Risk Of Insufficiency Fractures Research Articles

Sports Medicine Considerations When Caring for the Transgender Athlete

Orthopaedic surgeons and other orthopaedic care providers have expressed a desire to care for transgender patients but have a self-perceived knowledge deficit. Transgender athletes experience many psychosocial barriers to sport that are useful for clinicians to understand. Medical and surgical gender-affirming care can impact musculoskeletal physiology and pathophysiology. Transgender women (TW) have demonstrated an increased risk of insufficiency fractures and thromboembolism in patients receiving exogenous estrogen therapy. The impact of gender-affirming care on sex-based differences in athletic injuries is less well studied.

Association of Phantomless Dual-Energy CT-based Volumetric Bone Mineral Density with the Prevalence of Acute Insufficiency Fractures of the Spine

To evaluate the bone mineral density (BMD) of the lumbar spine derived from dual-energy CT (DECT)-based volumetric material decomposition and its association with acute insufficiency fractures of the thoracolumbar spine. L1 of 160 patients (77 men, 83 women; mean age 64.3 years, range, 22-94 years) who underwent third-generation dual-source DECT between January 2016 and December 2021 due to suspected insufficiency fractures was retrospectively analyzed. All depicted vertebrae were examined for signs of recent fractures. A dedicated DECT postprocessing software using material decomposition was applied for phantomless BMD assessment. Receiver-operating characteristic (ROC) analysis identified optimal BMD thresholds. Associations of BMD, sex, and age with the occurrence of insufficiency fractures were examined with logistic regression models. A DECT-derived BMD threshold of 120.40 mg/cm³ yielded 90.1% specificity and 59.32% sensitivity to differentiate patients with at least one insufficiency fracture from patients without fracture. No patient without fracture had a DECT-derived BMD below 85 mg/cm3. Lower DECT-derived bone mineral density was associated with an increased risk of insufficiency fractures (Odds ratio of 0.93, 95% CI, 0.91-0.96, p < 0.001). Overall ROC-derived AUC was 0.82 (p < 0.0001) for the differentiation of patients that sustained an insufficiency fracture from the control group. Dual-Energy CT-based BMD assessment can accurately differentiate patients with acute insufficiency fractures of the thoracolumbar spine from patients without fracture. This algorithm can be used for phantomless risk stratification of patients undergoing routine CT to sustain insufficiency fractures of the thoracolumbar spine The identified cut-off value of 120.4 mg/cm³is in line with current American College of Radiology (ACR) recommendations to differentiate healthy individuals from those with reduced bone mineral density.

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real-World Studies.

ABSTRACTBisphosphonates (BPs) are commonly used in the treatment of osteoporosis and are effective in the prevention of fragility fracture. Long‐term use has been associated with the development of atypical femur fractures (AFFs) and osteonecrosis of the jaw (ONJ). Drug holidays seek to reduce the risk of insufficiency fractures (AFFs) while maintaining durable effects of long‐term treatment in the prevention of fragility fracture. Guidelines suggest that BP drug holidays be considered after 3 to 5 years. However individual factors impacting this decision and outcomes are unclear. This review examines key factors in the planning of a safe BP drug holiday and surrogate markers of fracture risk in patients discontinuing treatment. Fifteen randomized control trials and 19 real‐world studies were included, including nationwide prospective studies from several countries. Increases in bone turnover markers (BTMs) and reductions in bone mineral density (BMD) were generally observed during BP drug holidays. Resurgent bone turnover was problematic in high‐risk patients in whom fractures recurred as early as 12 months following a drug holiday. Risk factors for holiday‐related fractures included older age, low hip BMD, underweight, low medication adherence, and prevalent/incident fractures. Zoledronic acid conferred the most durable reduction in fractures, particularly after six annual infusions. Five years of alendronate was insufficient in preventing vertebral fractures in high‐risk patients embarking on a drug holiday. Relatively faster offset of antiresorptive effect was seen in risedronate users with more frequent fractures than alendronate during a drug holiday. Studies directly counterbalancing effects of long‐term treatment on AFF risk versus drug holiday outcomes in the same population were lacking. In the absence of persistently high fracture risk and following a specific treatment duration dependent on the BP used, drug holidays are safe and mitigate the risk of AFF. However, anti‐resorptive effects diminish over time; ongoing monitoring and careful planning of BP resumption is necessary. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Pelvic insufficiency fractures –a late effect of radiotherapy

