Showing papers in "Osteoporosis International in 2020"

Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures

Abstract: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Clinical perspective and updated literature search. The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.

Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography

Abstract: The application of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture has grown rapidly since its introduction in 2005. As the use of HR-pQCT for clinical research continues to grow, there is an urgent need to form a consensus on imaging and analysis methodologies so that studies can be appropriately compared. In addition, with the recent introduction of the second-generation HrpQCT, which differs from the first-generation HR-pQCT in scan region, resolution, and morphological measurement techniques, there is a need for guidelines on appropriate reporting of results and considerations as the field adopts newer systems. A joint working group between the International Osteoporosis Foundation, American Society of Bone and Mineral Research, and European Calcified Tissue Society convened in person and by teleconference over several years to produce the guidelines and recommendations presented in this document. An overview and discussion is provided for (1) standardized protocol for imaging distal radius and tibia sites using HR-pQCT, with the importance of quality control and operator training discussed; (2) standardized terminology and recommendations on reporting results; (3) factors influencing accuracy and precision error, with considerations for longitudinal and multi-center study designs; and finally (4) comparison between scanner generations and other high-resolution CT systems. This article addresses the need for standardization of HR-pQCT imaging techniques and terminology, provides guidance on interpretation and reporting of results, and discusses unresolved issues in the field.

X-ray-based quantitative osteoporosis imaging at the spine.

Abstract: Osteoporosis is a metabolic bone disease with a high prevalence that affects the population worldwide, particularly the elderly. It is often due to fractures associated with bone fragility that the diagnosis of osteoporosis becomes clinically evident. However, early diagnosis would be necessary to initiate therapy and to prevent occurrence of further fractures, thus reducing morbidity and mortality. X-ray-based imaging plays a key role for fracture risk assessment and monitoring of osteoporosis. Whereas over decades dual-energy X-ray absorptiometry (DXA) has been the main method used and still reflects the reference standard, another modality reemerges with quantitative computed tomography (QCT) because of its three-dimensional advantages and the opportunistic exploitation of routine CT scans. Against this background, this article intends to review and evaluate recent advances in the field of X-ray-based quantitative imaging of osteoporosis at the spine. First, standard DXA with the recent addition of trabecular bone score (TBS) is presented. Secondly, standard QCT, dual-energy BMD quantification, and opportunistic BMD screening in non-dedicated CT exams are discussed. Lastly, finite element analysis and microstructural parameter analysis are reviewed.

Biomechanical Computed Tomography analysis (BCT) for clinical assessment of osteoporosis

Abstract: The surgeon general of the USA defines osteoporosis as "a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture." Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient's clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied "opportunistically" to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication. For the BCT test, no modifications are required to standard clinical CT imaging protocols. The analysis provides measurements of bone strength as well as a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) T-score at the hip and a volumetric BMD of trabecular bone at the spine. Based on both the bone strength and BMD measurements, a physician can identify osteoporosis and assess fracture risk (high, increased, not increased), without needing confirmation by DXA. To help introduce BCT to clinicians and health care professionals, we describe in this review the currently available clinical implementation of the test (VirtuOst), its application for managing patients, and the underlying supporting evidence; we also discuss its main limitations and how its results can be interpreted clinically. Together, this body of evidence supports BCT as an accurate and convenient diagnostic test for osteoporosis in both sexes, particularly when used opportunistically for patients already with CT. Biomechanical Computed Tomography analysis (BCT) uses a patient's CT scan to measure both bone strength and bone mineral density at the hip or spine. Performing at least as well as DXA for both diagnosing osteoporosis and assessing fracture risk, BCT is particularly well-suited to "opportunistic" use for the patient without a recent DXA who is undergoing or has previously undergone CT testing (including hip or spine regions) for an unrelated medical condition.

Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis

Abstract: We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.

A patient-level key performance indicator set to measure the effectiveness of fracture liaison services and guide quality improvement: a position paper of the IOF Capture the Fracture Working Group, National Osteoporosis Foundation and Fragility Fracture Network

Abstract: The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement. Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level. The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs. Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the 80% levels except for treatment recommendation where a level of 50% was used. This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.

Effects of dynamic resistance exercise on bone mineral density in postmenopausal women: a systematic review and meta-analysis with special emphasis on exercise parameters.

