Autoimmune Disease in Turner Syndrome in Sweden: An up to 25 Years' Controlled Follow-up Study.

CONTEXT: Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS. OBJECTIVE: This work aimed to study the prevalence of autoimmune diseases in TS. METHODS: A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured. RESULTS: Mean follow-up time (years) was 16 ± 7 for patients and 13 ± 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS. CONCLUSION: In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B12 deficiency and celiac disease throughout life is also recommended in women with TS.

Aortic size predicts aortic dissection in Turner syndrome - A 25-year prospective cohort study.

BACKGROUND: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. METHODS: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. RESULTS: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. CONCLUSIONS: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

Parathyroid Hormone Disturbances in Postmenopausal Women with Distal Forearm Fracture.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder with a wide range of adverse effects, such as osteoporosis. Many women are not diagnosed due to asymptomatic disease or vague symptoms but are still at risk of severe adverse effects. Early identification of patients with PHPT is therefore of importance. The aim of this study was to determine PHPT prevalence among postmenopausal women with a distal forearm fracture. METHODS: Recruitment was conducted in conjunction with the occurrence of a distal forearm fracture at Karolinska University Hospital. In total, 161 postmenopausal women were included in a cross-sectional study with repeated evaluations. Analyzes of serum calcium, ionized calcium, phosphate, parathyroid hormone (PTH), and vitamin D were performed. Diagnosis of PHPT was based on clinical evaluations and biochemical definitions of serum calcium and PTH in coherence with previous population prevalence reports. RESULTS: Mean age was 64.7 (9.5) years, serum calcium 2.33 (0.10) mmol/L, ionized calcium 1.25 (0.05) mmol/L and PTH 54 (26) ng/L. PTH was elevated in 32 (20%) women. In total, 11 (6.8%) women were diagnosed with PHPT; 6 with classical PHPT and 5 with mild PHPT. The prevalence of PHPT was significantly increased compared to the population prevalence of 3.4% (p = 0.022). CONCLUSION: Screening postmenopausal women in conjunction with low-energy distal forearm fracture revealed a large number of women with parathyroid disturbance. Evaluation of parathyroid hormone and calcium status in this group of patients seems beneficial.

Site-Specific Volumetric Skeletal Changes in Women with a Distal Forearm Fracture.

PURPOSE: To assess site-specific volumetric bone and muscle changes, as well as demographic and biochemical changes, in postmenopausal women with a low-energy distal forearm fracture. METHODS: In a cross-sectional case-control study, postmenopausal women with a distal forearm fracture were compared with age- and gender-matched controls. In total, 203 postmenopausal women (104 cases and 99 controls), with a mean age of 65 years, were included. Measurements included peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) as well as blood sampling and questionnaires. RESULTS: Forearm trabecular volumetric BMD and total BMD assessed with pQCT were significantly lower in fracture cases compared to controls (p < 0.001). Significantly higher cross-sectional area, lower cortical BMD, and lower cortical thickness were seen in women with fracture (p < 0.033, p < 0.001, and p < 0.001, respectively). Postmenopausal women with fracture had significantly lower hip and spine areal BMD assessed with DXA (p < 0.001). Activity level was higher and a history of falling was more frequent in women with fracture (p < 0.019 and p < 0.001, respectively). Vertebral fracture was observed in 24 women (22%) with a distal forearm fracture. Muscle area, muscle density, PTH, and 25OHD did not differ between fracture cases and controls. CONCLUSION: A distal forearm fracture was associated with site-specific and central bone changes. Postmenopausal women with fracture had a larger bone area in combination with a thinner cortex and lower site-specific total BMD. In addition, women with fracture had a higher activity level, an increased occurrence of previous fall accidents, and a high prevalence of vertebral fractures. Forearm muscle composition, PTH, and 25OHD were not associated with forearm fracture. Fracture preventive measures following a low-energy distal forearm fracture seem beneficial.

Sparing effect of peritoneal dialysis vs hemodialysis on BMD changes and its impact on mortality.