Keywords, late effects, pelvic radiotherapy Introduction: Pelvic insufficiency fractures are stress fractures caused by normal or physiological stress on weakened bone . Radiotherapy increases the risk of insufficiency fractures in patients(1). These fractures are underdiagnosed in younger women. Presenting symptoms include pelvic and back pain of which can substantially affect quality of life. Aim- To evaluate the characteristics of patients with pelvic insufficiency fractures following radiotherapy Methods: Four patients presented to pelvic late effects clinic between Jan-June 2019, with confirmed sacral insufficiency fractures on diagnostic magnetic resonance imaging (MRI). Radiotherapy technique 4 field brick 3D CRT (n=1), volumetric modulated arc therapy (VMAT) (n=3), 1 of these with a library of 3 adaptive plans. All patients had concurrent weekly cisplatin. Dose prescribed 50Gy/25# (n=2) and 45Gy/25# (n=2). All Ca Cervix patients had 4 Brachytherapy insertions (24Gy) and Ca Endometrium patient had no insertions. All patients presented with lower back pain. Retrospective planning CT dosimetric analysis, by delineation of the sacrum in Eclipse V15.5 (Varian Medical Systems,Palo Alto). A structure was created using boolean operator to define sacrum overlap with PTV. Dose volume histograms were exported for the sacrum structure and planning characteristics recorded. Results: Age range of patients was 32-73. Radiotherapy complete between Feb 2013-June 2018 for Ca Cervix (n=3) stages 2B (n=2), 11b2 (n=1) and Ca Endometrium grade 3 1B(n=1). 2 patients were pre-menopausal on hormone replacement therapy (HRT) with 2 remaining patients on no HRT. Time to confirmed diagnosis of insufficiency fractures from radiotherapy completion was mean 13 (4-26) months. The mean sacrum volume was 149.6cm3 (130.97-186.61). The mean sacrum overlap with PTV volume was 35.99 cm3 (30.73-40.75). The max dose to the sacrum was 53.27Gy and minimum 16.22Gy. The mean D50% of the sacrum was 40.24Gy (38.69-44.98) and mean D40% 42.91Gy (39.29-74.77). Conclusion/Discussion: The dose-effect relationship has been defined with a 22% risk of fracture at 35Gy and 45% at 40Gy for D50%(2). Our patients D50% were all above 35Gy. Dose received from Brachytherapy has not been accounted for. There is potential using dosimetric analysis to identify patients at high risk of fractures. Numerical

Risk of Pelvic Fracture With Radiation Therapy in Older Patients

Older patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality. This observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population. The 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture. IMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

Acute atraumatic bilateral acetabular insufficiency fractures

Bilateral acetabular fractures have been documented in the setting of high-energy trauma, but few reports regarding atraumatic bilateral acetabular fractures exist. The following is a case report of bilateral insufficiency acetabular fractures which occurred acutely in the absence of trauma in a 49-year-old female. The case highlights the importance of perioperative awareness of those patients at significant risk of insufficiency fractures and offers a relatively elegant, less invasive solution for early mobilization in the context of acetabula insufficiency fractures.

Vertebral body insufficiency fractures: detection of vertebrae at risk on standard CT images using texture analysis and machine learning.