Abstract: This systematic review and meta-analysis set out to determine the effect of dynamic resistance exercise (DRT) on areal bone mineral density (aBMD) in postmenopausal women and derive evidence-based recommendations for optimized training protocols. A systematic review of the literature according to the PRISMA statement included (a) controlled trials, (b) of isolated DRT with at least one exercise and one control group, (c) with intervention durations ≥ 6 months, (d) aBMD assessments at lumbar spine or proximal femur, (e) in cohorts of postmenopausal women. We searched eight electronic databases up to March 2019 without language restrictions. The meta-analysis was performed using a random-effects model. Standardized mean differences (SMD) for BMD changes at lumbar spine (LS), femoral neck (FN), and total hip (TH) were defined as outcome measures. Moderators of the exercise effects, i.e., “intervention length,” “type of DRT,” “training frequency,” “exercise intensity,” and “exercise volume,” were addressed by sub-group analyses. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42018095097. Seventeen articles with 20 exercise and 18 control groups were eligible. SMD average is 0.54 (95% CI 0.22–0.87) for LS-BMD, 0.22 (0.07–0.38) for FN-BMD, and 0.48 (0.22–0.75) for TH-BMD changes (all p ≤ 0.015). While sub-group analysis for FN-BMD revealed no differences within categories of moderators, lower training frequency (< 2 sessions/week) resulted in significantly higher BMD changes at LS and TH compared to higher training frequency (≥ 2 sessions/week). Additionally, free weight training was significantly superior to DRT devices for improving TH-BMD. This work provided further evidence for significant, albeit only low–moderate, effects of DRT on LS-, FN-, and TH-BMD. Unfortunately, sub-analysis results did not allow meaningful exercise recommendations to be derived. This systematic review and meta-analysis observed a significant low–moderate effect of dynamic resistance exercise on bone mineral density changes in postmenopausal women. However, sub-group analyses focusing on exercise characteristics found no results that enable the derivation of meaningful exercise recommendations in the area of exercise and osteoporosis prevention or therapy.

Fracture prevention by screening for high fracture risk: a systematic review and meta-analysis

Abstract: This systematic review and meta-analysis showed a significant reduction of (major) osteoporotic fractures and hip fractures after screening using fracture risk assessment and bone densitometry compared with usual care. The results indicate that screening is effective for fracture risk reduction, especially hip fractures. To perform a systematic review and meta-analysis of population screening for high fracture risk on fracture prevention compared with usual care. MEDLINE and Embase were searched for studies published until June 20th 2019. Randomized studies were selected that screened for high fracture risk using at least bone densitometry, screened in a general population, provided subsequent treatment with anti-osteoporosis medication, had a usual care group as comparator, and had at least one fracture-related outcome (all fractures, (major) osteoporotic fractures, or hip fractures). The primary assessment was the hazard ratio (HR) for fracture-related outcomes. All-cause mortality was a secondary outcome. Random-effects models were used to estimate pooled HRs. We identified 1186 potentially eligible articles and included three randomized studies: the ROSE study, the SCOOP study, and the SOS with a total number of N = 42,009 participants. Respectively, 11%, 15%, and 18% of the participants in the intervention group started medication. Meta-analysis showed a statistically significant and clinically relevant reduction of osteoporotic fractures (HR = 0.95, 95% confidence interval (CI) = 0.89–1.00), major osteoporotic fractures (HR = 0.91; 95%CI = 0.84–0.98), and hip fractures (HR = 0.80; 95%CI = 0.71–0.91), but no reduction of all fractures (HR = 0.95; 95%CI = 0.89–1.02). The pooled HR for the secondary outcome all-cause mortality was 1.04 (95% CI = 0.95–1.14). Numbers needed to screen to prevent one fracture were 247 and 272 for osteoporotic fractures and hip fractures, respectively (corresponding to 113 and 124 performed bone densitometry examinations, and 25 and 28 persons being treated). This meta-analysis showed that population screening is effective to reduce osteoporotic fractures and hip fractures. Implementation of screening in older women should be considered as serious option to prevent osteoporotic fractures, especially hip fractures.

Adjusting conventional FRAX estimates of fracture probability according to the recency of sentinel fractures

Abstract: The risk of a recurrent fragility fracture is particularly high immediately following the fracture. This study provides adjustments to FRAX-based fracture probabilities accounting for the site of a recent fracture. The recency of prior fractures affects subsequent fracture risk. The aim of this study was to quantify the effect of a recent sentinel fracture, by site, on the 10-year probability of fracture determined with FRAX. The study used data from the Reykjavik Study fracture register that documented prospectively all fractures at all skeletal sites in a large sample of the population of Iceland. Fracture probabilities were determined after a sentinel fracture (humeral, clinical vertebral, forearm and hip fracture) from the hazards of death and fracture. Fracture probabilities were computed on the one hand for sentinel fractures occurring within the previous 2 years and on the other hand, probabilities for a prior osteoporotic fracture irrespective of recency. The probability ratios provided adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures. Probability ratios to adjust 10-year FRAX probabilities of a major osteoporotic fracture for recent sentinel fractures were age dependent, decreasing with age in both men and women. Probability ratios varied according to the site of sentinel fracture with higher ratios for hip and vertebral fracture than for humerus or forearm fracture. Probability ratios to adjust 10-year FRAX probabilities of a hip fracture for recent sentinel fractures were also age dependent, decreasing with age in both men and women with the exception of forearm fractures. The probability ratios provide adjustments to conventional FRAX estimates of fracture probability for recent sentinel fractures.

