Secondary fracture prevention in primary care: a narrative review.

The global burden of osteoporosis continues to rise with an ageing population. Untreated osteoporotic fractures not only heighten the risk of subsequent fractures but are associated with excess mortality. Although primary care guidelines consistently stress the importance of secondary fracture prevention, fewer than 20% of patients are appropriately treated for osteoporosis following an initial osteoporotic fracture. This worldwide phenomenon is known as the osteoporosis care gap. This literature review examines the barriers to secondary fracture prevention in primary care and evaluates the effectiveness of targeted primary care interventions. Common themes emerged from the majority of qualitative studies, including a need for improved communication between the hospital team and primary care, better defined responsibilities and osteoporosis-directed education for the primary care physicians. Quantitative studies demonstrated that most targeted, intensive interventions aimed at educating patients and their primary care physician about osteoporosis treatment significantly increased rates of investigation and treatment. Greater uptake of models of secondary fracture prevention in primary care is urgently needed to address the osteoporosis care gap.

Examining treatment targets and equity in bone-active medication use within secondary fracture prevention: a systematic review and meta-analysis.

PURPOSE: This systematic review seeks to evaluate the proportion of fragility fracture patients screened in secondary fracture prevention programs who were indicated for pharmacological treatment, received prescriptions for bone-active medications, and initiated the prescribed medication. Additionally, the study aims to analyze equity in pharmacological treatment by examining equity-related variables including age, sex, gender, race, education, income, and geographic location. METHODS: We conducted a systematic review to ascertain the proportion of fragility fracture patients indicated for treatment who received prescriptions and/or initiated bone-active medication through secondary fracture prevention programs. We also examined treatment indications reported in studies and eligibility criteria to confirm patients who were eligible for treatment. To compute the pooled proportions for medication prescription and initiation, we carried out a single group proportional meta-analysis. We also extracted the proportions of patients who received a prescription and/or began treatment based on age, sex, race, education, socioeconomic status, location, and chronic conditions. RESULTS: This review included 122 studies covering 114 programs. The pooled prescription rate was 77%, and the estimated medication initiation rate was 71%. Subgroup analysis revealed no significant difference in treatment initiation between the Fracture Liaison Service and other programs. Across all studies, age, sex, and socioeconomic status were the only equity variables reported in relation to treatment outcomes. CONCLUSION: Our systematic review emphasizes the need for standardized reporting guidelines in post-fracture interventions. Moreover, considering equity stratifiers in the analysis of health outcomes will help address inequities and improve the overall quality and reach of secondary fracture prevention programs.

Introduction of an order set after hip fracture improves osteoporosis medication initiation and persistence: a population-based before-after analysis.

We found that a standardized order set after hip fracture increased initiation of anti-osteoporosis medication and increased persistence at 1 year, but did not reduce secondary fractures. BACKGROUND: A treatment gap exists after osteoporosis-related fractures. Introducing standardized care can improve treatment. We evaluated the impact of a hip fracture order set (OS) on anti-osteoporosis medication (AOM) initiation, persistence, and secondary fracture prevention. METHODS: In 2015, one hospital in Manitoba, Canada, introduced a hip fracture OS including recommendations for the initiation of AOM (OS group). A control group was identified from the other hospitals in the same region. A retrospective cohort study was conducted using linked administrative health data. All individuals 50 + years with surgical treatment for low-energy hip fracture between 2010 and 2019 were included and followed for AOM initiation, medication persistence at 1 year, and secondary fractures. Between-group differences for each year were assessed using chi-square tests. Logistic regression models tested the impact of socio-demographic and clinical factors on initiation, persistence of AOM. Cox regression tested the risk of secondary fracture. RESULTS: No baseline differences between OS group (813 patients) and control group (2150 patients) were observed in demographics, socioeconomic factors, or comorbidities. An increase in post-fracture AOM initiation was seen with OS introduction (OS group year before 16.7% versus year after 48.6%, p < 0.001). No change was seen in the control group. Persistence on AOM also increased (OS group year before 17.7% versus year after 28.4%, p < 0.001). No difference in secondary fractures was observed (OS group 19.8% versus control group 18.8%, p = 0.38). CONCLUSION: Introduction of a hip fracture OS significantly increased AOM initiation and persistence at 1-year post-fracture. There was no significant difference in secondary fractures.

