Validation of forearm fracture diagnoses in administrative patient registers.

The validity of forearm fracture diagnoses recorded in five Norwegian hospitals was investigated using image reports and medical records as gold standard. A relatively high completeness and correctness of the diagnoses was found. Algorithms used to define forearm fractures in administrative data should depend on study purpose. PURPOSE: In Norway, forearm fractures are routinely recorded in the Norwegian Patient Registry (NPR). However, these data have not been validated. Data from patient administrative systems (PAS) at hospitals are sent unabridged to NPR. By using data from PAS, we aimed to examine (1) the validity of the forearm fracture diagnoses and (2) the usefulness of washout periods, follow-up codes, and procedure codes to define incident forearm fracture cases. METHODS: This hospital-based validation study included women and men aged ≥ 19 years referred to five hospitals for treatment of a forearm fracture during selected periods in 2015. Administrative data for the ICD-10 forearm fracture code S52 (with all subgroups) in PAS and the medical records were reviewed. X-ray and computed tomography (CT) reports from examinations of forearms were reviewed independently and linked to the data from PAS. Sensitivity and positive predictive values (PPVs) were calculated using image reports and/or review of medical records as gold standard. RESULTS: Among the 8482 reviewed image reports and medical records, 624 patients were identified with an incident forearm fracture during the study period. The sensitivity of PAS registrations was 90.4% (95% CI: 87.8-92.6). The PPV increased from 73.9% (95% CI: 70.6-77.0) in crude data to 90.5% (95% CI: 88.0-92.7) when using a washout period of 6 months. Using procedure codes and follow-up codes in addition to 6-months washout increased the PPV to 94.0%, but the sensitivity fell to 69.0%. CONCLUSION: A relatively high sensitivity of forearm fracture diagnoses was found in PAS. PPV varied depending on the algorithms used to define cases. Choice of algorithm should therefore depend on study purposes. The results give useful measures of forearm fracture diagnoses from administrative patient registers. Depending on local coding practices and treatment pathways, we infer that the findings are relevant to other fracture diagnoses and registers.

Impact of Total Hip Replacements on the Incidence of Hip Fractures in Norway During 1999-2019. A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) Study.

The knowledge about why hip fracture rates in Norway have declined is sparse. Concurrent with decreasing hip fracture rates, the rates of total hip replacements (THRs) have increased. We wanted to investigate if hip fracture rates continued to decline, and whether the increase in THRs had any influence on this decline, assuming that living with a hip prosthesis precludes fracture of the operated hip. Information on hip fractures in Norway 1999-2019 was available from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database and population size were available in official population tables from Statistics Norway. Primary THRs (for any cause except hip fracture) 1989-2019 were obtained from the Norwegian Arthroplasty Register. We calculated the annual age-standardized incidence rates of hip fracture by sex for the period 1999-2019. The hip fracture rates in a scenario with no hip prostheses were calculated by subtracting 0.5 persons from the population at risk for each prevalent hip prosthesis, considering that each person has two hips at risk of fracture. We estimated how much of the decline could be attributed to the increased prevalence of hip prostheses. From 1999 to 2019, age-standardized incidence rates of hip fracture decreased by 27% in women and 20% in men. The rates remained stable in those under 70 years and decreased in those 70 years and above. Excluding replaced hips from the population at risk led to higher incidence rates, and this impact was considerably larger at higher ages. The increased prevalence of hip prostheses over the period accounted for approximately 18% (20% in women and 11% in men) of the observed decline in hip fracture rates. In conclusion, the incidence of hip fractures continued to decline, and the increasing number of people living with hip prostheses contributed significantly to the observed declining time trends. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures.

