Trine Elisabeth Finnes

• Solbakken, Siri Marie; Meyer, Haakon Eduard; Dahl, Cecilie; Finnes, Trine Elisabeth; Hjellvik, Vidar & Nielsen, Christopher Sivert [Show all 9 contributors for this article] (2024). The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study. BMC Medicine. ISSN 1741-7015. 22(1), p. 1–9. doi: 10.1186/s12916-024-03335-w. Full text in Research Archive Show summary

  Background Few previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture. Methods Individual-level data on medications dispensed from pharmacies (2005–2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006–2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model. Results During 2006–2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1–5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21–25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51–65 years. Conclusions Rx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

• Strømmen, Ruth Cecilie; Godang, Kristin; Finnes, Trine Elisabeth; Smerud, Knut Terje; Reisæter, Anna Varberg & Hartmann, Anders [Show all 9 contributors for this article] (2023). Trabecular Bone Score Improves Early After Successful Kidney Transplantation Irrespective of Antiresorptive Therapy and Changes in Bone Mineral Density. Transplantation direct. ISSN 2373-8731. 10(1). doi: 10.1097/TXD.0000000000001566. Full text in Research Archive
• Koivisto-Mørk, Anu; Steffen, Kathrin; Finnes, Trine Elisabeth; Pretorius, Mikkel & Berge, Hilde Moseby (2023). High prevalence of low bone mineral density but normal trabecular bone score in Norwegian elite Para athletes. Frontiers in Sports and Active Living. ISSN 2624-9367. 5. doi: 10.3389/fspor.2023.1246828. Full text in Research Archive Show summary

  Background: Low bone mineral density (BMD) increases the risk of bone stress injuries (BSI) and is one of several clinical concerns in Para athlete sports medicine. However, whether bone microarchitecture is altered in Para athletes is not known. Objective: We aimed to investigate BMD, bone microarchitecture and incidence of bone stress injuries in Norwegian elite Para athletes. Design: In this cross-sectional study in Para athletes, Dual energy x-ray absorptiometry (iDXA, Lunar, GE Health Care) derived areal BMD, trabecular bone score (TBS), a surrogate marker for bone microarchitecture, and body composition (body weight (BW), lean body mass (LBM), fat mass (FM), fat percentage) were investigated and compared between ambulant and non-ambulant athletes. Also, the association between BMD, TBS and body composition variables was investigated. Incidence of BSI was assessed with a questionnaire and confirmed by a sports physician in a clinical interview. BMD Z-score <−1 was defined as low and ≤−2 as osteoporotic. TBS ≥ 1.31 was normal, 1.23–1.31 intermediate and <1.23 low. Results: Among 38 athletes (26 ± 6 yrs, 14 females), BMD Z-score was low in 19 athletes, and osteoporotic in 11 athletes' lumbar spine (LS) or femoral neck (FN). BMD was lower in non-ambulant vs. ambulant athletes both in LS (1.13 ± 0.19 vs. 1.25 ± 0.14 g/cm2, p = 0.030) and FN (0.90 ± 0.15 vs. 1.07 ± 0.16 g/cm2, p = 0.003). TBS was normal for all athletes. BMD Z-score in LS was positively associated with TBS (r = 0.408, p = 0.013), body weight (r = 0.326, p = 0.046) and lean body mass (r = 0.414, p = 0.010), but not with fat mass or fat percentage. None of the athletes reported any BSI. Conclusions: Half of the Norwegian elite Para athletes had low BMD, and 29% had BMD Z-score <−2 suggesting osteoporosis. Non-ambulant athletes were more prone to low BMD than ambulant athletes. However, despite high prevalence of low BMD, TBS was normal in all athletes, and BSI was absent in this young population.

• Sævik, Åse Bjorvatn; Ueland, Grethe Åstrøm; Åkerman, Anna-Karin; Methlie, Paal; Quinkler, Marcus & Jørgensen, Anders Palmstrøm [Show all 26 contributors for this article] (2023). Altered biomarkers for cardiovascular disease and inflammation in autoimmune Addison's disease - a cross-sectional study. European Journal of Endocrinology (EJE). ISSN 0804-4643. 189(4), p. 438–447. doi: 10.1093/ejendo/lvad136. Full text in Research Archive Show summary

  Increased prevalence of cardiovascular disease has been reported in autoimmune Addison's disease (AAD), but pathomechanisms are poorly understood. Design Cross-sectional study. Methods We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH. Results Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = −0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (−0.15 normalized protein expression [NPX], P = .0001, and −0.25 NPX, P = .0003, respectively). Conclusions We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small.

