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Epidemiological aspects of drug-related vitamin D deficiency and osteoporotic fractures
Linnaeus University, Faculty of Health and Life Sciences, Department of Medicine and Optometry. Linnaeus University, Linnaeus Knowledge Environments, Sustainable Health.ORCID iD: 0000-0003-2149-8998
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Sustainable development
SDG 3: Ensure healthy lives and promote well-being for all at all ages
Abstract [en]

Background: Vitamin D deficiency, secondary osteoporosis and low-energy fractures (LEF) as side effects of specific drugs were first described more than half a century ago. These effects are recognized in guidelines where patients prescribed risk drugs are recommended follow-up with testing and supplementation. How these drugs are managed within Swedish healthcare has not been previously investigated. 

Aim: To study epidemiological aspects of drug-related vitamin D deficiency and osteoporotic fractures.

Methods: The association between drugs for continual use and vitamin D levels in the elderly was investigated in a clinical study including more than 550 patients (paper I). Real-world data on drug prescriptions, laboratory testing and demographic variables from electronic health records were thereafter used to assess the clinical management and vitamin D levels. More than 12 000 patients prescribed risk drugs were included in this cross-sectional study (paper II). Focus group interviews were then undertaken to explore determinants of risk drug management among physicians from seven primary care centers. Thematic analysis with an inductive approach was used to create a framework addressing adherence to medical guidelines (paper III). Finally, a multifactorial risk assessment tool was developed from LEF risk factors in more than    15 000 patients prescribed antiepileptic risk drugs in a retrospective open cohort study (paper IV).

Results: A weak inverse association between the number of prescribed drugs and levels of vitamin D was found (paper I). Fewer than one in fifteen patients prescribed risk drugs were tested for vitamin D while close to a third were supplemented. Differences in management and vitamin D levels with regard to type of risk drug were found (paper II). Awareness levels, expressed beliefs and perceived responsibility were reasons behind these differences (paper III). The Kalmar Epilepsy Fracture Risk Index (KEFRI) confirmed previously suggested risk factors (paper IV). 

Conclusions: Drugs generating vitamin D deficiency, secondary osteoporosis and LEF are often overlooked in healthcare. Awareness and attitudes need to be improved and strategies to better manage patients prescribed these drugs are required in order to avoid unnecessary side effects. The KEFRI could aid clinicians in treatment decisions, potentially reducing fracture risks in specific patient groups. 

Place, publisher, year, edition, pages
Växjö: Linnaeus University Press, 2022. , p. 51
Series
Linnaeus University Dissertations ; 466/2022
Keywords [en]
vitamin D, secondary osteoporosis, fractures, drug risk management, medical guideline adherence, electronic health records, real-world data, risk assessment, awareness, attitudes, personalised medicine, cross-sectional study, cohort study, qualitative analysis, thematic analysis, pharmacoepidemiology
National Category
Social and Clinical Pharmacy
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-116844DOI: 10.15626/LUD.466.2022ISBN: 9789189709430 (print)ISBN: 9789189709447 (electronic)OAI: oai:DiVA.org:lnu-116844DiVA, id: diva2:1703273
Public defence
2022-11-11, Aula Sienna, Universitetsplatsen 1, Kalmar, 13:00 (Swedish)
Opponent
Supervisors
Funder
The Kamprad Family FoundationMedical Research Council of Southeast Sweden (FORSS)Available from: 2022-10-13 Created: 2022-10-12 Last updated: 2024-03-12Bibliographically approved
List of papers
1. Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden
Open this publication in new window or tab >>Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden
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2016 (English)In: Nutrients, E-ISSN 2072-6643, Vol. 8, no 11, article id 717Article in journal (Refereed) Published
Abstract [en]

Controversy pervades the definition of adequate and optimal vitamin D status. The Institutes of Medicine have recommended serum 25(OH) D levels above 50 nmol/L based upon evidence related to bone health, but some experts, including the Endocrine Society and International Osteoporosis Foundation, suggest a minimum serum 25(OH) D level of 75 nmol/L to reduce the risk of falls and fractures in older adults. In a cross-sectional study, we compared vitamin D status in people >= 75 years selected from four groups with a frailty phenotype, combined with a control group free from serious illness, and who considered themselves completely healthy. Only 13% of the 169 controls were vitamin D deficient (S-25(OH) D) < 50 nmol/L), in contrast with 49% of orthopedic patients with hip fractures (n = 133), 31% of stroke patients (n = 122), 39% of patients visiting the hospital's emergency department >= 4 times a year (n = 81), and 75% of homebound adult residents in long-term care nursing homes (n = 51). The mean vitamin D concentration of the healthy control group (74 nmol/L) was similar to a suggested optimal level based on physiological data and mortality studies, and much higher than that of many officially recommended cut-off levels for vitamin D deficiency (< 50 nmol/L). The present study provides a basis for planning and implementing public guidelines for the screening of vitamin D deficiency and vitamin D treatment for frail elderly patients.

