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  • 1
    Electronic Resource
    Electronic Resource
    Polymorphisms of the Vitamin D Receptor, Infant Growth, and Adult Bone Mass (1997)
    Springer
    Calcified tissue international 60 (1997), S. 233 -235 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Bone density — Vitamin D receptor — Polymorphism — Growth — Genetic.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Family and twin studies have demonstrated a strong genetic component to the development of peak bone mass. Early fetal and infant environment has also been shown to influence bone mass through an effect on skeletal size and mineral content. We report a retrospective study that has examined whether early infant growth is regulated by genetic factors shown to be associated with bone mass. We have determined the vitamin D receptor (VDR) gene alleles for 66 women (mean age 65.5 years) on whom detailed birth records were available. There was a statistically significant trend (P= 0.04) for VDR genotype against weight at the age of 1 year, with the ``tt'' homozygote group having 7% higher weight. We conclude that early fetal or infant environment may interact with an individual's underlying genotype to program early skeletal growth, and that this may track through later life to influence adult characteristics. Further prospective studies are required, however, to fully clarify the precise environmental and genetic mechanisms underlying these findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900220
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  • 2
    Electronic Resource
    Electronic Resource
    The Effects of 10 Weeks Military Training on Heel Ultrasound and Bone Turnover (1999)
    Springer
    Calcified tissue international 64 (1999), S. 389-393 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Exercise — Bone — Turnover — Ultrasound — Military.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. To measure the physiological changes in bone in response to strenuous exercise we performed a prospective study of male army recruits over 10 weeks of basic training. Measurements performed at the start and completion of training consisted of ultrasound (US) measurements of the heel: velocity of sound (VOS in m/seconds) and broadband ultrasound attenuation (BUA in dB/MHz) and bone turnover markers; osteocalcin (OC), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP). Forty subjects were recruited for the study and 26 completed training. Over the 10-week study period there was a significant 1.7% fall in mean VOS [mean paired difference (mpd) 27.2 m/second, SEM 9.5 (95% CI 7.5–46.8) P= 0.009] and a nonsignificant 3.4% increase in BUA (P= 0.159). There were significant falls in markers of bone formation OC [11.6%, mpd 0.11 μg/liter (95% CI 0.07–0.14) P 〈 0.001] and BALP [13.3%, mpd 3.49 U/liter (CI 0.80–6.18) P= 0.013] and a nonsignificant 9.5% fall in TRAP a marker of bone resorption. The 10 recruits subsequently injured had a significantly lower VOS on entry [mean difference 24.2 m/seconds (95% CI 4.6–43.7) P= 0.017] and nonsignificantly raised BUA and baseline levels of all bone markers. The ultrasound changes may be accounted for by increase in trabecular separation and a fall in trabecular connectivity due to microfracture. The decrease in bone markers implies a fall in bone turnover.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005820
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  • 3
    Electronic Resource
    Electronic Resource
    Role and evolution of therapeutic options (1996)
    Springer
    Osteoporosis international 6 (1996), S. 16-20 
    Details
    ISSN: 1433-2965
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions The incidence of osteoporosis has increased over the last 30 years, and is expected to continue to increase into the next century. Drug treatment for this condition has evolved with an understanding of the disordered processes that underlie the development of low bone mass and fracture. At present, a number of different drugs can be used safely with the expectation of preventing an initial or subsequent osteoporotic fracture. HRT remains the mainstay of treatment, although many women receive therapy for a time period that is insufficient to have any major impact on fracture risk. It is likely that non-bleed preparations and oestrogen antagonists will be used widely in the future in an attempt to improve compliance, although concern will still exist about the long-term safety of these therapies. New bisphosphonates appear good alternatives for women who are unable or unwilling to take HRT. Data from clinical trials in progress with these agents are eagerly awaited to assess their impact on hip fracture prevention. Other therapies under investigation will also soon be available for treatment in the clinical setting. Exactly who will benefit from a particular therapy, the duration of treatment and the use of combinations of bone-forming and anti-resorptive agents are the challenges for the next decade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01625237
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of Current and Past Hormone Replacement Therapy on Bone Mineral Density: A Study of Discordant Postmenopausal Twins (1999)
