Anti-osteoporosis Medications Research Articles

Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia.

SummaryCOVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent.PurposeNo study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period.MethodWe conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital’s electronic prescription platform and patients’ pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence.ResultsA total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836–3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430–0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444–2.158; p < 0.001).ConclusionAdherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further.

Correlation of Sagittal Imbalance and Recollapse after Percutaneous Vertebroplasty for Thoracolumbar Osteoporotic Vertebral Compression Fracture: A Multivariate Study of Risk Factors.

Study DesignA retrospective case control study.PurposeThis study aimed to assess the clinical significance of sagittal balance for predicting and managing the recollapse of cemented vertebra following percutaneous vertebroplasty (PVP) in patients with thoracolumbar osteoporotic vertebral fracture (OVF).Overview of LiteratureRecently, the recollapse of cemented vertebra following PVP for OVF has been reported. Although the risk factors for recollapse have been determined, the association between sagittal spinopelvic parameters and sagittal imbalance with recollapse has not been established.MethodsAmbulatory patients who underwent single-level PVP for thoracolumbar OVF with a follow-up of at least 24 months were retrospectively reviewed. The patients were divided into two groups depending on the presence of symptomatic recollapse at the cemented vertebra: (1) recollapsed (RC) group and (2) noncollapsed (NC) group. The patient characteristics and radiographic measurements associated with sagittal imbalance were analyzed at each follow-up visit.ResultsOverall, 134 patients (RC group, n=28; NC group, n=106) were enrolled. The mean fracture-free interval was 3.2 months (range, 1.2–25.1 months). The multivariate binary logistic regression analysis identified low bone mineral density (p=0.047), degree of dynamic mobility within the vertebra (p=0.025), and sagittal imbalance as significant risk factors for recollapse (p=0.013; odds ratio, 5.405). The progression of sagittal imbalance and thoracolumbar kyphosis (T10–L2) was more significant in the RC and sagittal imbalance groups than in the NC group (both p=0.000).ConclusionsSagittal imbalance, lower bone mineral density, and dynamic mobility within the vertebra are associated with the recollapse of cemented vertebrae following PVP. Sagittal imbalance, rather than local kyphosis or thoracolumbar kyphosis, is particularly significant in that it results in more progressive collapse and sagittal deformity and is accompanied by substantial back pain and neurological deficits. Therefore, a stricter and more active management, including anti-osteoporosis medication, is required for the treatment of OVF with sagittal imbalance of the spine.

Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus.

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation in vitro through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency in vivo. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.

Clinical characteristics and impact of treatment gap of fragility fractures in Colombia: experience of 10 Fracture Liaison Services (FLS)

Background &amp; aims. Fragility fractures are those caused by low-energy trauma or falls from standing height. The mortality after the first year of suffering a hip fracture ranges from 15 to 30%. This problem has been addressed through the creation of interdisciplinary programs for fragility fracture early diagnosis and prevention. Describing the clinical characteristics of a cohort of patients diagnosed with fragility fractures in 10 fracture liaison services in Colombia. Methods. Led by the Asociaci n Colombiana de Osteoporosis y Metabolismo Mineral, this is a cross-sectional descriptive study, in patients with a diagnosis of fragility fracture in 10 fracture liaison services. Demographic and clinical variables were described for one year from the diagnosis of the fracture. Results. were analyzed 1699 records of patient fractures between 50 and 101 years of age, 1334 were women (76.5%), 581/1484 (39.1%) had previous fragility fractures, 570/1599 (35.7%) had a previous diagnosis of osteoporosis. Of these, 70/1051 (7%) received anti-osteoporosis medication, and 311/733 (42.4%) received it post-fracture. Of the total records with information, 65/707 (9.2%) died the following year of the fracture. Conclusions. Fracture prevention programs in institutions allow for de16 A. Medina et al. tecting patients with fragility fractures, clinical characteristics of these, in addition to strengthening the conditions of a centralized national registry, based on the parameters of the International Osteoporosis Foundation - Capture the Fracture program, through strategies with multidisciplinary personnel.

