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The presence of anticardiolipin antibodies in adults may be influenced by infections in infancy.

18 September 2018

OBJECTIVES: There has been limited success defining environmental factors important in the development of antiphospholipid (Hughes) syndrome (APS). Recent work suggests that the perinatal environment may be important in the development of other autoimmune diseases. We measured anticardiolipin antibodies (aCL) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with aCL positivity in adult life. METHODS: aCLs were measured using an ELISA in 1384 individuals from the Hertfordshire cohort study. We investigated associations between the presence of aCL and early growth and infectious exposure in infancy in men and women. RESULTS: ELISA positive aCL (IgM and IgG) was present in 22 (3%) men and 15 (2%) women. Using the highest octile of aCL results, in men higher birth weight (per lb of birth weight: OR 1.18, 95% CI 1.02-1.36, P = 0.02) and diarrhoeal infection in the first year of life (OR 2.55, 95% CI 1.10, 5.92, P = 0.03) were associated with an increased likelihood of being aCL positive. In women, diarrhoeal infection in the first year of life was also associated with an increased likelihood of aCL positivity (OR 2.23, 95% CI 1.01, 4.91, P = 0.05). For IgG titre in men, significant relationships were found with sharing a bedroom (regression coefficient 1.13; 95% CI 1.05, 1.22; P = 0.02) and diarrhoea in the first year (coefficient 1.25; 95% CI 1.00, 1.56; P = 0.05). CONCLUSION: A developing immune system when exposed to the infectious environment may influence the likelihood of producing aCL in adult life.

Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee--the MOVE consensus.

18 September 2018

OBJECTIVES: Exercise is an effective and commonly prescribed intervention for lower limb osteoarthritis (OA). Many unanswered questions remain, however, concerning the practical delivery of exercise therapy. We have produced evidence-based recommendations to guide health-care practitioners. METHODS: A multidisciplinary guideline development group was formed from representatives of professional bodies to which OA is of relevance and other interested parties. Each participant contributed up to 10 propositions describing key clinical points regarding exercise therapy for OA of the hip or knee. Ten final recommendations were agreed by the Delphi technique. The research evidence for each was determined. A literature search was undertaken in the Medline, PubMed, EMBASE, PEDro, CINAHL and Cochrane databases. The methodological quality of each retrieved publication was assessed. Outcome data were abstracted and effect sizes calculated. The evidence for each recommendation was assessed and expert consensus highlighted by the allocation of two categories: (1) strength of evidence and (2) strength of recommendation. RESULTS: The first round of the Delphi process produced 123 propositions. This was reduced to 10 after four rounds. These related to aerobic and strengthening exercise, group versus home exercise, adherence, contraindications and predictors of response. The literature search identified 910 articles; 57 intervention trials relating to knee OA, 9 to hip OA and 73 to adherence. The evidence to support each proposition is presented. CONCLUSION: These are the first recommendations for exercise in hip and knee OA to clearly differentiate research evidence and expert opinion. Gaps in the literature are identified and issues requiring further study highlighted.

Intestinal perforation and jejunal haemorrhage due to Wegener's granulomatosis.

18 September 2018

Early life influences on serum 1,25 (OH) vitamin D.

18 September 2018

There is increasing evidence to support the role of the intrauterine and early postnatal environment in determining adult bone mass and risk of fracture. The mechanisms by which this occurs are uncertain but include perturbations in several endocrine axes. Vitamin D is integrally involved in bone metabolism and is therefore an ideal candidate. This study assesses whether birthweight and weight at 1 year of age are associated with the calcium vitamin D axis in elderly women. Vitamin D metabolites, parathyroid hormone, bone mineral density and biochemical markers of bone turnover were measured in 129 healthy women (mean age 65.5 years) from the MRC Hertfordshire Cohort Study whose birthweight and weight at 1 year were available from records. Serum 1,25 (OH)2 vitamin D concentrations were reduced with increasing weight at 1 year (19.1% reduction between the lowest and highest tertiles, P <0.01). A similar, but weaker trend was seen for birthweight. These associations were not explained by serum levels of serum calcium, phosphate, PTH, creatinine or sex hormones. The association of serum calcium with 1,25 (OH)2 vitamin D was greatest in the lowest tertile with little association in the highest tertile suggesting an increased sensitivity of renal 1-alpha hydroxylase in the lowest tertile. Highest levels of 1,25 (OH)2 vitamin D were associated with low BMD and high levels of urinary N-telopeptide suggesting that vitamin D metabolism may mediate the intrauterine and early postnatal environmental effects on adult BMD.

Umbilical venous IGF-1 concentration, neonatal bone mass, and body composition.

18 September 2018

UNLABELLED: IGF-1 is a key growth factor during fetal life. Using DXA, we found that the concentration of IGF-1 in umbilical cord serum is strongly related to neonatal whole body bone mineral content, lean mass, and fat mass. However IGF-1 did not explain the relationships of maternal smoking, fat mass, and physical activity with neonatal bone mass. The study supports a direct role for circulating IGF-1 in growth of the fetal skeleton. INTRODUCTION: Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences during intrauterine and early postnatal life. We previously reported that maternal birthweight, smoking, fat stores, and physical activity during pregnancy predict neonatal bone mass. While the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is an important determinant of postnatal skeletal growth, there are few data relating the concentration of growth factors in umbilical cord blood to bone mineral content (BMC) and other indices of body composition in the newborn infant. MATERIALS AND METHODS: We conducted a population-based study in a cohort of full-term, newborn infants whose mothers were characterized for lifestyle, body composition, and nutrition through their normal pregnancies. In a sample of 119 infants from the cohort, we related cord serum IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 concentrations to neonatal body composition measured by DXA and evaluated the extent to which this cytokine mediates the previously reported effects of maternal diet and lifestyle on neonatal bone mass. RESULTS: There were strong positive associations between cord serum IGF-1 concentration and whole body BMC (r = 0.38, p < 0.001), whole body lean mass (r = 0.40, p < 0.001), and whole body fat mass (r = 0.50, p < 0.001) after adjusting for gestational age and sex. There was no association between cord serum IGF-1 and BMC adjusted for bone size. Neither cord serum IGF-1 nor IGFBP-3 explained the relationships that we previously reported between maternal influences and neonatal bone mass. CONCLUSIONS: Cord serum IGF-1 is more closely related to the size of the neonatal skeleton than to its degree of mineralization. Documented maternal determinants of neonatal bone mass seem to mediate their effects independently of variations in cord serum IGF-1 in healthy pregnancies.