INTRODUCTION: Bone loss in end stage renal disease (ESRD) patients associates with fractures, vascular calcification, cardiovascular disease (CVD) and increased mortality. We investigated factors associated with changes of bone mineral density (ΔBMD) during the initial year on dialysis therapy and associations of ΔBMD with subsequent mortality in ESRD patients initiating dialysis. MATERIALS AND METHODS: In 242 ESRD patients (median age 55 years, 61% men) starting dialysis with peritoneal dialysis (PD; n = 138) or hemodialysis (HD; n = 104), whole-body dual-energy X-ray absorptiometry (DXA), body composition, nutritional status and circulating biomarkers were assessed at baseline and 1 year after dialysis start. We used multivariate linear regression analysis to determine factors associated with ΔBMD, and fine and gray competing risk analysis to determine associations of ΔBMD with subsequent mortality risk. RESULTS: BMD decreased significantly in HD patients (significant reductions of BMDtotal and BMDleg, trunk, rib, pelvis and spine) but not in PD patients. HD compared to PD therapy associated with negative changes in BMDtotal (ß=- 0.15), BMDhead (ß=- 0.14), BMDleg (ß=- 0.18) and BMDtrunk (ß=- 0.16). Better preservation of BMD associated with significantly lower all-cause mortality for ΔBMDtotal (sub-hazard ratio, sHR, 0.91), ΔBMDhead (sHR 0.91) and ΔBMDleg (sHR 0.92), while only ΔBMDhead (sHR 0.92) had a beneficial effect on CVD-mortality. CONCLUSIONS: PD had beneficial effect compared with HD on BMD changes during first year of dialysis therapy. Better preservation of BMD, especially in bone sites rich in cortical bone, associated with lower subsequent mortality. BMD in cortical bone may have stronger association with clinical outcome than BMD in trabecular bone.

Bone health in adolescents with idiopathic scoliosis.

AIMS: Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls. METHODS: We included 78 adolescents with idiopathic scoliosis (57 female patients) at a mean age of 13.7 years (8.5 to 19.6) and 52 age- and sex-matched healthy controls (39 female patients) at a mean age of 13.8 years (9.1 to 17.6). Mean skeletal age, estimated according to the Tanner-Whitehouse 3 system (TW3), was 13.4 years (7.4 to 17.8) for those with idiopathic scoliosis, and 13.1 years (7.4 to 16.5) for the controls. Mean Cobb angle for those with idiopathic scoliosis was 29° (SD 11°). All individuals were scanned with dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) of the left radius and tibia to assess bone density. Statistical analyses were performed with independent-samples t-test, the Mann-Whitney U test, and the chi-squared test. RESULTS: Compared with controls, adolescents with idiopathic scoliosis had mean lower DXA values in the left femoral neck (0.94 g/cm2 (SD 0.14) vs 1.00 g/cm2 (SD 0.15)), left total hip (0.94 g/cm2 (SD 0.14) vs 1.01 g/cm2 (SD 0.17)), L1 to L4 (0.99 g/cm2 (SD 0.15) vs 1.06 g/cm2 (SD 0.17)) and distal radius (0.35 g/cm2 (SD 0.07) vs 0.39 g/cm2 (SD 0.08; all p ≤ 0.024), but not in the mid-radius (0.72 g/cm2 vs 0.74 g/cm2; p = 0.198, independent t-test) and total body less head (1,559 g (SD 380) vs 1,649 g (SD 492; p = 0.0.247, independent t-test). Compared with controls, adolescents with idiopathic scoliosis had lower trabecular volume bone mineral density (BMD) on pQCT in the distal radius (184.7 mg/cm3 (SD 40.0) vs 201.7 mg/cm3 (SD 46.8); p = 0.029), but not in other parts of the radius or the tibia (p ≥ 0.062, Mann-Whitney U test). CONCLUSION: In the present study, idiopathic scoliosis patients seemed to have lower BMD at central skeletal sites and less evident differences at peripheral skeletal sites when compared with controls. Cite this article: Bone Joint J 2020;102-B(2):268-272.

Bone mineral density at different sites and 5 years mortality in end-stage renal disease patients: A cohort study.

