ionized calcium 1.23 mmol/l (NL: 1.09-1.30)]. Thyroid sonogram was normal. We recommended active annual surveillance with biochemical markers and imaging along with genetic testing of the RET gene in his children. Conclusion: The V804M RET variant has been often associated with MTC or MEN2A phenotypes [1]. However, the variable expression of this variant may lead to a mild clinical phenotype or even absence of MTC/MEN2A manifestations. Hence, active surveillance as opposed to radical surgery like prophylactic thyroidectomy would be more beneficial in patients with no clinical or biochemical evidence of disease. Reference: Pinna et al., 2007, V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype. Thyroid, 17(2), 101-104. Presentation Date: Saturday, June 17, 2023

THU470 Blood - Bone Connection? A Case Of A Young Woman With Bilateral Hip Osteonecrosis And Prothrombin Mutation

Abstract Disclosure: A. Sliwinska: None. C. Vanek: None. Introduction: Osteonecrosis of the femoral head (ONFH) is a localized bone disease responsible for 10% of total hip replacements in the United States. Although the condition is a separate entity from osteoporosis, it may co-occur representing underlying systemic bone disease. Many risk factors (steroids, trauma, infections, thrombophilia, blood cell dyscrasias) can predispose to ONFH, therefore, diligent evaluation is required to reveal the underlying cause. There are no FDA approved therapies. Here, we present a case of young woman with bilateral osteonecrosis of femoral head who was found to have prothrombin gene mutation, severe osteoporosis, and was successfully treated with PTH analog therapy with abaloparatide. Case Description: 33-year-old Asian female with no past medical history presented to the Endocrinology clinic for a metabolic bone disease assessment. Two years prior, she developed progressive bilateral hip pain which prompted radiographic evaluation, discovering bilateral ONFH. She was managed non-surgically with a 6-month trial of oral alendronate. Worsening pain prompted left hip decompression surgery with stem cell transfer. Patient had no history of fragility fractures nor family history of bone disease. A bone density revealed Z scores of -3.9 and -3.5 in lumbar spine and total hip, respectively. She was taking 2000 IU vitamin D3 and 600 mg of elemental calcium daily. Her blood tests revealed normal basic metabolic panel, normal complete blood count and liver function tests. Calcium was 9.0 mg/dl (ref:8.6-10.2), albumin 4.6 mg/dl (3.5-4.7 mg/dl), phosphorus 4.0 mg/dl (2.4-4.7 mg/dl), PTH of 28 pg/ml (18-88 pg/ml), Vitamin D 25-hydroxy 41.3 ng/ml (30-80 ng/ml), and TSH was 1.66 mIU/L (0.39-4.17 mIU/L). Patient had an infectious, metabolic and rheumatological work-up that was negative. A thrombosis workup showed a heterozygous prothrombin gene (G20210A) mutation. Factor V Leiden mutation was negative. Repeat Hip MRI showed progression of her ONFH with marked bone marrow edema in femoral head bilaterally. Patient was then started on abaloparatide. After 6 months, hip MRI showed marked improvement with no bone marrow edema. Discussion: Osteonecrosis of the femoral head is a complex disease that can affect young individuals. Bilateral ONFH suggests systemic disease and a thorough work-up is necessary. Although the exact mechanism is unclear, it has been hypothesized that thrombin plays a role in bone homeostasis therefore hematologic disorders may predispose patients to both ONFH and osteoporosis. Medical treatment of ONFH, including bisphosphonates, statins, or anticoagulants, have been suggested. Recently the PTH analog, teriparatide, has shown promising results and found to be beneficial in treating osteonecrosis. Our case highlights importance of thorough work-up for patients with bilateral ONFH and successful use of anabolic agent in this population. Presentation: Thursday, June 15, 2023

FRI690 Should Treatment For Osteoporosis Be Started In Patients With Primary Hyperparathyroidism Within The First Year After Parathyroidectomy?

