Bisphosphonate Prescription Research Articles

Trends in osteoporosis assessment, diagnosis after fragility fractures, and treatment for hospitalized patients with osteoporosis or fragility fractures between 2012 and 2021.

The goal of the current study is to explore trends in assessment, diagnosis after fragility fractures, and osteoporosis treatment among hospitalized patients in Xiamen, China, between 2012 and 2021. We conducted a retrospective cross-sectional study, using the Cochran-Armitage trend test to describe trends. Logistic regression was performed to identify the influencing factors of anti-osteoporosis medication (AOM) treatment. We performed a sensitivity analysis to verify the robustness of our findings. From 2012 to 2021, the rates of dual-energy X-ray absorptiometry (DXA) scans and bone turnover marker (BTM) examinations increased from 0 to 37% and 36.5%, respectively. 29.3% of patients with fragility fractures were diagnosed with osteoporosis. The use rate of AOM was only 22.7%. There was an upward trend in the prescription of bisphosphonates, increasing from 1% in 2012 to 16.8% in 2021. The use of calcitonin ranged from 4.1% (2014) to 32.7% (2021). Calcium and vitamin D supplementation prescribing increased significantly from 5.6% in 2012 to 78.7% in 2021. Logistic regression analysis showed that old age, female sex, history of fractures, DXA scans, and osteoporosis diagnosis were significantly associated with increased AOM use. Tobacco use, hypertension, diabetes, congestive heart failure, cerebral vascular accidents, and severe liver diseases were associated with a reduced likelihood of AOM treatment. Although assessment, diagnosis after fragility fractures, and osteoporosis treatment have increased over the past decade, there are still deficiencies in the management of osteoporosis. In the future, it will be necessary to further strengthen management of osteoporosis.

A Retrospective Audit of Osteoporosis Management Following Fragility Fractures in a Hospital Setting.

Background Fragility fractures, often caused by osteoporosis, are a major public health concern among the growing population of the United Kingdom (UK). In addition to being a major source of illness and mortality, the rising incidence of osteoporosis places a heavy strain on healthcare systems if it is not adequately managed. In order to lower the risk of additional fractures, current guidelines place a strong emphasis on the timely evaluation and treatment of fragility fractures. Methods This retrospective audit was carried out in Warrington Hospital, UK, to examine the management of fragility fractures in patients aged 65 years and above across two cycles (January to March 2022 and April to May 2023, respectively). All data was obtained from electronic medical records, and management was assessed, including treatment with bisphosphonates, vitamin D, dual-energy X-ray absorptiometry (DEXA) scansand further referrals for metabolic bone clinics. Results The first cycle included 144 inpatients and showed significant under-utilization with only 16% receiving bisphosphonates treatment (23 inpatient prescriptions), low referrals for DEXA scan and metabolic bone clinics. Assessment and supplementation of vitamin D was also suboptimal. The second cycle of the audit reviewed 165 patients and showed minor improvement in bisphosphonates prescription, although post-discharge rates were low with around 80% of patients (104 of 131, as 34 patients were prescribed while inpatient) not receiving medications. The DEXA scans and metabolic bone clinic referrals also remained inadequate in the second cycle. Conclusions This audit highlighted the significant gap in the management of fragility fractures and persistent deficiencies in spite of robust guidelines and interventions set by various bodies. The implementation of treatment guidelines for osteoporotic patients at hospital level can help in timely initiation of antiresorptive therapy, DEXA scans and utilisation of metabolic bone clinics to optimise outcomes and reduce the burden on healthcare systems. There is a need for further research and education to improve this adherence to set guidelines and improve outcomes.

