Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis.

BACKGROUND: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. OBJECTIVE: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). METHODS: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. RESULTS: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. CONCLUSIONS: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. TRIAL REGISTRATION: PROSPERO 2020 CRD42020177166.

Guideline for the management of hip fractures 2020: Guideline by the Association of Anaesthetists.

We convened a multidisciplinary Working Party on behalf of the Association of Anaesthetists to update the 2011 guidance on the peri-operative management of people with hip fracture. Importantly, these guidelines describe the core aims and principles of peri-operative management, recommending greater standardisation of anaesthetic practice as a component of multidisciplinary care. Although much of the 2011 guidance remains applicable to contemporary practice, new evidence and consensus inform the additional recommendations made in this document. Specific changes to the 2011 guidance relate to analgesia, medicolegal practice, risk assessment, bone cement implantation syndrome and regional review networks. Areas of controversy remain, and we discuss these in further detail, relating to the mode of anaesthesia, surgical delay, blood management and transfusion thresholds, echocardiography, anticoagulant and antiplatelet management and postoperative discharge destination. Finally, these guidelines provide links to supplemental online material that can be used at readers' institutions, key references and UK national guidance about the peri-operative care of people with hip and periprosthetic fractures during the COVID-19 pandemic.

Integration of a vertebral fracture identification service into a fracture liaison service: a quality improvement project.

Integration of a vertebral fracture identification service into a Fracture Liaison Service is possible. Almost one-fifth of computerised tomography scans performed identified an individual with a fracture. This increase in workload needs to be considered by any FLS that wants to utilise such a service. INTRODUCTION: This service improvement project aimed to improve detection of incidental vertebral fractures on routine imaging. It embedded a vertebral fracture identification service (Optasia Medical, OM) on routine computerised tomography (CT) scans performed in this hospital as part of its Fracture Liaison Service (FLS). METHODS: The service was integrated into the hospital's CT workstream. Scans of patients aged ≥ 50 years for 3 months were prospectively retrieved, alongside their clinical history and the CT report. Fractures were identified via OM's machine learning algorithm and cross-checked by the OM radiologist. Fractures identified were then added as an addendum to the original CT report and the hospital FLS informed. The FLS made recommendations based on an agreed algorithm. RESULTS: In total, 4461 patients with CT scans were retrieved over the 3-month period of which 850 patients had vertebra fractures identified (19.1%). Only 49% had the fractures described on hospital radiology report. On average, 61 patients were identified each week with a median of two fractures. Thirty-six percent were identified by the FLS for further action and recommendations were made to either primary care or the community osteoporosis team within 3 months of fracture detection. Of the 64% not identified for further action, almost half was because the CT was part of cancer assessment or treatment. The remaining were due to a combination of only ≤ 2 mild fractures; already known to a bone health specialist; in the terminal stages of any chronic illness; significant dependency for activities of daily living; or a life expectancy of less than 12 months CONCLUSION: It was feasible to integrate a commercial vertebral fracture identification service into the daily working of a FLS. There was a significant increase in workload which needs to be considered by any future FLS planning to incorporate such a service into their clinical practice.

The Nottingham Spinal Health (NoSH) Study: a cohort study of patients hospitalised with vertebral fragility fractures.

Patients hospitalised with vertebral fragility fractures were elderly, multimorbid and frail and lead to poor outcomes. Their hospital treatment needs to consider this alongside their acute fracture. A systematic organised model of care, such as an adaptation of orthogeriatric hip fracture care, will offer a more holistic approach potentially improving their outcomes. PURPOSE: Patients admitted to hospital with vertebral fragility fractures are elderly and have complex care needs who may benefit from specialist multidisciplinary input. To date, their characteristics and outcomes have not been reported sufficiently. This study aims to justify such a service. METHODS: Patients admitted with an acute vertebral fragility fracture over 12 months were prospectively recruited from a university hospital in England. Data were collected soon after their admission, at discharge from hospital and 6 months after their hospital discharge on their characteristics, pain, physical functioning, and clinical outcomes. RESULTS: Data from 90 participants were analysed. They were mainly elderly (mean age 79.7 years), multimorbid (69% had ≥ 3 comorbid condition), frail (56% had a Clinical Frailty Scale score ≥ 5), cognitively impaired (54% had a MoCA score of < 23) and at high risk of falls (65% had fallen ≥ 2 in the previous year). Eighteen percent died at 6 months. At 6 months post-hospital discharge, 12% required a new care home admission, 37% still reported their pain to be severe and physical functioning was worse compared with their preadmission state. CONCLUSION: Patients hospitalised with vertebral fragility fractures were elderly, multimorbid, frail and are susceptible to persistent pain and disability. Their treatment in hospital needs to consider this alongside their acute fracture. A systematic organised model of care, such as an adaptation of orthogeriatric hip fracture care, will offer a more holistic approach potentially improving their outcomes.

