Biomedical subjects

G C Nicholson

Publications and source records attributed to G C Nicholson.

At least 19 recordsLinked to original sources

PubMed2006

The population burden of fractures originates in women with osteopenia, not osteoporosis.

INTRODUCTION: Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture. METHODS: We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60-94 years and followed these individuals for a median of 5.6 years (IQR 3.9-6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture. RESULTS: Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32-2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01-1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40-2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone. CONCLUSIONS: Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.

Aged↗

PubMed2006

Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal allergic responses.

BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.

Administration, Intranasal↗

PubMed2005

Femoral neck geometry and hip fracture risk: the Geelong osteoporosis study.

To determine the relationship between femoral neck geometry and the risk of hip fracture in post-menopausal Caucasian women, we conducted a retrospective study comparing the femoral neck dimensions of 62 hip fracture cases to those of 608 randomly selected controls. Measurements were made from dual-energy X-ray absorptiometry scans (Lunar DPX-L), using the manufacturer's ruler function, and included: hip axis length (HAL), femoral neck axis length (FNAL), femoral neck width (FNW), femoral shaft width (FSW), medial femoral shaft cortical thickness (FSCT(med)), and lateral femoral shaft cortical thickness (FSCT(lat)). The fracture group was older (median age 78.3 years vs 73.8 years), lighter (median weight 59.9 kg vs 64.5 kg), and, after adjustment for age, taller (mean height 158.7+/-0.8 cm vs 156.7+/-0.2 cm) than the controls. Furthermore, bone mineral density was lower in this group (0.682+/-0.016 g/cm(2) vs 0.791+/-0.006 g/cm(2)). After adjustment for age, bone mineral content (BMC) or height, hip fracture patients had greater FNW (up to 6.6%) and FSW (up to 6.3%) than did the controls. Each standard deviation increase in FNW and FSW was associated with a 1.7-fold (95% CI 1.3-2.3) and a 2.4-fold (95% CI 1.8-3.2) increase in the fracture risk, respectively. BMC-adjusted FNAL was greater in the fracture group (+2.1%) than in the controls, while the age-adjusted FSCT(med) was reduced (-7.2%). There was a trend towards longer HAL (up to 2.1%) after adjustment for age or BMC, and thinner age-adjusted FSCT(lat) (-1.7%) in fracture patients that did not reach statistical significance. In multivariate analysis, the risk of hip fracture was predicted by the combination of age, FNW, FSW, BMC and FSCT(med). HAL was not analyzed because of the small number of HAL measurements among fracture cases. We conclude that post-menopausal women with hip fractures have wider femoral necks and shafts, thinner femoral cortices and longer femoral neck axis lengths than do women with no fractures. Alteration in hip geometry is associated with the risk of hip fracture.

Absorptiometry, Photon↗

PubMed2005

Risedronate prevents bone loss in early postmenopausal women: a prospective randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and tolerability of risedronate, a pyridinyl bisphosphonate, in preventing loss of bone mineral density (BMD) of the lumbar spine and proximal femur in early postmenopausal women. METHODS: A total of 383 patients were randomly assigned to receive risedronate 2.5 or 5 mg or placebo once daily for 24 months. All patients received 1 g elemental calcium daily. BMD was measured by dual X-ray absorptiometry at baseline and at 3, 6, 12, 18, and 24 months. RESULTS: Risedronate 5 mg significantly increased BMD at the lumbar spine and femoral neck and trochanter in early postmenopausal women. Significant results were observed as early as 3 months. In the control calcium-supplemented group, BMD decreased steadily at each site throughout the study. The mean percentage change from baseline in BMD in the risedronate 5 mg group was significantly different from that in the control group at each determination at each site. At 24 months, the differences were 4.5 +/- 0.45% at the lumbar spine, 3.3 +/- 0.49% at the femoral neck, and 4.3 +/- 0.67% at the femoral trochanter. Risedronate 2.5 mg maintained BMD at each site, although the effect was less pronounced than that of risedronate 5 mg. Risedronate was well tolerated and was not associated with an increased incidence of overall or upper gastrointestinal adverse events. CONCLUSIONS: Risedronate 5 mg prevents bone loss in early postmenopausal women, is well tolerated, and represents an effective choice to maintain bone mass and prevent osteoporosis.

