A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.

Bisphosphonate alternative regimens for the prevention of osteoporotic fragility fractures: BLAST-OFF, a mixed-methods study.

Background: Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives: 1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. 2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. 3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods: The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: • Stage 1A - we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. • Stage 1B - we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. • Stage 2 - we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates. Results: Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting. Conclusions: Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs. Future work: Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting. Limitations: Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates. Trial registration: This trial is registered as ISRCTN10491361. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.

Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear. Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients. The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: a review of the published evidence on patients' and doctors' views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals. Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money. Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments. Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money. Bisphosphonates are effective in reducing the risk of fracture, but 'continuing with treatment', particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community.

The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

Quantitative Segmentation Analysis of the Radiological Changes by Using ITK-SNAP: Risk Assessment of the Severity and Recurrence of Medication-related Osteonecrosis of the Jaw.

Background and purpose: Medication-related osteonecrosis of the jaw (MRONJ) severely impairs patients' quality of life and is remarkably refractory to treatment. There are lots of studies about identification of the radiographic features of MRONJ, yet reports about quantitative radiographic analysis for the risk assessment of the severity and recurrence of MRONJ are rarely heard. The aim of this study was to investigate the volumes of osteolytic lesions and radiodensity values of osteosclerotic lesions in MRONJ patients by using ITK-SNAP for severity prediction and prognosis evaluation. Materials and methods: Of 78 MRONJ patients (78 lesions) involved in this retrospective study, 53 were presented as osteolytic lesions and 25 were presented as osteosclerotic changes alone. Comprehensive CBCT images, demographics and clinical data of patients were investigated. The volumetric analysis and radiodensity measurement were performed by ITK-SNAP. SPSS 25.0 were used for statistical analysis. Results: The osteolytic lesion volumes in MRONJ patients receiving intravenous bisphosphonates (P=0.004) and patients without osteoporosis (P=0.027) were significantly large. No significant correlation between the volumes and bisphosphonates duration was found (P=0.094). The radiodensity values of osteosclerotic lesions was significantly correlated with bisphosphonates duration (P=0.040). The surrounding area of post-surgical lesions in MRONJ patients with recurrence showed significantly great radiodensity values (P=0.025). No significant correlation between the radiodensity values and the transformation from osteosclerotic lesions to osteolytic lesions was observed (P=0.507). Conclusion: MRONJ patients receiving intravenous bisphosphonates develop into large volumes of osteolytic lesions more easily. Long-term bisphosphonates duration is possibly related with higher bone density of osteosclerotic lesions, while higher density is not associated with the transformation from osteosclerotic lesions to osteolytic lesions. A rise of bone mineral density nearby post-surgical lesions is probably a predictor for MRONJ recurrence.

Assessment of the efficacy of teriparatide treatment for osteoporosis on lumbar fusion surgery outcomes: a systematic review and meta-analysis.

Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures. Anecdotal and limited surgical series have described the utility of this treatment for osteoporotic patients prior to spinal fusion surgery, but there is variability in adoption of this strategy as well as consensus regarding optimal treatment duration before and after surgery. In this study, the clinical results of the use of teriparatide for this application are reviewed and critically examined. We conducted a systematic review of electronic databases using different MeSH terms from 1980 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as either mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). A total of 771 patients from 12 studies were identified. Three hundred seventy-seven patients (90.8% females) were treated with teriparatide. Lumbar spinal fusion rates were significantly higher among patients who received teriparatide compared to the non-teriparatide group (OR 2.15, 95%CI 1.56-2.97, p < 0.00001). Subgroup analysis revealed that patients receiving teriparatide demonstrated 2.12-fold and 2.23-fold higher likelihood of fusion compared to those in the bisphosphonate (OR 2.12, 95%CI 1.45-3.11, p = 0.0001) and placebo (OR 2.23, 95%CI 1.22-4.08, p = 0.009) cohorts, respectively. The treatment effect of teriparatide was associated with significantly reduced subsequent vertebral fractures (OR 0.16, 95%CI 0.06-0.41, p = 0.0002), sagittal malalignment (MD - 3.85, 95%CI: -6.49 to - 1.21, p = 0.004), limb visual analogue score (VAS) (MD - 0.36, 95%CI - 0.64 to - 0.09, p = 0.008), and spinal VAS (MD - 0.24, 95%CI - 0.44 to - 0.04, p = 0.02) compared to the non-teriparatide group. Patients using teriparatide had 30% less likelihood of screw loosening at last follow-up compared to the non-teriparatide group; however, this was not statistically significant (OR 0.70, 95%CI 0.43-1.14, p = 0.15). There did not exist any statistically significant difference between the two comparative groups in terms of pseudoarthrosis (OR 0.54, 95%CI 0.24-1.21, p = 0.13), cage subsidence (OR 1.30, 95%CI 0.38-4.52, p = 0.68), and bone mineral density (MD 0.04, 95%CI - 0.19-0.29, p = 0.74) at last follow-up examination. This meta-analysis corroborates the effectiveness of teriparatide resulting in higher fusion rates. Further study is required to determine the optimal duration of treatment and timing of surgery.