• Åkerman, Anna-Karin; Sævik, Åse Bjorvatn; Thorsby, Per Medbøe; Methlie, Paal; Quinkler, Marcus & Jørgensen, Anders Palmstrøm [Show all 26 contributors for this article] (2023). Plasma-Metanephrines in Patients with Autoimmune Addison’s Disease with and without Residual Adrenocortical Function. Journal of Clinical Medicine. ISSN 2077-0383. 12:3602(10), p. 1–10. doi: 10.3390/jcm12103602. Full text in Research Archive Show summary

  Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.

• Riska, Brit Solvor Lyse; Gunnes, Nina; Stigum, Hein; Finnes, Trine E.; Meyer, Haakon E. & Omsland, Tone K. [Show all 7 contributors for this article] (2023). Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). Osteoporosis International. ISSN 0937-941X. 34(8), p. 1369–1379. doi: 10.1007/s00198-023-06752-4. Full text in Research Archive Show summary

  We investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures. Purpose To investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index. Methods Norwegian women aged 50–89 in 2005–2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis. Results Of 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91–0.99) for bisphosphonate use and 0.60 (95% CI: 0.47–0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29–0.61) compared with the unexposed population. Conclusions In population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

• Holvik, Kristin; Ellingsen, Christian Lycke; Solbakken, Siri Marie; Finnes, Trine Elisabeth; Talsnes, Ove & Grimnes, Guri [Show all 9 contributors for this article] (2023). Cause-specific excess mortality after hip fracture: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). BMC Geriatrics. ISSN 1471-2318. 23(1). doi: 10.1186/s12877-023-03910-5. Full text in Research Archive Show summary

  Background: Information on cause of death may help appraise the degree to which the high excess mortality after hip fracture reflects pre-existing comorbidities or the injury itself. We aimed to describe causes of death and cause-specific excess mortality through the first year after hip fracture. Methods: For studying the distribution of causes of death by time after hip fracture, we calculated age-adjusted cause-specific mortality at 1, 3, 6 and 12 months in patients hospitalized with hip fracture in Norway 1999-2016. Underlying causes of death were obtained from the Norwegian Cause of Death Registry and grouped by the European Shortlist for Causes of Death. For estimating excess mortality, we performed flexible parametric survival analyses comparing mortality hazard in patients with hip fracture (2002-2017) with that of age- and sex matched controls drawn from the Population and Housing Census 2001. Results: Of 146,132 Norwegians with a first hip fracture, a total of 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (mainly the fall causing the fracture) were the underlying cause for 53.8% of deaths, followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioural disorders (2.0%) and diseases of the nervous system (1.3%). By one-year post-fracture, external causes and circulatory diseases together accounted for approximately half of deaths (26.1% and 27.0%, respectively). In the period 2002-2017, cause-specific one-year relative mortality hazard in hip fracture patients vs. population controls ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system in women, and correspondingly, from 2.4 to 5.3 in men. Conclusions: Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the most frequently reported underlying cause of death among older patients who survive less than one year after their fracture.

• Stokland, Ann-Elin Meling; Ueland, Grethe Åstrøm; Lima, Kari; Grønning, Kaja; Finnes, Trine Elisabeth & Svendsen, Margrethe [Show all 22 contributors for this article] (2022). Autoimmune Thyroid Disorders in Autoimmune Addison Disease. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 107(6), p. e2331–e2338. doi: 10.1210/clinem/dgac089. Full text in Research Archive Show summary