Abstract Disclosure: K. Swe: None. A. Chiu: None. E. Pelley: None. Osteoporosis is one of the indications for parathyroidectomy in patients with primary hyperparathyroidism. Studies show the improvement of bone mineral density (BMD) in the lumbar spine and hip within the first year after parathyroidectomy. Therefore, the decision to treat osteoporosis has usually been delayed until a follow-up bone densitometry scan (DXA) at least one year after parathyroidectomy. To study the BMD changes with or without osteoporosis treatment till first follow-up DXA after parathyroidectomy, we retrospectively reviewed a prospective database of patients undergoing parathyroidectomy for primary hyperparathyroidism between 2010 to 2017 at our institution. We included both male and female patients between the ages 50 to 80, with a history of fragility fracture and/ or T score less than -2.4, and normal renal function. We excluded patients with persistent hyperparathyroidism post-surgery, osteoporosis medication within 3 years before surgery, and DXA performed outside of our facility. Patients who received osteoporosis medication between surgery and the first follow-up DXA were compared to those who underwent surgery alone. We compared the changes in BMD at the total hip and lumbar spine (L1-L4) between baseline and the first follow-up DXA for the two groups. Data was evaluated using a student’s t-test. A total of 386 patients underwent parathyroidectomy during the study period of which 92 patients met the inclusion criteria. Among them, 28 patients were treated after surgery and 64 patients had parathyroidectomy alone. The mean duration to treatment initiation after surgery was approximately 4 months (SD +/- 3 months), and the mean duration until the first follow-up DXA after the surgery was 17 months (SD +/- 8 months). There was no difference in the change of BMD at the total hip between two groups. Both increased by 0.01 g/cm2 (p=0.74). However, there was a greater increase in BMD at the lumber spine for those treated (0.047 g/cm2 increase) compared to surgery alone (0.019 g/cm2 increase) (p=0.02). We concluded that initiation of osteoporosis treatment within the first year after parathyroidectomy led to similar BMD outcomes at the total hip, but the treatment group experienced greater gains in BMD at the lumbar spine compared to parathyroidectomy alone, in patients with primary hyperparathyroidism and osteoporosis. Presentation: Friday, June 16, 2023

Radiofrequency Echographic Multispectrometry (REMS): A New Option in the Assessment Bone Status in Adults with Osteogenesis Imperfecta.

This study aimed to estimate the utility of the Radiofrequency Echographic Multispectrometry (REMS) approach in the assessment of bone mineral density (BMD) in subjects with osteogenesis imperfecta (OI). In 41 subjects (40.5 ± 18.7 years) with OI and in 36 healthy controls, we measured BMD at the lumbar spine (LS-BMD), femoral neck (FN-BMD) and total hip (TH-BMD), employing a dual-energy X-ray absorptiometry tool. Additionally, REMS scans were also performed at the lumbar and femoral sites. The presence and number of reported fractures were assessed in the study population. Patients characterized by a history of fragility fractures represented 84.5% of the study population. OI subjects showed significantly reduced BMD values both at the level of the lumbar spine and the femoral subregions (p < 0.01) compared to healthy controls when performed using both the DXA and the REMS method. Dividing OI patients on the basis of the Sillence classification, no differences were found between the LS-BMD values carried out using the DXA technique between the OI type I group and OI Type III and IV groups. On the contrary, the OI Type III and IV groups presented significantly lower values of both Trabecular Bone Score (TBS) and LS-BMD through REMS with respect to OI type I patients (p < 0.05). Based on the data of this study, it is possible to conclude that even the new REMS assessment, which does not use ionizing radiation, represents an excellent method for studying the bone status in subjects affected by OI.

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.

Relationship between bone marrow adipose tissue and kidney function in postmenopausal women

