Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Pulsed resources affect the timing of first breeding and lifetime reproductive success of tawny owls.

1. According to life-history theory, environmental variability and costs of reproduction account for the prevalence of delayed reproduction in many taxa. Empirical estimates of the fitness consequences of different ages at first breeding in a variable environment are few however such that the contributions of environmental and individual variability remains poorly known. 2. Our objectives were to elucidate processes that underpin variation in delayed reproduction and to assess lifetime consequences of the age of first breeding in a site-faithful predator, the tawny owl Strix aluco L. subjected to fluctuating selection linked to cyclical variation in vole density (typically 3-year cycles with low, increasing and decreasing vole densities in successive years). 3. A multistate capture-recapture model revealed that owl cohorts had strikingly different juvenile survival prospects, with estimates ranging from 0.08 to 0.33 respectively for birds born in Decrease and Increase phases of the vole cycle. This resulted in a highly skewed population structure with >75% of local recruits being reared during Increase years. In contrast, adult survival remained constant throughout a vole cycle. The probability of commencing reproduction was lower at age 1 than at older ages, and especially so for females. From age 2 onwards, pre-breeders had high probabilities of entering the breeding population. 4. Variation in lifetime reproductive success was driven by the phase of the vole cycle in which female owls started their breeding career (26-47% of variance explained, whether based on the number of local recruits or fledglings), more than by age at first breeding or by conditions experienced at birth. Females who postponed reproduction to breed for the first time at age 3 during an Increase phase, produced more recruits, even when accounting for birds that may have died before reproduction. No such effects were detected for males. 5. Sex-specific costs of early reproduction may have accounted for females being more prone to delay reproduction. Contrary to expectations from a best-of-a-bad job strategy, early-hatched, hence potentially higher-quality females were more likely to breed at age 1, but then experienced rapidly declining food resources and so seemed caught in a life-history trap set by the multiannual vole cycle.

Spatial asynchrony and periodic travelling waves in cyclic populations of field voles.

We demonstrate evidence for the presence of travelling waves in a cyclic population of field voles in northern Britain by fitting simple, empirical models to spatially referenced time series data. Population cycles were broadly synchronous at all sites, but use of Mantel correlations suggested a strong spatial pattern along one axis at a projection line 72 degrees from North. We then fitted a generalized additive model to log population density assuming a fixed-form travelling wave in one spatial dimension for which the density at each site was offset in time by a constant amount from a standard density-time curve. We assumed that the magnitude of this offset would be proportional to the spatial separation between any given site and the centroid of the sampling sites, where separation is the distance between sites in a fixed direction. After fitting this model, we estimated that the wave moved at an average speed of 19 km yr-1, heading from West to East at an angle of 78 degrees from North. Nomadic avian predators which could synchronize populations over large areas are scarce and the travelling wave may be caused by density-dependent dispersal by field voles and/or predation by weasels, both of which act at a suitably small spatial scale.

Pregnancy detection and the effects of age, body weight, and previous reproductive performance on pregnancy status and weaning rates of farmed fallow deer (Dama dama).

Fallow does (n = 502) of different ages (mature, 2-yr-old, and yearling) were maintained with bucks for a 60-d breeding season to determine whether previous reproductive performance and changes in BW affect doe pregnancy rates and to compare the effectiveness of ultrasonography and serum pregnancy-specific protein B (PSPB) for the detection of pregnancy in fallow does. Ultrasonography was performed, blood samples collected, and BW recorded at buck removal (d 0) and at 30 and 90 d after buck removal. Lactational status (lactating = WET; nonlactating = DRY) were determined from farm records taken at weaning prior to each breeding season (autumn 1990 through autumn 1994). Ultrasonography and PSPB for determining pregnancy were in agreement 93% of the time. Overall pregnancy rates did not differ (P>.10) relative to age of the doe; the combined pregnancy rate was 92%. We also determined that 82.9% of does conceived early in the breeding season and that the incidence of embryonal-fetal mortality during the first 90 d after buck removal was 2.8%. In general, mature and 2-yr-old DRY does were heavier and had lower pregnancy rates than WET does. The overall weaning rate for all does was 77.9%. Loss in the number of fawns from pregnancy detection to weaning was equivalent to 14.8% for mature does, 24.7% for 2 yr old does, and 42.5% for yearling does. These data indicate that even though pregnancy rates were relatively high, further study is needed to determine the causes associated with subsequent fawn losses, particularly among yearling does. As a production tool, lactational WET/ DRY status testing was found to be an acceptable means for determining the reproductive potential of individual does within the herd. In addition, serum PSPB may be used in place of ultrasonography for pregnancy diagnosis in fallow deer as early as d 30 after buck removal.