Preoperative bone health assessment and optimization in spine surgery.

OBJECTIVE: The purpose of this investigation was to characterize the bone health in preoperative spine surgery patients. This information will provide a framework to understand the needs and methods for providing bone health optimization in elective spine surgery patients. METHODS: A retrospective study of 104 patients undergoing bone health optimization was performed. Patients were selected based on risk factors identified by the surgeon and suspected compromised bone health. Evaluation included history and examination, laboratory investigations, and bone mineral density (BMD) at 3 sites (femoral neck, lumbar spine, and radius). Patients' bone status was classified using WHO criteria and expanded criteria recommended by the National Osteoporosis Foundation (NOF). The 10-year Fracture Risk Assessment Tool (FRAX) scores of the hip and major osteoporotic fracture (MOF) were calculated with and without femoral neck BMD, with spine BMD, and with the trabecular bone score (TBS). Antiresorptive and anabolic agents were provided in accordance with meeting NOF criteria for treatment of osteoporosis. RESULTS: The mean patient age was 69.0 years, and 81% of patients were female. The mean historical height loss was 5.6 cm, and 54% of patients had a history of fracture. Secondary osteoporosis due to chronic renal failure, inflammatory arthritis, diabetes, and steroid use was common (51%). The mean 25-hydroxy vitamin D was 42.4 ng/ml and was normal in 81% of patients, with only 4 patients being deficient. The mean T-scores were -2.09 (SD 0.71) of the femoral neck, -0.54 (1.71) of the lumbar spine, and -1.65 (1.38) of the distal radius. These were significantly different. The 10-year FRAX MOF score was 20.7%, and that for hip fracture was 6.9% using the femoral neck BMD and was not significantly different without the use of BMD. The FRAX risk-adjusted score using the lumbar spine BMD and TBS was significantly lower than that for the hip. Osteoporosis was present in 32.1% according to WHO criteria compared with 81.6% according to NOF criteria. Antiresorptive medications were recommended in 31 patients and anabolic medications in 44 patients. CONCLUSIONS: Surgeons can reliably identify patients with poor bone health by using simple criteria, including historical height loss, history of fracture, comorbidities associated with osteoporosis, analysis of available imaging, and calculation of FRAX score without BMD. High-risk patients should have BMD testing and bone health assessment. In patients with osteoporosis, a comprehensive preoperative bone health assessment is recommended and, if warranted, pharmacological treatment should be started.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Survival in older women with early stage breast cancer receiving low-dose bisphosphonates or denosumab.

BACKGROUND: Bisphosphonates and denosumab, as adjuvant therapy in breast cancer, have been associated in some studies with improved cancer outcomes. The potential benefits of these drugs used at the lower doses commonly given for osteoporosis have not been established. The objective of this study was to investigate the association between therapy with bone-modifying agents (BMAs) and survival in older women with early breast cancer. METHODS: The authors conducted a retrospective cohort study of women aged ≥66 years with breast cancer who were included in the Surveillance, Epidemiology, and End Results and Texas Cancer Registry Medicare-linked databases. Associations were examined between the receipt of BMAs at dosages indicated for osteoporosis within 2 years after diagnosis and overall and breast cancer-specific survival. Cox proportional hazards models and propensity score adjustment and matching were used for the analyses. RESULTS: Of the 37,724 women included, 7925 (21%) received at least 6 months of a BMA within the first 2 years of breast cancer diagnosis, including bisphosphonates only in 6898 women (80.7%), denosumab only in 1204 (15.2%), and both classes of BMAs in 323 (4.1%). The median follow-up was 64 months. The receipt of a bisphosphonate was associated with improved overall survival (hazard ratio [HR], 0.87; 95% CI, 0.82-0.93) and breast cancer-specific survival (HR, 0.77; 95% CI, 0.64-0.92) after multivariable adjustment. Benefits were primarily seen for patients who had stage II and III disease. No benefits were observed with denosumab (stage II: HR, 1.05 [95% CI, 0.90-1.22]; stage III: HR, 1.09 [95% CI, 0.66-1.82]). CONCLUSIONS: Bisphosphonates at the doses recommended for osteoporosis are associated with improved survival in older postmenopausal women with early breast cancer.

