The Association Between Older Age, Co-Morbidity, and Treatment Status of Incident Osteoporotic Fractures: A Population-Based Nested Cohort Study

I attended and presented a poster at the International Symposium on Osteoporosis hosted by the National Osteoporosis Foundation in Las Vegas, NV. This was a very well attended conference with over 800 attendees including clinicians and researchers interested / working in the area of osteoporosis. The research I presented was well received and added to the body of knowledge related to osteoporosis and treatment of new fractures. Attending this conference allowed me to meet other researchers with similar research interests and I look forward to possible collaborations in the future.BACKGROUND: Despite strong evidence-based rationale for both the primary and secondary prevention of osteoporosis, there remains an overall low prevalence of osteoporosis treatment in older adults. Furthermore, there is some question whether low treatment rates in older adults are simply age related variations (in treatments) or due to the presence of co-morbid conditions. Therefore, we sought to examine the association between older age, co-morbidity, and the use of osteoporosis medications following an incident osteoporosis related fracture. METHODS: We performed a retrospective nested cohort analysis using de-identified administrative healthcare data from the province of British Columbia, Canada (pop. 4.1 million). We included patients 65 years and older, who had continuous enrollment in the provinces’ prescription drug plan, with a study-defined osteoporosis-related fracture during the study period of April 1, 1999 to March 31, 2002. A multivariate logistic regression model was used to examine the association between the dependent variable - osteoporosis medication dispensation within six months of index fracture and the predictor variables - age, sex, co-morbidity, fracture site, year of fracture, health region, and osteoporosis treatment prior to the index fracture. RESULTS: After exclusion criteria were applied, we identified 11,870 consecutive patients who had been hospitalized with 12,025 incident (study-defined) fractures during the study period. The mean age of the sample was 81.1 years (SD 7.7; range 65–104 years), and 74% of the subjects were women. The majority of patients (99%) sustained one fracture (range 1 to 4); the fractures were predominately of the hip (63%) followed by fractures of the wrist (17%), pelvis (9%), vertebra (7%), and ribs (4%). The majority of subjects had no co-morbid conditions or only one (63%); 31% had two to three co-morbidities, and 6% had four or more co-morbid conditions. Overall, there was a low rate of osteoporosis treatment before the incident fracture (15% treatment); this rate improved to 19% at six months post fracture. Those receiving treatment after the index fracture were significantly younger, more often female, and had fewer co-morbid conditions (P < .001). The use of an osteoporosis medication prior to the index fracture was the strongest predictor of post-fracture treatment (adjusted OR = 15.89; 95% CI = 9.69–26.04). Increasing age, more than one co-morbid condition, and male sex were all associated with a significant decrease in the likelihood of dispensing osteoporosis drugs when compared to younger and healthier women. CONCLUSION: Despite the wide availability of osteoporosis medications, our findings suggest that the majority of older adults, many of who have at least one co-morbid condition, are not receiving treatment to prevent the progression of the disease and to prevent further fractures

Physical trauma and risk of multiple sclerosis: A systematic review and meta-analysis of observational studies

AbstractBackgroundWe aimed to examine physical trauma as a risk factor for the subsequent diagnosis of MS.MethodsWe searched for observational studies that evaluated the risk for developing MS after physical trauma that occurred in childhood (≤20years) or “premorbid” (>20years). We performed a meta-analysis using a random effects model.ResultsWe identified 1362 individual studies, of which 36 case–control studies and 4 cohort studies met the inclusion criteria for the review. In high quality case–control studies, there were statistically significant associations between those sustaining head trauma in childhood (OR=1.27; 95% CI, 1.12–1.44; p<0.001), premorbid head trauma (OR=1.40; 95% CI, 1.08–1.81; p=0.01), and other traumas during childhood (OR=2.31; 95% CI, 1.06–5.04; p=0.04) and the risk of being diagnosed with MS. In lesser quality studies, there was a statistical association between “other traumas” premorbid and spinal injury premorbid. No association was found between spinal injury during childhood, or fractures and burns at any age and the diagnosis of MS. The pooled OR of four cohort studies looking at premorbid head trauma was not statistically significant.ConclusionsThe result of the meta-analyses of high quality case–control studies suggests a statistically significant association between premorbid head trauma and the risk for developing MS. However, cohort studies did not. Future prospective studies that define trauma based on validated instruments, and include frequency of traumas per study participant, are needed

Inhaled magnesium sulfate in the treatment of acute asthma.