Bisphosphonate Use in Patients Who Have Osteoporosis Does Not Increase the Risk of Periprosthetic Fracture Following Total Knee Arthroplasty

BackgroundThe purpose of this study was to evaluate the effect of preoperative bisphosphonate use in patients who have osteoporosis on the risk of complications following primary total knee arthroplasty (TKA). MethodsAn administrative claims database was queried for patients who have osteoporosis undergoing primary TKA between 2010 and 2019 with a minimum of 2-year follow-up. Bisphosphonate-naive patients and bisphosphonate users, defined as patients who had a continuous prescription for bisphosphonates for a minimum of 6 months preoperatively, were matched 1:1 based on age, sex, and comorbidity burden. Patients undergoing nonelective TKA on chronic glucocorticoid therapy or receiving any other pharmacologic treatment for osteoporosis were excluded. The final cohort included 21,058 matched pairs of patients. The incidence of postoperative complications was identified via International Classification of Disease coding and compared between matched groups. A subgroup analysis was performed to examine outcomes among patients who underwent cemented and cementless TKA. ResultsThere was no difference in the incidence of periprosthetic fracture on univariate (0.7 versus 0.8%, P = 0.068) or multivariate testing (OR [odds ratio]: 1.24, 95% confidence interval [0.99 to 1.56]; P = 0.060). Bisphosphonate users were statistically less likely to undergo all-cause revision TKA at 2 years (OR: 0.84 [0.72 to 0.97]; P = 0.021). Patients who had osteoporosis were found to have an increased risk of periprosthetic fracture when TKA was performed with cementless implants (1.6 versus 0.4%; P = 0.033). However, when treated with bisphosphonates, patients who have osteoporosis demonstrated equivalent fracture rates regardless of implant type (1.3 versus 1.0%; P = 1.000). ConclusionsWhile bisphosphonate use in patients who have osteoporosis did not decrease the risk of periprosthetic fracture, it did significantly lower the incidence of all-cause revision at 2 years, although the difference identified was small. Consideration should be given to performing cemented TKA in patients who have untreated osteoporosis, given the higher rate of periprosthetic fracture when cementless implants were utilized.

Preoperative prediction for periprosthetic bone loss and individual evaluation of bisphosphonate effect after total hip arthroplasty using artificial intelligence.

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss.

Safe prescribing of oral alendronic acid following hip fracture

In the UK, physiotherapists can train as independent prescribers and are working in increasing numbers as advanced clinical practitioners. This case study examines the safe prescribing of oral bisphosphonates following a fragility fracture of the hip and considers this process in the context of the Royal Pharmaceutical Society's competencies (2021) , which were adopted by the Health and Care Professions Council in 2016. Despite these medications being around since the 1960s, their utilisation in the treatment of osteoporosis remains limited, and low levels of patient adherence continues to present a problem. This case study will look at the ways in which these issues can be addressed and identifies areas for future development. It will also describe the process of bone health assessment, offering non-pharmacological approaches as a way to reduce fracture and falls risks. The shared care nature of osteoporosis management will also be considered, with communication and partnership between primary care and secondary care being key in the provision of this treatment.

Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study

SummaryBisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring.PurposeSuboptimal antiresorptive use is not well understood. This study investigated trajectories of oral bisphosphonate use following first hip fractures and factors associated with different adherence and persistence trajectories.MethodsWe conducted a retrospective study of all patients aged ≥ 50 years dispensed two or more bisphosphonate prescriptions following first hip fracture in Victoria, Australia, from 2012 to 2017. Twelve-month trajectories of bisphosphonate use were categorized using group-based trajectory modeling. Factors associated with different trajectories compared to the persistent adherence trajectory were assessed using multivariate multinomial logistic regression.ResultsWe identified four patterns of oral bisphosphonate use in 1811 patients: persistent adherence (66%); delayed dispensing (17%); early discontinuation (9%); and late discontinuation (9%). Pre-admission bisphosphonate use was associated with a lower risk of delayed dispensing in both sexes (relative risk [RR] 0.28, 95% confidence interval [CI] 0.21–0.39). Older patients (≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 85 years old versus 50–64 years old, RR 0.38, 95% CI 0.22–0.64) had a lower risk of delayed dispensing. Males with anxiety (RR 9.80, 95% CI 2.24–42.9) and females with previous falls had increased risk of early discontinuation (RR 1.80, 95% CI 1.16–2.78).ConclusionTwo-thirds of patients demonstrated good adherence to oral bisphosphonates over 12 months following hip fracture. Efforts to further increase post-discharge antiresorptive use should be sex-specific and address possible persistent uncertainty around delaying treatment initiation.