The effect of intravenous iron on erythropoiesis in older people with hip fracture.

BACKGROUND: anaemia following hip fracture is common and associated with worse outcomes. Intravenous iron is a potential non-transfusion treatment for this anaemia and has been found to reduce transfusion rates in previous observational studies. There is good evidence for its use in elective surgical populations. OBJECTIVE: to examine the impact of intravenous iron on erythropoiesis following hip fracture. DESIGN: two-centre, assessor-blinded, randomised, controlled trial of patients with primary hip fracture and no contra-indications to intravenous iron. METHOD: the intervention group received three doses of 200 mg iron sucrose over 30 min (Venofer, Vifor Pharma, Bagshot Park, UK) on three separate days. Primary outcome was reticulocyte count at day 7 after randomisation. Secondary outcomes included haemoglobin concentration, complications and discharge destination. Eighty participants were randomised. RESULTS: there was a statistically significantly greater absolute final reticulocyte count in the iron group (89.4 (78.9-101.3) × 109 cells l-1 (n = 39) vs. the control (72.2 (63.9-86.4)) × 109 cells l-1 (n = 41); P = 0.019; (mean (95% confidence intervals) of log-transformed data). There were no differences in final haemoglobin concentration (99.9 (95.7-104.2) vs. 102.0 (98.7-105.3) P = 0.454) or transfusion requirements in the first week (11 (28%) vs. 12 (29%); P = 0.899). Functional and safety outcomes were not different between the groups. CONCLUSIONS: although intravenous iron does stimulate erythropoiesis following hip fracture in older people, the effect is too small and too late to affect transfusion rates. Trial Registry Numbers: ISRCTN:76424792; EuDRACT: 2011-003233-34.

Rapid access imaging for occult fractured neck of femur.

UNLABELLED: We completed a full audit cycle to assess waiting times for inpatients with suspected occult femoral neck fracture to get MRI scan, identify the causes of delay and implement the changes to reduce the waiting times. We have proved that inpatient MRI waiting times can significantly be reduced by a targeted approach. INTRODUCTION: The timely management of hip fractures is now underpinned by NICE Guidance, June 2011. This includes a statement that magnetic resonance imaging (MRI) should be offered if occult femoral neck fracture is suspected and that MRI should be made available within 24 hours. We completed a full audit cycle: (1) analyse the time taken for inpatient MRI to be performed for suspected occult femoral neck fractures, (2) identify correctable reasons for delay, (3) develop and implement changes and (4) re-audit. METHODS: Data was collected from the computerised radiology information system on consecutive patients between 01/04/2010 and 31/03/2012. This data was presented at a number of directorate audit meetings. Following the development and implementation of targeted improvements, a prospective re-audit was carried out between 01/08/2012 and 31/07/2013. RESULTS: After the initial audit, various reasons of delay were identified. The correctable causes for delay were (1) duty radiologist not directly contacted by clinician to request urgent scan, (2) slow vetting and protocoling of electronic requests, (3) resistance to weekend scanning and (4) delay in completing MRI safety questionnaire. After implementing strategies to address these remediable causes of delay, the re-audit demonstrated a 16% improvement in patients scanned within 24 h. The mean waiting time to get an MRI was 2,025.4 min (SD 2,406.4) for the baseline audit and 1,374 min (SD 1,635.7) for the re-audit. Mean difference is 651.4 min (95% CI 85.21, 1,217.5; p = 0.0243). CONCLUSION: MRI is a useful and sensitive tool to investigate occult femoral neck fracture. Inpatient MRI waiting times can significantly be reduced by a targeted approach which embodies improved team working.

The direct cost of acute hip fracture care in care home residents in the UK.