The serum bone turnover markers (BTM) procollagen type 1 N-terminal propeptide (P1NP) and C-terminal cross-linking telopeptide of type 1 collagen (CTX) are recommended for monitoring adherence and response of antiresorptive drugs (ARD). BTM are elevated about 1 year after fracture and therefore BTM target values are most convenient in ARD treatment follow-up of fracture patients. In this prospective cohort study, we explored the cut-off values of P1NP and CTX showing the best discriminating ability with respect to adherence and treatment effects, reflected in bone mineral density (BMD) changes. Furthermore, we explored the ability of BTM to predict subsequent fractures and BTM variation during daytime in patients using ARD or not. After a fragility fracture, 228 consenting patients (82.2% women) were evaluated for ARD indication and followed for a mean of 4.6 years (SD 0.5 years). BMD was measured at baseline and after 2 years. Serum BTM were measured after 1 or 2 years. The largest area under the curve (AUC) for discrimination of patients taking ARD or not was shown for P1NP <30 µg/L and CTX <0.25 µg/L. AUC for discrimination of patients with >2% gain in BMD (lumbar spine and total hip) was largest at cut-off values for P1NP <30 µg/L and CTX <0.25 µg/L. Higher P1NP was associated with increased fracture risk in patients using ARD (hazard ratio [HR]logP1NP = 15.0; 95% confidence interval [CI] 2.7-83.3), p = 0.002. P1NP and CTX were stable during daytime, except in those patients not taking ARD, where CTX decreased by 21% per hour during daytime. In conclusion, P1NP <30 µg/L and CTX <0.25 µg/L yield the best discrimination between patients taking and not taking ARD and the best prediction of BMD gains after 2 years. Furthermore, higher P1NP is associated with increased fracture risk in patients on ARD. BTM can be measured at any time during the day in patients on ARD. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Associations of overweight, obesity and osteoporosis with ankle fractures.

BACKGROUND: Studies exploring risk factors for ankle fractures in adults are scarce, and with diverging conclusions. This study aims to investigate whether overweight, obesity and osteoporosis may be identified as risk factors for ankle fractures and ankle fracture subgroups according to the Danis-Weber (D-W) classification. METHODS: 108 patients ≥40 years with fracture of the lateral malleolus were included. Controls were 199 persons without a previous fracture history. Bone mineral density of the hips and spine was measured by dual-energy x-ray absorptiometry, and history of previous fracture, comorbidities, medication, physical activity, smoking habits, body mass index and nutritional factors were registered. RESULTS: Higher body mass index with increments of 5 gave an adjusted odds ratio (OR) of 1.30 (95% confidence interval (CI) 1.03-1.64) for ankle fracture, and an adjusted OR of 1.96 (CI 0.99-4.41) for sustaining a D-W type B or C fracture compared to type A. Compared to patients with normal bone mineral density, the odds of ankle fracture in patients with osteoporosis was 1.53, but the 95% CI was wide (0.79-2.98). Patients with osteoporosis had reduced odds of sustaining a D-W fracture type B or C compared to type A (OR 0.18, CI 0.03-0.83). CONCLUSIONS: Overweight increased the odds of ankle fractures and the odds of sustaining an ankle fracture with possible syndesmosis disruption and instability (D-W fracture type B or C) compared to the stable and more distal fibula fracture (D-W type A). Osteoporosis did not significantly increase the odds of ankle fractures, thus suffering an ankle fracture does not automatically warrant further osteoporosis assessment.

No association between osteoporosis and AO classification of distal radius fractures: an observational study of 289 patients.

BACKGROUND: It is mechanically plausible that osteoporosis leads to more severe peripheral fractures, but studies investigating associations between BMD and radiographically verified complexity of distal radius fractures are scarce. This study aims to study the association between osteoporosis, as well as other risk factors for fracture, and the AO classification of distal radius fractures. METHODS: In this observational study, 289 consecutive patients aged ≥40 years with a distal radius fracture were included. Bone mineral density (BMD) of the hips and spine was measured by dual-energy x-ray absorptiometry (DXA), and comorbidities, medication, physical activity, smoking habits, body mass index (BMI), and history of previous fracture were registered. The distal radius fractures were classified according to the Müller AO system (AO) (type B and C regarded as most complex). RESULTS: Patients with osteoporosis (n = 130) did not have increased odds of a more complex distal radius fracture (type B + C, n = 192)) (n = vs type A (n = 92) (OR 1.1 [95% CI 0.5 to 2.3]) compared to those with osteopenia /normal BMD (n = 159). Patients with AO fracture types A or C had a higher prevalence of osteoporosis than patients with type B fracture. CONCLUSIONS: Distal radius fracture patients with osteoporosis did not sustain more complex fractures than those with osteopenia/normal BMD according to the AO classification system. The AO classification of distal radius fracture cannot be used to decide which patients should be referred to DXA scan and considered for secondary fracture prevention.