Absorptiometry, Photon↗

PubMed2005

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Adrenal Cortex Hormones↗

PubMed2004

Dietary omega-3 fatty acids and depression in a community sample.

To evaluate the association between omega-3 polyunsaturated essential fatty acids and depression, data regarding prevalence rates of self-reported depression and median daily dietary intakes of these fatty acids were obtained from an age-stratified, population-based sample of women (n = 755; 23-97 year) in the Barwon Statistical Division of south-eastern Australia. A self-report questionnaire based on Diagnostic and Statistical Manual-IV criteria was utilised to determine 12-month prevalence rates of depression in this sample, and data from biennial food frequency questionnaires examining seafood and fish oil consumption over a 6-year period were examined. Differences in median dietary intakes of omega-3 fatty acids between the depressed and nondepressed cohorts were analysed and results were adjusted for age, weight and smoking status. No significant differences in median intakes were identified between the two groups of women (median, interquartile range; depressed = 0.09g/day, 0.04-0.18 versus nondepressed = 0.11 g/day, 0.05-0.22, p = 0.3), although overall average intakes of omega-3 fatty acids were lower than recommended and rates of depression within this sample higher than expected, based on previous data. Further research that takes into account ratios of omega-6 to omega-3 polyunsaturated essential fatty acids, as well as other dietary sources of omega-3 fatty acids, is warranted.

Adult↗

PubMed2004

Reference ranges for bone densitometers adopted Australia-wide: Geelong osteoporosis study.

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

Absorptiometry, Photon↗

PubMed2003

Bone density changes in Paget's disease 2 years after iv pamidronate: profound, sustained increases in pagetic bone with severity-related loss in forearm nonpagetic cortical bone.

Bone mineral density (BMD) was measured at three sites (forearm, spine, and hip) using dual X-ray and single-photon absorptiometry in 68 patients with Paget's disease before and after treatment with iv pamidronate. Patients were treated according to the severity of their disease; the mild category (Group I, hydroxyproline excretion (Hyp(E)) <5.0 micromol/L GF) received 120 mg, the moderate category (Group II, Hyp(E) 5.0-9.99 micromol/GF) 180 mg, and the severe category (Group III, > or = 10.0 micromol/GF) 240 mg. Group I was followed for 1 year, and both Groups II and III for 2 years. At the lumbar spine in pagetic bone there were no differences between groups in early responses, with a profound increase 6 months after treatment 20.5 +/- 2.0% above baseline values to 1.403 +/- 0.063 g/cm(2) (mean +/- SEM)(P < 0.001). This increase in BMD was sustained to 2 years (1.355 +/- 0.078 g/cm(2), P < 0.001) and was 15.0 +/- 2.2% above baseline values. The pagetic total hip BMD increased after treatment in all groups, with a mean rise of 10.4 +/- 1.4% at 1 year to 1.505 +/- 0.083 g/cm(2) (P < 0.01). At the pagetic femoral neck the response was similar, with a peak significant rise at 1 year of 10.7 +/- 1.7% to 1.403 +/- 0.097 g/cm(2) (P < 0.01). In nonpagetic spinal bone there were no differences between the group responses, with a combined mean increase of 4.3 +/- 0.7% at 1 year to 0.999 +/- 0.027 g/cm(2) (P < 0.01). In both Groups II and III the increase in BMD was significantly higher than baseline values at 1 and 2 years (P < 0.01). In the nonpagetic total hip BMD remained unchanged over the 2-year period and likewise, there were no significant changes from baseline at the nonpagetic femoral neck site. In the nonpagetic forearm we found a significant loss in BMD at the ultradistal (mainly trabecular), midregion (80% cortical), and proximal shaft (95% cortical) sites in Group III, persisting to 2 years at the latter two sites. The increase in bone density in pagetic bone, persisting at least 2 years, provides a new modality of assessment of the response of pagetic bone to treatment and suggests a mechanism for the reduction in fracture risk in such bone after effective bisphosphonate treatment. Severity-dependent nonpagetic forearm bone loss, persisting to 2 years at cortical sites, suggests a potential drug-induced fracture risk at the forearm and possibly elsewhere in the absence of appropriate preventive cotreatment.