BACKGROUND: Asthma exacerbations can be frequent and range in severity from mild to life-threatening. The use of magnesium sulfate (MgSO₄) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO₄ has been demonstrated, the role of inhaled MgSO₄ is less clear. OBJECTIVES: To determine the efficacy and safety of inhaled MgSO₄ administered in acute asthma. SPECIFIC AIMS: to quantify the effects of inhaled MgSO₄ I) in addition to combination treatment with inhaled β₂-agonist and ipratropium bromide; ii) in addition to inhaled β₂-agonist; and iii) in comparison to inhaled β₂-agonist. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Group register of trials and online trials registries in September 2017. We supplemented these with searches of the reference lists of published studies and by contact with trialists. SELECTION CRITERIA: RCTs including adults or children with acute asthma were eligible for inclusion in the review. We included studies if patients were treated with nebulised MgSO₄ alone or in combination with β₂-agonist or ipratropium bromide or both, and were compared with the same co-intervention alone or inactive control. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial selection, data extraction and risk of bias. We made efforts to collect missing data from authors. We present results, with their 95% confidence intervals (CIs), as mean differences (MDs) or standardised mean differences (SMDs) for pulmonary function, clinical severity scores and vital signs; and risk ratios (RRs) for hospital admission. We used risk differences (RDs) to analyse adverse events because events were rare. MAIN RESULTS: Twenty-five trials (43 references) of varying methodological quality were eligible; they included 2907 randomised patients (2777 patients completed). Nine of the 25 included studies involved adults; four included adult and paediatric patients; eight studies enrolled paediatric patients; and in the remaining four studies the age of participants was not stated. The design, definitions, intervention and outcomes were different in all 25 studies; this heterogeneity made direct comparisons difficult. The quality of the evidence presented ranged from high to very low, with most outcomes graded as low or very low. This was largely due to concerns about the methodological quality of the included studies and imprecision in the pooled effect estimates. Inhaled magnesium sulfate in addition to inhaled β₂-agonist and ipratropiumWe included seven studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, results were inconsistent overall and the largest study reporting this outcome found no between-group difference at 60 minutes (MD -0.3 % predicted peak expiratory flow rate (PEFR), 95% CI -2.71% to 2.11%). Admissions to hospital at initial presentation may be reduced by the addition of inhaled magnesium sulfate (RR 0.95, 95% CI 0.91 to 1.00; participants = 1308; studies = 4; I² = 52%) but no difference was detected for re-admissions or escalation of care to ITU/HDU. Serious adverse events during admission were rare. There was no difference between groups for all adverse events during admission (RD 0.01, 95% CI -0.03 to 0.05; participants = 1197; studies = 2). Inhaled magnesium sulfate in addition to inhaled β₂-agonistWe included 13 studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, none of the pooled results showed a conclusive benefit as measured by FEV1 or PEFR. Pooled results for hospital admission showed a point estimate that favoured the combination of MgSO₄ and β₂-agonist, but the confidence interval includes the possibility of admissions increasing in the intervention group (RR 0.78, 95% CI 0.52 to 1.15; participants = 375; studies = 6; I² = 0%). There were no serious adverse events reported by any of the included studies and no between-group difference for all adverse events (RD -0.01, 95% CI -0.05 to 0.03; participants = 694; studies = 5). Inhaled magnesium sulfate versus inhaled β₂-agonistWe included four studies in this comparison. The evidence for the efficacy of β₂-agonists in acute asthma is well-established and therefore this could be considered a historical comparison. Two studies reported a benefit of β₂-agonist over MgSO₄ alone for PEFR and two studies reported no difference; we did not pool these results. Admissions to hospital were only reported by one small study and events were rare, leading to an uncertain result. No serious adverse events were reported in any of the studies in this comparison; one small study reported mild to moderate adverse events but the result is imprecise. AUTHORS' CONCLUSIONS: Treatment with nebulised MgSO₄ may result in modest additional benefits for lung function and hospital admission when added to inhaled β₂-agonists and ipratropium bromide, but our confidence in the evidence is low and there remains substantial uncertainty. The recent large, well-designed trials have generally not demonstrated clinically important benefits. Nebulised MgSO₄ does not appear to be associated with an increase in serious adverse events. Individual studies suggest that those with more severe attacks and attacks of shorter duration may experience a greater benefit but further research into subgroups is warranted.Despite including 24 trials in this review update we were unable to pool data for all outcomes of interest and this has limited the strength of the conclusions reached. A core outcomes set for studies in acute asthma is needed. This is particularly important in paediatric studies where measuring lung function at the time of an exacerbation may not be possible. Placebo-controlled trials in patients not responding to standard maximal treatment, including inhaled β₂-agonists and ipratropium bromide and systemic steroids, may help establish if nebulised MgSO₄ has a role in acute asthma. However, the accumulating evidence suggests that a substantial benefit may be unlikely

Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all

The Association Between Dementia Status, Co-morbidity, and Osteoporosis Treatment: A Population-Based Nested Case-Control Study

