Management of Osteoporosis in Men: A Narrative Review

Male osteoporosis is a still largely underdiagnosed pathological condition. As a consequence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteoporotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women.

Diabetes, Obesity, and Osteoporosis in an Ethnically Diverse Population of Women Receiving Osteoporosis Screening

Osteoporosis screening by bone density (BMD) testing is recommended for women aged 65-75 years. However, patients with diabetes, a risk factor for fracture, often have higher body mass index (BMI) which contributes to higher BMD. These factors may vary by race/ethnicity. The relationship of diabetes (≥2 diagnoses and treatment), obesity (BMI ≥30), and BMD-defined osteoporosis (femoral neck BMD T-score ≤ -2.5) was examined in a diverse primary care population of 44,313 non-Hispanic White, 6,103 Black, 7,777 Hispanic, and 12,634 Asian women aged 65-75 years who underwent BMD screening. Those with recent fracture, osteoporosis treatment, bone disorders, and metastatic cancer were excluded. Modified log-Poisson regression was used to examine the association of diabetes and BMD-osteoporosis. Among 70,827 women, 18% had diabetes. The prevalence of diabetes was 2-fold higher in Black, Hispanic and Asian women compared to White women. Overall, women with diabetes (versus no diabetes) were more likely to be obese and, except for Hispanic women, less likely to have BMD-osteoporosis. In unadjusted analyses, diabetes was associated with lower risk of BMD-defined osteoporosis in White, Black, and Asian women, but not Hispanic women. However, the association was attenuated or no longer evident after adjusting for BMI, suggesting that the lower burden of BMD-osteoporosis in women with diabetes is mediated in part by higher BMI. These findings support consideration of diabetes when assessing fracture risk in women undergoing osteoporosis screening. However, more studies in non-White populations with a high burden of diabetes are important since these relationships appear to differ by race/ethnicity.

Screening of Corticosteroid-Induced Osteoporosis in Patients with Immune Thrombocytopenia or Warm Autoimmune Hemolytic Anemia in the Outpatient Setting