BACKGROUND: Bone disease with osteoporosis and renal osteodystrophy is common in end stage renal disease (ESRD) patients and associates with cardiovascular disease (CVD) and increased morbimortality. We investigated associations of low bone mineral density (BMD) at various bone sites with five year all-cause and CVD mortality in ESRD patients. METHODS: In a post hoc analysis of 426 ESRD patients (median age 56 years, 62% men) starting dialysis, BMD (whole-body dual-energy X-ray absorptiometry, DXA), body composition, nutritional status (subjective global assessment, SGA), handgrip strength (%HGS), Framingham CVD risk score (FRS) and biochemical biomarkers of nutrition and inflammation were assessed. We used the Fine and Gray competing risk regression analysis to assess survival analysis. RESULTS: In multivariate logistic regression analysis, %HGS and intact parathyroid hormone associated with low tertile of: BMDtotal, BMDhead and BMDpelvis, after adjusting for FRS, SGA, %HGS, s-albumin, hsCRP, lean body mass index and year of recruitment. Patients with high FRS had low BMDhead (p<0.001). Low tertile of BMDtotal (sHR, 1.53), BMDhead (sHR 1.54) and BMDpelvis (sHR 1.60) associated with increased all-cause mortality whereas no such associations were found for the trabecular bone rich sites BMD arm, leg, trunk, rib or spine. Low tertile of BMDtotal (sHR 1.94), BMDhead (sHR 1.68), BMDleg (sHR 2.25) and BMDpelvis (sHR 2.45) associated with increased CVD mortality whereas BMD at other sites did not associate with CVD mortality. CONCLUSION: Low head and pelvis BMD, and low total BMD, as assessed by whole-body DXA, were independent predictors of increased risk of all-cause and CVD mortality. Cortical BMD appeared to have stronger association to survival in ESRD than trabecular BMD.

From being restrained to recapturing vitality: non-western immigrant women's experiences of undergoing vitamin D treatment after childbirth.

Purpose: Vitamin D deficiency is a complex topic in human health and ill-health and has been studied in a variety of contexts and populations. Few studies examine Vitamin D deficiency among non-western immigrant women and even fewer examine women's perspective on daily life while living with low vitamin D levels after childbirth and undergoing vitamin D treatment. The aim was, therefore, to explore health and ill-health among non-western immigrant women living with low vitamin D levels after childbirth and reaching normalized levels after one year of vitamin D treatment. Method: An explorative qualitative study using qualitative content analysis. Six women aged 25 to 38 years, diagnosed with low 25-hydroxyvitamin D levels during pregnancy, were recruited after having undergone vitamin D treatment. Results: The women told about living a restrained life which gradually transformed into an experience of recaptured vitality. They also experienced a need for continuity in medication, as an interruption of treatment meant returning symptoms. Conclusion: In this study, non-western immigrant women described benefits in everyday life, increased strength, relieved pain and improved sleep quality. The findings can provide valuable knowledge for healthcare providers meeting women with physical weakness, musculoskeletal pain and/or poor sleep quality after childbirth. Further studies using a longitudinal design and larger samples are warranted.

Lower pain and higher muscular strength in immigrant women with vitamin D deficiency following vitamin D treatment.

BACKGROUND: Vitamin D deficiency is common among immigrants in the Nordic region. It may lead to osteomalacia with severe musculoskeletal pain. There are reports that vitamin D deficiency without osteomalacia may lead to pain but little is known of the effect of treatment. OBJECTIVE: To investigate whether a moderate dose of cholecalciferol and calcium improves strength and pain in a group of vitamin D deficient women. DESIGN: Twentyfive immigrant women with vitamin D deficiency diagnosed during pregnancy were treated postpartum with a daily dose of 1,600 IU cholecalciferol and 1,000 mg of calcium. They were examined at the start of treatment and again after 3 months of treatement and the results were statistically compared. SETTING: Southern parts of Stockholm. MAIN OUTCOME MEASURES: Serum 25-hydroyvitamin D (25(OH)D), serum-parathyroid hormone (PTH), pain measured by a visual analogue scale (VAS), musculoskeletal strength by performance on a chair stand test (seconds), and bone tenderness by pressure algometer (kilo-Pascal). RESULTS: Following the treatment, the 21 women attending had lowered cm in VAS, improved musculoskeletal strength, - and 25(OH)D levels were normalized. CONCLUSIONS: A moderate dose of vitamin D normalized l vitamin D levels, improved muscular strength and reduced pain in this group of vitamin D deficient immigrant women.

