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Diaz Cruz, M. A., Lundh, D., Szekeres, F., Karlsson, S., Faresjö, M. & Larsson, D. (2021). Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems. Open Medicine (Poland), 16(1), 640-650
Öppna denna publikation i ny flik eller fönster >>Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
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2021 (Engelska)Ingår i: Open Medicine (Poland), ISSN 2391-5463, Vol. 16, nr 1, s. 640-650Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.

Ort, förlag, år, upplaga, sidor
Walter de Gruyter, 2021
Nyckelord
conserved sequences, crosstalk, nuclear receptor binding domains, splicing sites, transcription factor binding sites
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:hj:diva-52373 (URN)10.1515/med-2021-0264 (DOI)000645596800001 ()33954257 (PubMedID)2-s2.0-85104533727 (Scopus ID)GOA;;738320 (Lokalt ID)GOA;;738320 (Arkivnummer)GOA;;738320 (OAI)
Tillgänglig från: 2021-05-03 Skapad: 2021-05-03 Senast uppdaterad: 2022-03-07Bibliografiskt granskad
Diaz Cruz, M. A., Karlsson, S., Szekeres, F., Faresjö, M., Lund, D. & Larsson, D. (2021). Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer. Molecular Biology Reports, 48, 2429-2436
Öppna denna publikation i ny flik eller fönster >>Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
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2021 (Engelska)Ingår i: Molecular Biology Reports, ISSN 0301-4851, E-ISSN 1573-4978, Vol. 48, s. 2429-2436Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression.

Ort, förlag, år, upplaga, sidor
Springer, 2021
Nyckelord
Androgen dependency, PDIA3, PDIA3N, Prostate cancer, VDR, Vitamin D
Nationell ämneskategori
Cancer och onkologi Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:hj:diva-52111 (URN)10.1007/s11033-021-06277-1 (DOI)000632300000004 ()33761087 (PubMedID)2-s2.0-85103162678 (Scopus ID)HOA;;731562 (Lokalt ID)HOA;;731562 (Arkivnummer)HOA;;731562 (OAI)
Tillgänglig från: 2021-03-29 Skapad: 2021-03-29 Senast uppdaterad: 2022-03-07Bibliografiskt granskad
Axelsson, K. F., Johansson, H., Lundh, D., Möller, M. & Lorentzon, M. (2020). Association between recurrent fracture risk and implementation of fracture liaison services in four Swedish hospitals: A cohort study. Journal of Bone and Mineral Research, 35(7), 1216-1223
Öppna denna publikation i ny flik eller fönster >>Association between recurrent fracture risk and implementation of fracture liaison services in four Swedish hospitals: A cohort study
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2020 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 35, nr 7, s. 1216-1223Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention-to-treat analysis. Time periods corresponding to the FLS hospitals were used for the non-FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow-up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = 0.001), corresponding to a 3-year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. 

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2020
Nyckelord
Fracture, Fracture Liaison Service, Osteoporosis, Recurrent Fracture
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:hj:diva-48204 (URN)10.1002/jbmr.3990 (DOI)000547662100003 ()32097504 (PubMedID)2-s2.0-85082142028 (Scopus ID)HOA HHH 2020;HHJÖvrigtIS (Lokalt ID)HOA HHH 2020;HHJÖvrigtIS (Arkivnummer)HOA HHH 2020;HHJÖvrigtIS (OAI)
Forskningsfinansiär
Vetenskapsrådet, 2017‐02229
Tillgänglig från: 2020-04-24 Skapad: 2020-04-24 Senast uppdaterad: 2021-01-27Bibliografiskt granskad
Axelsson, K., Lorentzon, M., Lundh, D., Johansson, H. & Moller, M. (2019). Implementation of Fracture Liaison Services in two Swedish hospitals was associated with reduced risk of recurrent clinical fractures in patients with osteoporotic fracture. Paper presented at Annual Meeting of the American-Society-for-Bone-and Mineral Research, SEP 20-23, 2019, Orlando, FL. Journal of Bone and Mineral Research, 34(1), 43-44
Öppna denna publikation i ny flik eller fönster >>Implementation of Fracture Liaison Services in two Swedish hospitals was associated with reduced risk of recurrent clinical fractures in patients with osteoporotic fracture
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2019 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 34, nr 1, s. 43-44Artikel i tidskrift, Meeting abstract (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
Wiley-Blackwell, 2019
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:hj:diva-47820 (URN)000508614700127 ()
Konferens
Annual Meeting of the American-Society-for-Bone-and Mineral Research, SEP 20-23, 2019, Orlando, FL
Tillgänglig från: 2020-02-18 Skapad: 2020-02-18 Senast uppdaterad: 2020-03-24Bibliografiskt granskad
Wallander, M., Axelsson, K. F., Lundh, D. & Lorentzon, M. (2019). Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures - a study from the fractures and fall injuries in the elderly cohort (FRAILCO). Osteoporosis International, 30(1), 115-125
Öppna denna publikation i ny flik eller fönster >>Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures - a study from the fractures and fall injuries in the elderly cohort (FRAILCO)
2019 (Engelska)Ingår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, nr 1, s. 115-125Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Summary

Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures.