Collateral effects of the COVID-19 pandemic on endocrine treatments for breast and prostate cancer in the UK: a cohort study.

The COVID-19 pandemic affected cancer screening, diagnosis and treatments. Many surgeries were substituted with bridging therapies during the initial lockdown, yet consideration of treatment side effects and their management was not a priority. To examine how the changing social restrictions imposed by the pandemic affected incidence and trends of endocrine treatment prescriptions in newly diagnosed (incident) breast and prostate cancer patients and, secondarily, endocrine treatment-related outcomes (including bisphosphonate prescriptions, osteopenia and osteoporosis), in UK clinical practice from March 2020 to June 2022. Population-based cohort study using UK primary care Clinical Practice Research Datalink GOLD database. There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with ⩾1-year data availability since diagnosis between January 2017 and June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions. In breast cancer patients, aromatase inhibitor (AI) prescriptions increased during lockdown versus pre-pandemic [IRR: 1.22 (95% confidence interval (CI): 1.11-1.34)], followed by a decrease post-first lockdown [IRR: 0.79 (95% CI: 0.69-0.89)]. In prostate cancer patients, first-generation antiandrogen prescriptions increased versus pre-pandemic [IRR: 1.23 (95% CI: 1.08-1.4)]. For breast cancer patients on AIs, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods versus pre-pandemic (IRR range: 0.31-0.62). During the first 2 years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side effects will help assess resource allocation for patients at high risk for bone-related complications.

Low screening rates and high prevalence of osteoporosis in cirrhosis: A real-world retrospective analysis.

Patients with cirrhosis are at increased risk for osteoporosis, and those who suffer a fracture are at high risk for mortality. Despite this, osteoporosis is often overlooked and undertreated. This study aimed to evaluate osteoporosis screening, management, and adverse osteoporosis medication events in patients with cirrhosis. We performed a retrospective chart review of adult outpatients with compensated and decompensated cirrhosis seen in single health system over a 6-year period. Patient demographics, liver and bone health comorbidities, DEXA scan results, and medications were abstracted. In total, 5398 patients met criteria. The cohort was predominately white (79.1%) and older (age 59). 44.4% were female. 64.6% had decompensated cirrhosis. Median MELD-Na score was 12.8. 23.5% had a DEXA scan ordered, approximately 50% completed this test. Patients who were older, female, white, with more severe liver disease, and other osteoporosis risk factors were more likely to have a DEXA scan ordered. 48.5% of patients had osteopenia and 30.2% had osteoporosis on DEXA scan. Only 22.6% of patients with osteoporosis received treatment, most commonly oral bisphosphonates. Oral bisphosphonate prescription was not associated with variceal bleeding (8.4% without vs. 4.8% with, p = 0.487). A minority of patients with cirrhosis were screened for osteoporosis. The majority screened had osteopenia or osteoporosis on DEXA scan. Less than a quarter of patients with osteoporosis were started on treatment. Real-world experience of oral bisphosphonate use did not reveal higher rates of gastrointestinal bleeding. There is room for improvement in all aspects of bone health care in cirrhosis.

Bisphosphonate use for glucocorticoid-induced osteoporosis in older patients with immune thrombocytopenia: a clinical perspective.

Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. Recently, we found that prescription of bisphosphonate during initial loading of prednisolone may prevent reduction in bone mineral density and development of glucocorticoid-induced osteoporosis (GIO) in older patients with ITP receiving prolonged steroid therapy. In this review, I describe the treatment options for older patients with ITP, and present the best practices for screening, evaluating, and diagnosing ITP. I also summarize the literature from 2017 to 2022 on the treatment options for ITP, including discussions on the contraindications and side effects, with an emphasis on GIO, and the relative merits of bisphosphonates as a co-treatment for prevention of GIO. Finally, I present a perspective and an expert recommendation on how older patients with ITP would best be served in the future.

Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy

Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P=.02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P=.004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P=.0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P=.05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P=.08). This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.

Fracture risk in women with osteoporosis initiated on gastro-resistant risedronate versus immediate release risedronate or alendronate: a claims data analysis in the USA

SummaryThe study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start.PurposeUsing a US claims database (2009–2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate.MethodsWomen aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups.ResultsaIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year.ConclusionsDiscontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years.

Bisphosphonates Prescription for Patients With Hip Fractures Based on Evaluation by a Dentist.

Background The purpose of this study is to clarify the current status of the prescription of postoperative bisphosphonates for patients with hip fractures and to explore the factors that prevent the postoperative prescription of bisphosphonates. Methods Of 180 patients with hip fractures treated surgically at our hospital between August 2019 and April 2020, 149 patients (46 men and 103 women; mean age: 83.9 ± 9.0 years), excluding 31 patients already prescribed bisphosphonates or denosumab, were included in the study. All patients were treated based on our clinical pathway, and their risk of jaw osteonecrosis was evaluated prior to the initiation of bisphosphonates by a dentist in our hospital. We collected data from the medical records on osteoporosis treatment interventions at admission and discharge, the reasons why postoperative bisphosphonates could not be prescribed at discharge, the proportion of patients who had follow-ups at our hospital, and patients' osteoporosis treatment status. Results Eighteen (12.8%) and 95 (63.8%) patients were prescribed anti-osteoporosis drugs at admission and discharge, respectively. One hundred and twenty-one patients (86.8%) could not be prescribed postoperative bisphosphonates at discharge - 71 (58.7%) because of oral hygiene problems, 34 (28.1%) because they did not have regular dental consultations, seven (5.8%) because of renal dysfunction, eight (6.6%) because of poor cognitive and swallowing function, and one (0.8%) because of medication side effects. Forty-nine patients (32.9%) went to our hospital for follow-up and 11 were introduced to bisphosphonates or denosumab at follow-up. Conclusions The number of patients with hip fractures who were prescribed postoperative bisphosphonates was low in our study. The oral hygiene problems identified by dentists accounted for responsible for the low prescription rate of postoperative bisphosphonates. Therefore, coordination with dentists may be important to increase the postoperative bisphosphonate prescription.

Effectiveness of a computerized clinical decision support system for prevention of glucocorticoid-induced osteoporosis

Glucocorticoids are widely used for a variety of diseases, but the prevention of glucocorticoid-induced osteoporosis is sometimes neglected. Therefore, the effectiveness of a computerized clinical decision support system (CDSS) to improve the performance rate of preventive care for glucocorticoid-induced osteoporosis was evaluated. We conducted a prospective cohort study of outpatients who used glucocorticoids for three months or longer and who met the indication for preventive care based on a guideline. The CDSS recommended bisphosphonate (BP) prescription and bone mineral density (BMD) testing based on the risk of osteoporosis. The observation period was one year (phase 1: October 2017–September 2018) before implementation and the following one year (phase 2: October 2018–September 2019) after implementation of the CDSS. Potential alerts were collected without displaying them during phase 1, and the alerts were displayed during phase 2. We measured BP prescriptions and BMD testing for long-term prescription of glucocorticoids. A total of 938 patients (phase 1, 457 patients; phase 2, 481 patients) were included, and the baseline characteristics were similar between the phases. The median age was 71 years, and men accounted for 51%. The primary disease for prescription of glucocorticoids was rheumatic disease (28%), followed by hematologic diseases (18%). The prevalence of patients who needed an alert for BP prescription (67% vs. 63%, P = 0.24) and the acceptance rate of BP prescription (16% vs. 19%, P = 0.33) were similar between the phases. The number of patients who had orders for BMD testing was significantly increased (4% vs. 24%, P < 0.001) after CDSS implementation. The number of patients who needed an alert for BMD testing was significantly decreased from 93% in phase 1 to 87% in phase 2 (P = 0.004). In conclusion, the CDSS significantly increased BMD testing in patients with a higher risk of glucocorticoid-induced osteoporosis, but did not increase BP prescription.

