K Hynes

Sex and site differences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life.

OBJECTIVE To test the hypothesis that sex-related and joint compartment-related differences in the risk of osteoarthritis (OA) of the knee might be associated with variations in cartilage development, we investigated knee cartilage volume in healthy children. METHODS We studied 92 children who were randomly selected from among students in grades 3-12 of a single school in Hobart, Tasmania (49 boys, 43 girls; age range 9-18 years). Articular cartilage thickness and volume were determined at the patella, medial tibial compartment, and lateral tibial compartment by magnetic resonance imaging (MRI). Sagittal T1-weighted fat-suppressed MRI images were obtained and processed on an independent computer work station. RESULTS Males had significantly more knee cartilage than females. Sex accounted for 6-36% of the variation in cartilage thickness and volume, which was statistically significant at all sites. Even after adjustment for age, body mass index, bone area, and physical activity, males had 16-31% higher cartilage volume; this was most marked at the medial tibial site. In addition, lateral tibial thickness was greater than medial tibial thickness (5.9 versus 3.6 mm; P < 0.0001) and lateral tibial volume was greater than medial tibial volume (2,823 versus 2,299 microl; P < 0.0001). Furthermore, physical activity was a significant explanatory factor for cartilage volume at all sites (R2 7-14% depending on site; all P < 0.05). The most consistent activity association was with vigorous activity in the previous 2 weeks (difference between any vigorous activity versus none 22-25% greater; all P < 0.05). CONCLUSION Sex- and joint compartment-related differences in cartilage development may be one explanation for variations in the pattern of knee OA seen in later life. Furthermore, the physical activity associations suggest that cartilage development is amenable to modification.

Knee Articular Cartilage Development in Children: A Longitudinal Study of the Effect of Sex, Growth, Body Composition, and Physical Activity

The aim of this study was to describe the effect of sex, growth, Tanner stage, and physical activity on knee articular cartilage volume development. A total of 74 randomly selected male and female children aged 9–18 y were measured on two occasions at an average interval of 1.6 y (range 1.3–1.9). Articular cartilage volume was determined at the patella, medial tibial, and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance. Height, weight, and BMI were measured while Tanner stage and physical activity were assessed by questionnaire. Articular cartilage volume increased at all sites peaking in Tanner stage two. Males gained articular cartilage faster than females at all sites (patella +233 μL/y, 95% CI −7, +473, medial tibial +350 μL/y, 95% CI +118, +582, lateral tibial +256 μL/y, 95% CI +22, +488). In both sexes, articular cartilage volume accrual at tibial but not patella sites correlated significantly with height change but not weight change. Overweight children did not differ significantly from normal children in articular cartilage volume either cross-sectionally or longitudinally. The most consistent physical activity association was with average intensity of sport with those above the median gaining approximately twice as much as those below the median at tibial (p < 0.05) but not patella sites. In conclusion, most children gain articular cartilage during growth, but there is wide variation in the amount of articular cartilage accrual. In particular, younger children, males, and those undertaking more vigorous sports have substantially higher accrual rates. These results provide novel data on articular cartilage development in humans. The long-term significance of these results with regard to osteoarthritis of the knee in later life remains hypothetical.

Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose

Objectives To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA). Methods A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score. Results Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years. Conclusions In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404).

Persistent iodine deficiency in a cohort of Tasmanian school children: associations with socio-economic status, geographical location and dietary factors.

Objective: To determine the adequacy of iodine nutrition of Tasmanian primary school‐aged children and to examine possible associations with socio‐economic status (SES), location and dietary factors.

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males

Objective: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys.Design: Randomized double-blind placebo-controlled trial.Setting: Single school in northwest Tasmania.Participants: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y).Interventions: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up.Results: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR.Conclusions: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.Sponsorship: National Health and Medical Research Council of Australia, Arthritis Foundation of Australia.

Maternal alcohol intake and offspring pulse wave velocity

Background: Intrauterine exposure to alcohol may affect cardiovascular development, increasing risk of cardiovascular malformations. Intrauterine exposure to light maternal alcohol intake has been reported to affect human umbilical arterial contractility, and adult sheep exposed in utero have had altered cerebrovascular reactivity. In human adults, alcohol intake affects arterial stiffness. Objectives: We investigated whether intrauterine exposure to alcohol was associated with childhood pulse wave velocity (PWV), a measure of arterial stiffness. Methods: On postnatal day 4, mothers of 147 twin pairs born in Tasmania from 1991 to 1993 reported alcohol intake during each trimester of pregnancy. At 9 years, child PWV was assessed over carotid-femoral and femoral-dorsalis pedis arterial segments by applanation tonometry. Results: Carotid-femoral PWV was 0.2 m/s (95% CI 0.06, 0.4) higher (indicating stiffer vessels) in children whose mothers drank alcohol in the 2nd trimester rather than abstained, after adjusting for potential confounding factors. A similar effect was not seen for femoral-dorsalis pedis PWV. Findings were independent of child blood pressure which correlated strongly with PWV. Alcohol intake varied little between trimesters, so it was not possible to assess the effect of timing of exposure. Conclusions: Carotid-femoral PWV in adults is predictive of cardiovascular morbidity and mortality. The degree of continuity between childhood and adulthood PWV is unknown, but as we found an association between prenatal alcohol exposure and carotid-femoral PWV at 9 years, a permanent change in vessel wall structure or function is possible. These findings need to be confirmed in other and larger cohorts, and mechanistic animal studies are needed.