  Context: Autoimmune thyroid disease is the most common endocrine co-morbidity in autoimmune Addison's disease (AAD), but detailed investigations of prevalence and clinical course is lacking. Objective: Provide comprehensive epidemiological and clinical data on autoimmune thyroid disorders in AAD. Design and patients: A nationwide registry-based study including 442 patients with AAD and autoimmune thyroid disease, identified through the Norwegian National Registry of Autoimmune Diseases. Results: Of 912 registered AAD patients, 442 (48%) were diagnosed with autoimmune thyroid disease. Three hundred and eighty (42%) had autoimmune hypothyroidism. Of the 302 with available thyroid function tests at time for diagnosis, 20% had overt hypothyroidism, 73% had subclinical hypothyroidism and 7% had thyroid levels in the normal range. Negative thyroid peroxidase antibodies was found in 32%. Ninety-eight percent were treated with levothyroxine, 5% with combination therapy with liothyronine or thyroid extracts, and 1% were observed without treatment. Seventy-eight patients (9%) were diagnosed with Graves' disease (GD), of whom 16 (21%) were diagnosed with autoimmune hypothyroidism either before onset or after remission of GD. At the end of follow-up 33% had normal thyroid hormone levels without antithyroid-drugs or levothyroxine treatment. The remaining had either active disease (5%), had undergone ablative treatment (41%), or had developed autoimmune hypothyroidism (21%). Conclusion: The true prevalence of hypothyroidism in AAD is lower than reported in current literature. Careful consideration of the indication to start thyroxin therapy is warranted. Long-term remission rates in GD patients with AAD are comparable to recent reports on long-term follow-up of patients without AAD.

• Dahl, Jesper; Holvik, Kristin; Heldal, Einar; Grimnes, Guri; Hoff, Mari & Finnes, Trine [Show all 8 contributors for this article] (2020). Individual variation in adaptive immune responses and risk of hip fracture - A NOREPOS population-based cohort study. Journal of Bone and Mineral Research. ISSN 0884-0431. p. 1–8. doi: 10.1002/jbmr.4135. Full text in Research Archive
• Sævik, Åse Bjorvatn; Åkerman, Anna-Karin; Methlie, Paal; Quinkler, Marcus; Jørgensen, Anders Palmstrøm & Høybye, Charlotte [Show all 26 contributors for this article] (2020). Residual Corticosteroid Production in Autoimmune Addison Disease. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 105(7), p. 2430–2441. doi: 10.1210/clinem/dgaa256. Full text in Research Archive Show summary

  Design: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography–tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. Results: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = –0.487; P < 0.001). Conclusion: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life. (J Clin Endocrinol Metab 105: 1–12, 2020) Key words: Adrenal failure; adrenal steroids; Autoimmune Addison disease; cortisol; primary adrenal insufficiency; residual function

• Sævik, Åse Bjorvatn; Åkerman, Anna Karin; Grønning, Kaja; Nermoen, Ingrid; Valland, Susanna Fonneland & Finnes, Trine Elisabeth [Show all 22 contributors for this article] (2017). Clues for early detection of autoimmune Addison's disease - myths and realities. Journal of Internal Medicine. ISSN 0954-6820. 283(2), p. 190–199. doi: 10.1111/joim.12699.
• Finnes, Trine Elisabeth; Lofthus, Cathrine Marie; Meyer, Haakon E; Søgaard, Anne-Johanne; Tell, Grethe Seppola & Apalset, Ellen M [Show all 12 contributors for this article] (2016). A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study. Osteoporosis International. ISSN 0937-941X. 27(4), p. 1645–1652. doi: 10.1007/s00198-015-3435-0.
• Finnes, Trine Elisabeth; Lofthus, Cathrine Marie; Meyer, Haakon E.; Eriksen, Erik Fink; Apalset, Ellen M & Tell, Grethe S [Show all 9 contributors for this article] (2014). Procollagen type 1 amino-terminal propeptide (P1NP) and risk of hip fractures in elderly Norwegian men and women. A NOREPOS study. Bone. ISSN 8756-3282. 64, p. 1–7. doi: 10.1016/j.bone.2014.03.010. Show summary

  The current study aimed to assess a possible association between the bone turnover marker procollagen type 1 amino-terminal propeptide (P1NP) and future hip fractures in elderly Norwegian men and women and to elucidate the relation between P1NP, bone mineral density and 25-hydroxyvitamin D (25(OH)D). Men and women aged 71 to 77 from two population based health studies in Norway (1999-2001) were followed for a median period of 7.3years with respect to hip fractures. The study was designed as a case-cohort study. P1NP and 25(OH)D were analysed in frozen serum samples obtained at baseline in hip fracture patients (n=340) and in randomly selected sex stratified sub-cohorts. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) in a subset of participants. Cox proportional hazards regression with inverse probability weighting and robust variance was performed. No significant correlation between 25(OH)D and P1NP was found. A negative correlation between P1NP and BMD was observed in women (Rho=-0.36, p=0.001). A similar trend was observed in men. No association between quartiles of P1NP and rate of subsequent hip fractures was found. Spline analyses suggested a higher rate of hip fracture at P1NP levels above 60μg/L in both men and women. A higher hip fracture rate, which was independent of BMD, was also indicated in women with very low levels of P1NP.