IntroductionBone marrow adipose tissue (BMAT) is associated with aging, osteoporosis, and chronic kidney disease (CKD). To date, the association between BMAT and kidney function in postmenopausal women has not been thoroughly investigated. The main purpose of this study was to determine whether a relationship exists between proton density fat fraction (PDFF) and kidney function in postmenopausal women. MethodsWe investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) – calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation – and PDFF – measured at the lumbar spine and proximal femur using Water Fat Imaging (WFI) MRI – in 199 postmenopausal women from the ADIMOS cohort study. We also performed DXA scans and laboratory measurements of sclerostin and c-terminal Fibroblast Growth Factor 23 (cFGF23). ResultsParticipants' mean age was 67.5 (standard deviation, SD 10.0) years. Their median eGFR was 85.0 (interquartile range, IQR 72.2–95.0) ml/min/1.73 cm2, and their mean lumbar spine PDFF was 57.9 % (SD 9.6). When classified by eGFR-based CKD stages, 41.7 % of the cohort had an eGFR ≥ 90 (n = 83), 47.2 % had an eGFR of 60–89.9 (n = 94), and 11.1 % had an eGFR of 30–59.9 (n = 22). Participants with eGFR ≥ 90 had a lower lumbar spine PDFF than those with eGFR 60–89.9 (mean 55.8 % (9.8) vs. 58.9 % (9.0), p = 0.031) and those with eGFR 30–59.9 (55.8 % (9.8) vs. 60.8 % (9.8), p = 0.043). However, the differences did not remain significant after adjusting for predetermined confounders, including age, diabetes, Charlson comorbidity index, recent history of fragility fracture, appendicular lean mass, and lumbar spine BMD. The inclusion of sclerostin and/or cFGF23 as suspected mediators did not alter the findings. When proximal hip imaging-based PDFF was considered, no significant differences were found between the eGFR categories in the unadjusted and adjusted analyses. ConclusionNo evidence of an association between kidney function and bone marrow adiposity was found either in the lumbar spine or proximal femur in a cohort of postmenopausal women.

Foot characteristics of the daily-life gait in postmenopausal females with distal radius fractures: a cross-sectional study

BackgroundGait decline in older adults is related to falling risk, some of which contribute to injurious falls requiring medical attention or restriction of activity of daily living. Among injurious falls, distal radius fracture (DRF) is a common initial fragility fracture associated with the subsequent fracture risk in postmenopausal females. The recent invention of an inertial measurement unit (IMU) facilitates the assessment of free-living gait; however, little is known about the daily gait characteristics related to the risk of subsequent fractures. We hypothesized that females with DRF might have early changes in foot kinematics in daily gait. The aim of this study was to evaluate the daily-life gait characteristics related to the risk of falls and fracture.MethodsIn this cross-sectional study, we recruited 27 postmenopausal females with DRF as their first fragility fracture and 28 age-matched females without a history of fragility fractures. The participants underwent daily gait assessments for several weeks using in-shoe IMU sensors. Eight gait parameters and each coefficient of variance were calculated. Some physical tests, such as hand grip strength and Timed Up and Go tests, were performed to check the baseline functional ability.ResultsThe fracture group showed lower foot angles of dorsiflexion and plantarflexion in the swing phase. The receiver operating characteristic curve analyses revealed that a total foot movement angle (TFMA) < 99.0 degrees was the risk of subsequent fracture.ConclusionsWe extracted the daily-life gait characteristics of patients with DRF using in-shoe IMU sensors. A lower foot angle in the swing phase, TFMA, may be associated with the risk of subsequent fractures, which may be effective in evaluating future fracture risk. Further studies to predict and prevent subsequent fractures from daily-life gait are warranted.

Zoledronic acid for osteoporosis after distal radius fracture surgery: Prospective longitudinal study

BackgroundDistal radius fractures (DRFs) are the most frequent first-ever osteoporotic fragility fractures. However, most patients are treated only for fractures and not for osteoporosis. Therefore, we investigated early osteoporosis intervention using zoledronic acid. MethodsThis prospective study enrolled 30 patients aged 50 years or older who had no history of fragility fractures or osteoporosis treatment and who underwent surgical treatment for DRFs. Patients whose lumbar spine or femur bone mineral density (BMD) values were less than 80% of the young adult mean (YAM) were treated with a 5-mg intravenous infusion of zoledronic acid. Lumbar spine and femur YAM BMD values, TRACP-5b and PINP were statistically evaluated using the paired t-test. The relationship between adverse effects, age, body mass index (BMI), and creatinine clearance (CCr) was statistically examined using Mann-Whitney's U test. The incidence of the bone fusion and secondary fractures within the 60-months postoperative period were assessed. ResultsThe mean lumbar spine and femur YAM BMD values before treatment were 76.1 ± 13.1% and 70.7 ± 8.5%. This indicates osteopenia in both locations. These values differed significantly between the pre-treatment period and each subsequent period. Five patients with a target YAM BMD value over 80% within 60 months after treatment were observed. The TRACP-5b and PINP values differed significantly between the pre-treatment period and each subsequent period. Adverse drug reactions were observed in 12 patients (40%). Age, BMI, and CCr did not show statistically significant differences in the occurrence of adverse effects. Bone fusion was confirmed at a mean of 3.6 months postoperatively. Secondary fractures were observed in 3 patients within 60 months after treatment. ConclusionDRFs occur at a younger age than other fragility fractures, and it is important to intervene aggressively with osteoporosis treatment to prevent secondary fractures. Level of evidenceLevel V.