To evaluate the diagnostic performance of bone texture analysis (TA) combined with machine learning (ML) algorithms in standard CT scans to identify patients with vertebrae at risk for insufficiency fractures. Standard CT scans of 58 patients with insufficiency fractures of the spine, performed between 2006 and 2013, were analyzed retrospectively. Every included patient had at least two CT scans. Intact vertebrae in a first scan that either fractured ("unstable") or remained intact ("stable") in the consecutive scan were manually segmented on mid-sagittal reformations. TA features for all vertebrae were extracted using open-source software (MaZda). In a paired control study, all vertebrae of the study cohort "cases" and matched controls were classified using ROC analysis of Hounsfield unit (HU) measurements and supervised ML techniques. In a within-subject vertebra comparison, vertebrae of the cases were classified into "unstable" and "stable" using identical techniques. One hundred twenty vertebrae were included. Classification of cases/controls using ROC analysis of HU measurements showed an AUC of 0.83 (95% confidence interval [CI], 0.77-0.88), and ML-based classification showed an AUC of 0.97 (CI, 0.97-0.98). Classification of unstable/stable vertebrae using ROC analysis showed an AUC of 0.52 (CI, 0.42-0.63), and ML-based classification showed an AUC of 0.64 (CI, 0.61-0.67). TA combined with ML allows to identifying patients who will suffer from vertebral insufficiency fractures in standard CT scans with high accuracy. However, identification of single vertebra at risk remains challenging. • Bone texture analysis combined with machine learning allows to identify patients at risk for vertebral body insufficiency fractures on standard CT scans with high accuracy. • Compared to mere Hounsfield unit measurements on CT scans, application of bone texture analysis combined with machine learning improve fracture risk prediction. • This analysis has the potential to identify vertebrae at risk for insufficiency fracture and may thus increase diagnostic value of standard CT scans.

Osteoporosis development and vertebral fractures after abdominal irradiation in patients with gastric cancer

BackgroundDecrease in bone mineral density, osteoporosis development, bone toxicity and resulting insufficiency fractures as late effect of radiotherapy are not well known. Osteoporosis development related to radiotherapy has not been investigated properly and insufficiency fractures are rarely reported for vertebral bones.MethodsNinety-seven patients with gastric adenocarcinoma were evaluated for adjuvant treatment after surgery. While 73 out of 97 patients treated with adjuvant chemoradiotherapy comprised the study group, 24 out of 97 patients with early stage disease without need of adjuvant treatment comprised the control group. Bone mineral densities (BMD) of lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry after surgery, and one year later in both groups.ResultsThere was statistically significant decline in BMDs after one year in each group itself, however the decline in BMDs of the patients in the irradiated group was more pronounced when compared with the patients in the control group; p values were 0.02 for the decline in BMDs of lumbar spine, and 0.01 for femoral neck respectively. Insufficiency fractures were observed only in the irradiated patients (7 out of 73 patients) with a cumulative incidence of 9.6%.ConclusionsAbdominal irradiation as in the adjuvant treatment of gastric cancer results in decrease in BMD and osteoporosis. Insufficiency fracture risk in the radiation exposed vertabral bones is increased. Calcium and vitamin D replacement and other measures for prevention of osteoporosis and insufficiency fractures should be considered after abdominal irradiation.

P-107 - Osteoporosis and insufficiency fracture risk developing in cases with stomach cancer after adjuvant radiochemotherapy

P-107 - Osteoporosis and insufficiency fracture risk developing in cases with stomach cancer after adjuvant radiochemotherapy

Mechanisms of bone fragility in a mouse model of glucocorticoid‐treated rheumatoid arthritis: Implications for insufficiency fracture risk

