Prevention Of Fragility Fractures Research Articles

The importance of reconstruction nailing for diaphyseal atypical femoral fractures: a comparative study with standard nailing

Subtrochanteric atypical femoral fractures (AFFs) usually require long cephalomedullary or reconstruction nailing to achieve satisfactory healing. Recently, this type of nailing has also been recommended to fix diaphyseal AFFs and prevent fragility fractures around the proximal femur, although standard antegrade nailing seems sufficient from a biomechanical perspective. This study aimed to compare treatment outcomes and complications between reconstruction and standard nailing for diaphyseal AFFs. A retrospective comparative study of 48 female patients with diaphyseal AFFs who underwent surgical treatment with either reconstruction or standard nailing was conducted. The reconstruction nailing group comprised 23 patients with a mean age of 74.4years and included 16 complete and 7 incomplete AFFs. The mean follow-up period was 30months. The standard nailing group comprised 25 patients with a mean age of 71.1years and included 16 complete and 9 incomplete AFFs. The mean follow-up period was 57.8months. The healing rate, time to union, and complications were analyzed and compared between the two groups. Bony union was achieved in all 23 cases (100%) of the reconstruction nailing group by a mean of 19.3weeks postoperative. In the standard nailing group, 23 of 25 cases healed (92%) by a mean of 16weeks postoperative. The standard nailing group included two delayed fragility fractures of the femoral neck (5 and 10years after the initial surgery), four cases of newly developed subtrochanteric AFFs at the distal screw of the proximal interlocking screws of the nail (one complete and three incomplete fractures), and two cases of nonunion. Complications only occurred in the standard nailing group (p = 0.01, Fisher's exact test). In diaphyseal AFFs, reconstruction nailing may achieve a satisfactory outcome and can also decrease delayed peri-implant fragility fractures of the hip, newly developed subtrochanteric AFFs, and nonunion.

Understanding the Experience of Osteoporosis Risk in Bariatric Surgical Patients.

Despite what is known about risk factors, preventive treatment, and increased prevalence of fragility fractures in post-bariatric surgical patients, little is known about how patient perspectives of osteoporosis risk inform their commitment to bone health. The purpose of this study was to examine the lived experience of osteoporosis risk in people who have had bariatric surgery. Interpretive phenomenology was used to explore osteoporosis from the perspectives of patients who have had bariatric surgery. Eligibility criteria included female, age older than 18 years, and able to understand and speak English. This research provided an understanding of the risk of osteoporosis from the constructed realities and experiences of those who have had bariatric surgery. Participants in this study incorrectly felt they had little to no risk for osteoporosis after bariatric surgery. Patients need to be aware of an increased risk for osteoporosis leading to the potential for fragility fractures after bariatric surgery; nurses are well positioned to enhance osteoporosis prevention efforts in this population through pre- and postoperative education.

Timing of Bisphosphonate (Alendronate) Initiation after Surgery for Fragility Fracture: A Population-Based Cohort Study.

Bisphosphonates are used as first-line treatment for the prevention of fragility fracture (FF); they act by inhibiting osteoclast-mediated bone resorption. The timing of their administration after FF surgery is controversial; thus, we compared the incidence of second FF, surgery for second FF, and adverse events associated with early initiation of bisphosphonates (EIBP, within 3 months of FF surgery) and late initiation of bisphosphonates (LIBP, 3 months after FF surgery) in bisphosphonate-naïve patients. This retrospective population-based cohort study used data from Taiwan’s Health and Welfare Data Science Center (2004–2012). A total of 298,377 patients received surgeries for FF between 2006 and 2010; of them, 1209 (937 EIBP and 272 LIBP) received first-time bisphosphonates (oral alendronate, 70 mg, once a week). The incidence of second FF (subdistribution hazard ratio (SHR) = 0.509; 95% confidence interval (CI): 0.352–0.735), second FF surgery (SHR = 0.452; 95% CI: 0.268–0.763), and adverse events (SHR = 0.728; 95% CI: 0.594–0.893) was significantly lower in the EIBP group than in the LIBP group. Our findings indicate that bisphosphonates should be initiated within 3 months after surgery for FF.