Effects of Humulus lupulus L. and its active ingredient xanthohumol on preventing glucocorticoid-induced osteoporosis

Objective To explore the effects of Humulus lupulus L. extract (HLE) and xanthohumol (XN) on preventing glucocorticoid-induced osteoporosis (GIOP). Methods The GIOP model was established by intraperitoneal injection of dexamethasone (DEX). Bone microstructure, bone mineral density and serum biochemical indexes were evaluated by Micro-CT and ELISA kits. The levels of cells proliferation and ALP activity, and the expression of bone formation related proteins were assayed with primary osteoblasts injured by DEX. Results HLE and XN significantly alleviated the bone microstructure damage, enhanced the bone mineral density, and improved the trabecular parameters in GIOP mice. In vitro experiments showed that HLE and XN can prevent bone loss not only by improving cell proliferation and ALP activity, but also through increasing the expression of bone γ-glutamic acid-containing proteins (BGP), bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (Runx-2). Conclusion This study confirmed that HLE and XN had anti-GIOP effects for the first time. It provides a new resource for the development of anti-osteoporosis medications.

A Hospitalist-Led Fracture Liaison Service Improves Care of Hip Fracture Patients

Background: Osteoporosis care traditionally falls to outpatient primary care providers despite the fact that over 300,000 elderly patients are hospitalized yearly with hip fractures in the United States. Internal medicine hospitalists are often involved in the co-management of their care on surgical teams and are skillful in osteoporosis recognition and management. Objective: A hospitalist-led Fracture Liaison Service (FLS) was established to provide improved care of hospitalized patients with hip fractures. Methods: A retrospective evaluation of inpatient and post-discharge management of patients admitted with low-impact hip fractures was performed before (8/17-2/18) and after (8/19 - 2/20) launch of the hospitalist Fracture Liaison Service (H-FLS). Results: Eighty-nine patients were admitted with a hip fracture in post-launch period compared to 73 admitted prior. 74% vs 11% of eligible patients (based on adequate renal function and vitamin D stores) were discharged with anti-osteoporosis medications (p<0.001), 82% vs 38% were discharged with vitamin D/calcium supplements (p<0.001), 22% vs 5% underwent a DXA scan after discharge (p<0.05) and 65% vs 0% were referred to outpatient osteoporosis-specific care at discharge (p<0.001). Conclusion: A hospitalist-led FLS is a unique approach to osteoporosis care that significantly improved quality metrics for elderly patients with osteoporotic hip fractures including initiation of anti-osteoporosis medication and bone density imaging. Outpatient follow-up data are needed to evaluate adherence to this initial management over time.

Multimorbidity Increases Risk of Osteoporosis Under-Diagnosis and Under-Treatment in Patients at High Fracture Risk: 45 and up a Prospective Population Based-Study

