Maria Sääf

Perinatal outcomes after bariatric surgery: nationwide population based matched cohort study

Objective To compare perinatal outcomes in births of women with versus without a history of bariatric surgery. Design Population based matched cohort study. Setting Swedish national health service. Participants 1 742 702 singleton births identified in the Swedish medical birth register between 1992 and 2009. For each birth to a mother with a history of bariatric surgery (n=2562), up to five control births were matched by maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, educational level, and year of delivery. Secondary control cohorts, including women eligible for bariatric surgery (body mass index ≥35 or ≥40), were matched for the same factors except body mass index. History of maternal bariatric surgery was ascertained through the Swedish national patient register from 1980 to 2009. Main outcome measures Preterm birth (<37 weeks), small for gestational age birth, large for gestational age birth, stillbirth (≥28 weeks), and neonatal death (0-27 days). Results Post-surgery births were more often preterm than in matched controls (9.7% (243/2511) v 6.1% (750/12 379); odds ratio 1.7, 95% confidence interval 1.4 to 2.0; P<0.001). Body mass index seemed to be an effect modifier (P=0.01), and the increased risk of preterm birth was only observed in women with a body mass index <35. A history of bariatric surgery was associated with increased risks of both spontaneous (5.2% (130/2511) v 3.6% (441/12 379); odds ratio 1.5, 1.2 to 1.9; P<0.001) and medically indicated preterm birth (4.5% (113/2511) v 2.5% (309/12 379); odds ratio 1.8, 1.4 to 2.3; P<0.001). A history of bariatric surgery was also associated with an increased risk of a small for gestational age birth (5.2% (131/2507) v 3.0% (369/12 338); odds ratio 2.0, 1.5 to 2.5; P<0.001) and lower risk of a large for gestational age birth (4.2% (105/2507) v 7.3% (895/12 338); odds ratio 0.6, 0.4 to 0.7; P<0.001). No differences were detected for stillbirth or neonatal death. The increased risks for preterm and small for gestational age birth, as well as the decreased risk for large for gestational age birth, remained when post-surgery births were compared with births of women eligible for bariatric surgery. Conclusion Women with a history of bariatric surgery were at increased risk of preterm and small for gestational age births and should be regarded as a risk group during pregnancy.

Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism.

Aim:  To analyse serum levels of 25‐hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development.

Serum Levels of Insulin-like Growth Factor Binding Proteins (IGFBP)–4 and –5 Correlate with Bone Mineral Density in Growth Hormone (GH)–Deficient Adults and Increase with GH Replacement Therapy†

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin‐like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)‐4 and IGFBP‐5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP‐4 and IGFBP‐5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP‐5 and IGFBP‐4 were measured on samples from 20 patients (11 males) 22–57 years of age. All had IGF‐I serum values below –2 standard deviation score. The first 6 months were placebo controlled and all recieved 3 years of active treatment with the mean dose 0.23 ± 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP‐5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Wards triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP‐5 level increased by about 2‐fold within 3 months after the initiation of GH therapy and was correlated with serum IGF‐I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively, p < 0.001). A positive correlation between serum IGFBP‐5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP‐5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP‐5, serum IGFBP‐4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP‐4 levels also correlated with total body, femoral neck, trochanter, and Wards triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively, p < 0.05). The mean serum IGFBP‐4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF‐I levels. Although the above findings are consistent with the idea that GH‐induced changes in serum IGFBP‐5 and IGFBP‐4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.

Risk of hip fracture in Addison’s disease: a population‐based cohort study

Abstract.  Björnsdottir S, Sääf M, Bensing S, Kämpe O, Michaëlsson K, Ludvigsson JF (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; and Örebro University Hospital, Örebro; Sweden). Risk of hip fracture in Addison’s disease: a population‐based cohort study. J Intern Med 2011; 270: 187–195.