Aged↗

PubMed2003

The Taq IA and Ser311 Cys polymorphisms in the dopamine D2 receptor gene and obesity.

Dopamine D2 receptors (DRD2) in the central nervous system are involved in the regulation of feeding. It remains to be elucidated if mutations in the DRD2 gene contribute to the development of obesity. The aim of the present study was to investigate whether the Taq IA and Ser311Cys polymorphisms in the DRD2 gene are associated with obesity in Nauruan and Australian subjects. Subjects were selected based on extremes of the body mass index (BMI) distribution. Two groups of Australian women were selected. The leanest group had a mean BMI of 22.5 kg/m2 (range: 20.3-24.3) and the heaviest group had a mean of 36.1 kg/m2 (32.5-44.1). Four groups of Nauruan subjects were selected. Leanest men had a mean BMI of 33.0 kg/m2 (28.4-36.9), heaviest men had a mean of 52.8 kg/m2 (46.5-69.2), leanest women had a mean of 34.8 kg/m2 (28.2-41.8) and heaviest women had a mean of 55.1 kg/m2 (49.3-73.8). Subjects were genotyped for the Taq IA and Ser311Cys polymorphisms using polymerase chain reaction (PCR) restriction fragment length polymorphism analysis and allelic discrimination Taqman PCR respectively. Leanest and heaviest groups were examined for differences in genotype frequency. Taq IA and Ser311Cys genotype frequencies did not differ significantly between leanest and heaviest Nauruan groups, or between leanest and heaviest Australians. Haplotype frequencies of these polymorphisms did not differ between leanest and heaviest groups. The Taq IA and Ser311Cys polymorphisms in the DRD2 gene are unlikely to be common causes of obesity in these populations.

Adult↗

PubMed2002

A randomized trial of sodium fluoride (60 mg) +/- estrogen in postmenopausal osteoporotic vertebral fractures: increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures.

Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean +/- SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 31). In the second study 34 patients, age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17; E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to +/- NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p=0.004); total hip -4.1% (p = 0.003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p < 0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.

Adult↗

PubMed2002

Fracture thresholds revisited. Geelong Osteoporosis Study.

Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < -2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.

Adult↗

PubMed2002

Fracture rates lower in rural than urban communities: the Geelong Osteoporosis Study.

BACKGROUND: Urban and rural communities differ in the incidence of several diseases including coronary heart disease and some cancers. Lower hip fracture rates among rural than urban populations have been reported but few studies have compared rural and urban fractures at sites other than the hip. OBJECTIVE: To compare total and site specific fracture rates among adult residents of rural and urban communities within the same population. DESIGN AND SETTING: This is a population based study on osteoporosis in Australia. All fractures occurring in adult residents over a two year period were ascertained using radiological reports. The rural and urban areas are in close proximity, with the same medical, hospital, and radiological facilities permitting uniform fracture ascertainment. MAIN OUTCOME MEASURES: All fracture rates were age adjusted and sex adjusted to the Australian population according to the 1996 census of the Australian Bureau of Statistics and described as the rate per 10 000 person years. The p values refer to the adjusted rate difference. RESULTS: The hip fracture rate (incidence per 10 000 person years) was 32% lower (39 v 57, p<0.001), and the total fracture rate 15% lower (160 v 188, p=0.004) among rural than urban residents, respectively. The lower fracture rates in the rural population were also apparent for pelvic fractures. CONCLUSION: In the older rural population, lower fracture rates at sites typically associated with osteoporosis suggest environmental factors may have a different impact on bone health in this community. If the national rate of hip fracture could be reduced to that of the rural population, the projected increase in hip fracture number attributable to aging of the population could be prevented.