UNLABELLED: Data on the true acute care costs of hip fractures for patients admitted from care homes are limited. Detailed costing analysis was undertaken for 100 patients. Median cost was £9,429 [10,896], increasing to £14,435 [16,681], for those requiring an upgrade from residential to nursing home care. Seventy-six percent of costs were attributable to hospital bed days, and therefore, interventions targeted at reducing hospital stay may be cost effective. INTRODUCTION: Previous studies have estimated the costs associated with hip fracture, although these vary widely, and for patients admitted from care homes, who represent a significant fracture burden, there are limited data. The primary aim of this study was to perform a detailed assessment of the direct medical costs incurred and secondly compare this to the actual remuneration received by the hospital. METHODS: One hundred patients presenting from a care home in 2006 were randomly selected and a detailed case-note costing analysis was undertaken. This cost was then compared to the actual remuneration received by the hospital. RESULTS: Median cost per patient episode was £9,429 [10,896] (all patients) range £4,292-162,324 [4,960-187,582] (subdivided into hospital bed day costs £7,129 [8,238], operative costs £1,323 [1,529] and investigation costs £977 [1,129]). Twenty-two percent of the patients admitted from a residential home required upgrading to a nursing home. In this group, the median length of stay was 31 days (mean 38, range 10-88) median cost £14,435 [16,681]. Average remuneration received equated to £6,222 [7,190] per patient. This represents a mean loss in income, compared to actual calculated costs of £3,207 [3,706] per patient. CONCLUSION: The median cost was £9,429 [10,896], increasing to £14,435 [16,681], for those requiring an upgrade from residential to nursing home care at discharge. Significant cost differences were seen comparing the actual cost to remuneration received. Interventions targeted at reducing length of stay may be cost effective.

Nottingham Hip Fracture Score as a predictor of one year mortality in patients undergoing surgical repair of fractured neck of femur.

BACKGROUND: Surgical repair of hip fractures is associated with high postoperative mortality. The identification of high-risk patients might be of value in aiding clinical management decisions and resource allocation. The Nottingham Hip Fracture Score (NHFS) is a scoring system validated for the prediction of 30 day mortality after hip fracture surgery. It is made up of seven independent predictors of mortality that have been incorporated into a risk score: age (66-85 and ≥86 yr); sex (male); number of co-morbidities (≥2), admission mini-mental test score (≤6 out of 10), admission haemoglobin concentration (≤10 g dl(-1)), living in an institution; and the presence of malignancy. We investigated whether the NHFS was a predictor of 1 yr mortality in patients undergoing surgical repair of fractured neck of femur. METHODS: NHFS was retrospectively calculated for 6202 patients who had undergone hip fracture surgery between 1999 and 2009. One year and 30 day postoperative mortality data were collected both from hospital statistics and the Office of National Statistics. RESULTS: Overall mortality was 8.3% at 30 days and 29.3% at 1 yr. An NHFS of ≤4 was considered low risk and a score of ≥5 high risk. Survival was greater in the low-risk group at 30 days [96.5% vs 86.3% (P<0.001)] and at 1 yr [84.1% vs 54.5% (P<0.001)]. CONCLUSIONS: NHFS can be used to stratify the risk of 1 yr mortality after hip fracture surgery.

Community falls prevention for people who call an emergency ambulance after a fall: randomised controlled trial.

OBJECTIVE: To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital. DESIGN: Randomised controlled trial. SETTING: Community covered by four primary care trusts, England. PARTICIPANTS: 204 adults aged more than 60 living at home or in residential care who had fallen and called an emergency ambulance but were not taken to hospital. INTERVENTIONS: Referral to community fall prevention services or standard medical and social care. MAIN OUTCOME MEASURES: The primary outcome was the rate of falls over 12 months, ascertained from monthly diaries. Secondary outcomes were scores on the Barthel index, Nottingham extended activities of daily living scale, and falls efficacy scale at baseline and by postal questionnaire at 12 months. Analysis was by intention to treat. RESULTS: 102 people were allocated to each group. 99 (97%) participants in the intervention group received the intervention. Falls diaries were analysed for 88.6 person years in the intervention group and 84.5 person years in the control group. The incidence rates of falls per year were 3.46 in the intervention group and 7.68 in the control group (incidence rate ratio 0.45, 95% confidence interval 0.35 to 0.58, P<0.001). The intervention group achieved higher scores on the Barthel index and Nottingham extended activities of daily living and lower scores on the falls efficacy scale (all P<0.05) at the 12 month follow-up. The number of times an emergency ambulance was called because of a fall was significantly different during follow-up (incidence rate ratio 0.60, 95% confidence interval 0.40 to 0.92, P=0.018). CONCLUSION: A service to prevent falls in the community reduced the fall rate and improved clinical outcome in the high risk group of older people who call an emergency ambulance after a fall but are not taken to hospital. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67535605.

Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency.