• Finnes, Trine Elisabeth; Meyer, Haakon E; Falch, Jan Arvid; Medhus, Asle Wilhelm; Wentzel-Larsen, Tore & Lofthus, Cathrine Marie (2013). Secular reduction of excess mortality in hip fracture patients > 85 years. BMC Geriatrics. ISSN 1471-2318. 13. doi: 10.1186/1471-2318-13-25. Full text in Research Archive

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• Solbakken, Siri Marie; Meyer, Haakon Eduard; Dahl, Cecilie; Finnes, Trine Elisabeth; Hjellvik, Vidar & Nielsen, Christopher Sivert [Show all 9 contributors for this article] (2023). The medication-based Rx-Risk Comorbidity Index and risk of hip fracture. A nationwide NOREPOS cohort study. Norsk Epidemiologi, Supplement. ISSN 0803-4206. 31(1), p. 19–19.
• Finnes, Trine Elisabeth; Hjellvik, Vidar; Meyer, Haakon Eduard & Holvik, Kristin (2023). Atorvastatin dose is not associated with risk of hip fracture in men after adjustment for comorbidity: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). Aging Clinical and Experimental Research. ISSN 1594-0667.
• Holvik, Kristin; Ellingsen, Christian Lycke; Solbakken, Siri Marie; Finnes, Trine Elisabeth; Talsnes, Ove & Grimnes, Guri [Show all 9 contributors for this article] (2023). Correction to: Cause-specific excess mortality after hip fracture: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). BMC Geriatrics. ISSN 1471-2318. 23(1). doi: 10.1186/s12877-023-04013-x.
• Riska, Brit Solvor Lyse; Gunnes, Nina; Stigum, Hein; Finnes, Trine Elisabeth; Meyer, Haakon Eduard & Omsland, Tone Kristin [Show all 7 contributors for this article] (2022). Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture – a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). Norsk Epidemiologi, Supplement. ISSN 0803-4206. 30(1), p. 19–19. Show summary

  Introduction: Norway has a high hip fracture incidence. Bisphosphonates and denosumab have been shown to prevent hip fractures in clinical trials, but there is a lack of population studies. Aims: To investigate whether use of bisphosphonates and denosumab reduce the risk of first-time hip fracture in Norway when adjusting for morbidity by the medication-based Rx-Risk Comorbidity index. Methods: The population was defined as inhabitants identified in the national census of 2001 who were still alive and resident by 1 January 2005. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk score. Information on previous and incident hip fracture was available in the quality-assured NOREPOS hip fracture database. Persons 50 years or older were included starting from January 2005 and observed through December 2016. Sex-stratified Cox regression and flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years, or 31 December 2016, whichever occurred first). Rx-Risk score was included as a time-varying covariate, updated every two years. Other covariates were marital status, education, and time-varying use of bisphosphonates/denosumab with another indication than osteoporosis. Mean time to hip fracture within the observation period (restricted mean survival time) was estimated for the two different treatment exposures. Results: Of 1,044,661 women and 1,040,782 men, 74,775 (7.2%) and 13,417 (1.3%), respectively, were ever-exposed to either drug. Women exposed to bisphosphonates had a hazard ratio (HR) of 1.09 (95% CI: 1.05–1.13) for hip fracture (age as time-scale), while women exposed to denosumab had an HR of 0.68 (95% CI: 0.53–0.87). The corresponding fully adjusted HRs were 0.95 (95% CI: 0.91–0.99) and 0.58 (95% CI: 0.46–0.74) respectively. Exposure to either of the two drugs gave a longer hip fracture free period in women. For men exposed to either drug, the HRs was well above 1 – also when adjusted. Conclusions: In population-wide real-world data, women exposed to bisphosphonates had a hip fracture risk around the same level as the unexposed population after adjusting for comorbidity. Exposure to denosumab was associated with a lower risk of hip fracture in women.