Gender differences and cognitive aspects on functional outcome after hip fracture—a 2 years’ follow-up of 2,134 patients

BACKGROUND hip fractures as well as cognitive dysfunction become increasingly prevalent in growing ageing populations. Hip fractures are approximately three times more common in elderly women. OBJECTIVE we analysed outcome after hip fracture with respect to gender and cognitive function. DESIGN population-based, prospective cohort study. SETTING four university hospitals in Stockholm, Sweden. SUBJECTS a total of 2,134 consecutive patients admitted with hip fracture during 2003. METHODS gender differences in residence, walking ability and activity of daily living (ADL) were analysed at baseline, after 4 and 24 months in patients with and without intact cognitive function. RESULTS women were older, more often living alone and had poorer walking ability (P < 0.001). Cognitive dysfunction was equally common by gender. Women were more often treated with a prosthesis (P < 0.001) and sent to rehabilitation (P < 0.001). In the cognitive dysfunction group, men had more co-morbidity (P < 0.001) and total loss of walking ability (P = 0.03), but more often resided in own homes (P = 0.03). There was no gender difference in ADL. CONCLUSION men had a higher risk for loss of walking ability and death only in patients with cognitive dysfunction. Cognitive function was the most important factor for returning to own home and regain pre-fracture function.

SERUM LEVELS OF INSULIN-LIKE GROWTH FACTOR I AND INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 1 CORRELATE WITH SERUM FREE TESTOSTERONE AND SEX HORMONE BINDING GLOBULIN LEVELS IN HEALTHY YOUNG AND MIDDLE-AGED MEN

OBJECTIVE Administration of testosterone has been reported to increase serum levels of IGF‐I in men with isolated hypogonadotrophic hypogonadism. An inverse relation between serum IGF‐I and sex hormone binding globulin (SHBG) is seen in GH deficient children. The biological action of IGF‐I is thought to be influenced by binding proteins, one of which is insulin‐like growth factor‐binding protein‐1 (IGFBP‐1), which is not only a carrier protein but also actively regulates the cellular actions of IGF‐I. These observations suggest associations between IGF‐I, IGFBP‐1, testosterone and SHBG in serum. The aim of the present study was to investigate these associations in normal healthy men.

Does Rehabilitation Matter in Patients With Femoral Neck Fracture and Cognitive Impairment? A Prospective Study of 246 Patients

UNLABELLED Al-Ani AN, Flodin L, Söderqvist A, Ackermann P, Samnegård E, Dalén N, Sääf M, Cederholm T, Hedström M. Does rehabilitation matter in patients with femoral neck fracture and cognitive impairment? A prospective study of 246 patients. OBJECTIVE To identify factors associated with preserved walking ability and Katz activities of daily living (ADLs) index at 4-month and 12-month follow-up in cognitively impaired patients with femoral neck fracture. DESIGN Population-based cohort study. SETTING A multicenter study of the Stockholm Hip Fracture Group including 4 university hospitals. PARTICIPANTS Consecutive patients (N=246) with femoral neck fracture, older than 65 years (mean, 84y; 72% women) with cognitive impairment (known dementia or low [0-2 points] score) in Short Portable Mental Status Questionnaire [0-10 points]) and able to walk before the fracture. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURE Walking ability and ADLs index at 4-month and 12-month follow-up. RESULTS Significant predictors of preserved walking ability at 12-month follow-up were discharge to rehabilitation unit (odds ratio [OR]=2.83; confidence interval [CI], 1.1-7.26; P=.03) and walking ability before the fracture (OR=8.98; CI, 3.52-22.93; P<.001), while type of surgery was not (P=.197). Analyses were adjusted for age, sex, American Society of Anesthesiologists score, fracture type, and surgical method. Corresponding predictors of preserved Katz ADLs index at 12-month follow-up, after adjustment for age and sex, were discharge to rehabilitation unit (OR=5.33; CI, 1.44-19.65; P=.012) and ADLs index before fracture (OR=2.51; CI, 1.8-3.5; P<.001), while type of surgery was not (P=.376). CONCLUSIONS Discharge to rehabilitation unit, a factor we can influence, was associated with preserved walking ability and ADLs index in cognitively impaired patients with hip fracture.