Glucocorticoid (GC) therapy is associated with increased risk of fracture in patients with rheumatoid arthritis (RA). To elucidate the cause of this increased risk, we examined the effects of chronic erosive inflammatory arthritis and GC treatment on bone quality, structure, and biomechanical properties in a murine model. Mice with established arthritis and expressing human tumor necrosis factor α (TNFα) transgene (Tg) and their wild-type (WT) littermates were continually treated with GC (prednisolone 5 mg/kg/day via subcutaneous controlled-release pellet) or placebo for 14, 28, or 42 days. Microstructure, biomechanical properties, chemical composition, and morphology of the tibiae and lumbar vertebral bodies were assessed by micro-computed tomography, biomechanical testing, Raman spectroscopy, and histology, respectively. Serum markers of bone turnover were also determined. TNF-Tg and GC treatment additively decreased mechanical strength and stiffness in both the tibiae and the vertebral bodies. GC treatment in the TNF-Tg mice increased the ductility of tibiae under torsional loading. These changes were associated with significant alterations in the biochemical and structural composition of the mineral and organic components of the bone matrix, a decrease in osteoblast activity and bone formation, and an increase in osteoclast activity. Our findings indicate that the concomitant decrease in bone strength and increase in bone ductility associated with chronic inflammation and GC therapy, coupled with the significant changes in the bone quality and structure, may increase the susceptibility of the bone to failure under low-energy loading. This may explain the mechanism of symptomatic insufficiency fractures in patients with RA receiving GC therapy who do not have radiographic manifestations of fracture.

F-18 Fluoride PET/CT in the Detection of Radiation-Induced Pelvic Insufficiency Fractures

Abstract:Radiotherapy for gynecologic malignancies puts the pelvic bones and the sacrum at risk for insufficiency fractures. Symptoms of sacral insufficiency fractures are nonspecific and can be mimicked by degenerative diseases and metastasis; the diagnosis thus is essentially based on imaging. We

Effects of bone density alterations on strain patterns in the pelvis: Application of a finite element model

Insufficiency fractures occur when physiological loads are applied to bone deficient in mechanical resistance. A better understanding of pelvic mechanics and the effect of bone density alterations could lead to improved diagnosis and treatment of insufficiency fractures. This study aimed to develop and validate a subject-specific three-dimensional (3D) finite element (FE) model of a pelvis, to analyse pelvic strains as a function of interior and cortical surface bone density, and to compare high strain regions with common insufficiency fracture sites. The FE model yielded strong agreement between experimental and model strains. By means of the response surface method, changes to cortical surface bone density using the FE model were found to have a 60 per cent greater influence compared with changes in interior bone density. A small interaction was also found to exist between surface and interior bone densities (< 3 per cent), and a non-linear effect of surface bone density on strain was observed. Areas with greater increases in average principal strains with reductions in density in the FE model corresponded to areas prone to insufficiency fracture. Owing to the influence of cortical surface bone density on strain, it may be considered a strong global (non-linear) indicator for insufficiency fracture risk.

Low-Energy Femoral Shaft Fractures Associated With Alendronate Use

Increasing evidence suggests long-term alendronate use may overly suppress bone metabolism, limiting repair of microdamage and creating risk for insufficiency fractures. The purpose of this study is to demonstrate an association between alendronate use and a specific pattern of low-energy femoral shaft fracture. A retrospective review was performed of patients with femoral shaft fractures admitted to a Level 1 trauma center between January 2002 and March 2007. Seventy low-energy fractures were identified. The medical records were reviewed, and the incidence and duration of alendronate use were recorded. The incidence of a specific femoral shaft fracture in those patients taking alendronate compared with those not being treated was determined. There were 59 females and 11 males. The average age was 74.7 years. Twenty-five (36%) were being treated with alendronate. None of the patients had used or were using other bisphosphonates. Nineteen (76%) of these 25 patients demonstrated a simple, transverse fracture with a unicortical beak in an area of cortical hypertrophy. This fracture pattern was seen in only 1 patient (2%) not being treated with alendronate. Alendronate use was a significant risk factor for the fracture pattern (odds ratio [OR]) 139.33, 95% CI [19.0-939.4], P < 0.0001). This pattern was 98% specific to alendronate users. The average duration of alendronate use in those with the pattern was significantly longer than those who did not exhibit the pattern but were taking alendronate, 6.9 years versus 2.5 years of use, respectively (P = 0.002). Only 1 patient with the fracture pattern had been taking alendronate for less than 4 years. Low-energy fractures of the femoral shaft with a simple, transverse pattern and hypertrophy of the diaphyseal cortex are associated with alendronate use. This may result from propagation of a stress fracture whose repair is retarded by diminished osteoclast activity and impaired microdamage repair resulting from its prolonged use.