A country-specific FRAX model for Botswana

IntroductionHip fracture rates in Botswana were used to create a FRAX® model for fracture risk assessment.ObjectiveThis paper describes the development and characteristics of a country-specific FRAX model for Botswana.MethodsAge-specific and sex-specific incidence of hip fracture and national mortality rates was incorporated into a FRAX model for Botswana. Ten-year fracture probabilities were compared with those from African countries having a FRAX model and African Americans from the USA.ResultsThe probabilities of hip fracture and major osteoporotic fracture were low compared with those from South Africa (Black and Coloured) and US Blacks. Probabilities were marginally higher than for Tunisia.ConclusionThe creation of a FRAX model is expected to help guide decisions about the prevention and treatment of fragility fractures in Botswana.

Clinical characteristics and impact of treatment gap of fragility fractures in Colombia: experience of 10 Fracture Liaison Services (FLS)

Background & aims. Fragility fractures are those caused by low-energy trauma or falls from standing height. The mortality after the first year of suffering a hip fracture ranges from 15 to 30%. This problem has been addressed through the creation of interdisciplinary programs for fragility fracture early diagnosis and prevention. Describing the clinical characteristics of a cohort of patients diagnosed with fragility fractures in 10 fracture liaison services in Colombia. Methods. Led by the Asociaci n Colombiana de Osteoporosis y Metabolismo Mineral, this is a cross-sectional descriptive study, in patients with a diagnosis of fragility fracture in 10 fracture liaison services. Demographic and clinical variables were described for one year from the diagnosis of the fracture. Results. were analyzed 1699 records of patient fractures between 50 and 101 years of age, 1334 were women (76.5%), 581/1484 (39.1%) had previous fragility fractures, 570/1599 (35.7%) had a previous diagnosis of osteoporosis. Of these, 70/1051 (7%) received anti-osteoporosis medication, and 311/733 (42.4%) received it post-fracture. Of the total records with information, 65/707 (9.2%) died the following year of the fracture. Conclusions. Fracture prevention programs in institutions allow for de16 A. Medina et al. tecting patients with fragility fractures, clinical characteristics of these, in addition to strengthening the conditions of a centralized national registry, based on the parameters of the International Osteoporosis Foundation - Capture the Fracture program, through strategies with multidisciplinary personnel.