Fracture liaison service-a multidisciplinary approach to osteoporosis management.

A fracture liaison service is a systems-level multidisciplinary approach designed to reduce subsequent fracture risk in patients who recently sustained fragility fractures. It is estimated that one in three women and one in five men over the age of 50 years old have osteoporosis. Nonetheless, only 9 to 20% of patients who sustain an initial fragility fracture eventually receive any osteoporosis treatment. With the aim of preventing subsequent fractures, a fracture liaison service (FLS) works through identifying patients presenting with fragility fractures to the hospital and providing them with easier access to osteoporosis care through referrals for bone health and fracture risk assessment and recommendation or initiation of osteoporosis treatment. Currently, there are four major types of FLS models ranging from services that only identify at-risk patients and inform and educate the patient but take no further part in communicating their findings to other stakeholders in patients' care, to services that identify, investigate, and initiate treatment at the other end of the spectrum. In this article, we review the benefits, challenges, and outcomes of FLS in the American healthcare system with further exploration of the roles each member of the multidisciplinary team can play in improving patients' bone health.

Opportunistic Identification of Vertebral Compression Fractures on CT Scans of the Chest and Abdomen, Using an AI Algorithm, in a Real-Life Setting.

This study evaluated the performance of a vertebral fracture detection algorithm (HealthVCF) in a real-life setting and assessed the impact on treatment and diagnostic workflow. HealthVCF was used to identify moderate and severe vertebral compression fractures (VCF) at a Danish hospital. Around 10,000 CT scans were processed by the HealthVCF and CT scans positive for VCF formed both the baseline and 6-months follow-up cohort. To determine performance of the algorithm 1000 CT scans were evaluated by specialized radiographers to determine performance of the algorithm. Sensitivity was 0.68 (CI 0.581-0.776) and specificity 0.91 (CI 0.89-0.928). At 6-months follow-up, 18% of the 538 patients in the retrospective cohort were dead, 78 patients had been referred for a DXA scan, while 25 patients had been diagnosed with osteoporosis. A higher mortality rate was seen in patients not known with osteoporosis at baseline compared to patients known with osteoporosis at baseline, 12.8% versus 22.6% (p = 0.003). Patients receiving bisphosphonates had a lower mortality rate (9.6%) compared to the rest of the population (20.9%) (p = 0.003). HealthVCF demonstrated a poorer performance than expected, and the tested version is not generalizable to the Danish population. Based on its specificity, the HealthVCF can be used as a tool to prioritize resources in opportunistic identification of VCF's. Implementing such a tool on its own only resulted in a small number of new diagnoses of osteoporosis and referrals to DXA scans during a 6-month follow-up period. To increase efficiency, the HealthVCF should be integrated with Fracture Liaison Services (FLS).

Taking care of inpatients with fragility hip fractures: the hip-padua osteosarcopenia (Hip-POS) fracture liaison service model.

PURPOSE: Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences. METHODS: The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits. RESULTS: During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%. CONCLUSIONS: We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes.

3D Topographical Scanning for the Detection of Osteoporosis.

Objectives: Osteoporosis is associated with greater risk of fracture, which can lead to increased morbidity and mortality. DEXA scans are often inaccessible for patients, leaving many cases of osteoporosis undetected. A portable 3D topographical scan offers an easily accessible and inexpensive potential adjunct screening tool. We hypothesized that 3D scanning of arm and calf circumference and volume would correlate with DEXA T-scores. Methods: 96 female patients were enrolled. Patients were consented and completed a topographical scan of bilateral arms and lower legs with a mobile 3D scanner for arm and calf circumference and volume in clinic. Patient charts were then retrospectively reviewed for DEXA T-scores. Results: Forearm DEXA T-score was positively correlated with arm circumference (r = 0.49, p<0.01), arm volume (r=0.62, p<0.01), and calf volume (r=0.47, p<0.01). Femoral neck DEXA T-score was positively correlated with calf circumference (r=0.36, p<0.01) and calf volume (r=0.36, p<0.01). Conclusions: Our results showed significant correlations between DEXA T-scores and topographical measurements from mobile device acquired 3D scans, although these were in the "moderate" range. Mobile device-based 3D scanning may hold promise as an adjunct screening tool for osteoporosis when DEXA scanning is not available or feasible for patients, although further studies are needed to elucidate the full potential of its clinical utility. At a minimum, identifying a patient as high risk may promote earlier diagnostic DEXA scanning.