Introduction: Corticosteroids (CS) are the standard first line treatment for immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (WAIHA). Current guidelines advise against long-term CS (LTCS) use to minimize associated toxicities. Despite these guidelines, a number of patients remain on LTCS. For example, in a retrospective study of 53 patients with WAIHA, the mean duration of CS therapy was 15 months (mo) with 20% of patients with CS-induced diabetes, 10% with worsening of pre-existing diabetes, 10% with osteoporosis (OP) with fracture, and 4% with osteonecrosis of the femoral head (Roumier 2014). It is our observation that our hematology clinic patients may benefit from the application of guidelines for the prevention of CS-induced OP. The 2017 American College of Rheumatology (ACR) guidelines for prevention and treatment of CS-induced OP include a baseline clinical fracture risk assessment within 6 mo of the start of LTCS therapy (≥3 mo) followed by age and risk-adapted OP screening (Buckley 2017). Adults <40 years old (yo) with OP risk factors or prior OP fracture should undergo baseline bone mineral density (BMD) testing within 6 months of the start of CS therapy. For patients ≥40 yo, the Fracture Risk Assessment Tool (FRAX) with CS dose correction and BMD testing should be done within 6 mo of the start of CS therapy. With no similar national hematology guidelines, we applied 2017 American College of Rheumatology (ACR) guidelines for the prevention of CS-induced OP to our hematology clinic patients. The aim of the study was to improve screening for CS-induced OP in patients with ITP or WAIHA. Methods: We retrospectively identified patients with ITP or WAIHA by ICD-10 codes who were seen in the hematology clinic at LAC+USC Medical Center, Los Angeles, CA, from October 1, 2020 to March 31, 2021. The electronic medical record (EMR) was reviewed for demographic data and to confirm diagnosis. The relevant clinical history including CS dose/duration, common adverse events (AEs) from LTCS use, and BMD screening with a dual-energy X-ray absorptiometry (DEXA) scan. The patients were assessed for whether they underwent appropriate screening for CS-induced OP based on ACR guidelines. Results: Of the 2256 patient encounters in the hematology clinic during the 6-mo study period, 54 patients were identified with either ITP and/or WAIHA. The median age was 49 yo (range: 21-87), 74% were female (40/54) and 85.2% (46/54) were Hispanic. Of these 54 patients, 46 patients had prior or current CS therapy with either prednisone or dexamethasone. The most common AEs associated with CS included: weight gain (34.8%, 16/54), hypertriglyceridemia (34.8%, 16/54), worsening of diabetes (7.4%, 4/54), and worsening hypertension (3.7%, 2/54). Of the 15 patients <40 yo, 7 received LTCS therapy for ≥3 months and 42.9% (3/7) underwent screening with a DEXA scan. 1 had a normal BMD, 1 had osteopenia and 1 had OP. Of the 39 patients ≥40 years, 14 had received LTCS therapy for ≥3 months and 14.3% (2/14) had a screening DEXA scan; both demonstrated osteopenia. 2 patients with <3 months of CS therapy underwent screening - 1 for CS use, which showed osteopenia and one for age-appropriate screening of OP, which also showed osteopenia. Of the 6 patients with osteopenia or OP, 83.3% (5/6) were on vitamin D and calcium supplementation prior to screening. After diagnosis of osteopenia, one patient was not started on vitamin D and calcium supplementation. Bisphosphate therapy was initiated after diagnosis of OP in 1 patient. Conclusions: The majority of patients with ITP or WAIHA seen in our hematology clinic who were treated with LTCS ≥3 months did not receive a screening DEXA scan for OP as recommended by ACR guidelines. With this baseline data, we propose a quality improvement initiative in our clinic to ensure that all patients on LTCS are assessed for OP risk. Planned interventions include resident/fellow education, creation of a handout of the ACR guidelines posted in clinic, implementation of clinical fracture risk reassessment at baseline and every 12 months with BMD as indicated, and implementation of an EMR template to ensure uniform documentation. More broadly, our findings serve as a reminder of the importance for monitoring CS duration and suggest a need for a structured approach to monitoring for short and long-term toxicities of CS for the field of hematology. The creation of hematology-specific guidelines may be beneficial in this effort. Disclosures Piatek: Apellis: Research Funding; Alexion: Consultancy, Research Funding; Rigel: Consultancy, Research Funding; Dova: Consultancy, Speakers Bureau.

201. Frequency of Pseudomonas aeruginosa (PA) Discrete Inner Colonies and Comparison of Minimal Inhibitory Concentration (MIC) Values between Parent and Inner Colony Isolates Following Fosfomycin Disk Diffusion (DD) Testing

Background Fosfomycin combination therapy is a potential approach for treatment of multidrug-resistant (MDR) PA infections despite a lack of approved susceptibility breakpoints for this organism. While DD testing is commonly used for fosfomycin, growth of discrete inner colonies (IC) within the zone of inhibition has been observed for multiple organisms following DD. Criteria recommended by CLSI and EUCAST are contradictory for interpreting these inner colonies. We therefore sought to determine the frequency of inner colonies and MIC differences between PA parent-inner colony pairs from an international isolate collection. Methods A convenience collection of 198 clinical PA isolates from three U.S institutions (n = 82), two Australian institutions (n = 72), and the CDC & FDA Antibiotic Resistance Isolate Bank (n = 44) were included. Fosfomycin MIC values were determined in duplicate on separate days by DD and broth microdilution (BMD) testing. For parent isolates with discrete IC observed during DD, IC isolates were subcultured and MIC values were determined and then compared to their corresponding parent isolates. MIC values were interpreted using CLSI Escherichia coli (EC) breakpoints (susceptible: MIC ≤ 64 μg/mL, intermediate: MIC = 128, resistant: MIC ≥ 256 μg/mL). Results Parent isolate BMD MIC values ranged from < 4 to > 256 μg/mL while IC isolate BMD MIC values ranged from 128 to > 1024 μg/mL. MIC50/90 values were 128/256 μg/mL and > 1024/ > 1024 μg/mL for the parent and IC isolates, respectively. A high frequency of 45% (89/198) of parent isolates displayed discrete IC which also demonstrated a higher frequency of resistance (97.8%) compared to the parent isolates (23.7%). Conclusion IC MIC values were higher overall compared to parent MIC values, with an average fold difference of ~18 between the parent-inner colony pairs. The frequency of IC found in this study (45%) is considerably higher than previously observed in EC clinical isolates. These data highlight the need to further investigate the importance of these IC and warrant caution for extrapolation of EC breakpoints for fosfomycin susceptibility testing against PA. Disclosures All Authors: No reported disclosures