• Eik-Nes, Sindre; Valland, Susanna Fonneland; Talsnes, Ove; Østlie, Kristin; Holvik, Kristin & Finnes, Trine Elisabeth (2022). Increasing overrepresentation of diabetes in non-traumatic lower limb amputations. Endocrine Abstracts. ISSN 1479-6848. doi: 10.1530/endoabs.81.P331. Show summary

  Background and Aim: Recent international studies indicate a secular decrease in the proportion of patients with diabetes who undergo lower limb amputations (LLA), and the same trend is observed in the national quality indicator. The validity of electronic databases and quality indicators are limited by multiple discharges and precision of coding. Furthermore, amputation codes included in the quality indicator do not include all amputations. We therefore aim to investigate the recent incidence of LLA in the catchment area of a middle-sized Norwegian hospital, and to compare it with data collected during 1990–99. Methodes: Medical records for all patients identified with LLA by the electronic discharge registers at Innlandet Hospital, Elverum, from 2013 through 2019 were retrieved. All codes for amputations and exarticulations were included, and amputations were verified by manual review by two of the authors. Traumatic and cancer-related amputations were excluded. Both minor and major amputations were included in further analyses. Diabetes was defined by the WHO criteria. The prevalence of diabetes was calculated using data from the Norwegian Prescription Database and Statistics Norway. Results: We identified 169 non-traumatic, non-cancer related amputations in 127 patients, of which 77 had diabetes. The proportion of amputees with diabetes had increased from 44% in the previous period to 61% in the recent data. Ten percent had type 1 diabetes compared to 4% during 1990–99. We estimated that 0.23% of individuals on antidiabetic drugs in the catchment area, underwent an amputation per year in the period 2013–19, compared to 0.31 % in 1990–99. The average absolute number of diabetics undergoing an LLA per year was 11 in both periods. Multiple amputations were common both in persons with and without diabetes and was present in 26% of the amputees, even though a high proportion in both groups underwent vascular surgery before amputation. Detailed information and further results will be provided. Conclusion: Our findings suggest that the proportion of diabetics among patients undergoing non-traumatic, non-cancer related lower limb amputations has increased over the past decades. Multiple amputations are still common, despite comprehensive preoperative investigations and other surgical interventions.

• Riska, Brit Solvor Lyse; Gunnes, Nina; Meyer, Haakon Eduard; Finnes, Trine Elisabeth; Omsland, Tone Kristin & Stigum, Hein [Show all 7 contributors for this article] (2022). Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture – a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).
• Holvik, Kristin; Ellingsen, Christian Lycke; Solbakken, Siri Marie; Finnes, Trine Elisabeth; Talsnes, Ove & Grimnes, Guri [Show all 9 contributors for this article] (2022). Causes of death and cause-specific excess mortality after hip fracture. The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). Show summary

  Background: A hip fracture is a serious injury particularly affecting older people with multimorbidity, and it is associated with high excess mortality. Information on causes of death may help appraise the degree to which this excess mortality reflects pre-existing comorbidities or the hip fracture trauma. We aimed to describe leading causes of excess mortality through the first year after a hip fracture. Methods: Information on all hospital-treated hip fractures in Norway 1999-2016 from the NOREPOS database were linked with age- and sex-matched population controls and the Norwegian Cause of Death Registry through 2017. Underlying causes of death were coded according to ICD-10 and grouped by the Eurostat shortlist. Results: Of 146,132 Norwegians with a first incident hip fracture, 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (usually the fall causing the fracture) were defined as the underlying cause for the majority of deaths (53.8%), followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioral disorders (2.0%) and diseases of the nervous system (1.3%). By one year post-fracture, external and circulatory causes together accounted for half of deaths (26.1% and 27.0%). When comparing cause-specific mortality (from causes other than external causes) after hip fracture with population controls, relative mortality risks in women ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system. Corresponding relative risks in men ranged from 2.4 for circulatory diseases to 5.3 for diseases of the nervous system. Early excess mortality (first month) was particularly high in all cause of death categories. Conclusion: Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the leading underlying cause of death the first year after the fracture, underlining the importance of preventing falls and fractures in older adults.

• Holvik, Kristin; Ellingsen, Christian Lycke; Solbakken, Siri Marie; Finnes, Trine Elisabeth; Talsnes, Ove & Grimnes, Guri [Show all 9 contributors for this article] (2022). Causes of death and cause-specific excess mortality after hip fracture. The Norwegian Epidemiologic Osteoporosis Studies (NOREPOS). Show summary