The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena.

BACKGROUND: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. METHODS: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient's organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. RESULTS: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. CONCLUSION: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 "relatively new statements" that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.

Vertebral compression fractures at abdominal CT: underdiagnosis, undertreatment, and evaluation of an AI algorithm.

Vertebral compression fractures (VCFs) are common and indicate a high future risk of additional osteoporotic fractures. However, many VCFs are unreported by radiologists, and even if reported, many patients do not receive treatment. The purpose of the study was to evaluate a new artificial intelligence (AI) algorithm for the detection of VCFs and to assess the prevalence of reported and unreported VCFs. This retrospective cohort study included patients over age 60 yr with an abdominal CT between January 18, 2019 and January 18, 2020. Images and radiology reports were reviewed to identify reported and unreported VCFs, and the images were processed by an AI algorithm. For reported VCFs, the electronic health records were reviewed regarding subsequent osteoporosis screening and treatment. Totally, 1112 patients were included. Of these, 187 patients (16.8%) had a VCF, of which 62 had an incident VCF and 49 had a previously unknown prevalent VCF. The radiologist reporting rate of these VCFs was 30% (33/111). For moderate and severe (grade 2-3) VCF, the AI algorithm had 85.2% sensitivity, 92.3% specificity, 57.8% positive predictive value, and 98.1% negative predictive value. Three of 30 patients with reported VCFs started osteoporosis treatment within a year. The AI algorithm had high accuracy for the detection of VCFs and could be very useful in increasing the detection rate of VCFs, as there was a substantial underdiagnosis of VCFs. However, as undertreatment in reported cases was substantial, to fully realize the potential of AI, changes to the management pathway outside of the radiology department are imperative.

Vertebral compression fractures (VCFs) are the most common osteoporotic fractures. However, they often go undetected leading to a high risk of further fractures. In this study, we tested a new artificial intelligence (AI) algorithm to detect VCFs in abdominal CT scans in patients over 60 yr of age and assessed how often VCFs were missed by radiologists. We found that VCFs were underreported, with only 30% being identified by the radiologists. The AI algorithm showed promising results and had high accuracy for detecting VCFs. However, many patients with a detected VCF still did not receive treatment. The results suggest that AI could increase the detection rate of VCFs, but also highlight the need for changes beyond radiology to ensure that patients with detected fractures are appropriately treated.

Postfracture survival in a population-based study of adults aged ≥66 yr: a call to action at hospital discharge.

Postfracture survival rates provide prognostic information but are rarely reported along with other mortality outcomes in adults aged ≥50 yr. The timing of survival change following a fracture also needs to be further elucidated. This population-based, matched-cohort, retrospective database study examined 98 474 patients (73% women) aged ≥66 yr with an index fracture occurring at an osteoporotic site (hip, clinical vertebral, proximal non-hip non-vertebral [pNHNV], and distal non-hip non-vertebral [dNHNV]) from 2011 to 2015, who were matched (1:1) to nonfracture individuals based on sex, age, and comorbidities. All-cause 1- and 5-yr overall survival and relative survival ratios (RSRs) were assessed, and time trends in survival changes were characterized starting immediately after a fracture. In both sexes, overall survival was markedly decreased over 6 yr of follow-up after hip, vertebral, and pNHNV fractures, and as expected, worse survival rates were observed in older patients and males. The lowest 5-yr RSRs were observed after hip fractures in males (66-85 yr, 51.9%-63.9%; ≥86 yr, 34.5%), followed by vertebral fractures in males (66-85 yr, 53.2%-69.4%; ≥86 yr, 35.5%), and hip fractures in females (66-85 yr, 69.8%-79.0%; ≥86 yr, 52.8%). Although RSRs did not decrease as markedly after dNHNV fractures in younger patients, relatively low 5-yr RSRs were observed in females (75.9%) and males (69.5%) aged ≥86 yr. The greatest reduction in survival occurred within the initial month after hip, vertebral, and pNHNV fractures, indicating a high relative impact of short-term factors, with survival-reduction effects persisting over time. Therefore, the most critical period for implementing interventions aimed at improving post-fracture prognosis appears to be immediately after a fracture; however, considering the immediate need for introducing such interventions, primary fracture prevention is also crucial to prevent the occurrence of the initial fracture in high-risk patients.