FRAX-Based Intervention Thresholds for Osteoporosis Treatment in Ukraine

Objectives. Osteoporosis, in addition to its consequent fracture burden, is a common and costly condition. FRAX® is a well-established, validated, web-based tool which calculates the 10-year probability of fragility fractures. A FRAX model for Ukraine has been available since 2016 but its output has not yet been translated into intervention thresholds for the treatment of osteoporosis in Ukraine; we aimed to address this unmet need in this analysis. Methods. In a referral population sample of 3790 Ukrainian women, 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture separately were calculated using the Ukrainian FRAX model, with and without femoral neck bone mineral density (BMD). We used a similar approach to that first proposed by the UK National Osteoporosis Guideline Group, whereby treatment is indicated if the probability equals or exceeds that of a woman of the same age with a prior fracture. Results. The MOF intervention threshold in females (the age-specific 10-year fracture probability) increased with age from 5.5% at the age of 40 years to 11% at the age of 75 years where it plateaued and then decreased slightly at age 90 (10%). Lower and upper thresholds were also defined to determine the need for BMD, if not already measured; the approach targets BMD measurements to those at or near the intervention threshold. The proportion of the referral populations eligible for treatment, based on prior fracture or similar or greater probability, ranged from 44% to 69% depending on age. The prevalence of the previous fracture rose with age, as did the proportion eligible for treatment. In contrast, the requirement for BMD testing decreased with age. Conclusions. The present study describes the development and application of FRAX-based assessment guidelines in Ukraine. The thresholds can be used in the presence or absence of access to BMD and optimize the use of BMD where access is restricted.

POS0303 PREVENTION OF CHRONIC DISEASES DUE TO INFLAMMATION IN INFLAMMATORY ARTHRITIS: RESULTS OF A DELPHI PROCESS TO SELECT CARE RECOMMENDATIONS FOR AN ELECTRONIC MEDICAL RECORD (EMR) INTERVENTION

Background:Inflammatory arthritis (IA) predisposes patients to several chronic conditions including cardiovascular diseases (CVD), diabetes (DM), osteoporosis (OP) and infections, likely due to systemic effects of inflammation. Studies have found that patients with IA often receive suboptimal care for screening and managing these conditions.Objectives:This is the first phase of a study which will develop and pilot test automated EMR reminders for family physicians. The reminders will prompt family physicians to screen for and address risk factors for these conditions. We conducted a Delphi process to select care recommendations to be addressed by the EMR reminders.Methods:We conducted a review of current BC, Canadian and international guidelines for screening and addressing risk factors for CVD, DM, OP and infection. A list of 22 care recommendations, including their level of evidence and risks/benefits of implementation, was reviewed by a panel of six family physicians, three rheumatologists and three IA patients, in a three-round online modified Delphi process. Panelists rated each care recommendation, using 9-point scales, on 1) their clinical importance, 2) their likelihood of improving outcomes, and 3) implementation feasibility. Results were discussed in an online forum. Panelists then rated slightly revised care recommendations, modified based on feedback from the discussion. Care recommendations were retained if the median rating was ≥7 with no disagreement as defined by the RAND/UCLA Method handbook.Results:A list of 15 care recommendations was selected by the Delphi process for EMR integration, including recommendations that address CVD risk assessment (1), hypertension screening (1), DM screening (2), fracture risk assessment (1), BMD testing (1), osteoporosis prevention (1) and treatment (1) with bisphosphonates, preventing infections through immunization (2), minimizing steroids (1) and hepatitis screening (1), screening for hydroxychloroquine retinal toxicity (1), and counselling for lifestyle modifications (2). We excluded 7 recommendations which addressed lipid testing (1), BMD testing in steroid users (1), immunizations (2), weight management (1), and DMARD laboratory test monitoring (2). Recommendations were excluded on the basis of importance (1) or feasibility (6).Conclusion:The results of the Delphi process will inform the development of reminders, integrated in EMRs, that will support family physicians in their efforts to engage IA patients in addressing risk factors for chronic diseases related to inflammation. We hope to improve the prevention of these diseases, which represent an important cause of morbidity and mortality for people with inflammatory arthritis.Acknowledgements:Iman Sheriff’s work on this project was funded by the CRA summer studentship programme. Dr. Lacaille is supported by the Mary Pack Chair in Arthritis Research from UBC and The Arthritis Society of Canada. Thank you to all who participated in the Delphi survey.Disclosure of Interests:None declared