Risk Factors Associated with Bisphosphonates Related Osteonecrosis of the Jaw: A National Insurance Senior Cohort Database Study

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe side effect of bisphosphonate, which is usually prescribed as a treatment for diseases such as multiple myeloma, bone metastases, osteoporosis, and Paget disease. To investigate the risk factors of BRONJ, we conducted a nested case-control study using the Korean National Insurance Health Service-senior cohort. Patients newly diagnosed with BRONJ were selected as the case group, while the control group included patients who were never diagnosed with BRONJ. A risk-set sampling method was used to select the control group using age, sex, the date of the first prescription of bisphosphonate, and follow-up duration. Of the 22,236 subjects, 4,455 were included in the case group. Arthrosis, rheumatoid arthritis, neuropathies, myocardial infarction, renal disease, cancer, liver disease, and tooth extraction were associated with a higher incidence of BRONJ than subjects without such conditions (aOR, 95% CI: 1.58 [1.47-1.71], 1.46 [1.30-1.63], 1.31 [1.20-1.42], 1.23 [1.01-1.49], 1.36 [1.10-1.68], 1.27 [1.12-1.45], 1.63 [1.10-2.43], and 1.64 [1.53-1.76] respectively). In conclusion, of the factors examined, we confirmed that liver disease and tooth extraction were related to an increased risk of BRONJ.

Treatment thresholds and minimal clinically important effect sizes of antiosteoporotic medication-Survey among physicians and lay persons in Germany.

BackgroundPatient decisions to take preventative treatments for osteoporosis depend on their perceptions of fracture risk, medication effect sizes (ES) of benefits and harms. However, physicians and lay persons may have differing perceptions of risks and medication efficacy. Both tend to overestimate medication benefits. This study surveyed at what risk physicians would prescribe and lay persons would be willing to take bisphosphonates, the minimum ES both groups do demand and the physicians estimates of the actual benefit of bisphosphonates.DesignCross-sectional online questionnaire survey.MethodsRespondents were confronted with a case vignette with an osteoporotic patient (10-year femoral fracture risk: 32%). They were asked at what threshold of 10-year-risk of femoral neck fracture they would prescribe or take a drug. They were asked for the minimum ES (absolute risk reduction, ARR) they demand from bisphosphonates to prescribe or take them. Physicians were asked to provide their estimate of the actual ARR of bisphosphonates.Results114 physicians and 140 lay persons answered (convenience sample/snowball distribution). The 10-year-risk threshold of lay persons (Mdnlay = 60%) willing to take medication was twice as high as the physicians’ threshold (Mdnphy = 30%) to prescribe it (p < .001). The median minimum ARR physicians demanded for bisphosphonates prescription was 17%, whereas lay persons demanded 22% (p < .001). Physicians estimated the actual ARR of bisphosphonates to be 12%. This estimated effect size was below their own minimum threshold for prescription.ConclusionsLay persons tolerate a higher fracture risk and demand a larger benefit of antiosteoporotic medication for fracture prevention than physicians. Physicians demand higher minimum benefits than their own estimates which in turn are above the benefit evidence suggests. Physicians should be more familiar with ES of antiosteoporotic drugs concerning patient outcomes and actively advise lay persons before preventive treatment decisions are taken.

Dispensing anti-osteoporotic drugs changed during the COVID-19 pandemic.