An Emergency Department-based system intervention to improve osteoporosis screening for older adults at high-risk of fracture.

Falls and osteoporosis are risk factors for fragility fractures. Bone mineral density (BMD) assessment is associated with better preventative osteoporosis care, but it is underutilized by those at high fracture risk. We created a novel electronic medical record (EMR) alert-driven protocol to screen patients in the Emergency Department (ED) for fracture risk and tested its feasibility and effectiveness in generating and completing referrals for outpatient BMD testing after discharge. The EMR alert was configured in 2 tertiary-care EDs and triggered by the term "fall" in the chief complaint, age (≥65 years for women, ≥70 years for men), and high fall risk (Morse score ≥ 45). The alert electronically notified ED study staff of potentially eligible patients. Participants received osteoporosis screening education and had BMD testing ordered. From November 15, 2020 to December 4, 2021, there were 2,608 EMR alerts among 2,509 patients. We identified 558 patients at high-risk of fracture who were screened for BMD testing referral. Participants were excluded for: serious illness (N = 141), no documented health insurance to cover BMD testing (N = 97), prior BMD testing/recent osteoporosis care (N = 58), research assistant unavailable to enroll (N = 53), concomitant fracture (N = 43), bedridden status (N = 38), chief complaint of fall documented in error (N = 38), long-term care residence (N = 34), participation refusal (N = 32), or hospitalization (N = 3). Of the 16 participants who had BMD testing ordered, 7 scheduled and 5 completed BMD testing. EMR alerts can help identify subpopulations who may benefit from osteoporosis screening, but there are significant barriers to identifying eligible and willing patients for screening in the ED. In our study targeting an innovative venue for osteoporosis care delivery, only about 1% of patients at high-risk of fracture scheduled BMD testing after an ED visit. Adequate resources during and after an ED visit are needed to ensure that older adults participate in preventative osteoporosis care.

Development and Comparison of Treatment Decision Tools for Glucocorticoid-Induced Osteoporosis.

Long-term Glucocorticoid (GC) use results in compromised bone strength and fractures, and several treatment recommendations have been developed to prevent fractures, but none have been validated in a real-world setting. This study aims to create a treatment decision tool and compares this tool to the treatment suggestions from the American College of Rheumatology (ACR), International Osteoporosis Foundation and European Calcified Tissue Society (IOF-ECTS), and GC-adjusted Fracture Risk Assessment Tool (GC-FRAX), above the intervention threshold. We utilized registry data gathered at Chang Gung Memorial Hospital at Kaohsiung, Taiwan, between September 2014 and April 2021. This research is a single-center, observational, and case-controlled study. We recruited participants using prednisone for at least 2.5 mg/day or the equivalent dose for over 3 months, excluding those younger than 40, those with malignancies, or those currently undergoing anti-osteoporosis therapy. The primary endpoint was new fragility fractures within 3 years, including morphometric vertebral fractures detected at baseline and with a follow-up thoracic-lumbar spine X-ray. Participants were randomly allocated into derivation and validation sets. We developed the Steroid-Associated Fracture Evaluation (SAFE) tool in the derivation cohort by assessing the weights of exploratory variables via logistic regression. Prediction performance was compared in the validation set by the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and sensitivity and specificity. A total of 424 treatment-naïve subjects were enrolled, and 83 (19.6%) experienced new fractures within 3 years. The final formula of the SAFE tool includes osteoporosis (1 point), an accumulated GC dose ≥ 750 mg within 6 months (or equivalent prednisolone of ≥4.5 mg/day for 6 months) (1 point), a BMI ≥ 23.5 (1 point), previous fractures (1 point), and elderliness of ≥70 years (2 points). In the validation set, a treatment decision based on the SAFE ≥ 2 points demonstrated an AUC of 0.65, with a sensitivity/specificity/accuracy of 75.9/54.0/58.9, with an ACR of 0.56 (100.0/11.0/31.0), IOF-ECTS 0.61 (75.9/46.0/52.7), and GC-FRAX 0.62 (82.8/42.0/51.2). Among current GIOP recommendations, the SAFE score serves as an appropriate treatment decision tool with increased accuracy and specificity.