POS1102 TEMPORAL TRENDS AND FACTORS ASSOCIATED WITH VITAMIN D PRESCRIPTION AND INTAKE

Background:Vitamin D has proven skeletal effects and its administration is recommended in patients with osteoporosis by many national and international guidelines. Nevertheless, the compliance to treatment of patients with osteoporosis is scarce. Understanding the factors associated with low vitamin D intake and prescription might help design future intervention aimed to improve adherence.Objectives:This study aims to investigate the temporal trends and factors associated with vitamin D prescription and intake.Methods:Using a web-based fracture risk-assessment tool, we collected demographic, densitometric and clinical data of women at high risk for fractures. To determine the factors associated with low vitamin D intake we ran a multivariable logistic regression analysis. We described the public general interest in the term “vitamin D” using the Google Trends tool.Results:12,419 women were included in the study. 6,748 (54.4%) individuals had a prevalent fragility fracture and 8,950 (72.1%) individuals were on <800 IU of vitamin D per day and 11,434 (92.1%) were taking <1,200 IU of vitamin D per day. The factors associated with vitamin D intake were evaluated with a multivariable logistic regression analysis, which results are presented in Table 1. We found that low BMD levels, the presence of associated comorbidities and glucocorticoid utilization were associated with greater vitamin D intake. Falls were associated only with lower risk of receiving very low dose of vitamin D (<250 IU day). Smoking status was associated with lower vitamin D intake. Overall, the internet interest in vitamin D was higher during the winter season Figure 1.Figure 1.Google trends interest in the term “vitamin D” from January 2010 to October 2020Conclusion:Low vitamin D intake (<800 IU day) was common in our cohort of women at high risk for fractures. The factors associated with greater vitamin D intake were: having low BMD levels, associated rheumatic diseases and glucocorticoid use. Falls were associated with lower risk of receiving very low dose of vitamin D (<250 IU day). Smoking status was associated with lower vitamin D intake.Table 1.Binary logistic regression to predict the risk of low vitamin D intake (<800 IU/day)>800 IU day REFaOR (95% CI)p value400-800 IU dayAge1.001 (0.995-1.007)NST-score1.422 (1.342-1.508)<0.001No comorbiditiesREFRheumatoid arthritis0.732 (0.583-0.920)<0.001Psoriatic arthritis0.362 (0.218-0.607)<0.001Connective tissue disease0.630 (0.486-0.816)<0.001No cigarette smokingREFCigarette smoking1.040 (0.893-1.212)NSAlcohol <3 unit dayREFAlcohol ≥3 unit day1.201 (0.660-2.187)NSNo glucocorticoidsREFGlucocorticoids 2.5-5 mg/day0.688 (0.550-0.860)<0.001Glucocorticoids ≥5 mg/day0.739 (0.554-0.986)<0.001No fallsREFFalls0.875 (0.754-1.015)NS250-400 IU dayAge0.994 (0.985-1.002)NST-score1.223 (1.117-1.339)<0.001No comorbiditiesREFRheumatoid arthritis0.670 (0.463-0.970)<0.001Psoriatic arthritis0.300 (0.119-0.752)<0.001Connective tissue disease0.651 (0.435-0.975)<0.001No cigarette smokingREFCigarette smoking1.371 (1.104-1.702)<0.001Alcohol <3 unit dayREFAlcohol ≥3 unit day1.824 (0.865-3.887)NSNo glucocorticoidsREFGlucocorticoids 2.5-5 mg/day0.930 (0.666-1.297)NSGlucocorticoids ≥5 mg/day0.743 (0.464-1.189)NSNo fallsREFFalls0.934 (0.741-1.176)NS<250 IU dayAge0.993 (0.988-0.998)<0.01T-score1.139 (1.079-1.202)<0.001No comorbiditiesREFRheumatoid arthritis0.645 (0.522-0.795)<0.001Psoriatic arthritis0.553 (0.376-0.812)<0.001Connective tissue disease0.697 (0.558-0.871)<0.001No cigarette smokingREFCigarette smoking1.339 (1.171-1.532)<0.001Alcohol <3 unit dayREFAlcohol ≥3 unit day1.267 (0.749-2.145)NSNo glucocorticoidsREFGlucocorticoids <5 mg/day0.964 (0.796-1.168)NSGlucocorticoids ≥5 mg/day0.946 (0.736-1.215)NSNo fallsREFFalls0.615 (0.530-0.712)<0.001Disclosure of Interests:None declared.