Diabetes mellitus a risk for osteoporosis?

Localized lesions at the foot skeleton are a serious and well recognized complication of diabetes mellitus which may impair the clinical outcome of the patients remarkably. In contrast, the presence of a generalized bone disease or osteoporosis related to diabetes mellitus is less acknowledged and its clinical relevance is less obvious. This paper is a clinically focused review of the literature on osteoporosis related to diabetes mellitus. Due to the different pathogenesis of diabetes mellitus type 1 and type 2 it is not surprising that there is no uniform entity of diabetic osteopathy. The majority of clinical studies in subjects with diabetes mellitus type 1 showed a moderately decreased bone mass at the forearm, while bone mass at the femur or lumbar spine was either decreased or not different from non-diabetic controls. In patients with diabetes mellitus type 2 the risk of osteopenia is not as clear as in type 1 diabetes. Bone mineral density at the forearm in patients with type 2 diabetes mellitus was decreased, unchanged or even increased in comparison to controls, while bone mineral density at the vertebrae or femoral neck was either not significantly different or increased, but rarely decreased. The underlying mechanisms triggering changes in bone mass in patients with diabetes mellitus type 1 and type 2 are not well known. In most studies there was no consistent relationship between the metabolic control of diabetes and bone mineral density. Biochemical parameters of the calcium and bone metabolism showed no clear relationship to the bone mineral density measurements. From few bone histology studies in humans and experimental studies there is evidence that a decreased bone formation is one major mechanism leading to reduced bone mass in diabetics. Microangiopathy at the bone tissue was also discussed as a possible reason for diabetic osteopenia. It was shown that insulin and insulin like growth factors (IGF-1, IGF-2) have an influence on bone metabolism itself and other growth factors, cytokines and hormones may determine changes in diabetic bone metabolism. Recent findings suggest that leptin is involved in the regulation of osteoblast function and bone mass, which is of special interest in diabetes mellitus type 2. The clinical relevance of osteoporosis or osteopenia is determined by the increased risk for insufficiency fractures. Few studies found an increased fracture risk, especially in older women with type 1 diabetes mellitus, while others did not show an increased risk for fractures or even found a decreased rate of fractures in women with diabetes mellitus type 2. There is a need for further longitudinal studies, including the incidence and risk factors for osteoporotic fractures. In clinical routine the extent of diagnostic and therapeutic activities in patients with type 1 or type 2 diabetes mellitus in respect to generalized bone disease or diabetic osteopenia should be based on individual conditions and risk profile for osteoporosis.

Risk of vertebral insufficiency fractures in relation to compressive strength predicted by quantitative computed tomography

Vertebral insufficiency fractures may result from excessive loading of normal and routine loading of osteoporotic spines. Fracture occurs when the mechanical load exceeds the vertebral compressive strength, i.e., the maximum load a vertebra can tolerate. Vertebral compressive strength is determined by trabecular bone density and the size of endplate area. Both parameters can be measured non-invasively by quantitative computed tomography (QCT). In 75 patients compressive strength (i.e., trabecular bone density and endplate area) of the vertebra L3 was determined using QCT. In addition, conventional radiographs of the spines were analysed for the prevalence of insufficiency fractures in each case. By relating fracture prevalence to strength, three fracture risk groups were found: a high-risk group with strength values of L3 < 3 kN (kilo Newton) and a fracture risk of 100%, an intermediate group with strength values from 3 to 5 kN and a steeply increasing risk with decreasing strength, and a low-risk group with strength values > 5 kN and a fracture risk near 0%. Biomechanical measurements and model calculations indicate that spinal loads of 3 to 4 kN at L 3 4 will be common in everyday activities. These data and the results described above suggest that spines with strength values of L3 < 3 kN are at an extremely high risk of insufficiency fractures in daily life. Advantages of fracture risk assessment by strength determination over risk estimation based on clinically used trabecular bone density measurements are discussed.