Assessing the interaction effects of mitochondrial DNA polymorphisms and lifestyle on heel bone mineral density.

BACKGROUND: Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear. Therefore, we aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis. METHODS: Our analysis included 119,120 white participants (Nfemale=65,949 and Nmale=53,171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and five life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis. RESULTS: Our study identified four mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T>C (MT-DLOOP; P =1.50×10-3) in total samples. Multiple candidate mtDNA×lifetsyle interactions were also detected for heel BMD, such as MT-ND2×physical activity (P = 2.88×10-3) in total samples and MT-ND1×smoking (P = 8.54×10-4) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with five life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P =1.13×10-3). CONCLUSIONS: Our study suggests the candidate interaction between mitochondria and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.

Following hip fracture, hospital organizational factors associated with prescription of anti-osteoporosis medication on discharge, to address imminent refracture risk: a record-linkage study.

Patients who sustain a hip fracture are known to be at imminent refracture risk. Their complex multidisciplinary rehabilitation needs to include falls prevention and anti-osteoporosis medication (AOM) to prevent such fractures. This study aimed to determine which hospital-level organizational factors predict prescription of post-hip fracture AOM and refracture risk. A cohort of 178 757 patients aged ≥60 yr who sustained a hip fracture in England and Wales (2016-2019) was examined and followed for 1 yr. Patient-level hospital admission datasets from 172 hospitals, the National Hip Fracture Database, and mortality data were linked to 71 metrics extracted from 18 hospital-level organizational reports. Multilevel models determined organizational factors, independent of patient case-mix, associated with (1) AOM prescription and (2) refracture (by ICD10 coding). Patients were mean (SD) 82.7 (8.6) yr old, 71% female, with 18% admitted from care homes. Overall, 101 735 (57%) were prescribed AOM during admission, while 50 354 (28%) died during 1-yr follow-up, 12 240 (7%) refractured. Twelve organizational factors were associated with AOM prescription, for example, orthogeriatrician-led care compared to traditional care models (odds ratio [OR] 4.65 [95% CI, 2.25-9.59]); AOM was 9% (95% CI, 6%-13%) more likely to be prescribed in hospitals providing routine bone health assessment to all patients. Refracture occurred at median 126 d (IQR 59-234). Eight organizational factors were associated with refracture risk; hospitals providing orthogeriatrician assessment to all patients within 72 h of admission had an 18% (95% CI, 2%-31%) lower refracture risk, weekend physiotherapy provision had an 8% (95% CI, 3%-14%) lower risk, and where occupational therapists attended clinical governance meetings, a 7% (95% CI, 2%-12%) lower risk. Delays initiating post-discharge community rehabilitation were associated with a 15% (95% CI, 3%-29%) greater refracture risk. These novel, national findings highlight the importance of orthogeriatrician, physiotherapist, and occupational therapist involvement in secondary fracture prevention post hip fracture; notably, fracture risk reductions were seen within 12 mo of hip fracture.