Background: Management of osteoporosis following fracture is suboptimal. Multimorbidity adds to clinical management complexity in the elderly but its contribution to the osteoporosis treatment gap has never been investigated. Objectives: To determine the impact of multimorbidity on fracture risk and on osteoporosis investigation and treatment in patients at high fracture risk. Design and Setting: The 45 and Up Study is a prospective population-based cohort study in NSW, Australia with questionnaire data linked to hospital records by the Centre for Health Record Linkage (CHeReL) and the Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Scheme (MBS) data provided by Department of Human Services. Fractures identified from hospital records, comorbidities from questionnaires, hospital and PBS records. Bone mineral density (BMD) investigation obtained from MBS and treatment for osteoporosis from PBS. Participants: 16191 women and 9089 men with incident low-trauma fracture (2000 - 2017) classified in a high and low-risk group based on 10-year fracture risk threshold of 20% from the Garvan Fracture Risk Calculator (age, gender, prior fracture and falls). Main Outcome Measurements: Association of Charlson comorbidity index (CCI) with fracture. Likelihood of BMD investigation and treatment initiation. Outcomes ascertained by logistic regression and re-fracture risk by Cox models. Results: Individuals at high fracture risk were significantly older [women (mean age ±SD) 77 ± 10 vs 57 ±4 for high- vs low risk and men 86±5 vs 65±8 for high vs low risk] and had a higher morbidity burden [women, CCI ≥ 2 40% vs 12% for high- vs low-risk and men 53% vs 26% for high vs low risk]. Being in the high-risk group as well as a higher CCI were independently associated with > 2-fold higher risk of re-fracture. However, in the high-risk group, only 28% (48% women and 17% men) had a BMD investigation and 31% (24% women and 14% men) received anti-osteoporosis medication post-fracture. A higher CCI was associated with a lower probability of both BMD investigation [CCI 2–3 vs 0–1, RR 0.73 (0.65–0.82) for women, and 0.50 (0.40–0.64) for men and CCI ≥4 vs 0–1, RR 0.50 (0.41- 0.62) for women and 0.36 (0.25–0.52) for men] and treatment initiation [CCI 2–3 vs 0–1, RR 0.88 (0.77–0.98) for women and 0.75 (0.60–0.95) for men and CCI ≥4 vs 0–1, RR 0.75 (0.59- 0.95) for women and 0.35 (0.23–0.53) for men]. Conclusion: Multimorbidity, despite being associated with the highest fracture risk, significantly lowers the likelihood of osteoporosis investigation and treatment. These findings suggest that fracture risk is either under-estimated or under-prioritized in the context of multimorbidity. Our findings highlight the need for improved delivery of fracture preventive care in this setting. More generally, they also point out the need for a better understanding of how problems are prioritized in complex clinical situations.

P111 Osteoporosis is a significant predictor of frailty in older community dwelling adults: findings from the Hertfordshire Cohort Study

Abstract Background/Aims Frailty is associated with a range of adverse health outcomes, including falls and fractures. Previous work in a Japanese cohort found that the presence of both osteoporosis (OP) and sarcopenia (SP) increased the risk of frailty compared to the presence of OP or SP alone. We examined these relationships in a comparable cohort of community dwelling older people in the UK. Methods Our study comprised of 432 participants (216 men and 216 women) of the UK the Hertfordshire Cohort Study (HCS). Participants were assessed at baseline and followed up 5 years later with questionnaires, clinical examination, measures of physical performance and grip strength. Proximal femur bone mineral density (BMD) values were determined using dual-energy X-ray absorptiometry. OP was defined at BMD T- scores &amp;lt; = -2.5 at the femoral neck or use of anti-osteoporosis medication. Cut-offs for low grip strength; &amp;lt;30kg for men and &amp;lt;20kg for women and ALM index &amp;lt; =7.23kg/m2 for men, &amp;lt; =5.67kg/m2 for women, were used to define SP. Frailty was defined using the Fried definition. Logistic regressions were performed to analyse associations of OP/SP as explanatory variables for frailty. Results The mean (SD) age of participants was 75.7 (2.6) years. At baseline, the prevalence of frailty and pre-frailty was 12.2% (men, 8%, women, 16.3 %), and 57% (men, 55.7%; women, 58.2%) respectively. Individuals living with frailty were older, tended to drink less alcohol, have lower physical activity, lower walking speed and grip strength (P &amp;lt; 0.001). They were more likely to be female compared to non-frail subjects (P = 0.007). Co-existence of SP, OP and frailty was observed in 0.6% of the population; 0.6% had SP and frailty; 1.6% had OP and frailty and 1.6% of the study population had SP and OP. 71.8% did not have SP, OP or frailty at baseline. SP was significantly associated with frailty at baseline (p &amp;lt; 0.001). The cumulative incidence of frailty during the 5-year period was 2.47% /year (2.13%/year in men, 2.89%/year in women) and that of SP was 2.14%/year (2.84% in men, 1.35%/year in women). The presence of OP at baseline was a significant predictive factor for the occurrence of frailty at follow-up (odds ratio [OR], 3.04; 95% confidence interval [95% CI], 1.11,8.38; P = 0.031), while the risk of developing frailty was also increased in those participants who were both osteoporotic and sarcopenic at baseline; though this was not significant (OR; 10.08, 95% CI,0.55,186.08; P = 0.12). Conclusion Our findings demonstrate that the presence of OP is a significant predictive factor for developing frailty and might be used as a trigger for appropriate interventions to reduce or reverse its development in older adults. Our findings are in accordance with the previous reports in Asian populations and warrant further investigation in other national cohorts. Disclosure F. Laskou: None. K. Jameson: None. E. Dennison: None.