Bone Breaking Triglycerides

A 40 yo African American female with pmhx of T2DM, DLD was admitted for worsening leg and arm pain that started a year prior but had worsened in the last 6 months. Pain started in the right arm and progressed to include the right leg and left leg. She had presented to the ER 3 times in the last 3 weeks with no diagnosis and prescribed anti-inflammatories. On ROS she had unintended weight loss of 50 lbs. Pain was not relieved with anti-inflammatories or narcotics. She was diagnosed with diabetes in the previous 5 years and had not been compliant with her medications. Plain x-rays showed OA of the hip. An osseus survey showed multiple expansile, bubbly, and lucent intramedullary lesions consistent with polyostotic fibrous dysplasia versus multiple myeloma. CT showed a radiolucent lesion of the left femur with absence of normal bone trabeculae. Her labs showed normal calcium, phosphorous, renal function, PTH and no evidence of monoclonal gammopathy. Vitamin D was low at 8.2 ng/ml (6.6–49 ng/ml). CT CAP showed no concern for malignancy in other organs. A lipid profile was done and showed elevated fasting triglycerides of 2617 mg/dL (<150 mg/dl) and LDL direct 54 mg/dl (<100 mg/dl). A1c was 11.2% on admission. She denied any use of alcohol, estrogens, SSRI’s. No history of pancreatitis. On physical exam she did not have tendinous xanthomas, eruptive xanthomas, palmar xanthomas, or lipemia retinalis. Family history not significant for lipid disorders. Patient was fasted for 24 hours and then started on intensive insulin regimen as well as fenofibrate for hypertriglyceridemia. Triglycerides came down to less than 500 over 7 days. She was evaluated by ortho for her bone lesions and underwent bone lesion biopsy as well as prophylactic IMN of her bilateral femurs for prevention of impending fragility fractures. Bone biopsy was significant for xanthoma of the bone. Following discharge, she remained on fenofibrate and fish oil as well as a basal/bolus insulin regimen. Triglycerides remained controlled. She has not followed up outpatient for further workup. This case highlights an atypical presentation of triglyceride deposition in the setting of hypertriglyceridemia. It shows that hypertriglyceridemia should be included in the differential for lytic lesions when preliminary workup is negative. It also highlights that complications other than pancreatitis and cardiovascular disease can significantly alter a patient’s life if triglycerides go untreated.

Targeting the Fragility Fracture Prevention Message

Abstract Background: The impact of fragility fractures on human suffering is underappreciated. Fragility fractures increase mortality and the risk of recurrent fracture. Notwithstanding these facts, only a minority of patients suffering osteoporotic fractures receive fracture preventing therapy. Education about the burden of disease and the benefits of prompt treatment are important means to increase the treatment rate. We propose that the focus of the educational message should be varied for distinct audiences. Method: We searched existing literature to determine perceptions about the importance of treating fractures and osteoporosis among the following groups: the general population, primary care physicians, specialist physicians, hospital administrators, and government health officials. Result: Extensive data focusing on patients and primary care physicians exist about barriers to treatment initiation. In these groups, lack of perceived treatment benefit is a widespread, common finding. To address this gap, we have produced a primary care education toolkit, patient booklet and education directory as Asia Pacific Fragility Fracture Alliance (APFFA)-sponsored initiatives. Data are more limited for specialist physicians, hospital administrators, and government officials. Health economic arguments have been found to be persuasive among policy makers. Conclusion: Information about the importance of treating fragility fractures and osteoporosis is far more abundant with reference to patients and primary care providers than to specialty physicians, hospital administrators, and government officials. Understanding the state of knowledge and belief is an essential first step in developing educational materials that address the concerns and misperceptions of each key constituency. Existing data suggest that patients will be more receptive to materials emphasising independence and quality of life, while policy makers will be more receptive to materials highlighting the burden of disease.

Vertebral compression fractures: Still an unpredictable aspect of osteoporosis

Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP.

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel

AimBone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. Data synthesisThe following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. ConclusionsClinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.

O03 Prevalence of fragility fractures and medication prescription for osteoporosis in patients with polymyalgia rheumatica: results from the PMR Cohort Study