Nutritional status, as determined by the Mini-Nutritional Assessment, and osteoporosis: a cross-sectional study of an elderly female population

Objective:To investigate the relationship between osteoporosis and nutritional status as determined by the Mini-Nutritional Assessment (MNA).Design:A cross-sectional study.Setting:Stockholm, Sweden.Subjects:A total of 351 elderly free-living women (mean age 73±2.3 years).Methods:MNA (range 0–30 points; <17 indicates malnutrition, 17.5–23.5 risk of malnutrition and ⩾24 well nourished), measurements of bone mineral density of the left hip and lumbar spine using Hologic QDR 4500, and of the heel using Calscan DEXA-T.Results:The median MNA score was 27 (range 12.5–30). One woman was classified as malnourished and 7.4% were at risk of malnutrition. Osteoporosis of the femoral neck was observed in 22% and a fracture after the age of 50 was reported by 31% of the participants. The following items in the MNA questionnaire exhibited an increased risk of having osteoporosis in the femoral neck and/or total hip: an MNA score of <27 (odds ratio (OR)=2.09; CI=1.14–3.83); a mid-arm circumference of less than 28 cm (OR=2.97; CI=1.29–6.81); and regular use of more than 3 drugs each day (OR=2.12; CI=1.00–4.50). A body weight of more than 70 kg exhibited a decreased risk of having osteoporosis (OR=0.31; CI=0.14–0.70).Conclusions:In general, the nutritional status was good in this population of free-living elderly women. Nevertheless, half of the women who displayed an MNA score <27 points had a twofold increased risk of having osteoporosis.Sponsorship:Karolinska Institutet, Stockholm County Council.

Different Responses of Bone Alkaline Phosphatase Isoforms During Recombinant Insulin‐like Growth Factor‐I (IGF‐I) and During Growth Hormone Therapy in Adults with Growth Hormone Deficiency

We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of bone turnover in growth hormone–deficient (GHD) adults (n = 22). The patients were followed during 1 week of insulin‐like growth factor‐I (IGF‐I) administration, 40 μg/kg of body weight/day (n = 6), and during 24 months of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were separated and quantified by high‐performance liquid chromatography: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. At baseline, the mean levels of B1, B2, and osteocalcin were higher in GHD adults than in healthy adults. After 1 week of IGF‐I administration and 1 month of GH therapy, only B1 was decreased. We suggest that the initial decrease of B1 during GH therapy could be an effect of endocrine IGF‐I action mediated by GH. After 3 months of GH therapy, both B1 and B2 increased as compared with placebo. Osteocalcin, carboxy‐terminal propeptide of type I procollagen (PICP), cross‐linked carboxy‐terminal telopeptide of type I collagen (ICTP), and urinary pyridinoline cross‐links/creatinine ratio increased during GH therapy. PICP increased significantly before bone ALP and osteocalcin, indicating an early stimulation of type I collagen synthesis as previously demonstrated by in vitro models. Different responses of the bone ALP isoforms during IGF‐I and during GH therapy suggest different regulations in vivo.

Osteoblast Dysfunction in Male Idiopathic Osteoporosis

The etiology of primary osteoporosis in young and middle-aged men is unknown. We have studied osteoblast function in cells derived from men with idiopathic osteoporosis and in control cells from age-matched men with osteoarthrosis. Osteoblasts were isolated from transiliac bone biopsies. Osteoblast function was measured as vitamin D-stimulated osteocalcin production and production of cytokines and factors involved in osteoclast activation and bone formation. Cell proliferation was measured as 3H-thymidine incorporation. Parathyroid hormone-related peptide (PTHrP) mRNA was measured using reverse-transcriptase polymerase chain reaction. In osteoporotic men, bone mineral density at the femoral neck was correlated to in vitro production of osteocalcin. Osteoblasts from osteoporotic men produced significantly less osteocalcin after vitamin D stimulation but had increased production of macrophage colony-stimulating factor (M-CSF) compared to controls. The osteocalcin response was negatively correlated to production of M-CSF, interleukin-6, and C-terminal propeptide of type I collagen. Basal 3H-thymidine incorporation was similar in cells from osteoporotic patients and controls. PTHrP (10−9 M) significantly increased cell proliferation in control cells but not in osteoporotic cells. Basal PTHrP mRNA levels were significantly higher in osteoporotic cells than in cells from controls. The results are in agreement with previous histomorphologic studies indicating that men with idiopathic osteoporosis have an osteoblast dysfunction with decreased osteocalcin production and increased production of factors stimulating osteoclast activation. This indicates a catabolic cellular metabolic balance leading to negative bone turnover, resulting in osteoporosis. The cause of such cellular dysfunction needs further evaluation.