Initiation of anti-osteoporotic drugs in high-risk female patients starting glucocorticoid treatment: a population study in Norway.

Glucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively. PURPOSE: Use of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis. METHODS: We used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010-2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses. RESULTS: Among 105,477 women initiating GC treatment during 2010-2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016. CONCLUSIONS: Having had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated.

Individual Variation in Adaptive Immune Responses and Risk of Hip Fracture-A NOREPOS Population-Based Cohort Study.

Immune-mediated bone loss significantly impacts fracture risk in patients with autoimmune disease, but to what extent individual variations in immune responses affect fracture risk on a population level is unknown. To examine how immune responses relate to risk of hip fracture, we looked at the individual variation in a post-vaccination skin test response that involves some of the immune pathways that also drive bone loss. From 1963 to 1975, the vast majority of the Norwegian adult population was examined as part of the compulsory nationwide Norwegian mass tuberculosis screening. These examinations included standardized tuberculin skin tests (TSTs). Our study population included young individuals (born 1940 to 1960 and aged 14 to 30 years at examination) who had all received Bacille Calmette-Guerin (BCG) vaccination after a negative TST at least 1 year prior and had no signs of tuberculosis upon clinical examination. The study population ultimately included 244,607 individuals, whose data were linked with a national database of all hospitalized hip fractures in Norway from 1994 to 2013. There were 3517 incident hip fractures during follow-up. Using a predefined Cox model, we found that men with a positive or a strong positive TST result had a 20% (hazard ratio [HR] = 1.20, 95% confidence interval [CI] 1.01-1.44) and 24% (HR = 1.24, 95% CI 1.03-1.49) increased risk of hip fracture, respectively, compared with men with a negative TST. This association was strengthened in sensitivity analyses. Total hip bone mineral density (BMD) was available for a limited subsample and similarly revealed a non-significantly reduced BMD among men with a positive TST. Interestingly, no such clear association was observed in women. An increased immune response after vaccination is associated with an increased risk of hip fracture decades later among men, possibly because of increased immune-mediated bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT.

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1-SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm2 ), total hip (800 versus 876 mg/cm2 ), and lumbar spine (1024 versus 1062 mg/cm2 ); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2-SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1-SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Monitoring children and adolescents with severe obesity: body mass index (BMI), BMI z-score or percentage above the International Obesity Task Force overweight cut-off?

AIM: Body mass index (BMI) metrics are widely used as a proxy for adiposity in children with severe obesity. The BMI expressed as the percentage of a cut-off percentile for overweight or obesity has been proposed as a better alternative than BMI z-scores when monitoring children and adolescents with severe obesity. METHODS: Annual changes in BMI, BMI z-score and the percentage above the International Obesity Task Force overweight cut-off (%IOTF-25) were compared with dual-energy X-ray absorptiometry (DXA) derived body fat (%BF-DXA) in 59 children and adolescents with severe obesity. RESULTS: The change in %BF-DXA was correlated with the change in %IOTF-25 (r = 0.68) and BMI (r = 0.70), and somewhat less with the BMI z-score (r = 0.57). Cohen's Kappa statistic to detect an increase or decrease in %BF-DXA was fair for %IOTF-25 (κ = 0.25; p = 0.04) and BMI (κ = 0.33; p = 0.01), but not for the BMI z-score (κ = 0.08; p = 0.5). The change in BMI was positively biased due to a natural increase with age. CONCLUSION: Changes in the BMI metrics included in the study are associated differently with changes in %BF-DXA. The BMI z-score is widely used to monitor changes in adiposity in children and adolescents with severe obesity, but the %IOTF-25 might be a better alternative.

Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors.

BACKGROUND: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. OBJECTIVE: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. METHODS: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. RESULTS: At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02). CONCLUSION: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.

High prevalence of vertebral fractures and low trabecular bone score in patients with fragility fractures: A cross-sectional sub-study of NoFRACT.

PURPOSE: Norway has among the highest incidence rates of fractures in the world. Vertebral fracture assessment (VFA) and trabecular bone score (TBS) provide information about fracture risk, but their importance have not been studied in Norwegian patients with fragility fractures. The objectives of this study were to examine the clinical characteristics of a cohort of women and men with fragility fractures, their prevalence of vertebral fractures using VFA and prevalence of low TBS, and explore the differences between the sexes and patients with and without vertebral fractures. METHODS: This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative (NoFRACT) included 839 patients with fragility fractures. Of these, 804 patients had bone mineral density (BMD) of the total hip, femoral neck and/or spine assessed using dual energy x-ray absorptiometry, 679 underwent concomitant VFA, 771 had TBS calculated and 696 responded to a questionnaire. RESULTS: Mean age was 65.8 (SD 8.8) years and 80.5% were women. VFA revealed vertebral fractures in 34.8% of the patients and 34.0% had low TBS (≤ 1.23), with no differences between the sexes. In all patients with valid measures of both VFA and TBS, 53.8% had either vertebral fractures, low TBS, or both. In the patients with osteopenia at the femoral neck, 53.6% had either vertebral fractures, low TBS, or both. Femoral neck BMD T-score ≤ -2.5 was found in 13.8% of all patients, whereas the corresponding figure was 27.4% using the skeletal site with lowest T-score. Women exhibited lower BMD at all sites and lower TBS than men (1.27 vs. 1.29), (all p < 0.05). Patients with prevalent vertebral fractures were older (69.4 vs. 64.0 years), exhibited lower BMD at all sites and lower TBS (1.25 vs.1.29) than those without vertebral fractures (all p < 0.05). Before assessment, 8.2% were taking anti-osteoporotic drugs (AOD), and after assessment, the prescription rate increased to 56.2%. CONCLUSIONS: More than half of the patients with fragility fractures had vertebral fractures, low TBS or both. The prescription of AOD increased seven fold from before assessment to after assessment, emphasizing the importance of risk assessment after a fragility fracture.

Total and lean fish intake is positively associated with bone mineral density in older women in the community-based Hordaland Health Study.

PURPOSE: Fish is a source of various nutrients beneficial for bone health, but few studies have investigated the association between bone mineral density (BMD) and fish consumption. Thus, the aim was to investigate the relationship between total fish intake and BMD and between both lean and fatty fish intake and BMD. METHOD: These cross-sectional analyses include 4656 participants in the Hordaland Health Study, a community-based study conducted in 1997-1999. The study includes two birth cohorts of men and women from Hordaland county (Norway) born in 1950-1951 and 1925-1927. BMD was measured by dual-energy X-ray absorptiometry and dietary intake was obtained from a semi-quantitative food-frequency questionnaire. RESULTS: The average total fish intake was 33 ± 18 g/1000 kcal and was primarily lean fish. Older women had significantly lower BMD than older men and middle-aged men and women. In older women, total and lean fish intake (50 g/1000 kcal) was significantly and positively associated with BMD also after multivariate adjustments (ß-coefficient 0.018, p = 0.017 and 0.026, p = 0.021). CONCLUSION: A high intake of fish, in particular lean fish, was positively associated with BMD in older women. No association between intake of fatty fish and BMD was found in either of the age and sex groups.