Reduced Educational Outcomes Persist into Adolescence Following Mild Iodine Deficiency in Utero, Despite Adequacy in Childhood: 15-Year Follow-Up of the Gestational Iodine Cohort Investigating Auditory Processing Speed and Working Memory

There is increasing evidence that even mild gestational iodine deficiency (GID) results in adverse neurocognitive impacts on offspring. It’s unclear, however, if these persist long-term and whether they can be ameliorated by iodine sufficiency in childhood. We followed a unique cohort (Gestational Iodine Cohort, n = 266) where gestation occurred during a period of mild population iodine deficiency, with children subsequently growing-up in an iodine replete environment. We investigated whether associations between mild GID and reductions in literacy outcomes, observed at age 9-years, persisted into adolescence. Comparisons were made between offspring of mothers with gestational urinary iodine concentrations (UICs) ≥ 150 μg/L and < 150 μg/L. Educational outcomes were measured using Australian National Assessment Program—Literacy and Numeracy (NAPLAN) tests. Children whose mothers had UICs < 150 μg/L exhibited persistent reductions in spelling from Year 3 (10%, −41.4 points (95% Confidence Interval −65.1 to −17.6, p = 0.001)) to Year 9 (5.6%, −31.6 (−57.0 to −6.2, p = 0.015)) compared to children whose mothers had UICs ≥ 150 μg/L. Associations remained after adjustment for biological factors, socioeconomic status and adolescent UIC. Results support the hypothesis that mild GID may impact working memory and auditory processing speed. The findings have important public health implications for management of iodine nutrition in pregnancy.

History of Iodine Deficiency in Schoolchildren in Tasmania, Australia

This chapter reviews the history of iodine deficiency, supplementation and monitoring of school age children in the state. The history of iodine nutrition from 1949, when the first survey and supplementation program was undertaken, to the late 1980s when the population was considered to be iodine sufficient is reviewed. Details of the surveys conducted to confirm the re-emergence of iodine deficiency following a period without regular monitoring are presented. And the outcomes of a subsequent voluntary program of bread fortification and a series of post-fortification urinary iodine surveys are discussed. The re-emergence of deficiency coincided with a decline in iodine levels in milk at a time when milk was the major dietary source of iodine for the population. Voluntary fortification of bread has led to improved iodine nutrition in Tasmanian children, although girls remain borderline deficient. Reliance on a serendipitous and nonlegislated supply of iodine, as was the case with milk, is dangerous and can lead to a rapid return to deficiency when industry practices change. Mandatory fortification, preferably universal salt iodization, is required to eliminate iodine deficiency in all groups in the population. Ongoing monitoring of the population will help ensure that iodine nutrition is adequate and does not return to deficiency.

The lack of effect of isoflavones on high-density lipoprotein cholesterol concentrations in adolescent boys: a 6-week randomised trial.

BACKGROUND A substantial fall in high-density lipoprotein cholesterol (HDL-C) during puberty in boys, but not girls, has been reported in Western populations. The fall in boys is believed to be due to hormonal changes--androgens have been shown to be associated with lower HDL-C, whereas oestrogens are associated with higher HDL-C. The fall in HDL-C during puberty was not observed, however, in a study of Moslem boys in Israel, nor in a group of Japanese boys. A diet high in phyto-oestrogens may account for the lack of a fall in HDL-C in these populations. OBJECTIVE To examine the effect of dietary supplementation with phyto-oestrogens on the HDL-C concentration of adolescent boys from a Western population. We hypothesised that dietary supplementation of 50 mg of the isoflavones daidzein and genistein would produce a 12% higher HDL-C concentration than in controls at the end of a 6-week intervention period. DESIGN A randomised controlled trial. SETTING Hellyer College in Burnie (Tasmania, Australia). SUBJECTS Adolescent boys (aged 16-18 years) were recruited through a letter sent to parents. A total of 132 eligible participants enrolled and five subjects withdrew from the trial. RESULTS No significant increase in HDL-C was observed in the treatment group (-0.02 mmol l(-1), standard error (SE)=0.03, P = 0.53) or the placebo group (0.05 mmol l(-1), SE = 0.03, P = 0.11). CONCLUSIONS Factors other than isolated dietary isoflavones may be responsible for the lack of fall in HDL-C during puberty in Japanese and Moslem boys.