  Introduction: Hip fracture is a serious injury which affects older multimorbid patients and involves excess mortality. We aimed to describe leading causes of mortality through the first year after a hip fracture. Material and Methods: Hospital-treated hip fractures in Norway 1999-2016 were linked with age- and sex-matched population controls and the Norwegian Cause of Death Registry through 2017. Underlying causes of death were coded according to ICD-10 and grouped by the Eurostat shortlist. Results: Of 146,132 Norwegians with a first incident hip fracture, 35,498 (24.3%) died within one year. By 30 days post-fracture, external causes (usually the fall causing the fracture) were defined as the underlying cause for 53.8% of deaths, followed by circulatory diseases (19.8%), neoplasms (9.4%), respiratory diseases (5.7%), mental and behavioral disorders (2.0%) and diseases of the nervous system (1.3%). By one year post-fracture, external and circulatory causes together accounted for half of deaths (26.1% and 27.0%, respectively). For causes other than external causes, one-year relative mortality risks in hip fracture patients compared with population controls ranged from 1.5 for circulatory diseases to 2.5 for diseases of the nervous system in women. In men, the corresponding relative risks ranged from 2.4 for circulatory diseases to 5.3 for diseases of the nervous system. Conclusions: Hip fractures entail high excess mortality from all major causes of death. However, the traumatic injury of a hip fracture is the leading underlying cause of death the first year after the fracture, underlining the importance of preventing falls and fractures in older adults.

• Riska, Brit Solvor Lyse; Holvik, Kristin; Gunnes, Nina; Omsland, Tone Kristin; Stigum, Hein & Meyer, Haakon Eduard [Show all 7 contributors for this article] (2022). Risk of hip fracture in Norwegians using anti-osteoporosis medication. Show summary

  Introduction: Norway has a high hip fracture incidence. Clinical trials have demonstrated fracture-preventive effects of bisphosphonates (BPs) and denosumab (DMab). We aimed to investigate whether BPs and DMab used in the population of Norway reduce risk of first-time hip fracture when adjusting for morbidity. Material and methods: Demographic information from participants in the Population and Housing Census 2001 who were alive and resident by 1 January 2005 was linked with filled prescriptions in the Norwegian prescription database (2005-2016) and the NOREPOS hip fracture database. Persons 50 years and older were included starting from January 2005 and observed through December 2016. Sex-stratified time-to-event analysis was used with age as time scale and time-varying exposure to BPs and DMab. The medication-based Rx-Risk Comorbidity Index was added as a time-varying covariate. Other covariates were marital status, education, and exposure to BPs/DMab with another indication than osteoporosis. Results: Of 1,044,661 women and 1,040,782 men, 74,775 (7.2%) and 13,417 (1.3%), respectively, were ever-users. Age-adjusted hazard ratio (HR) of hip fracture in women was 1.20 (95 % CI: 1.15–1.26) when using BPs, and HR 0.74 (0.55–0.99) when using DMab. Fully adjusted HRs were 1.01 (0.96–1.06) and 0.62 (0.46–0.83) respectively. For men exposed to BPs, HR was well above 1 – also when adjusted. Conclusions: In population-wide real-world data, women exposed to BPs had a hip fracture risk around the same level as the unexposed population after adjusting for comorbidity. Exposure to DMab was associated with a lower risk of hip fracture in women.

• Solberg, Lene Bergendal; Borgen, Tove Tveitan; Bjørnerem, Åshild & Finnes, Trine Elisabeth (2021). Vil regjeringen ta beinskjørhet på alvor? [Newspaper]. Dagens Medisin.
• Finnes, Trine Elisabeth; Hjellvik, Vidar; Meyer, Haakon Eduard & Holvik, Kristin (2021). Are High-Dose Statin Users at Higher Risk of Hip Fractures? A Population-Wide Registry-Based Cohort Study from NOREPOS. Journal of Bone and Mineral Research. ISSN 0884-0431. 36(Suppl. 1), p. 306–306.
• Holvik, Kristin; Ellingsen, Christian Lycke; Solbakken, Siri Marie; Finnes, Trine Elisabeth; Talsnes, Ove & Grimnes, Guri [Show all 9 contributors for this article] (2020). Causes of death after hip fracture in Norway. Therapeutic Advances in Musculoskeletal Disease (TAMD). ISSN 1759-720X. 12, p. 51–52. doi: 10.1177/1759720X20969289.
• Grytaas, Marianne; Breivik, Lars Ertesvåg; Anders Palmstrøm, Jørgensen; Finnes, Trine Elisabeth; Skavlan, Lena Adriana Denstad & Wiik, Robert [Show all 8 contributors for this article] (2020). Medisinsk koding til besvær. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 14. doi: 10.4045/tidsskr.20.0541. Show summary