Trichomoniasis in free-living goshawks (Accipiter gentilis gentilis) from Great Britain.

The goshawk Accipiter gentilis has recently been reintroduced into parts of Great Britain. During the course of a study of one population, lesions of stomatitis were observed in 14 young from five broods and all the affected birds died. Postmortem examination of three birds revealed live Trichomonas gallinae in exudate from one, and histological findings consistent with a diagnosis of trichomoniasis were made in this and one other bird. It is suggested that trichomoniasis may be a significant mortality factor in goshawks from Britain.

Anti-epileptic medication and bone health.

BACKGROUND: Epilepsy is a common chronic neurological disorder, usually requiring long-term treatment with anti-epileptic drugs (AED). Many studies have reported that AED therapy is associated with metabolic bone disease and is a major iatrogenic risk factor for fractures. There remains uncertainty about the type(s) of bone disease due to AED treatment, and the pathogenesis of AED-associated fractures. RATIONALE: Deficits in bone mineral density (BMD) are widely reported in AED-treated patient populations. However, much of the research conducted to date has been limited by factors such as small sample size, potentially biased subject selection, a lack of selection of appropriate control data, and failure to take account of important confounding influences. The pathogenesis of AED-associated fractures is likely to be multifactorial, due to factors including reduced BMD, impaired bone quality (due to osteoporosis and/or osteomalacia), increased propensity to fall, and fractures associated with seizures or loss of consciousness. RECOMMENDATIONS: Patients receiving long-term AED should be monitored for indices of bone health, including BMD and vitamin D status. Lifestyle factors should be optimized, vitamin D status maintained, and fall prevention strategies introduced as appropriate. Good seizure control is important. The use of additional, specific osteoporosis therapy is not evidence-based in this setting, but would appear reasonable in patients with clinically significant decreases in BMD, applying current treatment guidelines for osteoporosis. CONCLUSION: There is a pressing need for improved understanding of the pathogenesis of AED-associated bone disease, for better definition of the risk associated with specific AED regimens, and for the development of evidence-based preventive and treatment approaches in this common but neglected disorder.

Effect of antiepileptic medication on bone mineral measures.

OBJECTIVE: Long-term antiepileptic drug (AED) use has been associated with bone disease, but many previous studies have been limited by inadequate control subjects. We used a cotwin affected sib-pair model to investigate this issue. METHODS: The authors studied 31 female twin (15 monozygous and 16 dizygous) and four sibling pairs (< 3 years age difference) aged 21 to 75 years, in which one member had > 12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2) was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and total forearm (FA). Three primary a priori defined subgroups were analyzed: a) use for > 2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years. RESULTS: For all pairs (n = 35), there were no significant within-pair differences in any ABMD measure. However, in Subgroup a (n = 27), there was a within-pair difference at the FA (0.513 vs 0.534, -3.9%, p = 0.016). In Subgroup b (n = 29), there was also a within-pair difference at the FA for AED user vs nonuser (0.508 vs 0.529, -3.8%, p = 0.010). In Subgroup c (n = 15), there were within-pair differences at the FA (0.492 vs 0.524, -6.1%, p = 0.017) and the LS (0.884 vs 0.980, -9.8%, p = 0.036). CONCLUSIONS: Patients using AEDs for > 2 years, in particular those taking enzyme-inducing AEDs and those older than 40 years, have significantly lower bone mineral density at clinically relevant fracture risk sites.