An integrated experimental-computational framework to assess the influence of microstructure and material properties on fracture toughness in clinical specimens of human femoral cortical bone

Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance. However, the relative importance of these changes to the fracture resistance of cortical bone has not been quantified in detail. In this technical note, we developed an integrated experimental-computational framework utilizing human femoral cortical bone biopsies to advance the understanding of how fracture resistance of cortical bone is modulated due to modifications in its microstructure and material properties. Four human biopsy samples from individuals with varying fragility fracture history and osteoporosis treatment status were converted to finite element models incorporating specimen-specific material properties and were analyzed using fracture mechanics-based modeling. The results showed that cement line density and osteonal volume had a significant effect on crack volume. The removal of cement lines substantially increased the crack volume in the osteons and interstitial bone, representing straight crack growth, compared to models with cement lines due to the lack of crack deflection in the models without cement lines. Crack volume in the osteons and interstitial bone increased when mean elastic modulus and ultimate strength increased and mean fracture toughness decreased. Crack volume in the osteons and interstitial bone was reduced when material property heterogeneity was incorporated in the models. Although both the microstructure and the heterogeneity of the material properties of the cortical bone independently increased the fracture toughness, the relative contribution of the microstructure was more significant. The integrated experimental-computational framework developed here can identify the most critical microscale features of cortical bone modulated by pathological processes or pharmacological treatments that drive changes in fracture resistance and improve our understanding of the relative influence of microstructure and material properties on fracture resistance of cortical bone.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

Adjacent Fracture Rates Following Balloon Kyphoplasty in Osteoporotic Vertebral Compression Fractures: A Case Series.

Background Osteoporotic vertebral compression fractures (OVCF) represent a substantial concern, as they are associated with significant increases in morbidity and mortality. One option for the management of these patients is balloon kyphoplasty, in which a balloon is inflated within the collapsed vertebral body. Following this, the cavity is filled with polymethyl methacrylate (PMMA) cement to restore height and strength. Although this procedure has been shown to have great effectiveness, one complication that has been documented is an adjacent level refracture. This is thought to be due to the increased relative strength of the repaired vertebral body. Our study aims to quantify the rates of adjacent level refracture following balloon kyphoplastyas well as identify factors that may be associated with this event. Methods We reviewed the electronic medical records (EMR) of patients that underwent balloon kyphoplasty between January 1, 2017 and August 1, 2020. A single surgeon performed all procedures. Only adult patients who received a diagnosis of osteoporosis based on a history of fragility fracture or bone mineral density measurement were included. Patients with additional or confounding bone conditions, such as malignancy or other lytic lesions, were excluded. Data were analyzed in SPSS(IBM Corp., Armonk, NY, United States). Results We included 89 patients in our study. We observed an adjacent level refracture prevalence of 13.5% (n=12). We observed a significant increase in refracture rates among patients with unsatisfactory resolution of symptoms following initial balloon kyphoplasty, from 8.2% for satisfactory resolution of symptoms to 43.8% for those with unsatisfactory resolution. (p-value 0.011). Additionally, all 12 patients with adjacent level refractures occurred among patients with complex, multiple-level initial fracture patterns. Conclusions The treatment of OVCF with balloon kyphoplasty is a well-documented and effective method. The prevalence of adjacent-level refracture may be linked to several variables such as the initial fracture pattern. More research is needed to better predict refracture and improve patient outcomes.