Patients who have broken (fractured) a hip are at risk of having another fracture soon after. They have complex needs to avoid more fractures, which include being prescribed bone-strengthening medicines and taking measures to prevent falls. This study looked at which of the measurements, that describe how well a hospital is organized, are associated with whether bone-strengthening medicine is prescribed and the chance of having another fracture. We used data from 178 757 patients aged over 60 yr who had a hip fracture at 172 English and Welsh hospitals, linked to their hospital records, and other datasets that describe hospital services. Overall, 57% of patients were prescribed bone-strengthening medicines, and 7% went on to have another fracture. Bone-strengthening medicines were more likely to be prescribed in hospitals where patient care was led by a consultant specializing in the care of older people with fractures (called orthogeriatricians) and in hospitals which routinely checked patients' bone health. Patients attending hospitals that provided orthogeriatrician assessment to all patients within 72 h of being admitted, physiotherapy services at the weekend, or where occupational therapists attended meetings aimed at improving hospital services had a lower chance of having another fracture.

Osteoporosis treatment prevents hip fracture similarly in both sexes: the FOCUS observational study.

Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271 389 patients age ≥ 65 who had a hip-containing computed tomography scan during care between 2005-2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip bone mineral density T-score ≤ -2.5, measured from the CT scan using VirtuOst). We defined "treated" as at least six months of any osteoporosis medication by prescription fill data during follow up; "not-treated" was no prescription fill. Sex-specific odds ratios of hip fracture for treated versus not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, a BMD-treatment interaction, body mass index, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2211 patients) and 24.0% of the men (175/728 patients) were treated, primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated versus not-treated was 0.26 (95% confidence interval: 0.21-0.33) for women and 0.21 (0.13-0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47-1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.

Much evidence suggests that osteoporosis treatment should prevent hip fracture similarly in both sexes. However, because of their expense, randomized clinical trials to demonstrate that definitively have not been performed and may never be. As a result, osteoporosis testing and treatment is not as widely adopted for men as it is for women. Addressing that evidence gap, we analyzed data from over 250 000 patients in the Kaiser Permanente healthcare system in Southern California. Sampling a subset of all patients over a 13-year period who had had a computed tomography (CT or CAT) scan as part of their medical care for any reason, we measured bone mineral density from the CT scans to identify all patients who had osteoporosis at the hip and then used data from the electronic health records to determine statistically the risk of a future hip fracture for those who were treated for osteoporosis versus those who were not treated. We found that the reduction in risk of hip fracture associated with treatment did not differ between the sexes. These results demonstrate that treating osteoporosis in patients at high risk of hip fracture should reduce the risk of hip fracture similarly in both sexes.

Comparative effectiveness of denosumab vs alendronate among postmenopausal women with osteoporosis.

Although clinical trials have shown that denosumab significantly increases bone mineral density at key skeletal sites more than oral bisphosphonates, evidence is lacking from head-to-head randomized trials evaluating fracture outcomes. This retrospective cohort study uses administrative claims data from Medicare fee-for service beneficiaries to evaluate the comparative effectiveness of denosumab vs alendronate in reducing fracture risk among women with PMO in the US. Women with PMO ≥ 66 yr of age with no prior history of osteoporosis treatment, who initiated denosumab (n = 89 115) or alendronate (n = 389 536) from 2012 to 2018, were followed from treatment initiation until the first of a specific fracture outcome, treatment discontinuation or switch, end of study (December 31, 2019), or other censoring criteria. A doubly robust inverse-probability of treatment and censoring weighted function was used to estimate the risk ratio associated with the use of denosumab compared with alendronate for hip, nonvertebral (NV; includes hip, humerus, pelvis, radius/ulna, other femur), non-hip nonvertebral (NHNV), hospitalized vertebral (HV), and major osteoporotic (MOP; consisting of NV and HV) fractures. Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate. Denosumab reduced the risk of MOP fractures by 9% at year 1, 12% at year 2, 18% at year 3, and 31% at year 5. An increase in the magnitude of fracture risk reduction with increasing duration of exposure was also observed for other NV fracture outcomes. In this cohort of almost half-a-million treatment-naive women with PMO, we observed clinically significant reductions in the risk of MOP, hip, NV, NHNV, and HV fractures for patients on denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk.