Abstract Background/Aims Polymyalgia rheumatica (PMR) is one of the commonest indications for long term glucocorticoid (GC) use, leading to an increased risk of osteoporosis and fragility fractures. Clinical guidelines recommend prescribing medication including vitamin D, calcium and anti-resorptives, such as bisphosphonates. The aim of this study was to examine the association of reported falls and prescriptions of medications for osteoporosis with future fragility fractures in a cohort of people with PMR. Methods 652 people with an incident diagnosis of PMR responded to a baseline survey between June 2012 and June 2014. This included data on general health, sociodemographics, history of falls and medication. Data on fractures and prescriptions were collected at 12 and 24 months. Fragility fractures were defined as fractures of the hip, wrist or spine. Logistic regression models were used to assess the association between baseline characteristics and fractures at 12 and 24 months. Analysis was conducted unadjusted and adjusted for age, gender, reported medication use and falls history. Results 112 (17.2%) baseline respondents reported a previous fragility fracture. 60 (83.3%) of the 72 respondents who reported a fragility fracture between baseline and month 12 also reported a fragility fracture at baseline. 49 (79.1%) of the 60 respondents who reported a fragility fracture at between the month 12 and 24 also reported a fragility fracture at baseline. Falls before baseline was the most significant predictor of fragility fracture at 12 (OR 2.35 95% CI 1.35-4.12) and 24 (OR 1.91 95% CI 1.05-3.49) months. Fewer than 50% of respondents were ever prescribed treatment for osteoporosis. Being prescribed treatment for osteoporosis was associated with a reduced incidence of fragility fractures at 24 months (adjusted OR 0.28 95% CI 0.10-0.80), but an increased incidence at 12 months (adjusted OR 2.10 95% CI (1.3-3.48). Calcium and vitamin D prescription, gender and age were not significantly associated with fracture outcome. Conclusion Despite guidelines, fewer than 50% of patients were prescribed medications for osteoporosis. This data highlights the risks of fractures in PMR patients who have experienced previous falls. Over a period of two years, medication for osteoporosis was significantly protective, hence more needs to be done to encourage adherence to guidelines. Further studies need to address reasons for non-adherence to guidelines and the effects of long-term treatment. Disclosure B. Sokhal: None. S.L. Hider: None. Z. Paskins: None. C.D. Mallen: None. S. Muller: None.

Developing a service for the incidental identification of osteoporotic vertebral fractures and the secondary fragility fracture prevention using artificial intelligence

Developing a service for the incidental identification of osteoporotic vertebral fractures and the secondary fragility fracture prevention using artificial intelligence

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism.

ContextIn primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well.ObjectiveTo evaluate bone material properties using impact microindentation (IMI) in PHPT patients.MethodsIn this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status.ResultsMean age of PHPT patients and controls was 61.8 ± 13.3 and 61.0 ± 11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ± 0.15 vs 0.89 ± 0.11, P = .37) and the femoral neck (0.70 ± 0.11 vs 0.67 ± 0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ± 5.7 vs 82.8 ± 4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ± 6.0 vs 79.6 ± 5.0, P = .015).ConclusionOur data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

91 Mrs Bad Bones: Impact of COVID-19 on Secondary Prevention of Fragility Fractures

IntroductionManagement of osteoporosis is an important consideration for neck of femur fracture patients due to the morbidity and mortality it poses, and the significant financial burden to the NHS. Orthogeriatric teams input is invaluable in coordinating secondary fragility fracture prevention. The COVID-19 pandemic resulted in the rapid restructuring of healthcare teams and led to the redeployment of the orthogeriatricians to assist with the influx of medically unwell patients. This study explored the impact COVID-19 had on secondary fragility fracture prevention.MethodA retrospective audit looking at the prescription of vitamin D/calcium supplements, bone-sparing medications, and DEXA scan requests in consecutive neck of femur fracture patients admitted to a trauma and orthopaedic unit pre- and post- UK lockdown in response to the pandemic. A re-audit was conducted following the implementation of our new mnemonic, “MRS BAD BONES”: Medication Review Rheumatology/Renal Advice Smoking Cessation Blood tests Alcohol limits DEXA scan Bone-sparing medications Orthogeriatric review Nutrition Exercise Supplements.ResultsData for 50 patients was available in each phase. The orthogeriatric team reviewed 88% of patients pre-lockdown falling to 0% due to redeployment, before recovering to 38% in the post-intervention period. Upon lockdown there was a significant drop in the prescription of vitamin D/calcium supplements from 81.6% to 58.0% (p = 0.0156); of bone-sparing medications from 60.7% to 18.2% (p = 0.0037), and DEXA scan requests from 40.1% to 3.6% (p = 0.0027). Following the implementation of our mnemonic, there was a significant increase in the prescription of vitamin D/calcium supplements to 85.7% (p = 0.0034), bone-sparing medications to 72.4% (p = 0.0002) and DEXA scan requests to 60% (p < 0.0001).ConclusionCOVID-19 had a major impact on the secondary prevention of fragility fractures in this population. The “MRS BAD BONES” mnemonic significantly improved the management and could be considered for use in a wider setting.