Increasing the use of anti-osteoporosis medication in patients who use glucocortcoids remains a challenge

Increasing the use of anti-osteoporosis medication in patients who use glucocortcoids remains a challenge

Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study.

SummaryRomosozumab is an effective treatment for spine osteoporosis because it reduces the incidence of new fractures and significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications.IntroductionRomosozumab appeared as a new osteoporosis medication in Japan in 2019. It is an anti-sclerostin antibody, which increases bone formation and suppresses bone resorption. The aim of our study was to elucidate the clinical effects, safety, and predictors of the effects of one-year romosozumab treatment.MethodsThis study was an observational study designed as a pre–post study in 262 patients. Romosozumab (210 mg) was administered subcutaneously once every 4 weeks during 12 months. We focused on incidence of new fractures, safety, bone mineral density (BMD) at the spine and total hip, and bone metabolism markers.ResultsThere were five cases of new fractures during one-year romosozumab treatment. There were no fatal adverse events. Percent changes from baseline in the spine and total hip BMD after 12 months of romosozumab treatment were 10.67% and 2.04%, respectively. Romosozumab had better effects in cases of severe osteoporosis with low spine BMD, high TRACP-5b, and high iP1NP at the start of romosozumab treatment. The percent change in the spine BMD at 12 months was significantly lower in the group transitioning from bisphosphonates than in the group not previously treated with other anti-osteoporosis medications.ConclusionRomosozumab is an effective treatment for spine osteoporosis because it significantly increases the percent change in the spine BMD at 12 months. The percent change in the spine BMD is higher in patients not previously treated with other anti-osteoporosis medications.

Which patients are at risk for not receiving anti-osteoporosis treatment following hip fracture?: An ACS NSQIP analysis

BackgroundScreening and management of osteoporosis is often only considered by providers when patients present with multiple fragility fractures. The objective was to determine which patients are at risk for not receiving anti-osteoporotic medication and screening immediately following open reduction internal fixation (ORIF) for hip fracture. MethodsThe 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Hip Fracture Database was queried to identify patients ≥ 50 years old who underwent ORIF of femoral neck, intertrochanteric hip, and subtrochanteric hip fractures. Patients with concurrent polytrauma, malignancy, and other fragility fractures were excluded. Patients taking osteoporotic medications immediately prior to hospitalization were excluded to prevent an overlap in the screening and/or antiresorptive medication initiation rates. Multi-variate logistic regression was used to assess for factors associated with not receiving anti-osteoporotic medication immediately postoperatively. ResultsA total of 6179 patients were identified of whom 3304 (53.5%) were treated at a facility with a documented standardized hip fracture care program. Only 28.5% (N = 1766) patients received anti-osteoporosis medication immediately following ORIF. Independent factors associated with increased odds of not initiating bone protective medication were those without a standardized hip fracture care program (odds ratio [OR] 1.80 [1.58–2.06], P < 0.001), length of stay ≤ 5 days (odds ratio [OR] 1.47 [1.28–1.69], P < 0.001), patients waiting > 1 day until operation (odds ratio [OR] 1.35 [1.13–1.60], P = 0.001), patients requiring a mobility aid preoperatively (odds ratio [OR] 1.29 [1.13–1.47], P < 0.001), and patients who could not weight bear as tolerated (WBAT) on postoperative day 1 (POD 1) (odds ratio [OR] 1.25 [1.06–1.47], P = 0.008). ConclusionPatients starting anti-osteoporotic medication immediately following a hip fracture in the United States remains low (28.5%). Standardized hip fracture care programs have the greatest impact with regards to initiating anti-osteoporotic medication following hip fracture.