    Springer
    Osteoporosis international 9 (1999), S. 158-162 
    Details
    ISSN: 1433-2965
    Keywords: Key words: Matched case–control study – Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair differences in bone mineral density (BMD) in twins who were discordant for HRT use. Twin pairs in which only one co-twin had been exposed to HRT for more than 12 months continuously were selected from 365 postmenopausal monozygotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas’ Adult UK Twin Registry of normal volunteers. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Intrapair differences in BMD between HRT users and non-users were compared. A total of 65 HRT-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.4 years, median HRT duration: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair difference (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%; femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substantially smaller when past users and non-users were compared (lumbar spine IPD%: 2.4%, 95% CI: −3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: −5.3%, 6.0%). These differences remained little changed after adjusting for the potential confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results confirm, in a closely matched design, the findings of other observational research that current use of HRT has a major effect on BMD at the lumbar spine and femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be considered in those who discontinue HRT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001980050130
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  • 5
    Electronic Resource
    Electronic Resource
    The Role of Serum TGF-β Isoforms as Potential Markers of Osteoporosis (1999)
    Springer
    Osteoporosis international 9 (1999), S. 398-404 
    Details
    ISSN: 1433-2965
    Keywords: Key words:Bone mineral density – Osteoporosis – TGF-β
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Osteoporosis is a major public health problem characterized by low bone mineral density (BMD) that presently has no biochemical test useful for its diagnosis. The cytokine TGF-β has been postulated to play a role in controlling bone density by regulating the fine balance between bone matrix deposition by osteoblasts and its resorption by osteoclasts. We explored whether measurement of serum levels of different TGF-β isoforms could be useful as a clinical tool in osteoporosis. We measured the concentration of TGF-β1 antigen using the BDA19 capture sandwich enzyme-linked immunosorbent assay (ELISA), TGF-β2 antigen concentration using a Quantikine sandwich ELISA kit and TGF-β3 antigen concentration using a modified version of the TGF-β1 Quantikine sandwich ELISA kit. Subjects were 41 women with osteoporosis (with nontraumatic vertebral fracture or lumbar spine BMD Z-score 〈−1.5 SD) and a total of 199 control women from different sources. Serum concentrations of TGF-β1 and TGF-β2 were similar in all groups. However, detectable levels of TGF-β3 (〉0.2 ng/ml) were found in 35 of 41 patients with osteoporosis (median 7.2 (5.2–8.9) ng/ml) compared with 11 of 36 controls or 24 of 89 healthy women of unknown bone density. Differences among the groups could not be accounted for by age, weight, medications, use of hormone replacement therapy or the presence of osteoarthritis. Using the optimal cut-off of ≥2 ng/ml, the test was able to detect an individual with low spine BMD (Z-score 〈−1.5) with a sensitivity of 84% and a specificity of 53%, with similar results for the femoral neck. The odds ratio for osteoporosis associated with a positive test at this level was 5.93 (95% CI 2.41–11.59), and 4.1 (95% CI 1.66–10.11) using the WHO cut-off of T-score 〈−2.5. Serum TGF-β3 concentration is raised in osteoporotic women and the test appears to have potential as a marker for osteoporosis. The underlying mechanisms and the relationships between TGF-β3 and bone turnover and fractures remain to be explored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001980050163
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  • 6
    Electronic Resource
    Electronic Resource
    Geometric measurements of the proximal femur in UK women: Secular increase between the late 1950s and early 1990s (1996)
    Springer
    Osteoporosis international 6 (1996), S. 136-140 
    Details
    ISSN: 1433-2965
    Keywords: Epidemiology ; Hip axis length ; Hip fracture ; Osteoporosis ; Secular change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine whether hip axis or femoral length has increased in women in the United Kingdom between the late 1950s and early 1990s. Such an observation would be of interest as it might explain the rise in age-specific incidence of hip fracture observed during these years. We studied two sets of antero-posterior pelvic radiographs of women aged 55–69 years taken during the course of population-based studies in the UK, one in 1958–60 and the other in 1989–91. One observer (S.G.) recorded the following measurements at the right hip: hip axis length (HAL), femoral length (FL) and femoral width (FW). Two summary ratios, HAL/FW and FL/FW were calculated to allow for differences in radiographic technique. HAL, FL and FW were greater in the 1989-91 films compared with those taken in 1958–60. Both HAL and FL expressed as a ratio to FW were also greater in the later films. FL/FW increased by 4.5% (p〈0.05); HAL/FW increased by 2.3%, though this was not statistically significant. We conclude that there has been a small apparent change in geometric measurements of the hip during the past 36 years. Cautious extrapolation suggests that such a change may explain up to one third of the increase in incidence of hip fracture observed during this period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623937