Factors associated with referral for osteoporosis care in men: a real-life study of a nationwide dataset

Male osteoporosis is associated with an important clinical and economic burden worldwide; nevertheless, undertreatment of men with osteoporosis is common. Understanding the factors associated with referral to bone specialists may help to define future interventions to improve access to osteoporosis care for male patients. We conducted a retrospective analysis of a nationwide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk by considering clinical and densitometric risk factors, including the presence of prior hip or vertebral and non-vertebral or non-hip fractures. We compared the clinical characteristics of male individuals with an age-matched cohort of women. Propensity score generation with a 2:1 female-to-male ratio was performed using a logistic regression model to age-match the cohorts. We analyzed a sample of 4902 men at high risk for osteoporosis. We found that the factors associated with osteoporosis care utilization in men were the presence of comorbidities (OR 1.939, 95% CI 1.799-2.090), adjuvant hormonal therapy for prostate cancer (OR 1.482, 95% CI 1.315-1.670), the presence of vertebral or hip fractures (OR 1.490, 95% CI 1.378-1.611), and glucocorticoid treatment (OR 2.573, 95% CI 2.274-2.832). Men are more commonly referred to the bone specialist with a prevalent fragility fracture and/or diagnosis of secondary osteoporosis as compared with women. Our study suggests that there is a lack of screening for the primary prevention of osteoporosis in men as compared with that in women.

Vertebral Fractures After Denosumab Discontinuation in Breast Cancer Survivors: A Single Institution Experience.

Background: Denosumab is approved to prevent fragility fractures in patients with osteoporosis at high risk for fracture and to prevent bone loss in patients with breast and prostate cancer who receive endocrine therapy. The antiresorptive effect of denosumab rapidly dissipates when it is delayed or discontinued, but the risk for, and incidence of, multiple clinical vertebral fractures in patients with breast cancer after stopping denosumab is currently unclear. Question/Purposes: We sought to identify the incidence of clinical vertebral fractures in patients with breast cancer who received at least 2 doses of denosumab (60 mg) and then discontinued the medication. Methods: We conducted a retrospective chart review to identify patients with a history of breast cancer who were treated with denosumab between June 1, 2010, and July 18, 2018, at Memorial Sloan Kettering Cancer Center. We identified 335 postmenopausal women and 1 man with nonmetastatic breast cancer who received their final denosumab injection at least 6.5 months earlier. Data recorded included baseline bone density and the incidence of vertebral fractures after denosumab discontinuation. Results: The median age of patients was 62 years. Patients received between 2 and 13 denosumab doses before drug discontinuation. Most of the patients (310; 92.3%) were also treated with aromatase inhibitors. Of the 194 patients with baseline bone density data, 50 (25.8%) had normal bone density, 97 (50.0%) had osteopenia, and 47 (24.2%) had osteoporosis. The median follow-up duration from the last denosumab dose was 18.5 months. We identified 1 case of spontaneous vertebral fractures after denosumab stoppage. We found no cases of osteonecrosis of the jaw or atypical femur fracture. Most of the patients (88%) had a gap in denosumab dosing. Conclusions: Clinicians treating patients with breast cancer-especially those continuing to take aromatase inhibitors-should be aware of the possible risks of delaying doses of or discontinuing denosumab and should educate their patients accordingly. Prospective studies are needed to fully evaluate the risks of stopping or delaying denosumab.