Fracture risk following high-trauma versus low-trauma fracture: a registry-based cohort study

Abstract: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk.

The association between chronic kidney disease, falls, and fractures: a systematic review and meta-analysis

Abstract: Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. However, it is not well established how great the risk is for falls and fractures for the different stages of CKD compared to the general population. The objective of this systematic review and meta-analysis was to assess whether, and in which degree, CKD was associated with falls and fractures in adults. A systematic search in PubMed, Embase, CINAHL, and The Cochrane Library was performed on 7 September 2018. All retrospective, cross-sectional, and longitudinal studies of adults (18 years of older) that studied the association between CKD, fractures, and falls were included. Additional studies were identified by cross-referencing. A total of 39 publications were included, of which two publications assessed three types of outcome and four publications assessed two types of outcome. Ten studies focused on accidental falling; seventeen studies focused on hip, femur, and pelvis fractures; seven studies focused on vertebral fractures; and thirteen studies focused on any type of fracture without further specification. Generally, the risk of fractures increased when kidney function worsened, with the highest risks in the patients with stage 5 CKD or dialysis. This effect was most pronounced for hip fractures and any type of fractures. Furthermore, results on the association between CKD and accidental falling were contradictory. Compared to the general population, fractures are highly prevalent in patients with CKD. Besides more awareness of timely fracture risk assessment, there also should be more focus on fall prevention.

Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps

Abstract: Dairy products are included in dietary guidelines worldwide, as milk, yoghurt, and cheese are good sources of calcium and protein, vital nutrients for bones and muscle mass maintenance. Bone growth and mineralization occur during infancy and childhood, peak bone mass being attained after early adulthood. A low peak bone mass has consequences later in life, including increased risk of osteoporosis and fractures. Currently, more than 200 million people worldwide suffer from osteoporosis, with approximately 9 million fractures yearly. This poses a tremendous economic burden on health care. Between 5% and 10% of the elderly suffer from sarcopenia, the loss of muscle mass and strength, further increasing the risk of fractures due to falls. Evidence from interventional and observational studies support that fermented dairy products in particular exert beneficial effects on bone growth and mineralization, attenuation of bone loss, and reduce fracture risk. The effect cannot be explained by single nutrients in dairy, which suggests that a combined or matrix effect may be responsible similar to the matrix effects of foods on cardiometabolic health. Recently, several plant-based beverages and products have become available and marketed as substitutes for dairy products, even though their nutrient content differs substantially from dairy. Some of these products have been fortified, in efforts to mimic the nutritional profile of milk, but it is unknown whether the additives have the same bioavailability and beneficial effect as dairy. We conclude that the dairy matrix exerts an effect on bone and muscle health that is more than the sum of its nutrients, and we suggest that whole foods, not only single nutrients, need to be assessed in future observational and intervention studies of health outcomes. Furthermore, the importance of the matrix effect on health outcomes argues in favor of making future dietary guidelines food based.

Effects of a resistance and balance exercise programme on physical fitness, health-related quality of life and fear of falling in older women with osteoporosis and vertebral fracture: a randomized controlled trial.

Abstract: Exercise is recommended for people with osteoporosis, but the effect for people who have suffered vertebral fracture is uncertain. This study shows that a multicomponent exercise-program based on recommendations for people with osteoporosis improved muscle strength, balance, and fear of falling in older women with osteoporosis and vertebral fracture. Guidelines for exercise strongly recommend that older adults with osteoporosis or osteoporotic vertebral fracture should engage in a multicomponent exercise programme that includes resistance training in combination with balance training. Prior research is scarce and shows inconsistent findings. This study examines whether current exercise guidelines for osteoporosis, when applied to individuals with vertebral fractures, can improve health outcomes. This single blinded randomized controlled trial included 149 older women diagnosed with osteoporosis and vertebral fracture, 65+ years. The intervention group performed a 12-week multicomponent exercise programme, the control group received usual care. Primary outcome was habitual walking speed, secondary outcomes were physical fitness (Senior Fitness Test, Functional Reach and Four Square Step Test), health-related quality of life and fear of falling. Descriptive data was reported as mean (standard deviation) and count (percent). Data were analyzed following intention to treat principle and per protocol. Between-group differences were assessed using linear regression models (ANCOVA analysis). No statistically significant difference between the groups were found on the primary outcome, walking speed (mean difference 0.04 m/s, 95% CI − 0.01–0.09, p = 0.132). Statistically significant between-group differences in favour of intervention were found on FSST (dynamic balance) (mean difference − 0.80 s, 95% CI − 1.57 to − 0.02, p = 0.044), arm curl (mean difference 1.55, 95% CI 0.49–2.61, p = 0.005) and 30-s STS (mean difference 1.85, 95% CI 1.04–2.67, p < 0.001), as well as fear of falling (mean difference − 1.45, 95% CI − 2.64 to − 0.26, p = 0.018). No statistically significant differences between the groups were found on health-related quality of life. Twelve weeks of a supervised multicomponent resistance and balance exercise programme improves muscle strength and balance and reduces fear of falling, in women with osteoporosis and a history of vertebral fractures. ClincialTrials.gov Identifier: NCT02781974. Registered 25.05.16. Retrospectively registered.

