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This cross-sectional twin study examined the influence of constitutional, lifestyle, and genetic factors on bone mineral density (BMD) in elderly women. BMD, at the lumbar spine, femoral neck, Ward's triangle, total hip, and total forearm, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry in 69 volunteer female twin pairs (37 monozygotic [MZ], 32 dizygotic [DZ]) aged 60-89 years. Height and weight were measured. Medical history and lifetime tobacco and alcohol use were determined by questionnaire. In terms of within-pair differences, lean mass was independently associated with BMD at all sites. In contrast, fat mass was not associated with BMD at any site once allowance had been made for lean mass. Lifetime tobacco use was independently associated with BMD at the lumbar spine, total hip, and forearm. Total body BMC was independently predicted by lean mass, fat mass, tobacco use, and alcohol consumption. Age and the above independently predictive body composition and lifestyle factors accounted for 20-33% of variation in BMD. After allowing for these covariates, MZ and DZ correlations were consistent with about 75% of residual variation in BMD at the nonforearm sites being determined by genetic factors. For total body BMC, the covariates explained 75% of total variation, and genetic factors 76% of the residual variation. Therefore, at the proximal femur and lumbar spine, after taking into account the relation of BMD with lean mass and smoking, genetic factors appear to play a substantial role in explaining variation in BMD in elderly women.

Wolbachia pipientis is an obligate intracellular bacterium within the family Anaplasmataceae that infects many terrestrial arthropods and arthropod-transmitted nematodes (filariae). Several filarial species are major human pathogens, and antibiotics with activity against Wolbachia offer a promising new therapeutic approach, since the adult worms are relatively refractory to conventional anthelmintics but depend on Wolbachia for reproduction and viability. In a natural filarial parasite of cattle, Onchocerca ochengi, intermittent chemotherapy is adulticidal whereas the equivalent dose administered as a continuous treatment is not. To investigate this further and to aid the design of efficacious regimens for human therapy, we used Wolbachia-infected Aedes albopictus mosquito cells in vitro. Here, we describe for the first time the accelerated depletion of bacteria after antibiotic withdrawal relative to the rate of elimination in the continuous presence of the drug. Mosquito cells were incubated with doxycycline while changes in 16S (bacterial) and 18S (host) rRNA and rRNA genes were determined by quantitative PCR assays. In cultures treated for 7 or 14 days followed by 7 days of drug withdrawal, the Wolbachia-to-Aedes rRNA ratio declined by ϳ6 log, whereas immediately after 14 or 21 days of continuous treatment, the reduction was only ϳ4 log (P < 0.05). However, low levels of 16S rRNA remained after 21 days of treatment, irrespective of whether doxycycline was withdrawn. Application of similar methodology to related intracellular bacteria may reveal that this posttreatment effect is not restricted to Wolbachia and could have wider implications for the design of intermittent regimens for antibiotic chemotherapy.Wolbachia pipientis is an obligate intracellular bacterium within the order Rickettsiales and the family Anaplasmataceae (14) which infects a wide variety of arthropod taxa and is transmitted predominantly by the vertical route (39). In 1995 (38), the intracellular bacteria described 20 years earlier from several filarial nematode parasites (27) were identified as members of Wolbachia, and the acquisition of these organisms by the filariae is proposed to have occurred approximately 100 million years ago, via horizontal transfer from hematophagous arthropod vectors (4). Wolbachia spp. have been divided into six supergroups comprising A, B, E, and F in arthropods (4, 26) and C and D in filariae (4), but despite significant differences between the species at the 16S rRNA gene level, W. pipientis is the only formally recognized member of the genus (14).The major filarial diseases of humans, lymphatic filariasis and onchocerciasis (river blindness), are responsible for a combined global morbidity of 6.5 million disability-adjusted life years (35), and control and eradication strategies are constrained by the refractoriness of adult filariae to anthelmintics, such as ivermectin (7) and diethylcarbamazine (29). However, new opportunities for the adulticidal therapy of filarial diseases have arisen from the identif...

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