INTRODUCTION: Vitamin D insufficiency is common, however within individuals, not all manifest the biochemical effects of PTH excess. This further extends to patients with established osteoporosis. The mechanism underlying the blunted PTH response is unclear but may be related to magnesium (Mg) deficiency. The aims of this study were to compare in patients with established osteoporosis and differing degrees of vitamin D and PTH status : (1) the presence of Mg deficiency using the standard Mg loading test (2) evaluate the effects of Mg loading on the calcium-PTH endocrine axis (3) determine the effects of oral, short term Mg supplementation on the calcium-PTH endocrine axis and bone turnover. METHODS: 30 patients (10 women in 3 groups) were evaluated prospectively measuring calcium, PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D, Mg) and bone turnover markers (serum CTX & P1CP). Multivariate analysis controlling for potential confounding baseline variable was undertaken for the measured outcomes. RESULTS: All subjects, within the low vitamin D and low PTH group following the magnesium loading test had evidence of Mg depletion [mean(SD) retention 70.3%(12.5)] and showed an increase in calcium 0.06(0.01) mmol/l [95% CI 0.03, 0.09, p=0.007], together with a rise in PTH 13.3 ng/l (4.5) [95% CI 3.2, 23.4, p=0.016] compared to baseline. Following oral supplementation bone turnover increased: CTX 0.16 (0.06) mcg/l [95%CI 0.01, 0.32 p=0.047]; P1CP 13.1 (5.7) mcg/l [95% CI 0.29, 26.6 p=0.049]. In subjects with a low vitamin D and raised PTH mean retention was 55.9%(14.8) and in the vitamin replete group 36.1%(14.4), with little change in both acute markers of calcium homeostasis and bone turnover markers following both the loading test and oral supplementation. CONCLUSIONS: This study confirms that in patients with established osteoporosis, there is also a distinct group with a low vitamin D and a blunted PTH level and that Mg deficiency (as measured by the Mg loading test) is an important contributing factor.

Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study.

OBJECTIVES: To evaluate postoperative medical complications and the association between these complications and mortality at 30 days and one year after surgery for hip fracture and to examine the association between preoperative comorbidity and the risk of postoperative complications and mortality. DESIGN: Prospective observational cohort study. SETTING: University teaching hospital. PARTICIPANTS: 2448 consecutive patients admitted with an acute hip fracture over a four year period. We excluded 358 patients: all those aged < 60; those with periprosthetic fractures, pathological fractures, and fractures treated without surgery; and patients who died before surgery. INTERVENTIONS: Routine care for hip fractures. MAIN OUTCOME MEASURES: Postoperative complications and mortality at 30 days and one year. RESULTS: Mortality was 9.6% at 30 days and 33% at one year. The most common postoperative complications were chest infection (9%) and heart failure (5%). In patients who developed postoperative heart failure mortality was 65% at 30 days (hazard ratio 16.1, 95% confidence interval 12.2 to 21.3). Of these patients, 92% were dead by one year (11.3, 9.1 to 14.0). In patients who developed a postoperative chest infection mortality at 30 days was 43% (8.5, 6.6 to 11.1). Significant preoperative variables for increased mortality at 30 days included the presence of three or more comorbidities (2.5, 1.6 to 3.9), respiratory disease (1.8, 1.3 to 2.5), and malignancy (1.5, 1.01 to 2.3). CONCLUSIONS: In elderly people with hip fracture, the presence of three or more comorbidities is the strongest preoperative risk factor. Chest infection and heart failure are the most common postoperative complications and lead to increased mortality. These groups offer a clear target for specialist medical assessment.

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis.

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.

Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study.

BACKGROUND: calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients. OBJECTIVE: to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients. DESIGN: a population-based, prospective cohort study. METHODS: 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry. RESULTS: at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01). CONCLUSION: there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.

The contribution of nutritional factors to osteopenia in the elderly.

Calcium and vitamin D deficiency increase age-related bone loss by causing secondary hyperparathyroidism. Reduced endogenous vitamin D synthesis exacerbates the problem of dietary deficiency and involves elderly people living in their own homes, who are just as much at risk as those living in institutionalized care. The effects of secondary hyperparathyroidism may be offset by hypercalcaemia of the increased bone turnover of immobility, which has a direct adverse effect on the skeleton causing osteoporosis. Active vitamin D analogues are effective in suppressing secondary hyperparathyroidism caused by vitamin D deficiency. However, simple deficiency is optimally treated with parent vitamin D, which has a greater safety margin than active vitamin D therapy (1,25 dihydroxyvitamin D), which requires close monitoring in the elderly.