Determinants of imminent fracture risk in postmenopausal women with osteoporosis

Abstract: In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1–2 years) in postmenopausal women. This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk.

Exposure to heavy metals and the risk of osteopenia or osteoporosis: a systematic review and meta-analysis

Abstract: The relationship between heavy metal exposure and risk of osteopenia or osteoporosis has biological plausibility, yet it remains inconclusive; therefore, we conducted a systematic review and meta-analysis to evaluate the associations between exposure to heavy metals (i.e., cadmium, lead, and mercury) and the risk of osteopenia or osteoporosis. Databases of MEDLINE, Embase, Scopus, and Web of Science were searched through November 2019, to identify studies that evaluated the relationship between exposure to cadmium, lead, and mercury and risk of osteopenia or osteoporosis in adults. Fourteen eligible studies were included. Effect sizes expressed as pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using weighted random-effect models. Exposure to cadmium (OR = 1.35; 95% CI: 1.17 to 1.56; P ≤ 0.001) and lead (OR = 1.15; 95% CI: 1.00 to 1.32; P = 0.05) was associated with an increased risk of osteopenia or osteoporosis, unlike mercury. Subgroup analyses showed cadmium exposure increased the risk of osteopenia or osteoporosis in older (> 65 yrs.; OR = 1.43; 95%CI: 1.08 to 1.88, P = 0.01) compared with younger (18-65 yrs.; OR = 1.24; 95% CI: 1.02 to 1.52, P = 0.03) adults. Also, lead exposure increased the risk in men (OR = 1.55; 95% CI: 1.15 to 2.09, P = 0.007) unlike in women. By contrast to urinary levels, blood (OR = 1.26; 95% CI: 1.08 to 1.47, P = 0.003) and dietary (OR = 1.46; 95% CI: 1.28 to 1.67, P < 0.001) levels of cadmium were associated with an increased risk of osteopenia or osteoporosis. Exposure to cadmium and lead may be associated with an increased risk of osteopenia or osteoporosis, although high heterogeneity was detected.

Osteoporosis in the age of COVID-19.

Abstract: 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.

Interventions to improve adherence to anti-osteoporosis medications: an updated systematic review.

Abstract: An earlier systematic review on interventions to improve adherence and persistence was updated. Fifteen studies investigating the effectiveness of patient education, drug regimen, monitoring and supervision, and interdisciplinary collaboration as a single or multi-component intervention were appraised. Multicomponent interventions with active patient involvement were more effective. This study was conducted to update a systematic literature review on interventions to improve adherence to anti-osteoporosis medications. A systematic literature review was carried out in Medline (using PubMed), Embase (using Ovid), Cochrane Library, Current Controlled Trials, ClinicalTrials.gov , NHS Centre for Review and Dissemination, CINHAL, and PsycINFO to search for original studies that assessed interventions to improve adherence (comprising initiation, implementation, and discontinuation) and persistence to anti-osteoporosis medications among patients with osteoporosis, published between July 2012 and December 2018. Quality of included studies was assessed. Of 585 studies initially identified, 15 studies fulfilled the inclusion criteria of which 12 were randomized controlled trials. Interventions were classified as (1) patient education (n = 9), (2) drug regimen (n = 3), (3) monitoring and supervision (n = 2), and (4) interdisciplinary collaboration (n = 1). In most subtypes of interventions, mixed results on adherence (and persistence) were found. Multicomponent interventions based on patient education and counseling were the most effective interventions when aiming to increase adherence and/or persistence to osteoporosis medications. This updated review suggests that patient education, monitoring and supervision, change in drug regimen, and interdisciplinary collaboration have mixed results on medication adherence and persistence, with more positive effects for multicomponent interventions with active patient involvement. Compared with the previous review, a shift towards more patient involvement, counseling and shared decision-making, was seen, suggesting that individualized solutions, based on collaboration between the patient and the healthcare provider, are needed to improve adherence and persistence to osteoporosis medications.

Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab

Abstract: Romosozumab, an anti-sclerostin antibody, has been approved for prescription in the USA, Europe, Japan, and South Korea to treat patients with osteoporosis who have a high risk of fracture. The Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH) trial randomly assigned women to receive alendronate or romosozumab for 12 months. It found a difference between the alendronate and romosozumab group in the incidence of major cardiovascular events (CVD), also defined as adjudicated major adverse cardiovascular events (MACE) [1]. After 12 months, those in the alendronate group continued alendronate for a median of 33 months and those assigned to romosozumab switched to alendronate for the duration of the trial. When a randomized trial with balanced baseline characteristics of subjects finds a difference in rates of events, such as CVD, between two active drugs, such as alendronate and romosozumab, there are three explanations: (1) the difference is attributable to chance, (2) alendronate reduced the rate of CVD, or (3) romosozumab increased the rate of CVD. As the probabilities of these alternatives must all sum to 1.0, a decrease in the probability of one of these explanations increases the probability that the other alternatives are true. Importantly, the likelihood that any one of these explanations is true depends on other information. This Bayesian approach to the interpretation of trials is similar the Bayesian interpretation of diagnostic tests: the result of a test must be interpreted in the context of other information [2]. For instance, the probability that a positive test is true depends on the prior probability that the patient has the disease based on other information. If the prior probability is low, then a positive result of the test is more likely to be false. Similarly, the probability that a result of a trial is true critically depends on other information. The probability that a result is true, for example, that alendronate reduced CVD rates, depends on the prior probability that alendronate reduced CVD rates in other randomized trials. Although it is difficult to quantify these probabilities, other information is critical to judging which alternative explanation is true.

Persistence and compliance with osteoporosis therapies among postmenopausal women in the UK Clinical Practice Research Datalink

Abstract: Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving osteoporosis medications in the UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, long-term treatment persistence must be improved. Persistence with osteoporosis therapies has historically been poor. To treat this chronic and progressive disease, it is essential that patients receive the full benefit of these medications. We estimated persistence and compliance with osteoporosis therapies in a large sample of postmenopausal women in the UK. Data were obtained from the Clinical Practice Research Datalink for all women aged 50 years and over or women with early menopause, who received at least one prescription in primary care for any licensed osteoporosis therapy between January 1, 2010 and December 31, 2015. Persistence and compliance at 24 months (primary objective) and at 5 years (exploratory objective) were estimated in three patient cohorts: “All Patients,” “Naive Patients,” and “Drug-Specific.” The All Patients cohort included 72,256 women. Persistence with any therapy was 56.1%, 43.6%, 36.4%, and 31.0% at 6, 12, 18, and 24 months, respectively, and 23.2% and 13.1% at 3 years and 5 years, respectively. Patients were generally more persistent and compliant if evaluated from their first exposure to osteoporosis therapy (Naive Patients cohort). In the drug-specific analysis, 64% of patients receiving denosumab (administered subcutaneously every 6 months) were persistent at 24 months compared with 28% and 23% of those taking oral bisphosphonates and intravenous bisphosphonates, respectively. Only about one in three patients who received osteoporosis therapy continued to be on treatment after 2 years. There is a need to improve persistence with osteoporosis therapy, especially for high-risk patients

Osteoporotic fracture trends in a population of US managed care enrollees from 2007 to 2017.

Abstract: This study expands on previous findings that hip fracture rates may no longer be declining. We found that age- and sex-adjusted fracture rates in the US plateaued or increased through mid-2017 in a population of commercially insured and Medicare Advantage health plan enrollees, in contrast to a decline from 2007 to 2013. The purpose of this study was to evaluate fracture trends in US commercial and Medicare Advantage health plan members aged ≥ 50 years between 2007 and 2017. Retrospective analysis of the Optum Research Database from January 1, 2007, to May 31, 2017. Of 1,841,263 patients identified with an index fracture, 930,690 were case-qualifying and included in this analysis. The overall age- and sex-adjusted fracture rate decreased from 14.67/1000 person-years (py) in 2007 to 11.79/1000 py in 2013, followed by a plateau for the next 3 years and then an increase to 12.50/1000 py in mid-2017. In females aged ≥ 65 years, fracture rates declined from 27.49/1000 py in 2007 to 22.08/1000 py in 2013, then increased to 24.92/1000 py in mid-2017. Likewise, fracture rates in males aged ≥ 65 years declined from 2007 (12.00/1000 py) to 2013 (10.72/1000 py), then increased to 12.04/1000 py in mid-2017. The age- and sex-adjusted fracture rates for most fracture sites declined from 2007 to 2013 by 3.7% per year (P = 0.310). Following a consistent decline in fracture rate from 2007 to 2013, trends from 2014 to 2017 indicate fracture rates are no longer declining and, for some fracture types, rates are rising.