Can secondary osteoporosis be identified when screening for osteoporosis with digital X-ray radiogrammetry? Initial results from the Stockholm Osteoporosis Project (STOP).

OBJECTIVES: To identify causes of low age-adjusted bone mass at digital X-ray radiogrammetry (DXR) in individuals attending an osteoporosis screening program. STUDY DESIGN: In a descriptive observational cohort study, women aged 40-75 years who attended a general mammography screening program had their bone mass investigated with DXR and answered a questionnaire regarding several clinical risk factors for osteoporosis. Each month the 2% with the lowest Z-scores were selected for further clinical examination with DXA of the hip and lumbar spine and pre-defined blood tests. MAIN OUTCOME MEASURE: Causes of secondary osteoporosis determined by clinical and laboratory evaluation. RESULTS: 14,783 women attended mammography screening and had their bone mass evaluated. In total, 327 women had a low DXR BMD and 281 accepted further DXA examination. Of these, 93 (33.1%) had osteoporosis. The diagnosis was new in 79 cases (84.9%) and in 32 (34.4%) a potential underlying cause was identified. Primary hyperparathyroidism was found in 8.6% and secondary hyperparathyroidism in 13.5%. Several self-reported risk factors for osteoporosis, including rheumatic disease, insulin-treated diabetes, cortisone treatment, smoking, reduced mobility, hyperparathyroidism, and malabsorption, were significantly more common among those selected for DXA referral than in the total cohort. For example, rheumatic disease and insulin-treated diabetes were reported 3.4 and 2.3 times as often, respectively. CONCLUSION: The prevailing potential cause of secondary osteoporosis according to DXR was primary and secondary hyperparathyroidism. Most of the women with these conditions were previously undiagnosed, indicating that further follow-up of patients with low age-adjusted DXR BMD is justified.

Adipose tissue and metabolic alterations: regional differences in fat cell size and number matter, but differently: a cross-sectional study.

OBJECTIVE: White adipose tissue can expand by increasing the size and/or number of fat cells. Although increased sc and visceral fat cell size associates with an adverse metabolic profile, the relationship with fat cell number in either depot is unknown. We hypothesized that adipocyte number and size displayed different relationships with clinically relevant metabolic variables. METHODS: This was a cross-sectional study of 204 patients scheduled for gastric bypass surgery. Fat cell size and number were determined in visceral and abdominal sc adipose tissue and related to insulin sensitivity (by hyperinsulinemic euglycemic clamp), fasting plasma levels of insulin, triglycerides and high-density lipoprotein (HDL) cholesterol. RESULTS: Visceral and sc fat cell volumes were positively correlated with insulin and triglyceride levels and negatively with insulin sensitivity and HDL-cholesterol (P = .0020 or better). In contrast, although visceral fat cell number did not associate with any metabolic parameter, sc adipocyte number displayed a positive association with insulin sensitivity and HDL-cholesterol and a negative relationship with insulin and triglyceride levels (P = .0014 or better). All results were independent of body fat mass. CONCLUSIONS: Variations in fat cell size and number correlate differently with metabolic parameters in obesity. Increased fat cell size in visceral and sc depots associates with a pernicious metabolic profile, whereas increased sc, but not visceral, fat cell number correlates with a more beneficial phenotype. Whether determination of sc fat cell number, in addition to adipocyte size, may have a predictive value for the risk of type 2 diabetes needs to be demonstrated in prospective or mechanistic studies.

Long-term follow-up of bone density, general and reproductive health in female survivors after treatment for haematological malignancies.