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  • 7
    Electronic Resource
    Electronic Resource
    Can biochemical markers predict bone loss at the hip and spine?: A 4-year prospective study of 141 early postmenopausal women (1996)
    Springer
    Osteoporosis international 6 (1996), S. 399-406 
    Details
    ISSN: 1433-2965
    Keywords: Biochemical assay ; Bone densitometry ; Bone turnover ; Menopause ; Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0±3.3 years, mean menopause duration 20.4±5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at −20 °C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was −1.41% (0.18) at the lumbar spine and −0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623014
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  • 8
    Electronic Resource
    Electronic Resource
    Family History of Appendicular Fracture and Risk of Osteoporosis: A Population-Based Study (1999)
    Springer
    Osteoporosis international 10 (1999), S. 161-166 
    Details
    ISSN: 1433-2965
    Keywords: Key words:Colles’ fracture – Familial – Fracture – Genetic – Osteoporosis – Wrist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Family and twin studies demonstrate a strong genetic component to osteoporosis, suggesting that a positive family history for this disease may be an important clinical risk factor. We have therefore explored the extent to which a history of wrist fracture in a female first-degree relative was associated with an increased risk of prevalent fracture at both appendicular and vertebral sites in a cross-sectional study design. One thousand and three Caucasian women (age range 45–64 years) were studied from a UK population cohort. Bone mineral density (BMD) was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Appendicular fractures (wrist and hip) were recorded by questionnaire and validated from radiographs and hospital records. Vertebral fractures were assessed using radiologic survey of the thoracolumbar spine and semi-automated morphometric analysis. A positive family history of osteoporotic fracture (hip and/or wrist) in either a mother and/or sister was reported in 138 of the 1003 women. When compared with those with a negative family history of fracture, BMD was significantly reduced in those with a positive history at both the spine (p = 0.02) and the hip (p = 0.02). In total, there were 63 validated fragility fractures found in the 1003 women (16 wrist, 6 hip and 41 vertebral). Family history of osteoporotic fracture was associated with an increased total risk for osteoporotic fracture, with an odds ratio (95% confidence interval) of 2.02 (1.02, 3.78). Site-specific analysis showed that a positive family history of wrist fracture was associated with a considerably elevated risk of wrist fracture, with an odds ratio of 4.24 (1.44, 12.67). These increases in risk remained after adjustment for BMD, suggesting that other genetic factors account for the familial risk of osteoporosis and fracture.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001980050211
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  • 9
    Electronic Resource
    Electronic Resource
    Polymorphisms of the vitamin d receptor gene do not predict quantitative ultrasound of the calcaneus or hip axis length (1996)
    Springer
    Osteoporosis international 6 (1996), S. 334-337 
    Details
    ISSN: 1433-2965
    Keywords: Broadband ultrasound attenuation ; Hip axis length ; Osteoporosis ; Twins ; Velocity of sound ; Vitamin D receptor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative ultrasound of the calcaneus and hip axis length are independent predictors of hip fracture and have a major genetic component. Polymorphisms of the vitamin D receptor gene (VDR) have been associated with variations in bone density in a number of studies. The aim of this study was to examine the role of VDR on other parameters associated with the risk of fracture. One hundred and eighty-nine pairs of healthy female dizygous twins were genotyped and had calcaneal ultrasound (broadband ultrasound attenuation and velocity of sound) and hip axis length measurements performed. Twin analysis using intraclass correlation coefficients and intrapair differences failed to find an association between the VDR polymorphisms and hip axis length or calcaneal ultrasound. Analysing the twins as a population, irrespective of twinning, also failed to find any association. The search for alternative genes influencing bone fragility should continue as a research priority.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623395
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