| 1. |
- Brändström, Helena, et al.
(författare)
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Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women
- 2004
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:1, s. 18-24
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.
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| 2. |
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| 3. |
- Einarsdottir, E., et al.
(författare)
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CELSR2 is a candidate susceptibility gene in idiopathic scoliosis
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c. G6859A change in exon 21 (NM_001408), leading to a predicted p. V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.
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| 4. |
- Garg, Gaurav, et al.
(författare)
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Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061) and OPRA (age 75, n = 1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r(2) = 0.2-0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs.
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| 5. |
- Gerdhem, Paul, et al.
(författare)
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Accelerometer-measured daily physical activity among octogenerians: results and associations to other indices of physical performance and bone density
- 2008
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 102:2, s. 173-180
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Tidskriftsartikel (refereegranskat)abstract
- Information on objectively assessed physical activity in elderly people is scarce. The aim of this study was to investigate accelerometer measures in elderly women, and its relation to other indices of physical activity and bone density. A subset of 57 women, all 80 years old, (range 80.0-80.7) of the Malmo OPRA study was equipped with an MTI accelerometer for a period of 5-7 days. A 7-day activity log was used. At baseline a self-assessment questionnaire was used and isometric muscle strength (knee), gait speed, balance and bone density measurements [dual-energy X-ray absorptiometry (total body, hip, and spine), and quantitative ultrasound of the calcaneus] were measured. About 14% (8 out of 57) had a moderate to vigorous physical activity (MVPA) (>1,952 counts per min [CPM]) exceeding 30 min/day. The median CPM was 18. When compared to questionnaire data, the correlation between MVPA and physical activity was 0.50 (P < 0.001). The corresponding result for CPM was 0.48, P < 0.001. When compared to the activity log, the correlation between MVPA and physical activity away from home was 0.49 (P < 0.001). The corresponding result for CPM was 0.55, P < 0.001. The correlation between MVPA and gait speed was 0.41 (P = 0.002). The corresponding result for CPM was 0.40, P = 0.002. There were no correlations to the measurements of muscle strength, balance or bone density (all P >/= 0.07). Accelerometers can be used for measuring of physical activity also of the elderly. Questions on daily physical activity correlated modestly with accelerometer results in elderly women. Accelerometer results were not correlated to measures of balance, muscle strength and bone density.
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| 6. |
- Gerdhem, Paul, et al.
(författare)
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Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.
- 2005
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 16:Mar 3, s. 1425-1431
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.
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| 7. |
- Gerdhem, Paul, et al.
(författare)
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Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women
- 2004
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 74:3, s. 264-269
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Tidskriftsartikel (refereegranskat)abstract
- Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.
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| 8. |
- Gerdhem, Paul, et al.
(författare)
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Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.
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| 9. |
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| 10. |
- Gerdhem, Paul, et al.
(författare)
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Bone mass cannot be predicted by estimations of frailty in elderly ambulatory women.
- 2003
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Ingår i: Gerontology. - : S. Karger AG. - 1423-0003 .- 0304-324X. ; 49:3, s. 168-172
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Methods:</i> High biological age, or frailty, a possible risk factor for fragility fracture, and its relation to known risk factors for fracture (low bone mineral density (BMD), low muscle strength, poor gait performance and poor balance, previous falls, previous fractures and future risk of falls) were investigated in 993 randomly selected 75-year-old women. Frailty, which has no accepted definition, was here defined as a subjective immediate impression of an individual’s general health appearance and was transferred into an arbitrary scale. 993 individuals were scored by at least one of four observers. <i>Results:</i> The frailty score and BMD were not correlated. A high frailty score was significantly correlated to poor gait (r = 0.53–0.59, p < 0.0001), poor balance (r = –0.49, p < 0.0001), low muscle strength (r = –0.25 to –0.41, p < 0.0001), low activity level (r = –0.43, p < 0.0001) and a high risk of falling (r = 0.24, p < 0.0001). The group of women who had experienced at least one fall the previous year had a higher frailty score (p < 0.0001) compared to those who had not. Women who had sustained a hip or femoral fracture after the age of 70 had a higher frailty score than women with no earlier fracture at all. <i>Conclusions:</i> Bone mass cannot be predicted by our subjective frailty score in elderly, ambulant women. Since a high frailty score correlates with factors that affect or are likely to affect fall propensity, this could indicate that a high frailty score is a risk factor for fracture, independent of bone mass. Frailty may be regarded as a complex risk factor, including several assessments that can be objectively measured. Whether estimation of frailty is a method to improve the assessment of the patient at risk for a fragility fracture is yet to be proven and can only be shown in a prospective study of fracture occurrence.
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