ObjectivesCaring for osteoporosis patients has proven challenging during the COVID-19 pandemic due to repeated lockdowns in Austria. The distinct possibility of insufficient treatment regimens is therefore a matter of pressing concern. The aim of the study was to assess alterations in dispensing anti-osteoporotic drugs during the COVID-19 pandemic.Patients/methodsThis study was a nationwide retrospective register-based observational study which included all patients in Austria aged ≥50 who received at least one prescription for anti-osteoporotic medication between January 2016 and November 2020. Pseudonymised individual-level patients' data were obtained from social insurance authorities. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) to predict drug dispensing.ResultsThere were 2,884,374 dispensations of anti-osteoporotic drugs to 224,598 patients between 2016 and 2020. The mean monthly prescriptions for oral bisphosphonates (−14.5 %) and SERMs (−12.9 %) decreased during the COVID-19 pandemic when compared to the non-COVID-19 period. Dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased. Prescriptions for DMAB decreased during the first lock-down, however increased by 29.1 % for the total observation time.The Arima models showed that in March 2020 (beginning of the 1st COVID-19 lockdown), there was a decrease of 778 dispensings, with a further increase of 14 dispensings every month for denosumab; a decrease by 178 dispensings, with a further increase of 23 dispensings every month for zolendronic acid; a decrease by 2950 dispensings, but with a further increase of 236 dispensings every other month for ibandronate and a decrease by 1443 dispensing with a further decrease of 29 dispensings for alendronate than predicted, had the lockdown not occurred.ConclusionsThe total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during first COVID-19 lockdown. The observed decrease of DMAB during the first lockdown rebounded in the following months. Considering the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even during a pandemic.

P008 Fracture liaison service management of patients aged 85 and older who sustain fragility fractures: audit and quality improvement

Background/AimsOsteoporosis is a burdensome disease internationally, that is commonly diagnosed following fragility fracture. In line with national guidance, in 2018 the North Staffordshire Fracture Liaison Service (FLS) changed their management policy of patients aged ≥85 years who sustain fragility fractures. Instead of calling these patients for a dual-energy X-ray absorptiometry (DXA) scan, a letter was sent to the patient’s General Practitioner, advising the empirical commencement of oral bisphosphonates. This audit aimed to evaluate whether the recommendations in this letter were enacted by GPs. Following audit, the text of the letter was changed, and a re-audit conducted to evaluate changes in practice.MethodsPatients aged ≥85 years sustaining a fragility fracture between December 2018 and October 2020 were identified from FLS records. Summary Care Records (SCRs) were used to identify whether each patient was receiving a bisphosphonate prescription at time of audit (October 2020). Analysis was descriptive, to report the proportion of patients prescribed a bisphosphonate. Quality improvement methodology informed changes to the standard letter, using GP feedback. Re-audit of fragility fractures occurring between December 2020 and May 2021 was undertaken in July 2021 to assess possible impact.Results408 eligible patients were identified in the initial audit, of which 79% were female. SCR data was available for 396 patients; median time between fracture and data collection was 9 months. 160 patients (40%) had a bisphosphonate prescribed as an acute or repeat prescription, of which >90% were alendronic acid. Following the first audit cycle, the letter was changed to address barriers to clinical decision-making including advice on relative contraindications and referral. 74 patient SCRs were reviewed in the 2nd audit cycle (85% female) and 38 (51%) were recorded as prescribed a bisphosphonate (median time between fracture and assessment 5-months).ConclusionRates of bisphosphonate prescribing, in people aged ≥85 following a recommendation letter sent to the GP, have increased from 40% to 51% following quality improvement initiative. Furthermore, the proportion of patients prescribed a bisphosphonate is similar to previous national data in patients post-DXA. This is of interest, particularly given the de-prioritisation of non-communicable diseases during the COVID-19 pandemic, and demonstrates that an intervention which requires little time, can result in changes in practice. Limitations of this work include that the SCR only includes contemporaneous prescribing data so the period of time between drug recommendation and audit was different in 1st and 2nd cycles, meaning that adherence may be expected to be higher in the 2nd cycle, because the period of time between letter and data collection was shorter, and not because of a change in our intervention.Disclosure T. Appleyard: None. K. Bethwaite: None. N. Dale: None. F. Manning: None. Z. Paskins: None.

Bisphosphonates and the risk of atypical femur fractures.