Keywords
vitamin D, 25-hydroxyvitamin D, Sweden, emergency care, frail older adult
National Category
Nutrition and Dietetics
Research subject
Natural Science, Medicine
Identifiers
urn:nbn:se:lnu:diva-59470 (URN)10.3390/nu8110717 (DOI)000388666400051 ()2-s2.0-84995616155 (Scopus ID)
Available from: 2016-12-23 Created: 2016-12-23 Last updated: 2024-07-02Bibliographically approved
2. Adherence to risk management guidelines for drugs which cause vitamin D deficiency – big data from the Swedish health system
Open this publication in new window or tab >>Adherence to risk management guidelines for drugs which cause vitamin D deficiency – big data from the Swedish health system
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2019 (English)In: Drug, Healthcare and Patient Safety, E-ISSN 1179-1365, Vol. 11, p. 19-28Article in journal (Refereed) Published
Abstract [en]

Purpose: Several medications are known to cause vitamin D deficiency. The aim of this study is to describe vitamin D testing and supplementation in patients using these “risk medications”, thereby assessing adherence to medical guidelines.Patients and methods: A database with electronic health records for the population in a Swedish County (≈240,000 inhabitants) was screened for patients prescribed the pre-defined “risk medications” during a 2-year period (2014–2015). In total, 12,194 patients were prescribed “risk medications” pertaining to one of the three included pharmaceutical groups. Vitamin D testing and concomitant vitamin D supplementation, including differences between the included pharmaceutical groups, was explored by matching personal identification numbers.Results: Corticosteroids were prescribed to 10,003 of the patients, antiepileptic drugs to 1,101, and drugs mainly reducing vitamin D uptake to 864. Two hundred twenty-six patients were prescribed >1 “risk medication”. Seven hundred eighty-seven patients (6.5%) had been tested during the 2-year period. There were no differences regarding testing frequency between groups. Concomitant supplements were prescribed to 3,911 patients (32.1%). It was more common to be prescribed supplements when treated with corticosteroids. Vitamin D supplementation was more common among tested patients in all three groups. Women were tested and supplemented to a higher extent. The mean vitamin D level was 69 nmol/L. Vitamin D deficiency was found in 24.1% of tested patients, while 41.3% had optimal levels. It was less common to be deficient and more common to have optimal levels among patients prescribed corticosteroids.Conclusion: Adherence to medical guidelines comprising testing and supplementation of patients prescribed drugs causing vitamin D deficiency needs improvement in Sweden.

Place, publisher, year, edition, pages
Dove Medical Press Ltd, 2019
National Category
Pharmaceutical Sciences
Research subject
Biomedical Sciences, Pharmacology
Identifiers
urn:nbn:se:lnu:diva-81355 (URN)10.2147/DHPS.S188187 (DOI)000462173500001 ()2-s2.0-85073038615 (Scopus ID)
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2024-01-09Bibliographically approved
3. A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs
Open this publication in new window or tab >>A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs
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2021 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 8, article id e0256093Article in journal (Refereed) Published
Abstract [en]

Objective: To develop an index assessing the risks of low energy fractures (LEF) in patients prescribed antiepileptic drugs (AED) by exploring five previously suggested risk factors; age, gender, AED-type, epilepsy diagnosis and BMI.

Methods: In a population-based retrospective open cohort study we used real world data from the Electronic Health Register (EHR) in Region Kalmar County, Sweden. 23 209 patients prescribed AEDs at any time from January 2008 to November 2018 and 23 281 matching controls were followed from first registration in the EHR until the first documented LEF, disenrollment (or death) or until the end of the study period, whichever came first. Risks of LEF measured as hazard rate ratios in relation to the suggested risk factors and in comparison to matched controls were analyzed using Cox regression. The index was developed using a linear combination of the statistically significant variables multiplied by the corresponding regression coefficients.

Results: Data from 23 209 patients prescribed AEDs and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI). KEFRI = Age-category x (1.18) + Gender x (-0.51) + AED-type x (0.29) + Epilepsy diagnosis-category x (0.31) + BMI-category x (-0.35). All five previously suggested risk factors were confirmed. Women aged 75 years and older treated with an inducing AED against epilepsy and BMIs of 25 kg/m2 or below had 48 times higher LEF rates compared to men aged 50 years or younger, treated with a non-inducing AED for a condition other than epilepsy and BMIs above 25 kg/m2.

Conclusion: The KEFRI is the first weighted multifactorial assessment tool estimating risks of LEF in patients prescribed AEDs and could serve as a feasible guide within clinical practice.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2021
National Category
Orthopaedics Pharmacology and Toxicology
Research subject
Natural Science, Medicine
Identifiers
urn:nbn:se:lnu:diva-106628 (URN)10.1371/journal.pone.0256093 (DOI)000697186000031 ()34437569 (PubMedID)2-s2.0-85113770925 (Scopus ID)2021 (Local ID)2021 (Archive number)2021 (OAI)
Funder
The Kamprad Family Foundation
Available from: 2021-08-27 Created: 2021-08-27 Last updated: 2023-04-04Bibliographically approved

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