Osteoporosis in the age of COVID-19.

As the world grapples with the crisis of COVID-19, established economies and healthcare systems have been brought to their knees. Tough decisions regarding redirection of resources away from the management of conditions deemed "nonessential" are being made. How can we balance urgent resourcing of our acute crisis while not abandoning the real need of patients with osteoporosis? This article offers a few practical solutions.

Cost-effectiveness of sequential treatment with abaloparatide followed by alendronate vs. alendronate monotherapy in women at increased risk of fracture: A US payer perspective.

OBJECTIVES: Emerging evidence supports sequential therapy with anabolic followed by antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared to ALN monotherapy and to sequential treatment starting with antiresorptive therapy (ALN/ABL/ALN). METHODS: A previously validated Markov microsimulation model was used to estimate the cost-effectiveness of sequential ABL/ALN compared to ALN monotherapy and to sequential ALN/ABL/ALN from a lifetime US payer perspective. In line with practice guidelines, patients were assumed to receive ABL for 18 months followed by 5 years of ALN, or ALN monotherapy for 5 years, or a sequence of ALN for 2 years followed by 18 months of ABL and then by 3 years ALN. Evaluation was conducted for patients aged 50-80 years old with a BMD T-score ≤-3.5 and without a history of prior fracture, or with a T-score between -2.5 and -3.5 and a history of ≥ 1 osteoporotic fracture. RESULTS: Sequential ABL/ALN was cost-effective (threshold of US$150,000 per QALY) vs generic ALN monotherapy in women ≥60 years with a BMD T-score ≤-3.5 and in women with BMD T-score between -2.5 and -3.5 and history of osteoporotic fracture. In all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, more QALYs) compared with sequential ALN/ABL/ALN, resulting from limited effect of ABL in patients previously treated with an antiresorptive agent. CONCLUSIONS: Sequential ABL/ALN therapy is cost-effective vs ALN monotherapy for US postmenopausal women aged ≥60 years at increased risk of fractures.

Cost-effectiveness of denosumab for high-risk postmenopausal women with osteoporosis in Thailand.

Aims: This study assessed the cost-effectiveness of denosumab for treating postmenopausal women with osteoporosis (PMO) at high risk of fracture in Thailand.Materials and methods: A published Markov cohort cost-effectiveness model was populated with country-specific data as available and other published data as needed. The model used a societal perspective, lifetime horizon, efficacy data from network meta-analysis of trials, and included costs for direct medical and non-medical care, informal care, and osteoporosis treatments to compare denosumab to no pharmacologic treatment (calcium and vitamin D supplements only) and to oral weekly alendronate. The base case (high-risk population) included postmenopausal women with femoral neck T-score ≤-2.5, mean age 65 years at entry, and history of vertebral fracture.Results: High-risk women with osteoporosis using denosumab had the greatest number of life years and quality-adjusted life-years (QALYs) with higher reductions in hip and vertebral fracture incidence compared with patients with no pharmacologic treatment. The incremental cost-effectiveness ratio (ICER) was 119,575 Thai Baht (THB) per QALY for denosumab versus no pharmacologic treatment and 199,186 THB per QALY for denosumab versus alendronate. Among Thai postmenopausal women with high-risk of fractures, denosumab was cost-effective compared with no pharmacologic treatment at a willingness-to-pay threshold of 160,000 THB per QALY. One-way sensitivity analysis showed models were most sensitive to changes in denosumab pricing.Limitations: Data from other countries used when country-specific data were unavailable may not accurately reflect the true experience in Thailand. The model focused explicitly on hip, vertebral, and wrist fractures, and therefore provides a conservative estimate of the overall potential impact of osteoporosis-related fracture. The fracture risk was not adjusted to reflect potential changes in risk after denosumab treatment discontinuation.Conclusions: In Thailand, denosumab offers a cost-effective osteoporosis treatment option versus no pharmacologic treatment in postmenopausal women at high risk of fracture.