Secular trends in the initiation of therapy in secondary fracture prevention in Europe: a multi-national cohort study including data from Denmark, Catalonia, and the United Kingdom

Abstract: This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88–90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed. Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015. This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture. A total of 648,369 fracture patients were included. Mean age 70.2–78.9 years; 22.2–31.7% were men. In Denmark, the treatment gap was stable at approximately 88–90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap—though never smaller than 63%—was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women. Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years.

Stop (mis)classifying fractures as high- or low-trauma or as fragility fractures.

Abstract: We strongly recommend that caregivers for fractures stop classifying fractures as highor low-trauma, fragility fractures and provide the same care for fractures now mislabeled as “high trauma” as all other fractures. The study by Leslie and colleagues in the current issue of Osteoporosis International adds to the evidence that attempts to classify the degree of trauma deprive a large number of patients with fractures of appropriate evaluation and preventive treatment [1]. The study adds evidence to the case that it is time to abandon the mistaken beliefs that fractures rated as high trauma are not associated with decreased BMD, indicate no higher risk of subsequent fracture, or are less likely to be prevented by treatments for osteoporosis. Rather, the evidence shows that “hightrauma” fractures are associated with decreased BMD and increased risk of future fracture and reduction in risk by treatment. Fractures occur when, at skeletal site, the force of a trauma exceeds the strength of the bone. It seemed reasonable to posit that there is a degree force that exceeds the strength of any known bone. However, when an individual has suffered a fracture, it is not possible to retrospectively quantify the force of trauma or the strength of bone where the fracture occurred. Consider a fracture occurring during a car crash. The crash generates a wide array of forces that hit a body in innumerable possible locations, at different angles, where bones are variably protected by soft tissue and have different strengths at the point of impact. It is not possible to quantify array of forces generated by trauma “greater—or less—than generated by falling from more than standing height” as often used to classify fractures as high-trauma or fragility fractures. Even if it were possible to retrospectively estimate the degree of force that was applied to the bone that fractured, it would be true that given the same amount of trauma—such as a crash—the probability of fracture in any skeletal location will increase as bone strength decreases. If so, then, individuals who have fractures clinically classified as “traumatic” or “high-trauma” should have lower bone strength than those who have not had such fractures. Thus, those with a fracture resulting from a high-trauma event should have a greater risk of future fractures—both “low-” and “high-”trauma fractures. They should also have a lower average bone density. These suppositions have been supported by previous studies [2, 3]. The study by Leslie and colleagues in this issue of Osteoporosis International found that people with prior hightrauma fracture had BMD reduced to the same extent as those with prior low-trauma fracture and similar rates of subsequent low-trauma fracture. Interestingly, they found that patients with prior low-trauma fractures had a greater subsequent risk of high-trauma fractures and people without prior fractures [1]. These results are similar to those reported by Mackey and colleagues in the Study of Osteoporotic Fractures in women and MrOS study in men that found that individuals who sustained a fracture carefully defined as high trauma had similar risks of subsequent fractures of any type [3]. Specifically, they had a very similar risk of low-trauma fractures than did individuals with a fracture classified as low trauma. These associations remained similar when the analysis was limited to those with more extreme, “severe trauma” such as car crashes. Studies that have measured BMD in those with highand low-trauma fractures have found that the associations are also very similar. In SOF and MrOS, the associations between BMD of the hip and spine and risk of fracture were very similar for both lowand high-trauma fractures, and the prevalence of osteoporosis, defined as a T-score ≤ − 2.5 in the total * S. R. Cummings scummings@sfcc-cpmc.net

Effects of glucocorticoids on osteoporosis in rheumatoid arthritis: a systematic review and meta-analysis.

