Balance impairment in chronic antiepileptic drug users: a twin and sibling study.

PURPOSE: Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED-discordant, twin and sibling matched-pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer-duration AED; and falls history. METHODS: Twenty-nine same-sex (mean age 44.9 years, 59% female), ambulatory, community-dwelling twin and sibling pairs, discordant for AED exposure (and AED-indication), were recruited. Validated clinical and laboratory tests of strength, gait, and balance were performed. Relevant AED levels, and fasting serum samples for 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and immunoreactive parathyroid hormone (iPTH) levels were taken. RESULTS: There were significant mean within-pair differences in tests of static and dynamic balance, with the AED user having poorer balance function than the AED nonuser. No difference was seen in lower limb strength or gait measures. Increased duration of AED therapy and AED polytherapy were independent predictors of increased sway. No significant within-pair differences were seen in fasting serum levels of 1,25(OH)(2)D, 25OHD and iPTH after Bonferroni correction. DISCUSSION: Balance performance is impaired in AED users compared to their matched nonuser siblings. Pairs where the AED users took AED polytherapy, or had a longer duration of AED use, had more impaired balance performance. These balance deficits may contribute to the increased rate of fractures in this population.

Genetic and environmental influences on variation in balance performance among female twin pairs aged 21-82 years.

Genetic and environmental influences on variation in balance performance were measured in 93 monozygous and 83 dizygous female twin pairs aged 21-82 years (mean age, 50.5 years) in Melbourne, Australia, between 1999 and 2003. The authors administered clinical (Lord's Balance Test and Step Test) and laboratory tests of static and dynamic balance from the Chattecx Balance System with and without distractor tasks. The authors conducted factor analysis and estimated genetic and environmental variance components and heritability (defined as additive genetic variance as a proportion of all variance, after adjustment for age) using a multivariate normal model with the statistical package FISHER. Three factors were identified and adjusted for age. Heritability was 46% (standard error (SE), 9) for the "sensory balance tests" factor and 30% (SE, 9) for the "static and dynamic perturbations" factor. For both factors, the remaining variance was attributed to unique environmental effects. There was no evidence that genetic factors influenced variation in the "dynamic weight shift tests" factor, with environmental effects shared by twins accounting for 38% (SE, 7) of variance. Neither genetic nor environmental proportions of variance differed significantly between twin subgroups by age (50 years). An age-related decline in performance measures was found across the whole sample. These results imply that balance impairments may have a heritable element.

The effect of calcium supplementation on bone density in premenarcheal females: a co-twin approach.

The age and developmental stage at which calcium supplementation produces the greatest bone effects remain controversial. We tested the hypothesis that calcium supplementation may improve bone accrual in premenarcheal females. Fifty-one pairs of premenarcheal female twins (27 monozygotic and 24 dizygotic; mean +/- sd age, 10.3 +/- 1.5 yr) participated in a randomized, single-blind, placebo-controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate (Caltrate) supplement. Areal bone mineral density (aBMD) was measured at baseline and 6, 12, 18 and 24 months. There were no within-pair differences in height, weight, or calcium intake at baseline. Calcium supplementation was associated (P < 0.05) with increased aBMD compared with placebo, adjusted for age, height, and weight at the following time points from baseline: total hip, 6 months (1.9%), 12 months (1.6%), and 18 months (2.4%); lumbar spine, 12 months (1.0%); femoral neck, 6 months (1.9%). Adjusted total body bone mineral content was higher in the calcium group at 6 months (2.0%), 12 months (2.5%), 18 months (4.6%), and 24 months (3.7%), respectively (all P < 0.001). Calcium supplementation was effective in increasing aBMD at regional sites over the first 12-18 months, but these gains were not maintained to 24 months.

Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: a twin study.

BACKGROUND: The long-term effects of pregnancy and lactation on measures of bone mineral in women remain unclear. OBJECTIVE: We studied whether pregnancy or lactation has deleterious long-term effects on bone mineral in healthy women. DESIGN: We measured bone mineral density (BMD; g/cm(2)) in women aged > or = 18 y. Analyses were performed on 3 data sets: study 1, 83 female twin pairs (21 monozygous and 62 dizygous) aged (x +/- SD) 42.2 +/- 15.5 y who were discordant for ever having been pregnant beyond 20 wk; study 2, 498 twin pairs aged 42.3 +/- 15.0 y; and study 3, 1354 individual twins, their siblings, and family members. RESULTS: In study 1, there were no significant within-pair differences in unadjusted BMD or BMD adjusted for age, height, and fat mass at the lumbar spine or total-hip or in total-body bone mineral content (BMC; kg) (paired t tests). In study 2, there was no significant within-pair difference in measures of bone mineral or body composition related to the within-pair difference in number of pregnancies. In study 3, subjects with 1 or 2 (n = 455) and > or = 3 pregnancies (n = 473) had higher adjusted lumbar spine BMD (2.9% and 3.8%, respectively; P = 0.001) and total-body BMC (2.2% and 3.1%; P < 0.001) than did nulliparous women (n = 426). Parous women who breast-fed had higher adjusted total-body BMC (2.6%; P = 0.005), total-hip BMD (3.2%; P = 0.04), and lower fat mass (10.9%; P = 0.01) than did parous non-breast-feeders. CONCLUSION: We found no long-term detrimental effect of pregnancy or breast-feeding on bone mineral measures.

Hormone replacement therapy and bone mineral density: a co-twin approach.

OBJECTIVE: Our objective was to estimate the difference in bone mass at clinically relevant sites within female twin pairs who were discordant for use of hormone replacement therapy (HRT). METHODS: We studied 46 female twin pairs who were discordant for HRT use. Bone mineral content and density were measured at the lumbar spine, total hip, femoral neck, 13 total forearm, and the total body. HRT use, calcium intake, physical activity, alcohol intake, and lifetime smoking were determined by questionnaire. RESULTS: Within a pair, lumbar spine bone mineral density was significantly greater in past and current HRT users compared with nonusers (6.2% +/- 2.0%; P = 0.006). In those pairs who were currently using HRT, the within-pair difference in lumbar spine bone density was 7.8% +/- 2.1% (P = 0.002), and a significant within-pair difference in forearm bone density (5.1 +/- 2.1%; P = 0.02) was apparent. A significant difference (4.6%; P = 0.03) was observed in total body bone mineral content when an adjustment was made for age, lean mass, fat mass, and height. CONCLUSIONS: In keeping with randomized clinical trial findings, these results indicate that HRT in routine clinical use protects significantly against menopausal bone loss at the lumbar spine and the forearm. Our results also quantify the magnitude of the benefit of HRT on bone density that might be anticipated in clinical practice.