  Presis koding av sykdomsdiagnoser er viktig for god kvalitet i helsetjenestene. Kodingskvaliteten for primær binyrebarksvikt er for svak, noe som sannsynligvis ikke er unikt for denne diagnosen. Kodepraksis bør endres og profesjonaliseres

• Dahl, Jesper; Holvik, Kristin; Heldal, Einar; Grimnes, Guri; Hoff, Mari & Finnes, Trine Elisabeth [Show all 8 contributors for this article] (2019). Individual variation in adaptive immune responses and risk of hip fracture – A NOREPOS population-based cohort study. Journal of Bone and Mineral Research. ISSN 0884-0431. 34(suppl.)(2019 Annual Meeting of the ASBMR), p. 247–247. Show summary

  T-cell mediated immune responses may affect bone homeostasis, and subsequently the risk of fracture, through multiple pathways. Little is known about how individual variation in these responses contributes to the risk of fracture on a population-level. Tuberculin skin tests (TST) are likely one of the few tests directly reflecting in vivo T-cell responses to have been conducted on a population-scale, as part of the effort to prevent the spread of tuberculosis. The aim of this study was to estimate the impact of individual variation in these immune responses on the risk of hip fracture in the general population. The hypothesis was that individuals with a tendency towards pro-inflammatory responses have an increased risk of fracture.We used data from the compulsory nationwide Norwegian mass tuberculosis screening and BCG vaccination programme during 1963-1975, which covered an estimated 80-85% of the population. This data included results from standardized TST, as well as timing and status of BCG vaccination. Individuals aged 14-30 years at the time of TST measurement and born 1940-1960 were included in the current analysis. All included individuals had a negative TST followed by BCG vaccination in the past, and had no signs of tuberculosis upon examination. TST results at the screening were recorded in millimetres, and later categorized according to clinical guidelines (positive/negative). Our cohort constitutes 248 551 individuals who were alive and living in Norway at the start of the NORHIP database in 1994. This database includes records on all hospitalizations due to hip fractures in Norway during 1994-2013 (follow-up). Risk estimates were adjusted for county, BMI, age and time between BCG-TST, using Cox regression models. There were 3580 incident hip fractures during follow-up (first fractures), with a median age at the time of fracture of 61 years (range 36-73). Men with a positive TST had a 22% (HR 1.22, 95% CI 1.02-1.44) increased adjusted risk of hip fracture compared to men with a negative TST. This association was strengthened in sensitivity analyses limited to either those born 1945-1960 (post WW2) or aged 11-14 years at BCG vaccination (school vaccination). No clear association was observed in women. We conclude that men with a negative tuberculin skin test after BCG vaccination have a reduced risk of hip fracture decades later. Women do not demonstrate similar associations, potentially due to sex specific differences in immune responses.

• Finnes, Trine Elisabeth; Lofthus, Cathrine Marie; Søgaard, Anne-Johanne; Tell, Grethe Seppola; Apalset, Ellen M & Gjesdal, Clara Gram [Show all 12 contributors for this article] (2015). Low serum vitamin K1 increases the risk of hip fractures only at low vitamin D status. A NOREPOS study. European Geriatric Medicine. ISSN 1878-7649. 6, p. S17–S17.
• Dahl, Cecilie; Søgaard, Anne Johanne; Tell, Grethe S; Flaten, Trond Peder; Hongve, Dag & Omsland, Tone Kristin [Show all 10 contributors for this article] (2013). Do cadmium and lead in drinking water increase the risk of hip fracture? A NOREPOS study.
• Finnes, Trine Elisabeth; Lofthus, Cathrine Marie; Meyer, Haakon E; Eriksen, Erik Fink; Apalset, Ellen M & Tell, Grethe S [Show all 7 contributors for this article] (2013). Serum Levels of Procollagen type 1 Amino-terminal Propeptide and Risk of Hip Fracture in Elderly Men. Norwegian Epidemiologic Osteoporosis Studies (NOREPOS).
• Finnes, Trine Elisabeth; Meyer, Haakon E; Falch, Jan Arvid; Medhus, Asle Wilhelm; Wentzel-Larsen, Tore & Lofthus, Cathrine Marie (2012). DURATION OF EXCESS MORTALITY AFTER HIP FRACTURES IN OSLO, NORWAY: A LONG TERM FOLLOW UP. Osteoporosis International. ISSN 0937-941X. 23, p. S123–S124.

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