Use of an electronic medical record dashboard to identify gaps in osteoporosis care

Summary Using an electronic medical record (EMR)-based dashboard, this study explored osteoporosis care gaps in primary care. Eighty-four physicians shared their practice activities related to bone mineral density testing, 10-year fracture risk calculation and treatment for those at high risk. Significant gaps in fracture risk calculation and osteoporosis management were identified. Purpose To identify care gaps in osteoporosis management focusing on Canadian clinical practice guidelines (CPG) related to bone mineral density (BMD) testing, 10-year fracture risk calculation and treatment for those at high risk. Methods The ADVANTAGE OP EMR tool consists of an interactive algorithm to facilitate assessment and management of fracture risk using CPG. The FRAX® and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools were embedded to facilitate 10-year fracture risk calculation. Physicians managed patients as clinically indicated but with EMR reminders of guideline recommendations; participants shared practice level data on management activities after 18-month use of the tool. Results Eighty-four physicians (54%) of 154 who agreed to participate in this study shared their aggregate practice activities. Across all practices, there were 171,310 adult patients, 40 years of age and older, of whom 17,214 (10%) were at elevated risk for fracture. Sixty-two percent of patients potentially at elevated risk for fractures did not have BMD testing completed; most common reasons for this were intention to order BMD later (48%), physician belief that BMD was not required (15%) and patient refusal (20%). For patients with BMD completed, fracture risk was calculated in 29%; 19% were at high risk, of whom 37% were not treated with osteoporosis medications as recommended by CPG. Conclusion Despite access to CPG and fracture risk calculators through the ADVANTAGE OP EMR tool, significant gaps remain in fracture risk calculation and osteoporosis management. Additional strategies are needed to address this clinical inertia among family physicians.

THE EFFECT OF 'CONCERN FOR OSTEOPOROSIS' AND SELF-PERCEIVED 'RISK OF OSTEOPOROSIS AND FRACTURE' ON ANTI-OSTEOPOROSIS BEHAVIOR OF POST MENOPAUSAL WOMEN- A CROSS-SECTIONAL STUDY.