Bisphosphonates are effective in reducing hip and other fractures. However, concerns about atypical femur fractures (AFFs) have contributed to substantially decreased bisphosphonate use, and hip fracture rates may be increasing. Despite this impact, important uncertainties remain regarding AFF risks including the association between bisphosphonate use and other risk factors such as BMD, age, weight, and race. To address this evidence gap, a cohort study of 196,129 women ≥50years of age in the Southern California Kaiser Permanente HMO women (with ≥1 bisphosphonate prescription) were studied; the primary outcome was radiographically-adjudicated AFF between 2007 and 2017. Risk factors including bisphosphonate use and race were obtained from electronic health records. Multivariable Cox models were used for analysis. Benefit-risk was modeled for 1-10years of bisphosphonates to compare fractures prevented vs. AFFs associated. Among 196,129 women, 277 (0.1%) sustained AFFs. After multivariable adjustment, AFF risk increased with longer bisphosphonate duration: hazard ratio (HR) increased from HR=8.9 (95%CI: 2.8,28) for 3-5years to HR=43.5 (13.7138.1) for >8years. Hip BMD, surprisingly, was not associated with AFF risk. Other risk factors included Asian ancestry (HR=4.8 (3.6, 6.6)), short stature, overweight, and glucocorticoid use. Bisphosphonate discontinuation was associated with rapid decrease in AFF risk. Decreases in osteoporotic and hip fractures risk during 1-10years of bisphosphonates far outweighed the increase AFF risk in Caucasians, but less so in Asians. In Caucasians, after 3years 149 hip fractures were prevented with 2 AFFs associated compared to 91 and 8 in Asians. The evidence for several potential mechanisms is summarized with femoral geometry being the most likely to explain AFF risk differences between Asians and Caucasians. The results from this new study add to the evidence base for AFF risk factors and will help inform clinical decision-making for individual patients about initiation and duration of bisphosphonate therapy and drug holidays.

Gradual, but Not Sudden, Dose-Dependent Increase of ONJ Risk With Bisphosphonate Exposure: A Nationwide Cohort Study in Women With Osteoporosis.

BackgroundA causal relationship of bisphosphonate (BP) exposure with osteonecrosis of the jaw (ONJ) has been reported; however, a definite dose-dependent risk remains to be elucidated beyond current vague recommendations of 4-year oral BP for ONJ risk increase.ObjectiveTo identify the effect of bisphosphonate cumulative dose on ONJ development in women with osteoporosis.MethodsA retrospective cohort study was designed using the National Health Insurance Service—National Health Screening database of Korea. Females over the age of 50 were diagnosed with osteoporosis based on the International Classification of Diseases 10th revision (ICD-10) codes (M80, M81, and M82) with bisphosphonate prescriptions. The cumulative dose of bisphosphonate was calculated using defined daily doses (DDD) to provide an accurate BP cumulative effect on ONJ occurrence. Osteonecrosis of the jaw was identified using both ICD-10 codes and related procedure codes. The incidence rates of ONJ and hazard ratios were estimated according to the bisphosphonate cumulative dose.ResultsAmong 74,491 included subjects, 190 cases of ONJ were identified. The incidence rate substantially increased after BP cumulative dose over 1 year (25.75 for DDD < 365, which increased to 53.43 for 365 ≤ DDD < 730). Compared to subjects with a cumulative dose of DDD < 365, subjects with a cumulative dose of 365 ≤ DDD < 730 had 2.36-fold hazard for developing ONJ (p < 0.001).ConclusionA bisphosphonate cumulative dose of more than 1 year had an increased risk of ONJ development. A gradual, but not sudden, dose-dependent increase in ONJ risk with BP exposure needs to be considered in providing the optimal BP treatment duration.

Long-term bisphosphonate therapy and atypical femoral fracture: Can you have too much of a good thing?

The long-term, continuous use of bisphosphonates (beyond 5 years) is not wholly without risk. Atypical femoral fracture is an uncommon but potentially very serious adverse event associated with the long-term use of bisphosphonates. Here we consider the complexities of long-term bisphosphonate prescribing, particularly in those that are low risk of osteoporotic fracture, wherein the duration of therapy should be reviewed regularly with individualised risk assessment to ensure the duration of treatment is appropriate.