Validation of Ten Osteoporosis Screening Tools in Rural Communities of Taiwan.

PURPOSE: Patients with osteoporosis are at risk of fractures, which can lead to immobility and reduced quality of life. Early diagnosis and treatment are crucial for preventing fractures, but many patients are not diagnosed until after a fracture has occurred. This study aimed to evaluate the performance of 10 osteoporosis screening tools (OSTs) in rural communities of Taiwan. In this prospective study, a total of 567 senior citizens from rural communities underwent bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) and ten OSTs were administered. Discrimination analysis was performed using the area under the receiver operating characteristic curve (AUROC). Primary outcomes included area under curve (AUC) value, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The DXA examination revealed that 63.0% of females and 22.4% of males had osteoporosis. Among females, Osteoporosis Index of Risk (OSIRIS) and Osteoporosis Self-Assessment Tool for Asians (OSTA) presented the best AUC value with 0.71 (0.66-0.76) and 0.70 (0.66-0.75), respectively. Among males, BWC had the best AUC value of 0.77 (0.67-0.86), followed by OSTA, Simple Calculated Osteoporosis Risk Estimation (SCORE), and OSIRIS. OSTA and OSIRIS showed acceptable performance in both genders. The specificity of Fracture Risk Assessment Tool (FRAX-H), SCORE, National Osteoporosis Foundation Score, OSIRIS, Osteoporosis Risk Assessment Instrument, Age, Bulk, One or Never Estrogen (ABONE), and Body weight criteria increased in both genders after applying the optimum cut-off. Considering it high AUC and simplicity of use, OSTA appeared to be the recommended tool for seniors of both genders among the ten OSTs. This study provides a viable reference for future development of OSTs in Taiwan. Further adjustment according to epidemiological data and risk factors is recommended while applying OSTs to different cohorts.

Long-term surgical outcomes of hemiarthroplasty for patients with femoral neck fracture with metal versus ceramic head in Taiwan.

AIMS: Hip fractures are a significant health concern, especially in the elderly. Hemiarthroplasty has been the preferred treatment for displaced femoral neck fractures. The use of ceramic femoral heads has recently become popular due to their claimed durability. This study aimed to determine long-term outcomes associated with different implant choices in hemiarthroplasty. METHODS: The study sample included patients aged 50 years and above, with an index femoral neck fracture admission and hip hemiarthroplasty identified from Taiwan's National Health Insurance (NHI) claims data (2009-2019). To compare two groups of users of different heads, we performed 1:2 matching of the ceramic group versus metal group according to age, gender, index year, and six major comorbidities. Cumulative incidence rates were assessed for revision, post-operative complications, and medical complications. Cause-Specific hazard Cox models were used to estimate the hazard ratios for the two different implants groups. RESULTS: Among 47,158 patients, 2559 out of 2637 who received ceramic head hemiarthroplasty with co-payment, were successfully matched with 5118 receiving metal head prostheses fully covered by the NHI. Over a mean follow-up of 3.12 years, no significant differences were observed in revision rates between the ceramic and metal head groups. The ceramic head group demonstrated significantly lower risks of postoperative complications and medical complications within 90 days than the metal head group. CONCLUSIONS: This study found ceramic implant had lower postoperative complications and medical complication rates than metal head implant in hip hemiarthroplasty, but there was no difference in the revision rates between the two heads.

Ten existing osteoporosis prediction tools for the successful application of National Health Insurance-reimbursed anti-osteoporosis medications in long-term care residents in Taiwan.