Using administrative healthcare data, we examined the association between dementia, co-morbidity, and the prescription of osteoporosis medications among community-dwelling older adults. We found that despite the availability of osteoporosis medications, the majority of patients with a concurrent diagnosis of dementia and osteoporosis did not receive treatment to prevent osteoporosis complications.BACKGROUND: Increasing age and a diagnosis of dementia both dramatically increase the risk of serious osteoporosis related sequela. At the same time, there remains an overall low rate of osteoporosis treatment particularly in older, frail adults despite the availability of effective antiresorptive treatments such as bisphosphonate drugs. In addition, the frequency in which community dwelling persons with dementia are treated with osteoporosis medications has not been well described. Furthermore, existing literature does not adequately delineate whether the low treatment rates are simply age related variations (in treatments) or due to the presence of co-morbid conditions, particularly dementia. METHODS: We performed a retrospective population based nested case-control study using de-identified administrative healthcare data from a Canadian province (pop. 4.1 million). We included patients 65 years and older, with a diagnosis of osteoporosis, who had continuous prescription drug coverage during the study period of 1991 to 2007. A multivariate logistic regression model was assembled to examine the relationship between osteoporosis medication dispensation and dementia status while controlling for age, sex, co-morbidity, and residence. RESULTS: We included 39,452 patients in the osteoporosis cohort; the mean age of the sample was 80.1 years (SD 7.5; range 65–104 years), 79% of the subjects were female, and 34% had a dementia diagnosis. Only 5% of the sample had no co-morbid conditions; the majority of patients (52%) had at least 3 co-morbid conditions (SD 2.0; range 0–12 conditions). When stratified by dementia status, there were significant differences in age, frequency of co-morbidity, and residence by health region (P < .001) and sex (P < .05). Almost half of the total osteoporosis cohort were dispensed an osteoporosis medication during the study period (43%; P < .001). Those who had been dispensed drug treatment were more often younger, female, and had no diagnosis of dementia (P < .001). Drug dispensation was directly related to the frequency of co-morbid conditions; those with 4 or more conditions were dispensed treatment significantly more often (54%) than those with fewer co-morbid conditions (P < .001). A diagnosis of dementia was a significant negative predictor of drug dispensation (adjusted OR = 0.55; 95% CI = 0.44–0.69). Increasing age, male sex, and a more remote residence were all associated with a significant decrease in the likelihood of treatment. Increasing co-morbidity was significantly associated with receiving treatment (adjusted OR = 3.30; 95% CI = 2.88–3.78). CONCLUSION: Despite the wide availability of osteoporosis medications, our findings suggest that the majority of older adults with a diagnosis of dementia, but not necessarily fewer co-morbid conditions, are not receiving treatment to prevent progression of the disease including fragility fractures

Calcitonin for Treating Acute and Chronic Pain of Recent and Remote Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta Analysis

I attended and presented a poster at the joint conference of the International Society of Bone Densitometry and the National Osteoporosis Foundation in San Antonio, Texas. This was a very well attended conference with over 800 attendees including clinicians and researchers interested / working in the area of osteoporosis. The research I presented was well received and added to the body of knowledge related to osteoporosis and the non-narcotic treatment of fracture pain. Attending this conference allowed me to meet other researchers with similar research interests and I look forward to possible collaborations in the future.Background: Vertebral collapse is one of the most common fractures associated with osteoporosis. The subsequent back pain may be severe and often requires medications and bed rest to control pain and improve mobilization. Recent studies have suggested the use of calcitonin as an initial and adjunctive treatment for severe, unrelenting back pain secondary to an osteoporotic vertebral compression fracture (OVCF), as it exhibits known analgesic properties and does not produce the unpleasant side effects associated with narcotics. Therefore, we sought to determine the analgesic efficacy of calcitonin for the treatment of acute or chronic back pain in stable patients sustaining a recent or remote OVCF. Methods: We searched the Cochrane Musculoskeletal Group (CMSG) specialized trial register , the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and other databases and conference proceedings up until June 2009. Primary study authors and pharmaceutical manufacturers were contacted, and bibliographies of relevant papers were hand searched. We included randomized, placebo, and controlled trials that evaluated the analgesic efficacy of calcitonin on pain levels in people with acute or chronic back pain attributed to OVCFs. Two reviewer’s extracted data, scored trial quality, preformed numeric calculations, and extrapolated graphical data independently. Where appropriate, we calculated mean differences, standardized mean differences, or risk ratios using a fixed or random effects model. Results: The combined results from 13 controlled trials, involving 589 patients, determined that calcitonin significantly reduced the severity of acute pain in recent OVCFs. Pain at rest was reduced as early as one week (MD -3.42; 95% CI: -3.96, -2.88) and this effect continued weekly to four weeks (MD -4.49; 95% CI: -4.96, -4.03). A similar pattern was seen for pain scores with mobility; at week 4 the difference in pain scores between groups was even more profound (SMD -5.99; 95% CI: -6.78, -5.19). When chronic back pain of a more remote OVCF was examined with patients at rest, there was no statistical difference between groups. When the same patients were assessed while mobile at six months, there was a statistically significant difference between groups (SMD -0.49; 95% CI: -0.85, -0.13; P = 0.008). Side effects were generally mild and self-limiting with enteric disturbances (47%) and flushing (32%) reported most frequently. Conclusions: Calcitonin has proven efficacy in the management of acute back pain associated with a recent OVCF and improves the quality of life by shortening time to mobilization. Although there was a slight improvement in back pain for patients with chronic pain at six months, this is unlikely to be of clinical significance. Therefore, there is no convincing evidence to support the use of calcitonin for the chronic pain associated with remote fractures of the same origin