Introduction

Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer.

Methods

We included 179,744 men (79.17.9years (meanSD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures.

Results

In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)).

Conclusions

Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT.

Ort, förlag, år, upplaga, sidor
Springer, 2019
Nyckelord
Androgen deprivation therapy, Fall injuries, Fractures, Prostate cancer
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:hj:diva-45744 (URN)10.1007/s00198-018-4722-3 (DOI)000455809500009 ()30324413 (PubMedID)2-s2.0-85060047248 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Axelsson, K. F., Werling, M., Eliasson, B., Szabo, E., Näslund, I., Wedel, H., . . . Lorentzon, M. (2018). Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study. Journal of Bone and Mineral Research, 33(12), 2122-2131
Öppna denna publikation i ny flik eller fönster >>Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study
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2018 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 12, s. 2122-2131Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1-year postsurgery was investigated. During a median follow-up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2018
Nyckelord
Osteoporosis, Fracture Risk Assessment, General Population Studies
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:hj:diva-45745 (URN)10.1002/jbmr.3553 (DOI)000452301800005 ()30011091 (PubMedID)2-s2.0-85052618842 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Axelsson, K. F., Nilsson, A. G., Wedel, H., Lundh, D. & Lorentzon, M. (2017). Association between alendronate use and hip fracture risk in older patients using oral prednisolone. Journal of the American Medical Association (JAMA), 318(2), 146-155
Öppna denna publikation i ny flik eller fönster >>Association between alendronate use and hip fracture risk in older patients using oral prednisolone
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2017 (Engelska)Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 318, nr 2, s. 146-155Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.

OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects.

DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014.

EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation.

MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture.

RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group.

CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

Ort, förlag, år, upplaga, sidor
American Medical Association, 2017
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:hj:diva-45747 (URN)10.1001/jama.2017.8040 (DOI)000405190800016 ()28697254 (PubMedID)2-s2.0-85024381826 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Axelsson, K. F., Wallander, M., Johansson, H., Lundh, D. & Lorentzon, M. (2017). Hip fracture risk and safety with alendronate treatment in the oldest-old. Journal of Internal Medicine, 282(6), 546-559
Öppna denna publikation i ny flik eller fönster >>Hip fracture risk and safety with alendronate treatment in the oldest-old
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2017 (Engelska)Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, nr 6, s. 546-559Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied.

Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety.

Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term.

Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI.

Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2017
Nyckelord
alendronate, efficiency, elderly, fracture, osteoporosis, treatment
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:hj:diva-45746 (URN)10.1111/joim.12678 (DOI)000415928700007 ()28857352 (PubMedID)2-s2.0-85034421273 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Wallander, M., Axelsson, K. F., Nilsson, A. G., Lundh, D. & Lorentzon, M. (2017). Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco). Journal of Bone and Mineral Research, 32(3), 449-460
Öppna denna publikation i ny flik eller fönster >>Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco)
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2017 (Engelska)Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, nr 3, s. 449-460Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 +/- 8.2 years [mean +/- SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2017
Nyckelord
General Population Studies, Fracture Risk Assessment, Fracture Prevention, Type 2 Diabetes
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:hj:diva-45748 (URN)10.1002/jbmr.3002 (DOI)000398055900006 ()27664946 (PubMedID)2-s2.0-84997161453 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Landegren, N., Sharon, D., Shum, A. K., Khan, I. S., Fasano, K. J., Hallgren, Å., . . . Kampe, O. (2015). Transglutaminase 4 as a prostate autoantigen in male subfertility. Science Translational Medicine, 7(292), Article ID 292ra101.
Öppna denna publikation i ny flik eller fönster >>Transglutaminase 4 as a prostate autoantigen in male subfertility
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2015 (Engelska)Ingår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, nr 292, artikel-id 292ra101Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.

Ort, förlag, år, upplaga, sidor
American Association for the Advancement of Science, 2015
Nationell ämneskategori
Cellbiologi
Identifikatorer
urn:nbn:se:hj:diva-45749 (URN)10.1126/scitranslmed.aaa9186 (DOI)000356390500008 ()26084804 (PubMedID)2-s2.0-84931466170 (Scopus ID)
Tillgänglig från: 2019-08-29 Skapad: 2019-08-29 Senast uppdaterad: 2019-08-29Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-6549-086X

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