Quantitative ultrasound of the heel as triage test to measure bone mineral density compared with dual energy X-ray absorptiometry in men with prostate cancer commencing with androgen deprivation therapy.

OBJECTIVE: Androgen deprivation therapy (ADT) puts patients at an increased risk of developing osteoporosis. Assessment of bone mineral density (BMD) is most commonly performed by dual energy X-ray absorptiometry (DXA). Alternative ways of estimating BMD, such as quantitative ultrasound (QUS) measurement of the heel, are explored as DXA is expensive, non-portable and uses ionising radiation. We therefore investigated the diagnostic value of QUS as compared with DXA in patients commencing ADT. METHODS: In this cross-sectional study of 60 patients with prostate cancer who were about to start ADT, BMD was measured with DXA and QUS. The fracture risk score, as implemented by the Dutch National Osteoporosis Guideline, was also measured. RESULTS: No significant correlations were found between the separate DXA T scores and worst DXA T score, and the QUS T scores. Correlations between DXA T scores/QUS scores and fracture risk score were also non-significant. If QUS had been used as a screening tool, with a threshold of T ≤ -0.5 to perform DXA, then relevant osteopenia/osteoporosis (worst DXA T score ≤ -2.0) would have been missed in 1/18 (5.6%) patients. The negative predictive value is 0.95. Using QUS as a screening test prior to DXA and a QUS threshold T score ≤ -0.5 would avoid 21 (35%) DXA scans at the cost of missing one (5.6%) case. CONCLUSION: QUS testing cannot replace DXA scans fully as a diagnostic test. However, QUS can be incorporated as triage test prior to DXA to reduce the need for unnecessary DXA scans and the associated costs.

Mannose-binding lectin polymorphisms are not associated with rheumatoid arthritis--confirmation in two large cohorts.

OBJECTIVES: In RA, conflicting results have been described on the association between genotypes of the complement factor mannose-binding lectin (MBL) and disease susceptibility and severity. This might be due to underpowerment of previous research work and the fact that no confirmation cohorts were used. Therefore a different approach is warranted. METHODS: MBL2 gene polymorphisms were determined in two RA cohorts (378 and 261 cases) and 648 controls. Considering MBL polymorphisms, cases and controls were categorized in groups of high, intermediate and low MBL production. The total sample size allows detection of a potential association between RA susceptibility and MBL groups with an odds ratio of 1.37 (alpha < 0.05; 1-beta > 0.8). Disease severity as defined by the need for anti-TNF therapy was also analysed for possible associations with MBL groups. RESULTS: There was no difference in the frequencies between MBL genotypes of RA cases and controls that are associated with high (cases 54.4%, controls 57.0%), intermediate (cases 28.9%, controls 27.5%) or low (cases 16.7%, controls 15.5%) MBL production. Furthermore, there was no association between MBL groups and disease severity. CONCLUSIONS: MBL genotype groups are not associated with RA disease susceptibility or severity in this large study including a confirmation cohort. Compared with previous smaller studies these results add to more definite conclusions.

Mannose-binding lectin genotypes are associated with shorter gestational age. An evolutionary advantage of low MBL production genotypes?

BACKGROUND: The complement factor mannose-binding lectin (MBL) is associated with adverse pregnancy outcome. MBL serum concentrations are increased from early pregnancy onwards and depend upon several gene polymorphisms. We investigated whether MBL polymorphisms are associated with term and preterm birth, since preterm birth is the leading cause of neonatal morbidity and mortality. METHODS: MBL2 gene polymorphisms were determined in 157 nulliparous women. Considering MBL polymorphisms cases were categorized in groups of high (A), intermediate (B) and low (C) MBL production. Kaplan-Meier survival and multiple linear regression analysis were performed. RESULTS: Women with high MBL genotype group A had a shorter gestational age (274 days+/-S.D. 21) than the women with the intermediate MBL genotype group B (283 days+/-S.D. 12) and the low MBL genotype group C (284 days+/-S.D. 9). This difference in mean gestational age is almost totally attributable to premature births in group A, since 12 of the 14 preterm births were from women with the high MBL genotype group A and only two from the intermediate MBL genotype group B. CONCLUSIONS: We found an association between the maternal high MBL genotype group A and premature birth, suggesting that during pregnancy MBL-associated inflammation caused by higher MBL activity may contribute to earlier delivery. Furthermore, this finding might explain why so many individuals are MBL deficient in the general population.

Mannose-binding lectin levels during pregnancy: a longitudinal study.

BACKGROUND: Pregnancy is associated with changes in the immune system. Although previous studies have focussed mainly on adaptive immunity, there are indications that components of innate immunity, such as mannose-binding lectin (MBL), are associated with pregnancy outcome. Although this would suggest that pregnancy also involves adaptations in innate immunity, there are few studies in this area. Therefore, we aimed to determine whether MBL concentrations and the following steps in complement pathway activation are influenced by pregnancy. METHODS: MBL and Ficolin-2 concentrations, MBL-MBL-associated serine protease (MASP) complex activity, MBL pathway activity and classical complement pathway activity were determined by enzyme-linked immunosorbent assay (ELISA) in sera from pregnant women (n=32) during each trimester and post-partum. MBL genotyping was performed by PCR. RESULTS: During pregnancy, MBL concentrations increased to 140% [interquartile range (IQR) 116-181%, P < 0.0001]. This increase was already present at 12 weeks of pregnancy and was most pronounced in the high-production AA-genotype. Directly Post-partum MBL concentrations dropped to 57% of baseline (IQR 44-66%, P < 0.0001). Variations in MBL levels were reflected by similar changes in the following steps of complement activation, r > 0.93 (P < 0.01). Ficolin-2 levels and classical complement pathway activity were not similarly influenced by pregnancy. CONCLUSIONS: Pregnancy and the post-partum period profoundly influence MBL serum concentration and MBL complement pathway activity.