BACKGROUND/PURPOSE: Osteoporotic fracture introduce enormous societal and economic burden, especially for long-term care residents (LTCRs). Although osteoporosis prevention for LTCRs is urgently needed, obstacles such as frail status and inconvenient hospital visits hurdled them from necessary examinations and diagnoses. We aimed to test 10 existing osteoporosis screening tools (OSTs), which can be easily used in institutions and serve as a prediction, for accurately determining the outcome of a Taiwan's National Health Insurance (NHI)-reimbursed anti-osteoporosis medications (AOMs) application for LTCRs. METHODS: This prospective analysis recruited 444 patients from LTC institutions between October 2018 and November 2019. Predictions of whether the NHI-reimbursed AOMs criteria was met were tested for 10 OSTs. The results of OSTs categorized into self-reported or validated based on previous fracture history were self-reported by LTCRs or validated by imaging data and medical records, respectively. The receiver operating characteristic curve and the optimal cut-off points for LTCRs based on Youden's index were explored. RESULTS: Overall, the validated OSTs had a higher positive predictive value (PPV) and negative predictive value (NPV) summation than the corresponding reported OSTs. The validated FRAX-Major was the best OST (PPV = 63.6%, NPV = 82.4% for the male group and, PPV = 78.8%, NPV = 90.0% for the female group). After applying the optimum cut-off derived from Youden's index, the validated FRAX-Major (PPV = 75.4%, NPV = 92.0%)) remained performed best for men. In female population, validated FRAX-Major (PPV = 87.2%, NPV = 84.1%) and validated osteoporosis prescreening risk assessment (OPERA; PPV = 96.1%, NPV = 79.7%)) both provided good prediction results. CONCLUSION: FRAX-Major and OPERA have better prediction ability for LTCRs to acquire NHI-reimbursed AOMs. The validated fracture history and adjusted cut-off points could prominently increase the PPV during prediction.

Cost and effectiveness analyses of the anti-osteoporosis medication in patients with hip fracture in Taiwan: A population-based national claims database analysis.

BACKGROUND: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). RESULTS: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.

Epidemiology and clinical impact of osteoporosis in Taiwan: A 12-year trend of a nationwide population-based study.

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations.

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018.

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.

Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference.

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.

Diagnostic accuracy of algorithms to define incident and second hip fractures: A Taiwan validation study.

BACKGROUND: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. METHODS: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. RESULTS: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. CONCLUSION: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.

Increased fracture risk after discontinuation of anti-osteoporosis medications among hip fracture patients: A population-based cohort study.

BACKGROUND: To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. METHODS: We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. RESULTS: Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio [HR] = 1.60; 95% confidence interval [CI], 1.20-2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46-3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within 1 year post-discontinuation (HR = 2.90; 95% CI, 1.77-4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74-7.40). DISCUSSION: Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post-discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.

Use of dipeptidyl peptidase-4 inhibitors and the risk of arthralgia: Population-based cohort and nested case-control studies.

PURPOSE: The objective of this study was to investigate the association between the administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case-control study designs. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients who were newly prescribed with DPP-4 inhibitors, thiazolidinediones (TZDs), or acarbose between 1 March 2009 and 31 December 2012. The exposure of studied drugs was categorized into five exclusive categories: DPP-4 inhibitor, TZD, acarbose, combined use, or non-use, and assessed in a time-varying manner. Time-dependent Cox proportional hazard models were used to estimate the association between DPP-4 inhibitors and the risk of arthralgia. Particularly, we tested the impact of different cumulative duration, timing, and individual substance of DPP-4 inhibitors use on risk of arthralgia. A corresponding nested case-control study using conditional logistic regression was conducted to verify this association. RESULTS: An increased risk of arthralgia was observed during the first year after initiating DPP-4 inhibitors (adjusted Hazard Ratio = 1.35; 95% confidence interval [CI], 1.04-1.75) but the risk declined with cumulative use. This duration-response relation was not found in TZDs use and acarbose use. In the nested case-control study, there was a slightly increased risk of arthralgia (aOR = 1.08; 95% CI, 1.04-1.12) associated with current DPP-4 inhibitor use. CONCLUSION: A relatively higher risk of arthralgia was associated with the initial administration of DPP-4 inhibitors, however, the risk declined among long-term users.

Visualisation of the unmet treatment need of osteoporotic fracture in Taiwan: A nationwide cohort study.