Adult↗

PubMed2002

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo.

Fat mass is an important determinant of bone density, but the mechanism of this relationship is uncertain. Leptin, as a circulating peptide of adipocyte origin, is a potential contributor to this relationship. Recently it was shown that intracerebroventricular administration of leptin is associated with bone loss, suggesting that obesity should be associated with low bone mass, the opposite of what is actually found. Since leptin originates in the periphery, an examination of its direct effects on bone is necessary to address this major discrepancy. Leptin (>10(-11) m) increased proliferation of isolated fetal rat osteoblasts comparably with IGF-I, and these cells expressed the signalling form of the leptin receptor. In mouse bone marrow cultures, leptin (>or=10(-11) m) inhibited osteoclastogenesis, but it had no effect on bone resorption in two assays of mature osteoclasts. Systemic administration of leptin to adult male mice (20 injections of 43 micro g/day over 4 weeks) reduced bone fragility (increased work to fracture by 27% and displacement to fracture by 21%, P<0.001). Changes in tibial histomorphometry were not statistically significant apart from an increase in growth plate thickness in animals receiving leptin. Leptin stimulated proliferation of isolated chondrocytes, and these cells also expressed the signalling form of the leptin receptor. It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity. When administered systemically, the direct actions of leptin outweigh its centrally mediated effects on bone, the latter possibly being mediated by leptin's regulation of insulin sensitivity.

Animals↗

PubMed2001

Vitamin D status of women in the Geelong Osteoporosis Study: association with diet and casual exposure to sunlight.

OBJECTIVE: To assess vitamin D intake and casual exposure to sunshine in relation to serum 25-hydroxyvitamin D (25OHD) levels. DESIGN: Cross-sectional study of a population-based, random sample of women aged 20-92 years, assessed between 1994 and 1997. SETTING AND PARTICIPANTS: 861 women from the Barwon Statistical Division (population, 218000), which includes the city of Geelong (latitude 38 degrees south) in Victoria. MAIN OUTCOME MEASURES: Vitamin D intake; serum 25OHD level; season of assessment; exposure to sunshine. RESULTS: Median intake of vitamin D was 1.2 microg/day (range, 0.0-11.4 microg/day). Vitamin D supplements, taken by 7.9% of participants, increased intake by 8.1% to 1.3 microg/day (range, 0.0-101.2 microg/day) (P< 0.001). A dose-response relationship in serum 25OHD levels was observed for sunbathing frequency before and after adjusting for age (P< 0.05). During winter (May-October), serum 25OHD levels were dependent on vitamin D intake (partial r2= 0.01; P<0.05) and were lower than during summer (November-April) (age-adjusted mean, 59nmol/L [95% Cl, 57-62] v 81 nmol/L [95% CI, 78-84]; P<0.05). No association was detected between serum 25OHD and vitamin D intake during summer. The prevalences of low concentrations of serum 25OHD were, for <28nmol/L, 7.2% and 11.3% overall and in winter, respectively; and, for <50 nmol/L, 30.0% and 43.2% overall and in winter, respectively. CONCLUSIONS: At latitude 38 degrees south, the contribution of vitamin D from dietary sources appears to be insignificant during summer. However, during winter vitamin D status is influenced by dietary intake. Australia has no recommended dietary intake (RDI) for vitamin D, in the belief that adequate vitamin D can be obtained from solar irradiation alone. Our results suggest that an RDI may be needed.

Adult↗

PubMed2001

Genomewide search in familial Paget disease of bone shows evidence of genetic heterogeneity with candidate loci on chromosomes 2q36, 10p13, and 5q35.