The treatment gap after major osteoporotic fractures in Denmark 2005-2014: a combined analysis including both prescription-based and hospital-administered anti-osteoporosis medications

SummaryThis study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed.IntroductionThe purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients.MethodsIn this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code.ResultsThe treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients.ConclusionA significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.

Vitamin D is associated with blood lead exposure through bone turnover in type 2 diabetes patients.

BackgroundBone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.MethodsA total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.ResultsIn both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.ConclusionThe association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

Bisphosphonates to reduce bone fractures in stage 3B+ chronic kidney disease: a propensity score-matched cohort study.

Bisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects. The aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time. This was a new-user cohort study design with propensity score matching. Data were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1-3 and from the Danish Odense University Hospital Databases for work package 4. Patients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m2 were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m2 within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1-3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1-4. Bisphosphonate use, identified from primary care prescriptions (for work packages 1-3) or pharmacy dispensations (for work package 4), was the main exposure. Work package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change. Bisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users. Confounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively. Bisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness. Randomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data. This study is registered as EUPAS10029. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 17. See the NIHR Journals Library website for further project information. The project was also supported by the National Institute for Health Research Biomedical Research Centre, Oxford.

Risk of new-onset osteoporosis in single-center veteran population receiving direct oral anticoagulants versus warfarin

BackgroundOral anticoagulants (OAC) have shown to affect bone mineral density and cause osteoporosis. Limited studies have investigated the relationship between its use and risk of osteoporosis. We aim to compare the risk of osteoporosis in patients on warfarin versus direct oral anticoagulants (DOACs). MethodsA retrospective single-center cohort study was conducted in veterans age > 18 years of age in whom warfarin or DOACs were newly initiated between January 1st, 2012 to April 1st, 2020 at Salem VA Medical Center. Patients on OAC for at least 90 days qualified for inclusion and excluded if they were pregnant or had history of mechanical valve and mitral stenosis, on edoxaban or had previous history of osteoporosis or use of antiosteoporosis medication. Primary outcome was comparing incidence of new-onset osteoporosis between warfarin and DOACs. Secondary outcomes included comparing incidence of all clinical fractures, hip fractures, major bleeding and intracranial bleed between the treatments. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CI) comparing the two treatment groups were calculated. ResultsA total of 1526 patients on DOAC and 1121 in warfarin group were included in the study. After propensity-score (PS) matching, 943 patients were included in each arm.Baseline characteristics were similar after PS-matching. DOAC treatment was associated with lower incidence of new-onset osteoporosis as compared to warfarin in matched cohort (aHR: 0.19, 95% CI: 0.10–0.36; p < 0.0001). The risk of all clinical fracture and hip fracture was similar in patients receiving DOACs as versus warfarin (aHR: 1.18, 95% CI: 0.82–1.69; p = 0.3671). DOAC use was associated with lower risk of major bleed (aHR: 0.07, 95% CI: 0.03–0.15; p < 0.0001) and intracranial bleed (aHR: 0.14, 95% CI: 0.03–0.64; p = 0.0111). ConclusionOverall, as compared to warfarin, prolonged use of DOACs is associated with lower risk of new-onset osteoporosis. We hope that our study findings will enlighten current clinical practices assuring safe use of OAC in veteran patients.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services

SummaryVertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS.Summary points• Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture.• Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA.• Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds.• Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment.• Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

Osteoporosis in older adults.

The incidence of fragility fractures increases progressively with advance in age after 50 years, and the phenomenon of population ageing will lead to an increased proportion of the world population having osteoporosis and fractures. The consequences of fractures are more serious in older adults: all low-trauma fractures were associated with increased mortality risk and the risk of a second major osteoporotic fracture after a first one also increased with advance in age. Along with the decrease in bone mineral density, falls play an essential role in the occurrence of fragility fractures in older adults, and the assessment of the risk of falling is part of the fracture risk assessment. Despite advances in the diagnosis of osteoporosis, the assessment of fracture risk, and a wide range of effective anti-osteoporosis medications, with parenteral route which can improve observance, many data indicate that the therapeutic care gap is particularly wide in the elderly in whom the importance and impact of a treatment are high and even more in those living in institutions.