Osteoporosis-related fractures can have a significant impact on the health and quality of life of women with postmenopausal osteoporosis, as well as pose a significant burden to society. Although clinical trials have shown that denosumab is more effective at increasing bone mineral density compared with alendronate, there is a lack of evidence evaluating the fracture risk between these 2 commonly used osteoporosis therapies. In this study using Medicare claims data for almost 500 000 women with postmenopausal osteoporosis with no prior history of osteoporosis medication use, we compared the risk of fracture­an important outcome to patients and health care providers­between denosumab and alendronate. Advanced analytic methods were implemented to ensure the study results were valid and were not unduly influenced by biases common in observational studies. We observed clinically meaningful reductions (from 30% up to 50%) in the risk of hip, nonvertebral, non-hip nonvertebral, hospitalized vertebral, and major osteoporotic fractures for patients treated with denosumab compared with alendronate. Patients who remained on denosumab for longer periods of time experienced greater reductions in fracture risk than those who remained on alendronate.

Shoring Up Osteoporosis Management: A Fresh Start?

Anabolic bone agents, such as parathyroid hormone receptor agonists (teriparatide and abaloparatide) and sclerostin-inhibiting monoclonal antibody (romosozumab), are superior at preventing clinically significant fractures and/or vertebral fractures in women with and without severe osteoporosis compared with bisphosphonates.

Comparative effectiveness and safety outcomes between denosumab and bisphosphonate in South Korea.

Both bisphosphonates and denosumab are the mainstays of treatment for osteoporosis to prevent fractures. However, there are still few trials directly comparing the prevention of fractures and the safety of 2 drugs in the treatment of osteoporosis. We aimed to compare the efficacy and safety between denosumab and bisphosphonates using a nationwide claims database. The database was covered with 10 million, 20% of the whole Korean population sampled by age and sex stratification of the Health Insurance Review and Assessment Service in South Korea. Among 228 367 subjects who were over 50 yr of age and taking denosumab or bisphosphonate from January 2018 to April 2022, the analysis was performed on 91 460 subjects after 1:1 propensity score matching. The primary outcome was treatment effectiveness; total fracture, major osteoporotic fracture, femur fracture, pelvic fracture, vertebral fracture, adverse drug reactions; acute kidney injury, chronic kidney disease, and atypical femoral fracture. Total fracture and osteoporotic major fracture, as the main outcomes of efficacy, were comparable in the denosumab and bisphosphonate group (HR 1.06, 95% CI, 0.98-1.15, P = .14; HR 1.13, 95% CI, 0.97-1.32, P = .12, respectively). Safety for acute kidney injury, chronic kidney disease, and atypical femoral fracture also did not show any differences between the 2 groups. In subgroup analysis according to ages, the denosumab group under 70 yr of age had a significantly lower risk for occurrences of acute kidney injury compared to the bisphosphonate group under 70 yr of age (HR 0.53, 95% CI, 0.29-0.93, P = .03). In real-world data reflecting clinical practice, denosumab and bisphosphonate showed comparable effectiveness for total fractures and major osteoporosis fractures, as well as safety regarding acute kidney injury, chronic kidney disease, and atypical femoral fracture.

This study compared the effectiveness and safety of denosumab and bisphosphonates, 2 primary treatments for osteoporosis, using a large South Korean nationwide claims database. Analysis of data from 91 460 individuals over 50 yr old showed no significant difference in preventing fractures or in safety outcomes such as kidney injury and atypical femoral fractures between the 2 drugs. However, among patients under 70, denosumab was associated with a lower risk of acute kidney injury. Overall, both medications demonstrated similar effectiveness and safety in the real-world treatment of osteoporosis.

On-time denosumab dosing recovered rapidly during the COVID-19 pandemic, yet remains suboptimal.

Timely administration of denosumab every 6 mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66 yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/-30 d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or ≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: -17.8% (95% CI, -19.6, -16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: -3.2% (95% CI, -5.0, -1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.