The purpose of this study was to assess the ovarian function, fertility and bone mineral density in women who previously had treatment for different haematological malignancies (HMs). The overall survival and cure rates of patients with HMs have improved dramatically. The treatment affects fertility and bone density. Fifty-two premenopausal women, from Stockholm region, were included in the study between 1998 and 2002, followed until 2011. The diagnoses were acute lymphoblastic leukaemia (n = 6), acute myeloid leukaemia (n = 10), chronic lymphocytic leukaemia (n = 1), chronic myeloid leukaemia (n = 12), Hodgkin lymphoma (n = 12) and non-Hodgkin lymphoma (n = 11). Before treatment, women without children (43/52), when possible, were offered fertility preservation options. The mean age at diagnosis was 27, at final evaluation 39 yr. Thirty-seven patients received HSCT; 26 allogeneic, 11 autologous. Before allogeneic HSCT, nineteen patients had myeloablative conditioning; seven had reduced-intensity conditioning. Eleven patients got total body irradiation. Eight patients were transplanted with grafts from an HLA-identical sibling donor, while 18 had unrelated donors. All women were in a menopausal state post-therapy. Hormone replacement therapy (HRT) was given, and bone mineral density (BMD) was measured every other year. The serum levels of parathyroid hormone (PTH), free and bound calcium was within normal range. BMD measurements showed a slight increase over time in the spine with a mean of 0.015 g/cm(2) /yr. Four spontaneous pregnancies resulted in two babies and two discontinued pregnancies; two pregnancies were achieved with oocyte donation and surrogacy and one woman adopted a child. HRT sustains BMD in long-term survivors from HMs. This study highlights the importance of HRT and fertility issues in this patient group.

Observational study of vitamin D levels and pain in pregnant immigrant women living in Sweden.

The aim was to determine the prevalence of vitamin D insufficiency in pregnant immigrant women assessed by the levels of 25-hydroxyvitamin D, parathyroid hormone (PTH) and alkaline phosphatase (ALP) as well as the correlation to musculoskeletal pain. Sixty-eight pregnant immigrant women were included. Fifty-one native Swedish pregnant women served as controls. 25-hydroxyvitamin D, PTH, ALP and musculoskeletal pain, rated on a visual analogue scale, were analyzed in all women in gestational week 12 and in the immigrant women at 6-12 months postpartum. A significantly higher proportion of immigrant women (77.9%) had levels of 25-hydroxyvitamin D <25 nmol/l compared with 3.9% in controls. Of the immigrant women, 29.4% had 25-hydroxyvitamin D levels <12 nmol/l, but none of the controls. Musculoskeletal pain evaluated with a visual analogue scale (VAS) was significantly higher for the immigrant women than for the controls at gestational week 12. However, no within group correlation was seen between 25-hydroxyvitamin D levels, PTH or ALP and pain. A significant negative correlation between changes in 25-hydroxyvitamin D and pain from gestational week 12 to postpartum was observed. Hypovitaminosis D is prevalent in immigrant women living in Sweden. There is an indication that pain might be associated with hypovitaminosis D.

Vitamin D levels in children born to vitamin D-deficient mothers.

AIM: To determine whether a standard daily dose of 400 IU vitamin D is sufficient to normalize vitamin D levels in infants born to vitamin D-deficient mothers. METHODS: The children were recruited from a study cohort of 68 immigrant and 51 non-immigrant pregnant women living in Stockholm. The women were monitored at 12 weeks of pregnancy, at delivery and together with their children, 6-18 months after birth. During pregnancy, most immigrant women (78%) had 25(OH)D3 levels <25 nmol/l. We here report the outcome of 25 infants born to these mothers. All infants received a daily supplementation dose of 400 IU vitamin D from 2 weeks of age. RESULTS: At birth, most children in the immigrant group were vitamin D-deficient (23.3 nmol/l (12-54); mean and range) while at 6-18 months of age vitamin D levels were essentially normalized (82.8 nmol/l (38-142)) although 4 children still had subnormal levels consistent with vitamin D insufficiency. CONCLUSION: A daily recommended supplementation dose of 400 IU vitamin D is sufficient in most children of vitamin D-deficient immigrant women living in Sweden.

Women with anorexia nervosa should not be treated with estrogen or birth control pills in a bone-sparing effect.

Eating disorders are prevalent, serious conditions that affect mainly young women. An early and enduring sign of anorexia is amenorrhea. There is no evidence for benefits of hormone therapy in patients with anorexia; however, hormone medication and oral contraceptives are frequently prescribed for young women with anorexia as a prevention against and treatment for low bone mineral density. The use of estrogens may create a false picture indicating that the skeleton is being protected against osteoporosis. Thus the motivation to regain weight, and adhere to treatment of the eating disorder in itself, may be reduced. The most important intervention is to restore the menstrual periods through increased nutrition. Hormone and oral contraceptive therapy should not be prescribed for young women with amenorrhea and concurrent eating disorders.