Abstract: We evaluated the effects of glucocorticoids on bone mineral density (BMD), and prevalence of osteoporosis and fracture in rheumatoid arthritis (RA) by meta-analysis. Until June 26, 2019, we conducted a systematic literature search in EMBASE, Web of science, PubMed, and Cochrane Library to obtain BMD and the prevalence of osteoporosis and fracture in glucocorticoid-treated subjects with RA. The BMD of the treatment and control groups were analyzed by meta-analysis (Stata. version 15), and the 95% confidence interval (CI) was calculated. We identified 15 observational studies, including 46,711 RA subjects and 857 healthy controls. The BMD of the lumbar spine (− 0.038 g/cm2; CI, − 0.052, − 0.024) and femoral neck (− 0.017 g/cm2; − 0.030, − 0.003) in RA treated with glucocorticoids were significantly lower than those in RA controls. Compared with healthy control group, the BMD of the lumbar spine (− 0.094 g/cm2; − 0.126, − 0.061) and femoral neck (− 0.097 g/cm2, − 0.109, − 0.085) of RA treated with glucocorticoids decreased more significantly. The prevalence of osteoporosis in whole body, spine, and femur was 38.6% (0.305, 0.466), 32.9% (0.277, 0.381), and 21.7% (0.106, 0.328), respectively. And the prevalence of vertebral fracture was 13.0% (0.058, 0.203). Glucocorticoids may lead to a decline in skeletal health in subjects with RA, especially in vertebral and femoral BMD, compared with normal people or RA without glucocorticoid therapy. Meanwhile, osteoporosis and fractures were also common. Therapeutic measures should be targeted at individuals, which needs further study. Through meta-analysis, we found that glucocorticoids have some negative effects on the bone health of subjects with rheumatoid arthritis. Therefore, when using glucocorticoids to treat rheumatoid arthritis, we should take strategic measures to prevent the decline of bone quality.

Correction to: European guidance for the diagnosis and management of osteoporosis in postmenopausal women (Osteoporosis International, (2019), 30, 1, (3-44), 10.1007/s00198-018-4704-5)

Abstract: The original version of this article, published on 15 October 2018, unfortunately, contained a mistake.

Effects of isoflavone interventions on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials

Abstract: Isoflavones have a structure similar to 17β-estradiol, so they may be useful to postmenopausal women in preventing bone loss related to estrogen deficiency. The present study integrated the findings from 63 randomized controlled trials and found that isoflavone interventions may have benefits in the prevention and treatment of menopause-related osteoporosis. This study aimed to determine the efficacy of isoflavone interventions on bone density outcomes and the safety of isoflavone interventions in postmenopausal women by means of systematic review and meta-analysis. A systematic search was performed on three databases (PubMed, Scopus, and Cochrane Library). Included studies were limited to randomized controlled trials (RCTs) assessing the effects of isoflavone intervention on bone mineral density (BMD) in postmenopausal women. Mean difference (MD) in BMD or relative risk for adverse outcomes was used as a summary effect measure; pooled-effect estimates were calculated using a random-effects model. A total of 63 RCTs, involving 6427 postmenopausal women, were included in the meta-analysis. Statistically significant differences in BMD at the last follow-up visit between the two groups (isoflavones vs. control) were found at the lumbar spine (MD = 21.34 mg/cm2, 95% CI = 8.21 to 34.47 mg/cm2, p = 0.001), the femoral neck (MD = 28.88 mg/cm2, 95% CI = 15.05 to 42.71 mg/cm2, p < 0.0001), and the distal radius (MD = 19.27 mg/cm2, 95% CI = 5.65 to 32.89 mg/cm2, p = 0.006). The positive effects in improved BMD were primarily associated with two formulations, i.e., genistein 54 mg/day and ipriflavone 600 mg/day. Isoflavone interventions were generally safe and well tolerated. Isoflavone interventions, genistein (54 mg/day) and ipriflavone (600 mg/day) in particular, have beneficial effects on BMD outcomes and are safe in postmenopausal women. They may be considered as a complementary or alternative option in the prevention and treatment of menopause-related osteoporosis.

Understanding patient experiences and challenges to osteoporosis care delivered virtually by telemedicine: a mixed methods study

Abstract: This study sought to understand patient experiences, benefits, and challenges to osteoporosis care delivered virtually by telemedicine. Telemedicine bridges the access gap to specialized osteoporosis care in remote areas. Improving coordination of investigations, access to allied health members, and future initiatives may improve osteoporosis-related morbidity and mortality in this population. There is limited research on the role of telemedicine (TM) in the management of osteoporosis (OP). We previously reported that OP patients assessed by TM had a higher prevalence of fragility fractures, co-morbidities, and need for allied health resources than those serviced by the outpatient clinic. The purpose of this study is to understand the experiences, benefits, and challenges associated with receiving OP care by TM from the patient perspective. We adopted a convergent, mixed methods study design whereby both a quantitative component (mailed survey) and qualitative component (30-min telephone interviews) were conducted simultaneously. In addition to reporting survey data, thematic analysis was applied to interview data. Participants were comfortable with virtual technology and perceived that their quality of care by TM was comparable to in-person visits. Expressed benefits included the convenience of timely care close to home, reduced burden of travel and costs, and enhanced sense of confidence with being assessed by an osteoporosis specialist. Perceived barriers included poor follow-up with allied health professionals in the TM program (e.g., physiotherapist) and coordination of tests and investigations. Many participants indicated interest in an OP self-management program, with content focusing on diet and lifestyle factors. The TM program bridges the access gap for those living with OP in underserviced and remote areas. However, we identified the need to improve the existing processes to better coordinate access to allied health team members and arrangements for investigations. Participants also expressed interest for a virtual osteoporosis self-management program.