Introduction: Osteoporosis is more prevalent in women, especially following menopause. The total affected population would have been around 35 to 40 million. Morbidity due to disease includes decreased mobility, decreased quality of life, and increased risk of mortality following an osteoporotic fracture. The morbidity due to the disease may be decreased through diet, exercise, supplementation, and medication. The objective of this study is to determine the effect of 'concern for osteoporosis' and self-perceived 'risk of osteoporosis and fracture' on antiosteoporosis behaviour such as (1) calcium and vitamin D supplementation, (2) seeking medical advice, (3) undergoing bone mineral (BMD) testing, and (4) taking antiosteoporosis medication (AOM). Material And Method:The study was conducted on women attending outpatient clinic of the Obstretics and Gynaecology and Orthopaedics department. Patients were required to ll up the Global Longitudinal Osteoporosis in Women Questionnaire. Enrolled patients were contacted after one year by means of telephone calls, hospital visits and home visits and data was collected for self-reported use of supplements, self-reported seeking of medical advice regarding osteoporosis, self-reported BMD testing, and self-reported use of antiosteoporosis medications etc. Results:Total of 1562 women were enrolled for the study out of which data of only 1000 women was analyzed at end of one year. At the end of one year period 360 women reported use of Calcium and or Vitamin D. Table 4 depicts the association between the use of vitamin supplementation and concern and risk perception. Concern (P=0.61), risk perception to osteoporosis (P=0.13), and risk perception to fracture (P=0.29) were not signicantly associated with use of vitamin supplementation in the next 12 months (i.e., calcium and/or vitamin D). Concern (p= <0.001), risk perception to osteoporosis (p=<0.001), and risk perception to fracture (p=<0.001) were signicantly associated with women seeking medical care during the next one year. Concern (p=0.35) was not signicantly associated with undergoing BMD examination. Risk perception to osteoporosis (p=0.03) and risk perception to fracture (p=0.03) were signicantly associated with women undergoing BMD medical examination in one year. Concern about osteoporosis (p=0.64) was not signicantly associated with treatment with anti-osteoporotic medication. Risk perception to osteoporosis (p=0.06) and risk perception to fracture (p=0.002) were signicantly associated with women. Conclusion: Concern for osteoporosis is associated with likelihood of seeking medical advice. Perception of risk for Osteoporosis and fractures is positively associated with seeking medical advice, BMD examination and AOM treatment

Assessing the knowledge, attitude and practice of osteoporosis among Singaporean women aged 65 years and above at two SingHealth polyclinics

INTRODUCTION Singapore has one of the world’s most rapidly ageing populations. Osteoporosis is associated with significant morbidity and mortality from hip fractures in the elderly. This pilot study aims to evaluate the knowledge, attitude and practice of osteoporosis among Singaporean women aged ≥ 65 years, and assess barriers to osteoporosis screening. METHODS We conducted a cross-sectional survey of 99 English-speaking women aged ≥ 65 years at two SingHealth polyclinics by convenience sampling. The validated Osteoporosis Prevention and Awareness Tool was used to assess their knowledge about osteoporosis prevention and awareness and perceived barriers to osteoporosis screening. Osteoporosis health education was provided, and bone mineral density (BMD) screening was offered to all participants. RESULTS The response rate was 91.6%. The majority of the participants (54.5%) had low knowledge of osteoporosis, and only 12.1% had high knowledge scores. Higher education levels were associated with higher knowledge scores (p = 0.018). Although participants with higher knowledge scores were more willing to undergo osteoporosis screening, these findings did not reach statistical significance (p = 0.067). The top reasons for declining BMD testing were misconceptions that lifestyle management is sufficient to prevent osteoporosis, poor awareness and knowledge of the disease, and the perceived high cost of BMD testing. CONCLUSION Interventions should focus on osteoporosis education and, eventually, BMD screening for less-educated patients. Health education should rectify common misconceptions of the disease, increase awareness of osteoporosis and improve screening rates.

Low prevalence of bone mineral density testing in patients with systemic lupus erythematosus and glucocorticoid exposure

Summary Patients with systemic lupus erythematosus (SLE) have an increased risk of developing osteoporosis and fractures due to systemic inflammation and glucocorticoids (GCs). Professional organizations recommend bone mineral density (BMD) testing in SLE patients on GCs, especially within 6 months of initiation. Using a validated algorithm, we identified SLE patients in an electronic health record cohort with long-term GC exposure (≥90 days). Our primary outcome was ever BMD testing. We assessed the impact of patient and provider factors on testing. We identified 693 SLE cases with long-term GC exposure, 41% of whom had BMD testing performed. Only 18% of patients had BMD testing within 6 months of GC initiation. In a logistic regression model for BMD testing, male sex (OR = 0.49, 95% CI 0.27 – 0.87, p = 0.01) was associated with being less likely to have BMD testing after adjusting for race and ethnicity. In contrast, older age (OR = 1.04, p < 0.001) and nephritis (OR = 1.83, p = 0.003) were associated with being more likely to have BMD testing after adjusting for race and ethnicity. Bone health in SLE patients remains an area in need of improvement with attention to patients who are younger and male.