Treatment options for glucocorticoid-induced osteoporosis.

INTRODUCTION: Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation. AREAS COVERED: In this review, the authors summarize the pathophysiology of GIOP and give discussion to the clinical management of patients taking GCs, focusing on the currently available drugs that have antiresorptive or anabolic activity on bone. EXPERT OPINION: Despite the widespread use of GCs and their well-established detrimental skeletal effects, GIOP remains an under-diagnosed and under-treated condition. Indeed, the clinical management of GIOP is still debated, so that the recent guidelines differ in their indications for pharmacological intervention. Either bone mineral density (BMD) or algorithms such as FRAX do not completely account for the remarkable and rapid increase in fracture risk of most GC-treated patients. Moreover, while oral bisphosphonates remain the most used and cost-effective option, the potential increased benefits of more potent antiresorptive agents (e.g. denosumab and zoledronate) or anabolic compounds (e.g. teriparatide) warrant further investigation. Despite the above limitations, the assessment of fracture risk is recommended for all individuals committed to receiving oral GCs for 3 months or longer.

Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk.

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.

Medication Non-adherence in Patients with Osteoporosis: Implications for Clinical Pharmacists and Osteoporosis Care Providers.

BACKGROUND: Poor adherence to the prescribed therapy leads to low bone mineral density and enhance the development of osteoporosis complications and unnecessary hospitalization. OBJECTIVE: To explore factors associated with medication non-adherence in patients with osteoporosis. Findings would help guide the development of future pharmaceutical care interventions aim at improving health outcomes for patients with osteoporosis. METHODS: The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services Hospital. Variables including socio-demographics and medical factors were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop a model with variables that best predicted medication non-adherence in patients with osteoporosis in Jordan. RESULTS: A total of 296 patients participated in the study. Most of the study participants (72.3%) were found non-adherent. Patients were found less likely to adhere to the prescribed medications with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680) and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058). CONCLUSION: Medication adherence for patients with osteoporosis has considered scope for improvement in Jordan. Simplifying dosage regimen in addition to taking patients' preferences when selecting the medications should be taken into account in future interventions designed to improve health outcomes for patients with osteoporosis.

The value of routine laboratory screening in the neonatal intensive care unit.

BACKGROUND: Healthcare spending is expected to grow faster than the economy over the next decade, and the cost of prematurity increases annually. The aim of this study was to investigate the frequency of intervention after routine laboratory testing in preterm infants. METHODS: This was a retrospective study of preterm infants (≤34 weeks) admitted to the NYU Langone Health NICU from June 2013 to December 2014. Data collected included demographics, results of laboratory tests, and resulting interventions. Intervention after a hemogram was defined as a blood transfusion. Intervention after a hepatic panel was defined as initiation or termination of ursodiol or change in dose of vitamin D. Subjects were stratified into 3 groups based on gestation (<28 weeks, 28-31 6/7 weeks, 32-34 weeks). Chi-square analysis was used to compare the frequency of intervention between the groups. RESULTS: A total of 135 subjects were included in the study. The frequency of intervention after a hemogram was 8.4% in infants <28 weeks, 4.6% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks; this difference was found to be statistically significant (p = 0.02). The frequency of intervention after a hepatic panel was 4.2% in infants <28 weeks, 5.7% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks, which was not found to be a statistically significant different. CONCLUSION: No interventions were undertaken post-routine laboratory testing in any infant 32-34 weeks and routine testing in this population may be unnecessary. Further studies are needed to elucidate if routine testing affects neonatal outcomes.

Factors influencing bone loss in anorexia nervosa: assessment and therapeutic options.

Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up.

Chinese patients' preference for pharmaceutical treatments of osteoporosis: a discrete choice experiment.