Association between postoperative delirium and mortality in elderly patients undergoing hip fractures surgery: a meta-analysis

Abstract: Postoperative delirium (POD) is a common complication in elderly surgical patients. Patients undergoing hip fractures surgery who are often characterized by advanced age could be particularly prone to suffering POD. We performed a meta-analysis to assess the association between POD and mortality in elderly patients undergoing hip fractures surgery. This meta-analysis included twenty-one cohort studies, and the pooled outcomes demonstrated that approximated one-fourth of patients undergoing hipfracture surgery would develop POD, and delirium increased the mortality in these patients. We searched PubMed, Embase, Web of Science, and Scopus for studies that investigated the effect of POD on mortality in elderly patients undergoing hip fracture surgery. Two reviewers independently selected studies, assessed quality, and extracted data. Statistical analyses were performed by STATA 14.0 and RevMan 5.3. Risk ratios (RRs) with 95% confidence intervals (CIs) were derived using random or fixed-effects model. Twenty-one cohort studies enrolling a total of 6288 patients were included, and the pooled prevalence (95% CI) of POD was 28% (23–34%). POD was associated with an increase in perioperative mortality (30-day or in-hospital mortality) [12 studies, 3123 patients, relative risk (RR) (95% CI) 2.79 (1.97–3.93)], 6-month mortality [6 studies, 1673 patients, 2.51 (1.99–3.16)], 1-year mortality [6 studies, 1896 patients, 1.98 (1.62–2.41)], and more than 1-year mortality [8 studies, 1926 patients, 2.06 (1.60–2.64)]. Our meta-analysis demonstrated that approximated one-fourth of patients undergoing hip fracture surgery would develop POD, and delirium increased the short-term and long-term mortality in these patients.

Persistence and adherence to parenteral osteoporosis therapies: a systematic review

Abstract: Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10–87% (median 55%) at 1 year and 10–69% (median 29.5%) at 2 years, and adherence rates of 21–89% (median 53%) at 1 year and 37–68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34–73% (median 42%) for second dose and 20–54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31–58% (median 47.5%) in 1 year and 13–35% (median 25%) at 2 years, and adherence rates of 21–72% (median 47.3%) and 15–58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61–100% (median 81%) and 36–99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Current level of technology use, health and eHealth literacy in older Canadians with a recent fracture-a survey in orthopedic clinics.

Abstract: Among older adults who have recently sustained a fracture, there is substantial adoption of mobile technology. Furthermore, health and eHealth literacy level reported by participants supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management. Electronic health resources are increasingly used in the self-management of medical conditions. We aimed to identify the current level of technology adoption, health, and eHealth literacy among older adults with a recent fracture, to determine if the use of electronic interventions would be feasible and acceptable in this population. Adults ≥ 50 years with recent fractures were invited to complete a self-administered survey composed of 21 questions, including an 8-item perceived eHealth literacy scale. A total of 401 participants completed the survey (women, 64%; ≥ 65 years, 59%; university education, 32%). Most participants reported no difficulty in reading printed health material (67%) and felt confident in filling out medical forms (65%). Younger age and higher levels of education were associated with higher health literacy. Most respondents (81%) owned at least one mobile device (smartphone, 49%; tablet, 45%). eHEALS scores were similar among men (29, IQR 24–32) and women (29, IQR 25–33), and between younger age group categories (50–64 years, 30; IQR 26–33; and 65–74 years, 29; IQR 25–32), but lower in the oldest age group (≥ 75 years, 24; IQR 21–29; p < 0.05). Compared with the youngest group, those ≥ 75 years had higher odds of an eHEALS < 26 (odds ratio, 4.2; 95% confidence interval 2.0–8.9) after adjusting for sex and education level. There is significant adoption of mobile technology among older adults. Health and eHealth literacy reported by this study population supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management.

Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?

Abstract: Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia. RCTs have reported a 0.05–1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab. A retrospective analysis was conducted based on medical records (2010–2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5 mg/dL was defined as hypocalcemia. We included 2005 patients (93% women, mean age 76 ± 9 years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8 mg/dL): in 66 after 0.5–1 years; 48 after 1–2 years; 35 after > 2 years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5 mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3 mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31 mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (− 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than − 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value. Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.