The Role of Comorbidity in Mortality After Hip Fracture: A Nationwide Norwegian Study of 38,126 Women With Hip Fracture Matched to a General-Population Comparison Cohort.

Hip fracture patients often have comorbid conditions. We investigated whether the combination of comorbidity and hip fracture could explain the previously observed excess mortality among hip fracture patients as compared with the general population. Using a population-based matched study design with 38,126 Norwegian women who suffered a hip fracture during the period 2009-2015 and the same number of women in a matched comparison cohort, we matched participants on prefracture comorbidity, age, and education. We estimated relative survival and additive and multiplicative comorbidity-hip fracture interactions. An additive comorbidity-hip fracture interaction of 4 or 9 additional deaths per 100 patients, depending on Charlson Comorbidity Index (CCI) score, was observed 1 year after hip fracture. Among women with a CCI score of ≥3, 15 additional deaths per 100 patients were observed; of these, 9 deaths could be attributed to the interaction and 6 to the hip fracture per se. On the relative scale, we observed increasing heterogeneity in survival by comorbidity over time; survival was reduced by 39% after 6 years among patients with a CCI score of ≥3, while among women with no comorbidity, survival was reduced by 17% (hip fracture vs. no hip fracture). In summary, prefracture comorbidity was associated with short-term absolute excess mortality and long-term relative excess mortality.

Effect of a Fracture Liaison Service on the Rate of Subsequent Fracture Among Patients With a Fragility Fracture in the Norwegian Capture the Fracture Initiative (NoFRACT): A Trial Protocol.

Importance: Fragility fracture is a major health issue because of the accompanying morbidity, mortality, and financial cost. Despite the high cost to society and personal cost to affected individuals, secondary fracture prevention is suboptimal in Norway, mainly because most patients with osteoporotic fractures do not receive treatment with antiosteoporotic drugs after fracture repair. Objectives: To improve secondary fracture prevention by introducing a standardized intervention program and to investigate the effect of the program on the rate of subsequent fractures. Design, Setting, and Participants: Trial protocol of the Norwegian Capture the Fracture Initiative (NoFRACT), an ongoing, stepped wedge cluster randomized clinical trial in 7 hospitals in Norway. The participating hospitals were cluster randomized to an intervention starting date: May 1, 2015; September 1, 2015; and January 1, 2016. Follow-up is through December 31, 2019. The outcome data were merged from national registries of women and men 50 years and older with a recent fragility fracture treated at 1 of the 7 hospitals. Discussion: The NoFRACT trial is intended to enroll 82 000 patients (intervention period, 26 000 patients; control period, 56 000 patients), of whom 23 578 are currently enrolled by January 2018. Interventions include a standardized program for identification, assessment, and treatment of osteoporosis in patients with a fragility fracture that is led by a trained coordinating nurse. The primary outcome is rate of subsequent fracture (per 10 000 person-years) based on national registry data. Outcomes before (2008-2015; control period) and after (2015-2019; intervention period) the intervention will be compared, and each hospital will act as its own control. Use of outcomes from national registry data means that all patients are included in the analysis regardless of whether they are exposed to the intervention (intention to treat). A sensitivity analysis with a transition window will be performed to mitigate possible within-cluster contamination. Results: Results are planned to be disseminated through publications in peer-reviewed journals and presented at local, national, and international conferences. Conclusions: By introducing a standardized intervention program for assessment and treatment of osteoporosis in patients with fragility fractures, we expect to document reduced rates of subsequent fractures and fracture-related mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02536898.

Positive predictive values of ICD-10 codes to identify incident acute pancreatitis and incident primary malignancy in the Scandinavian national patient registries among women with postmenopausal osteoporosis.

