Paternal uniparental isodisomy of the entire chromosome 3 revealed in a person with no apparent phenotypic disorders.

Uniparental disomy (UPD) is a rare genetic abnormality. During a whole genome linkage study we identified a case of paternal uniparental isodisomy 3 serendipitously. This is the first ascertained human paternal UPD for chromosome 3 (UPD3pat).

Genomewide linkage scan for quantitative trait loci underlying variation in age at menarche.

Context: Age at menarche (AAM) is an important anthropological variable that has major implications for a woman's health later in life. Genetic influence has been shown to contribute greatly to AAM, but the specific genetic determinants are largely unknown.

Objective: The objective of this study was to identify the quantitative trait loci (QTL) underlying the variations in AAM.

Tests of linkage and association of PTH/PTHrP receptor type 1 gene with bone mineral density and height in Caucasians.

Parathyroid hormone/parathyroid hormone-related peptide receptor type 1 (PTHR1) plays an important role in calcium metabolism. It was previously shown to influence variation in bone mineral density (BMD). To investigate its importance in a typical U.

Predictive factors for age at menopause in Caucasian females.

Objective: Early onset of menopause results in the premature exposure to low estrogen levels and is associated with a number of postmenopausal health problems and higher risk of mortality. The aim of this study was to determine genetic and environmental factors associated with age at natural and surgical menopause.

Methods: Multiple regression analysis using a sample of Caucasians composed of 154 females with surgical and 248 with natural menopause.

Race and sex differences and contribution of height: a study on bone size in healthy Caucasians and Chinese.

Osteoporosis is characterized by a loss of bone strength, of which bone size (BS) is an important determinant. However, studies on the factors determining BS are relatively few. The present study evaluated the independent effects of height, age, weight, sex, and race on areal BS at the hip and spine, measured by dual-energy X-ray absorptiometry, while focusing on the differential contributions of height to BS across sex, race, and skeletal site.

Contribution of genotype and ethnicity to bone mineral density variation in Caucasians and Chinese: a test for five candidate genes for bone mass.

Background: Ethnicity is shown to be one of important factors affecting bone mineral density (BMD). The present study was performed to compare the association of six markers for five candidate genes with BMD variation in two populations of different ethnicity, Caucasian and Chinese, and the contribution of genotype and ethnicity to this variation in the populations.

Methods: The studied restriction fragment length polymorphisms were BsaH I of the calcium-sensing receptor gene, SacI of the alpha2HS-glycoprotein (AHSG) gene, PvuII and XbaI of the oestrogen receptor alpha gene, ApaI of the vitamin D receptor (VDR) gene and BstBI of the parathyroid hormone gene.

Searching for obesity genes: progress and prospects.

Obesity is a condition of excess body fat that causes or exacerbates several major public health problems. Remarkable progress has been made in the molecular elucidation of monogenic forms of obesity both in rodents and in humans. The most common form of obesity, however, is considered to be a polygenic disorder arising from the interaction of multiple genetic and environmental factors.

The elusive concept of bone quality.

This paper outlines information from recent publications that aid our understanding of bone quality in relation to osteoporosis. In practical terms, bone quality designates the properties of bone that contribute to strength but are not assessed by bone densitometry. While osteoporosis is still defined in terms of bone density, the limitations of this approach, long questioned, have become indisputable.

Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women.

Objective: To compare medication adherence with daily vs weekly bisphosphonate dosing for the treatment or prevention of osteoporosis in a broad US retail pharmacy database population.

Patients And Methods: From October 2002 through September 2003, the medication possession ratio (MPR = days of supply/365 days) was used to assess medication adherence. The MPR was calculated by use of daily and weekly bisphosphonate doses in a longitudinal cohort of patients who received prescriptions from 14,000 US retail pharmacies.

Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study.

Unlabelled: Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year.

A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes.

Bone mineral density (BMD) is a major risk factor for osteoporosis. Circulating monocytes may serve as early progenitors of osteoclasts and produce a wide variety of factors important to bone metabolism. However, little is known about the roles of circulating monocytes in relation to the pathophysiology of osteoporosis.

A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate.

Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules.

Linkage exclusion analysis of two candidate regions on chromosomes 7 and 11: leptin and UCP2/UCP3 are not QTLs for obesity in US Caucasians.

Leptin (LEP) and the uncoupling proteins 2 and 3 (UCP2/UCP3) are key molecules involved in the regulation of food intake and energy expenditure. However, their contribution to variation of obesity phenotypes in the general population remains controversial. The present study is to investigate whether chromosomal regions 7q and 11q, which contain LEP and UCP2/UCP3, respectively, can be excluded for linkage with obesity phenotypes.

Association tests of interleukin-6 (IL-6) and type II tumor necrosis factor receptor (TNFR2) genes with bone mineral density in Caucasians using a re-sampling approach.

Interleukin 6 (IL-6) and tumor necrosis factor (TNF) are important cytokines for bone turnover. In this study, a promoter C-174G single-nucleotide polymorphism (SNP) within the IL-6 gene affecting the transcription rate of IL-6 and an exon 6 T676G SNP of the TNF receptor 2 (TNFR2) gene causing an M196R amino-acid change were examined for their relationship with bone mineral density (BMD). Four hundred and five multi-offspring Caucasian families, including 389 male children and 744 female children, were used.

The genetics of osteoporosis.

Osteoporosis is a common health problem among the elderly, especially postmenopausal women. It is characterized by fragile bones susceptible to low-trauma fractures. Osteoporosis is a complex disease determined by genetic and environmental factors, as well as the possible interactions among these factors.

Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families.

Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Genetic variations in the UCP3 gene have been conceived to affect body weight in the general population. In this study, using the quantitative transmission disequilibrium test (QTDT), we assessed linkage and association between the UCP3 gene and obesity phenotypes in a large sample of 1,873 subjects from 405 United States Caucasian nuclear families.

Ibandronate produces significant, similar antifracture efficacy in North American and European women: new clinical findings from BONE.

Objectives: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2 months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here.

Patients And Methods: BONE was a randomized, double-blind, placebo-controlled, fractureprevention study in 2946 postmenopausal women (age 55 years-80 years; > or = 5 years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4-L4]).

Trabecular bone microarchitecture after alendronate treatment of osteoporotic women.

Objective: To compare the microarchitecture of iliac crest trabecular bone from women treated for two to three years with alendronate versus that of women treated with placebo.

Research Design And Methods: Three-dimensional micro-computed tomography (micro-CT; resolution 20 microm) and two-dimensional histomorphometry (resolution 5-7 microm) were used to examine trabecular bone from single transilial biopsies obtained at the completion of clinical trials.

Main Outcome Measures: Microarchitectural variables, including bone volume, trabecular number, trabecular thickness, and trabecular spacing in specimens from alendronate- and placebo-treated women were examined.

Risedronate for prevention and treatment of osteoporosis in postmenopausal women.

Risedronate sodium is an N-containing bisphosphonate that has been approved for the prevention and treatment of osteoporosis in postmenopausal women. An increase in the rate of bone remodelling is a regular feature of oestrogen withdrawal during the menopausal transition, but excessive remodelling leads to bone fragility. Risedronate and similar compounds reduce the rate of bone remodelling by suppressing the action of osteoclasts.

Quantitative ultrasound: use in screening for susceptibility to stress fractures in female army recruits.

Unlabelled: QUS measurements were made on 4139 female Army recruits at the beginning of basic training (BT). QUS predicted stress fracture in female recruits as well as it predicts hip fracture in elderly women. Recruits with low QUS values and a history of smoking and not exercising had an extremely high risk of stress fracture.