AIMS: Recent clinical guidelines have suggested that patients experience an osteoporotic fracture should initiate anti-osteoporosis medications (AOMs). However, whether clinical guidelines translate well in "real-world" practices remain questioned. This study aimed to evaluate the "real-world" prescription pattern of AOMs and visualise the unmet treatment needs in different geographical areas in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The treatment rate was defined as the proportion of patients receiving AOMs within 1 year after their index fracture. The qualitative geographical information systems approach was adopted to visualise the treatment needs of postfracture patients in different geographical areas. RESULTS: Our study included 276,492 patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The proportion of patients who received AOMs within 1 year after their index fracture increased with age and differed with fracture types and sex. For patients with hip fractures, the treatment rate ranged from 3.43% to 20.88% for female patients and from 0.69% to 10.04% for male patients in different age groups. For patients with vertebral fractures, the treatment rate ranged from 3.23% to 37.08% for female patients and from 1.85% to 23.05% for male patients. Cities in the mid-northern and southern areas of Taiwan had the highest unmet treatment need, with a treatment rate of less than 15%. CONCLUSION: The treatment rate of osteoporotic fractures with AOMs was diverse and suboptimal in Taiwan, especially among male patients. This study used a visualisation technique to display information about the treatment status in different geographical areas and help policymakers allocate resource appropriately.

Topical anesthesia for staple removal from surgical wounds on the knee: a prospective, double-blind, randomized trial.

BACKGROUND: Staple removal from surgical wounds is painful. Only a few articles have provided expert opinions using anesthetic cream for such a problem; however, direct application of the anesthetic cream to a wound may cause infection. A safe alternative can be an anesthetic patch without wound contact. MATERIALS AND METHODS: This was a prospective, double-blind, randomized clinical trial. Sixty patients who underwent primary total knee replacement were assigned to an experimental group or control group. One lidocaine patch was applied around the surgical wound for each patient in the experimental group. Alternatively, the adhesive sides of the lidocaine patches were shielded with waterproof films in the control group. A resident peeled off the patch before a single nursing practitioner removed the staples. Pain was assessed with the 10-cm visual analog scale, and a face pain scale-revised was performed. The patients and the nursing practitioner were blind to the management. RESULTS: Mean visual analog scale and face pain scale-revised scores were significantly lower in the experimental group. The mean pain score was significantly lower in the experimental group if the application time was >47 min; for patients with application time of 47 min or shorter, the score was comparable with the mean pain scores of the control group (P = 0.215). CONCLUSIONS: Removal of the metal skin staples after total knee arthroplasty is associated with moderate-to-severe pain. The lidocaine patch applied topically around the surgical wound could effectively reduce the pain during the procedure, without remarkable complications such as systemic adverse effects or wound contamination.

Real world clinical outcomes when discontinuing denosumab or bisphosphonates in patients with surgically managed osteoporotic vertebral compression fractures: a population-based cohort study.

BACKGROUND CONTEXT: Osteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSE: This study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGN: Retrospective nationwide cohort study PATIENT SAMPLE: A total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURES: The risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. METHODS: This is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their antiosteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, nonvertebral fractures and death. RESULTS: A total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16-2.32), 1.74 (95% CI, 1.25-2.42) and 1.53 (95% CI, 1.14-2.06). If osteoporotic fractures were divided into nonvertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54-1.88) for nonpersistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for nonpersistent bisphosphonate users. However, there was a significantly greater risk of nonvertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33-3.11), 1.80 (95% CI, 1.18-2.76) and 1.56 (95% CI, 1.06-2.27) for nonpersistent denosumab users, persistent bisphosphonate users and nonpersistent users. Noteworthy, nonpersistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22-4.38). CONCLUSIONS: In terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or nonpersistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

Determining patients with spinal metastases suitable for surgical intervention: A cost-effective analysis.

BACKGROUND: Both nonoperative and operative treatments for spinal metastasis are expensive interventions. Patients' expected 3-month survival is believed to be a key factor to determine the most suitable treatment. However, to the best of our knowledge, no previous study lends support to the hypothesis. We sought to determine the cost-effectiveness of operative and nonoperative interventions, stratified by patients' predicted probability of 3-month survival. METHODS: A Markov model with four defined health states was used to estimate the quality-adjusted life years (QALYs) and costs for operative intervention with postoperative radiotherapy and radiotherapy alone (palliative low-dose external beam radiotherapy) of spine metastases. Transition probabilities for the model, including the risks of mortality and functional deterioration, were obtained from secondary and our institutional data. Willingness to pay thresholds were prespecified at $100,000 and $150,000. The analyses were censored after 5-year simulation from a health system perspective and discounted outcomes at 3% per year. Sensitivity analyses were conducted to test the robustness of the study design. RESULTS: The incremental cost-effectiveness ratios were $140,907 per QALY for patients with a 3-month survival probability >50%, $3,178,510 per QALY for patients with a 3-month survival probability <50%, and $168,385 per QALY for patients with independent ambulatory and 3-month survival probability >50%. CONCLUSIONS: This study emphasizes the need to choose patients carefully and estimate preoperative survival for those with spinal metastases. In addition to reaffirming previous research regarding the influence of ambulatory status on cost-effectiveness, our study goes a step further by highlighting that operative intervention with postoperative radiotherapy could be more cost-effective than radiotherapy alone for patients with a better survival outlook. Accurate survival prediction tools and larger future studies could offer more detailed insights for clinical decisions.

Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan.

BACKGROUND: Since 2011, Taiwan's National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. METHODS: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. RESULTS: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old. CONCLUSION: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.

A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033. Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life. Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Timing of anti-osteoporosis medications initiation after a hip fracture affects the risk of subsequent fracture: A nationwide cohort study.

OBJECTIVE: The optimal time after hip fracture to start prophylactic anti-osteoporosis medications (AOMs) remains uncertain, especially in real-world practice. Therefore, we investigated how timing of AOMs initiation affects the risk of subsequent osteoporotic fractures, and what factors influence timing of AOMs prescription. METHOD: Patients ≥50 years old with diagnostic codes indicating hospitalization for hip fracture (n = 77,930) were identified from the Taiwan National Health Insurance Research Database; 9986 who were prescribed AOMs ≤1 year after a newly-diagnosed hip fracture were grouped into those who started AOMs from: ≤14 days (very early); 15-84 days (early); 85-252 days (late); and 253-365 days (very late). Associations with fracture-related hospitalizations after an index fracture were analyzed using a multivariate, time-dependent Cox proportional hazards model, and between-group differences compared by log-rank testing. Factors influencing timing of AOMs initiation were elucidated using multivariate logistic regression analyses. RESULTS: Compared to AOMs initiation from 15 to 84 days, initiation after 252 days was associated with significantly increased risk of fracture-related hospitalization (HR = 1.93, 95% CI 1.29-2.89). Both sensitivity and pre-specified subgroup analyses yield similar results. Among patients with high adherence to AOMs, the increased risk of subsequent fracture-related hospitalization among very late users was profound (HR = 2.56, 95% CI 1.41-4.64). CONCLUSION: Timing of AOMs initiation was significantly associated with age, index year, index hospital length of stay as well as the accreditation level and geographic region of index hospital. After adjusting factors associated with timing of AOMs initiation and patients' adherence, the anti-fracture benefit of AOMs still depends crucially on the timely initiation of AOMs.

Does fully-threaded Headless Compression Screw provide a length-stable fixation in undisplaced femoral neck fractures?

OBJECTIVE: Femoral neck shortening is a common complication after surgical treatment for intracapsular femoral neck fractures. This study investigated whether fully-threaded Headless Compression Screw (FTHCS) can be a more length-stable implant than partially-threaded cannulated screw (PTCS) in reducing femoral neck shortening. METHODS: A total of 50 patients with undisplaced femoral neck fractures (17 treated by internal fixation with three FTHCS, and 33 treated by three PTCS) from 2011 to 2014 were enrolled in this study. The radiography of the hips and medical records were reviewed for proximal femur geometry and complications. RESULTS: Significant shortening of the femoral neck length until union were noted in both group (FTHCS group: -2.5 mm, p = 0.045; PTCS group: -2.4 mm, p = 0.011). There was no significant difference in the length of femoral neck shortening between groups (p = 0.855). Age was the only significant risk factor for >5 mm of femoral neck shortening (p = 0.041). The femoral neck-shaft angle tended to reduce and become more varus in both groups (FTHCS: -2.7°, SD = 4.5, p = 0.028; PTCS: -5.0°, SD = 8.3, p = 0.002), but the differences between groups were nonsignificant (p = 0.577). The complication rates were similar between FTHCS and PTCS (17.6% and 21.2%, p > 0.999). CONCLUSION: The FTHCSs may be a substitute for PTCSs, but it cannot prevent femoral neck shortening and varus collapse after fracture fixation. Future studies should focus on how to preserve femoral neck length and hip function after femoral neck fractures.