BACKGROUND: Validation of definitions used to identify conditions of interest is imperative to epidemiologic studies based on routinely collected data. The objective of the study was thus to estimate positive predictive values (PPVs) of International Classification of Diseases, 10th Revision (ICD-10) codes to identify cases of incident acute pancreatitis leading to hospitalization and incident primary malignancy in the Scandinavian (Denmark, Norway, and Sweden) national patient registries in women with postmenopausal osteoporosis (PMO). METHODS: This validation study included postmenopausal (defined as 55 years or older) women with osteoporosis, identified between 2005-2014. Potential cases were sampled based on ICD-10 codes from the three national patient registries. Cases were adjudicated by physicians, using medical record review as gold standard. PPVs with corresponding 95% CIs were computed. RESULTS: Medical records of 286 of 325 (retrieval rate 88%) women with PMO were available for adjudication. Acute pancreatitis leading to hospitalization had a PPV of 87.6% (95% CI: 80.8%-90.2%). Incident primary malignancy had a PPV of 88.1% (95% CI: 81.3%-92.7%). The PPVs did not vary substantially across the three countries. CONCLUSION: ICD-10 codes to identify acute pancreatitis leading to hospitalization, and incident primary malignancy in the Scandinavian national patient registries had high PPVs among women with PMO. This allows identification of cases of acute pancreatitis and incident primary malignancy with reasonable validity and to use these as outcomes in comparative analyses.

Positive predictive values of International Classification of Diseases, 10th revision codes for dermatologic events and hypersensitivity leading to hospitalization or emergency room visit among women with postmenopausal osteoporosis in the Danish and Swedish national patient registries.

BACKGROUND: Clinical epidemiology research studies, including pharmacoepidemiology and pharmacovigilance studies, use routinely collected health data, such as diagnoses recorded in national health and administrative registries, to assess clinical effectiveness and safety of treatments. We estimated positive predictive values (PPVs) of International Classification of Diseases, 10th revision (ICD-10) codes for primary diagnoses of dermatologic events and hypersensitivity recorded at hospitalization or emergency room visit in the national patient registries of Denmark and Sweden among women with postmenopausal osteoporosis (PMO). METHODS: This validation study included women with PMO identified from the Danish and Swedish national patient registries (2005-2014). Medical charts of the potential cases served as the gold standard for the diagnosis confirmation and were reviewed and adjudicated by physicians. RESULTS: We obtained and reviewed 189 of 221 sampled medical records (86%). The overall PPV was 92.4% (95% confidence interval [CI], 85.1%-96.3%) for dermatologic events, while the PPVs for bullous events and erythematous dermatologic events were 52.5% (95% CI, 37.5%-67.1%) and 12.5% (95% CI, 2.2%-47.1%), respectively. The PPV was 59.0% (95% CI, 48.3%-69.0%) for hypersensitivity; however, the PPV of hypersensitivity increased to 100.0% (95% CI, 67.6%-100.0%) when restricting to diagnostic codes for anaphylaxis. The overall results did not vary by country. CONCLUSION: Among women with PMO, the PPV for any dermatologic event recorded as the primary diagnosis at hospitalization or at an emergency room visit was high and acceptable for epidemiologic research in the Danish and Swedish national patient registries. The PPV was substantially lower for hypersensitivity leading to hospitalization or emergency room visit.

Airflow limitation as a risk factor for low bone mineral density and hip fracture.

AIM: To investigate whether airflow limitation is associated with bone mineral density (BMD) and risk of hip fractures. METHODS: A community sample of 5,100 subjects 47-48 and 71-73 years old and living in Bergen was invited. Participants filled in questionnaires and performed a post-bronchodilator spirometry measuring forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). All attendants were invited to have a BMD measurement of the hip. During 10 years of follow-up, information on death was collected from the Norwegian Cause of Death Registry, and incident hip fractures were registered from regional hospital records of discharge diagnoses and surgical procedure codes. RESULTS: The attendance rate was 69% (n=3,506). The prevalence of chronic obstructive pulmonary disease (COPD) (FEV1/FVC<0.7) was 9%. In multiple logistic regression, the lowest quartile of BMD versus the three upper was significantly predicted by FEV1/FVC<0.7 and FEV1% predicted (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.11 to 2.25, and OR per increase of 10%: 0.92, 95% CI: 0.86 to 0.99, respectively). Hip fracture occurred in 126 (4%) participants. In a Cox regression analysis, FEV1% predicted was associated with a lowered risk of hip fracture (hazard ratio per increase of 10%: 0.89, 95% CI: 0.79 to 0.997). CONCLUSION: Airflow limitation is positively associated with low BMD and risk of hip fracture in middle-aged and elderly.