Size at birth, adult intestinal calcium absorption and 1,25(OH)(2) vitamin D.

18 September 2018

BACKGROUND: Adult bone mineral status is modified by early environmental influences, but the mechanism of this phenomenon is unknown. Intestinal calcium absorption and vitamin D metabolism are integrally involved in bone metabolism and may be programmed during early life. AIM: To examine the early-life influences on calcium absorption and its control in 322 post-menopausal female twins. METHODS: Intestinal calcium absorption was assessed by the stable strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)(2) vitamin D were measured and recalled birth weight recorded. RESULTS: Fractional intestinal Sr absorption (alpha Sr) was correlated with serum 1,25(OH)(2) vitamin D (p<0.001), but not with 25(OH) vitamin D. Birth weight was inversely associated with serum 1,25(OH)(2) vitamin D (p=0.04), the association being independent of serum calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated with alpha Sr (p=0.03), this association being independent of age, season, customary calcium intake and serum 25(OH) vitamin D; however, when serum 1,25(OH)(2) vitamin D was added into the model, the association became non-significant, suggesting that the association was partially mediated via serum 1,25(OH)(2) vitamin D. DISCUSSION: We found a significant inverse association between birth weight and intestinal calcium absorption that is partially explained by an association between serum 1,25(OH)(2) vitamin D and birth weight. This suggests a mechanism whereby the intra-uterine environment might affect adult skeletal status.

Osteoporosis in patients with inflammatory bowel disease.

18 September 2018

Genetic influence on bone turnover in postmenopausal twins.

18 September 2018

Postmenopausal bone mass is determined by both peak bone mass and subsequent bone loss. Previous studies have shown that peak bone mass is under genetic influence mediated partly by factors affecting bone formation. The rate of bone loss increases markedly after the menopause, but is highly variable from subject to subject. The aims of this study were to determine whether postmenopausal bone turnover was under genetic control, which should be linked to the genetic influence on the rate of postmenopausal bone loss. A classical twin study was performed that compared the intraclass correlations in monozygotic (MZ) twins with those in dizygotic (DZ) twins, with any difference assumed to be due to genetic factors. Markers of bone formation and resorption were measured in 240 untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0) postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific markers of bone formation, serum osteocalcin and bone-specific alkaline phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs. 0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs. 0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For serum propeptide of type I collagen, a type I collagen synthesis marker that exhibits only a slight increase after menopause, a high proportion of its variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33 (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three distinct urinary markers, total deoxypyridinoline and two cross-linked type I collagen peptides (CrossLaps and NTX), that increase markedly after menopause were higher in MZ than in DZ pairs, but the difference reached significance only for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone collagen degradation that increases moderately after menopause, the proportion of the variance explained by genetic factors was highly significant (P = 0.002). In conclusion, our data indicate that a proportion of the variance in postmenopausal levels of both bone formation and resorption markers are explained by genetic factors, but this contribution was clearly significant only for markers that do not change markedly at the menopause. These data suggest that the contribution of genetic factors to overall postmenopausal bone turnover and possibly bone loss is likely to be small.

Association of metabolic syndrome with knee and hand osteoarthritis: A community-based study of women.

18 September 2018

OBJECTIVE: It is unclear whether the association between osteoarthritis (OA) and metabolic syndrome (MetS) varies with the site of the affected joint and the presence of pain. Our aim was to describe the association between MetS and radiographic OA (ROA) affecting the knee or the hand in the presence or absence of concurrent joint pain. METHODS: Cross-sectional data of 952 women, aged 45-65 years from the Chingford study, a population-based longitudinal cohort of middle-aged women initiated in 1988-1989 in London (UK), was analysed. MetS was defined using the National Cholesterol Education Program Treatment Panel III criteria. Data was collected on components of MetS: waist circumference, triglycerides, high-density lipoprotein (HDL), blood pressure and blood glucose. The outcome was four knee and hand OA groups: painful ROA, ROA only, pain only and neither ROA nor pain (reference category). Multinomial logistic regression models adjusted for age and body mass index (BMI) were used to evaluate the effect of presence of MetS and its individual components on OA subgroups for knee and hand separately. RESULTS: 952 eligible women, aged 45-65 years was analysed. A significant association was observed between the presence and the number of MetS with painful knee ROA when adjusted for age; however, this association disappeared when BMI was included in the model. In contrast, the presence and the number of MetS were associated with painful interphalangeal (IPJ) OA after adjusting for both age and BMI. Four out of the five MetS components, including triglycerides, HDL-c, hypertension and glucose, were associated with painful IPJ OA. CONCLUSIONS: MetS is associated with painful IPJ OA but not with knee OA once BMI is taking into consideration. Further attention to MetS and OA at different sites is needed to understand the metabolic phenotype in OA.

Models of care for the delivery of secondary fracture prevention after hip fracture: a health service cost, clinical outcomes and cost-effectiveness study within a region of England

18 September 2018