The Prevalence of Vitamin D and Calcium Supplement use and Association with Serum 25-Hydroxy-vitamin D (25(OH)D) and Demographic and Socioeconomic Variables in Iranian Elderly.

Aims:The objective of this study was to determine the prevalence of vitamin D and calcium supplement use, and association with serum 25-hydroxy-vitamin D(25(OH)D) and demographic and socioeconomic variables in Iranian elderly.Settings and Design:This cross-sectional study was conducted in health centers of Tehran, capital of Iran.Methods:A total of 600 men and women were recruited using a two-stage cluster sampling method from 60 health centers. Participant's inclusion criteria included enrolling older adults over 60 years old who able to answer questions. We used valid and reliable questionnaires to record dietary intake of vitamin D and calcium. Any dietary supplements which included vitamin D/calcium were recorded. 25(OH)D level was measured. Participants were categorized as supplement users if they had taken supplements during last month.Results:The mean age of participants was 67.16 ± 6.07 years. Vitamin D supplements were used more often by females (OR = 11.89, 95% confidence interval (CI): 4.82–29.34), high educated subjects (OR = 3.49, 95% CI: 1.45–8.44), participants who did more physical activities (OR = 2.75, 95% CI: 1.52–5.00), and subjects who took antiosteoporosis medications (OR = 6.90, 95% CI: 2.84‑16.78). Calcium supplements were used more often by females (OR = 13.05, 95% CI: 5.19–32.81), more physical activities participants (OR = 2.17, 95% CI: 1.20–3.92), and antiosteoporosis users (OR = 8.31, 95% CI: 3.43–20.14). Significant positive associations were seen between 25(OH) D levels and osteoporosis (P = 0.020), vitamin D supplement use (P < 0.0001), and sun exposure (P = 0.093).Conclusion:In this population of Tehranian adults, the prevalence of vitamin D and calcium supplement use may be attributed to educational level and underlying disease. Vitamin D supplementation, osteoporosis, and sun exposure were the strong predictors of vitamin D status.

Pelvic Fragility Fractures: An Opportunity to Improve the Undertreatment of Osteoporosis.

Osteoporosis is often undiagnosed until patients experience fragility fractures. Pelvic fractures are common but underappreciated sentinel fractures. Screening patients with a pelvic fracture for osteoporosis may provide an opportunity to initiate appropriate treatments such as anti-osteoporosis therapy to prevent additional fractures. This retrospective cohort review examined the management of osteoporosis after pelvic fractures at a large tertiary care center without an established secondary fracture prevention program. Data were extracted from electronic medical records of all new patients with a pelvic fracture who were ≥50 years of age from this center and its affiliated community hospitals from 2008 to 2014. Outcome measures included the initiation of anti-osteoporosis therapy before the fracture, within the year following the fracture, >1 year following the fracture, or never and new osteoporotic fractures within 2 years after a pelvic fracture. From 2008 to 2014, 947 patients presented with pelvic fractures. Of these patients, 27.1% (257 patients) were taking anti-osteoporosis medications before the fracture. Four percent of treatment-naïve patients began anti-osteoporosis therapy within 1 year of fracture, with 1.2% (11 patients) starting after 1 year. Of the treatment-naïve patients, 92.3% (637 patients) were never prescribed anti-osteoporosis therapy. Treatment rates were consistent over time. Within 2 years, 41.0% (388 patients) developed fragility fractures at secondary sites: 12.0% (114 patients) experienced a hip fracture, and 16.4% (155 patients) experienced a vertebral fracture. Osteoporosis screening and initiation of secondary fracture prevention after a pelvic fracture were inadequate in the study population. Of the patients in this study, 909 (96.0%) never underwent a dual x-ray absorptiometry (DXA) scan during the study period. Of the 690 treatment-naïve patients, 637 (92.3%) were never administered anti-osteoporosis medications. Within 2 years, 41.0% of all patients developed additional osteoporotic fractures. This study demonstrates an opportunity to improve bone health by screening for and treating osteoporosis in patients with a pelvic fragility fracture. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.