Paget disease of bone (PDB) is a common disorder characterized by focal abnormalities of increased and disorganized bone turnover. Genetic factors are important in the pathogenesis of PDB, and previous studies have shown that the PDB-like bone dysplasia familial expansile osteolysis is caused by activating mutations in the TNFRSF11A gene that encodes receptor activator of nuclear factor kappa B (RANK); however, linkage studies, coupled with mutation screening, have excluded involvement of RANK in the vast majority of patients with PDB. To identify other candidate loci for PDB, we conducted a genomewide search in 319 individuals, from 62 kindreds with familial PDB, who were predominantly of British descent. The pattern of inheritance in the study group as a whole was consistent with autosomal dominant transmission of the disease. Parametric multipoint linkage analysis, under a model of heterogeneity, identified three chromosomal regions with LOD scores above the threshold for suggestive linkage. These were on chromosomes 2q36 (LOD score 2.7 at 218.24 cM), 5q35 (LOD score 3.0 at 189.63 cM), and 10p13 (LOD score 2.6 at 41.43 cM). For each of these loci, formal heterogeneity testing with HOMOG supported a model of linkage with heterogeneity, as opposed to no linkage or linkage with homogeneity. Two-point linkage analysis with a series of markers from the 5q35 region in another large kindred with autosomal dominant familial PDB also supported linkage to the candidate region with a maximum LOD score of 3.47 at D5S2034 (187.8 cM). These data indicate the presence of several susceptibility loci for PDB and identify a strong candidate locus for the disease, on chromosome 5q35.

Chromosome Mapping↗

PubMed2001

Serum leptin levels are associated with bone mass in nonobese women.

Both serum leptin and bone mineral density are positively correlated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r(2) = 0.019 to 0.036; all P < 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r(2) = 0.030; P = 0.011), was of borderline significance at the proximal femur sites (partial r(2) = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other sites. Our results demonstrate an association between serum leptin levels and bone mass consistent with the hypothesis that circulating leptin may play a role in regulating bone mass.

Adult↗

PubMed2001

Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study.

Osteoporosis in men is an emerging public health problem. As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women, we conducted a prospective study of this treatment in men with primary osteoporosis. Our study was a 2-yr, randomized, double masked, double placebo-controlled trial of calcitriol (0.25 microg twice daily) or calcium (500 mg twice daily) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture. Thirty-three men (85%) completed the study. There were no differences in baseline characteristics. Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups. Serum osteocalcin decreased in both groups by 30% (P < 0.05), whereas urine N-telopeptide cross-links decreased only in the calcium group by 30% (P < 0.05). After 2 yr, fractional calcium absorption increased by 34% (P < 0.01) in the calcitriol group. Nineteen incident fragility fractures occurred (14 vertebral and 5 nonvertebral) in 7 men. Over 2 yr, the number of men with vertebral fractures (6 vs. 1; P = 0.097) was similar in both groups. In conclusion, the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men.

Adult↗

PubMed2001

Assessment of fracture risk: value of random population-based samples--the Geelong Osteoporosis Study.

Fracture risk is determined by bone mineral density (BMD). The T-score, a measure of fracture risk, is the position of an individual's BMD in relation to a reference range. The aim of this study was to determine the magnitude of change in the T-score when different sampling techniques were used to produce the reference range. Reference ranges were derived from three samples, drawn from the same region: (1) an age-stratified population-based random sample, (2) unselected volunteers, and (3) a selected healthy subset of the population-based sample with no diseases or drugs known to affect bone. T-scores were calculated using the three reference ranges for a cohort of women who had sustained a fracture and as a group had a low mean BMD (ages 35-72 yr; n = 484). For most comparisons, the T-scores for the fracture cohort were more negative using the population reference range. The difference in T-scores reached 1.0 SD. The proportion of the fracture cohort classified as having osteoporosis at the spine was 26, 14, and 23% when the population, volunteer, and healthy reference ranges were applied, respectively. The use of inappropriate reference ranges results in substantial changes to T-scores and may lead to inappropriate management.

Absorptiometry, Photon↗