While adherence to osteoporosis treatment is low, patients' preference for osteoporosis treatment is unknown in Chinese patients. Chinese patients are willing to receive treatments with higher clinical efficacy and lower out-of-pocket cost. In addition, annual intravenous infusion and 6-month subcutaneous injection are preferred over weekly oral tablets. PURPOSE: This study was performed to elicit Chinese patients' preferences for osteoporosis medication treatment and to investigate the heterogeneities of the preferences in subgroups. METHODS: A discrete choice experiment comprising 15 choice sets with 4 important attributes was conducted in a Chinese population at risk of osteoporotic fracture. The four attributes were treatment efficacy in reducing the risk of fracture, out-of-pocket cost per year, adverse effects of treatment, and mode of administration. The patients were asked to choose between two hypothetical treatments; they could also choose no treatment. Mixed logit models were used, and any observed heterogeneity in the patients' preferences was further assessed in subgroup analyses. RESULTS: In total, 267 patients were analysed. On average, the patients preferred to receive treatment rather than no treatment. The patients preferred treatment with higher efficacy in preventing fracture and lower out-of-pocket cost. The least preferred adverse effect of medication was gastrointestinal disorders, followed by flu-like symptoms and finally skin reactions. The most preferred mode of administration was annual intravenous infusion, followed by 6-month subcutaneous injection, a weekly oral tablet, and daily nasal spray; daily oral tablets ranked as the least preferred mode of administration. The differences in the patients' preferences among all attributes were statistically significant (p < 0.05). Patients' age was found to contribute to the observed preference heterogeneity in most of the included attributes. CONCLUSIONS: This study revealed Chinese patients' preferences for osteoporosis treatments. Annual intravenous infusion and 6-month subcutaneous injection were significantly preferred over weekly oral tablets in this Chinese population.

A pharmacist-run anabolic osteoporosis clinic: An abaloparatide descriptive report.

OBJECTIVES: To review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. SETTING: This ambulatory-care health system endocrinology practice consists of 10 board-certified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. A pharmacist-run teriparatide clinic was implemented in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. PRACTICE DESCRIPTION: Patients are referred to a clinical pharmacist for initiation and education of anabolic osteoporosis therapy. The pharmacist is responsible for assessing for contraindications to anabolic therapy, securing managed care coverage of an anabolic agent, and providing medication counseling. This pharmacist is available as a resource to patients throughout their course of anabolic osteoporosis therapy. PRACTICE INNOVATION: This is the first description of a pharmacist-run abaloparatide clinic. EVALUATION: Not applicable. RESULTS: During its first year of availability, 52 patients were referred for abaloparatide therapy. Of these, 31 patients (59.6%) initiated treatment. The population predominately consisted of postmenopausal white women. Approximately two-thirds of patients had a history of an osteoporosis-related fracture, and half of patients had previously received antiresorptive therapy for osteoporosis. Mean baseline T-scores for the lumbar spine and femoral neck were -2.41 and -2.57, respectively. Twenty-one patients did not initiate abaloparatide therapy owing to cost (9), concerns of therapy (8), or contraindication to therapy (4). An additional 5 patients discontinued abaloparatide therapy owing to adverse effects. CONCLUSION: This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy indicates that significant barriers (e.g., high patient cost and safety concerns) remain.

Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review.

OBJECTIVES: This study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world settings. METHODS: A systematic review was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) and National Health Service Economic Evaluation Database NHS EED) databases were searched for studies published in English language up to April 2018. Prospective and retrospective observational studies that used prescription claim databases or hospital medical records to examine patient adherence and persistence to oral bisphosphonate treatment among adults with osteoporosis were included. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of included studies. RESULTS: The search yielded 540 published studies, of which 89 were deemed relevant and were included in this review. The mean age of patients included within the studies ranged between 53 to 80.8 years, and the follow-up varied from 3 months to 14 years. The mean persistence of oral bisphosphonates for 6 months, 1 year and 2 years ranged from 34.8% to 71.3%, 17.7% to 74.8% and 12.9% to 72.0%, respectively. The mean medication possession ratio ranged from 28.2% to 84.5%, 23% to 50%, 27.2% to 46% over 1 year, 2 years and 3 years, respectively. All studies included scored between 6 to 8 out of 9 on the NOS. The determinants of adherence and persistence to oral bisphosphonates included geographic residence, marital status, tobacco use, educational status, income, hospitalisation, medication type and dosing frequency. CONCLUSIONS: While a number of studies reported high levels of persistence and adherence, the findings of this review suggest that patient persistence and adherence with oral bisphosphonates medications was poor and reduced notably over time. Overall, adherence was suboptimal. To maximise adherence and persistence to oral bisphosphonates, it is important to consider possible determinants, including characteristics of the patients.