Bisphosphonates to reduce bone fractures in stage 3B+ chronic kidney disease: a propensity score-matched cohort study.

Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects. The aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time. This was a new-user cohort study design with propensity score matching. Data were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1-3 and from the Danish Odense University Hospital Databases for work package 4. Patients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m2 were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m2 within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1-3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1-4. Bisphosphonate use, identified from primary care prescriptions (for work packages 1-3) or pharmacy dispensations (for work package 4), was the main exposure. Work package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change. Bisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users. Confounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively. Bisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness. Randomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data. This study is registered as EUPAS10029. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 17. See the NIHR Journals Library website for further project information. The project was also supported by the National Institute for Health Research Biomedical Research Centre, Oxford.

Osteoporosis in Men: A Review of an Underestimated Bone Condition.

Osteoporosis is called the ‘silent disease’ because, although it does not give significant symptoms when it is not complicated, can cause fragility fractures, with serious consequences and death. Furthermore, the consequences of osteoporosis have been calculated to weigh heavily on the costs of health systems in all the countries. Osteoporosis is considered a female disease. Actually, the hormonal changes that occur after menopause certainly determine a significant increase in osteoporosis and the risk of fractures in women. However, while there is no doubt that women are more exposed to osteoporosis and fragility fractures, the literature clearly indicates that physicians tend to underestimate the osteoporosis in men. The review of the literature done by the authors shows that osteoporosis and fragility fractures have a high incidence also in men; and, furthermore, the risk of fatal complications in hip fractured men is higher than that for women. The authors report the evidence of the literature on male osteoporosis, dwelling on epidemiology, causes of osteoporosis in men, diagnosis, and treatment. The analysis of the literature shows that male osteoporosis is underscreened, underdiagnosed, and undertreated, both in primary and secondary prevention of fragility fractures.

SIGN on managing osteoporosis and fragility fracture prevention

The Scottish Intercollegiate Guidelines Network (SIGN) has recently revised its guideline on the management of osteoporosis and the prevention of fragility fractures (SIGN142), incorporating key recommendations on assessment of fracture risk, treating postmenopausal women and systems of care. This article provides a summary of the updated guidance.

Association between electronic cigarette use and fragility fractures among US adults

BackgroundThe popularity of electronic cigarette (e-cigarette) use continues to rise in the United States. While conventional cigarette smoking is an established risk factor for osteoporosis and osteoporotic fracture, the effects of e-cigarette use on bone health are unknown. We aimed to examine the association between e-cigarette use and fragility fractures. Research Design and MethodsWe pooled 2017–2018 data from the National Health and Nutrition Examination Survey (NHANES). We included men and women with complete information on key variables. E-cigarette use was categorized as either never or ever users. Ever users were further classified as former and current users. Fragility fracture was defined as a composite of self-reported fracture of the hip, spine or wrist which resulted from minimal trauma such as a fall from standing height or less. ResultsOf 5569 participants, there were 4519 (81.2%) never e-cigarette users, 1050 (18.8%) ever e-cigarette users, and 444 (8.0%) with self-reported fragility fracture. In adjusted models, ever e-cigarette users had a 46% higher prevalence of self-reported fragility fractures compared to never users (aPR: 1.46, 95% CI: 1.12, 1.89). We also observed a higher prevalence of fragility fractures among former and current e-cigarette users compared to never users (aPR: 1.89, 95% CI: 1.44, 2.48 and aPR: 1.77, 95% CI: 1.04, 3.02 respectively). ConclusionE-cigarette use was associated with a higher prevalence of self-reported fragility fracture. These findings suggest that e-cigarette use may be harmful to bone health. These data highlight the critical need for longitudinal studies exploring the potential effect(s) of e-cigarette use on bone health.