1,25-dihydroxyvitamin D and the vitamin D receptor gene polymorphism Apa1 influence bone mineral density in primary hyperparathyroidism.

OBJECTIVE: Parathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT. DESIGN/SUBJECTS: We conducted a cross-sectional study of 52 patients with PHPT. RESULTS: Mean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)(2)D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)(2)D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine. CONCLUSIONS: The results suggest that PHPT patients with high blood concentrations of 1,25(OH)(2)D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)(2)D and possibly enhances the adverse effects on the skeleton in patients with PHPT.

Intake of vitamin K1 and K2 and risk of hip fractures: The Hordaland Health Study.

BACKGROUND: Evidence of the effect of vitamin K on bone health is conflicting. The aim was to investigate the association between intake of vitamins K1 and K2 and subsequent risk of hip fracture in a general population sample, as well as potential effect modification by apolipoprotein E gene (APOE) status by presence of the E4 allele. METHODS: 1238 men and 1569 women 71-75 years of age were included in the community-based Hordaland Health Study 1997-1999 in Western Norway. Information on hip fracture was obtained from hospitalizations in the region from enrolment until 31 December 2009. Information on intake of vitamins K1 and K2 collected at baseline was used as potential predictors of hip fracture in Cox proportional hazards regression analyses. RESULTS: Participants in the lowest compared to the highest quartile of vitamin K1 intake had increased risk of suffering a hip fracture (hazard ratio (HR)=1.57 [95% CI 1.09, 2.26]). Vitamin K2 intake was not associated with hip fracture. Presence of APOE4-allele did not increase the risk of hip fracture, nor was there any effect modification with vitamin K1 in relation to risk of hip fracture. CONCLUSIONS: A low intake of vitamin K1, but not K2, was associated with an increased risk of hip fractures.

Prevalence, disease manifestations, and treatment of psoriatic arthritis in Western Norway.

OBJECTIVE: To estimate the prevalence of psoriatic arthritis (PsA) in a geographically defined population, and to characterize the clinical manifestations and medical treatment for PsA. METHODS: Prevalent cases were identified for the years 1999-2002 at the rheumatology centers for the population of 442,000 inhabitants. Clinical data were extracted from patient records. Cases with psoriasis and peripheral arthritis and/or radiographic evidence of spondyloarthritis were considered to have PsA, those with other arthritides were excluded. RESULTS: In total, 634 patients with PsA were identified from the adult population, equivalent to a prevalence of 1.95 per 1000 (1.80-2.10). There were no significant sex differences in rates; for both sexes the prevalence was highest in the age group 40 to 59 years. Polyarthritis was the most frequent subclass (68.6%). Oligoarthritis, monoarthritis, and arthritis confined to the spine or sacroiliac joints were seen in 22.9%, 5.8%, and 2.7% of cases, respectively. Mean age was higher (50.6 yrs for all cases), and mean disease duration was longer (10.7 yrs) with increasing number of joints affected. The mean erythrocyte sedimentation rate and C-reactive protein were higher with increasing number of joints affected and disease duration. Intraarticular injection of glucocorticoids had been administered to 40.0% of the patients during the last year. Disease modifying antirheumatic drugs were used by 40.0%, with oral methotrexate being the most frequently used. CONCLUSION: The estimated prevalence of PsA was 1.95 per 1000 adult inhabitants, which is higher than previously reported. The demographic data support the presence of a shift from mono- and oligoarthritis to polyarthritis and increased inflammatory activity with increasing disease duration. Methotrexate and intraarticular glucocorticoids were frequently used treatments.