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Osteoporosis in elderly women; Bone traits, fracture and the PTH gene complex

Tenne, Max LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:100.
Abstract
Background: Fragility fractures are a major health problem world wide and the numbers are growing due to ageing populations. Early identification of individuals at risk for osteoporosis and fracture, enabling preventive measures and treatment is essential. Bone strength is partly dependent on lifestyle but genetic factors account for approximately 70-80%. Parathyroid hormone (PTH) is the key regulator of calcium homeostasis in the human organism and in addition a powerful skeletal anabolic agent when administered as a drug. Dual energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD) in the hip and lumbar spine. However, at the lumbar spine in the elderly, degenerative changes frequently cause a... (More)
Background: Fragility fractures are a major health problem world wide and the numbers are growing due to ageing populations. Early identification of individuals at risk for osteoporosis and fracture, enabling preventive measures and treatment is essential. Bone strength is partly dependent on lifestyle but genetic factors account for approximately 70-80%. Parathyroid hormone (PTH) is the key regulator of calcium homeostasis in the human organism and in addition a powerful skeletal anabolic agent when administered as a drug. Dual energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD) in the hip and lumbar spine. However, at the lumbar spine in the elderly, degenerative changes frequently cause a falsely elevated BMD.



Aims: To evaluate a hypothesized relationship between variation in PTH pathway genes, BMD, fracture, degenerative changes and bone geometry in elderly women. To evaluate the prevalence and localization of degenerative changes at the lumbar spine in elderly women and its impact on DXA measurements.



Methods: 1044 women of the Osteoporosis Prospective Risk Assessment Study (OPRA) all 75 years at inclusion were measured by DXA at baseline, 5 and 10 years follow-up. Retrospective and prospective fractures were registered, a questionnaire regarding life style factors was answered and blood samples were obtained for genetic analysis. All lumbar DXA scan images were visually assessed regarding degenerative and other manifestations.



Results: Association analysis showed a significant relationship between PTH haplotypes and fracture but not BMD. There were also a significant correlation between PTH haplotypes and hip strength analysis (HSA) parameters. PTH receptor 2 gene was related to prevalence of lumbar degenerative changes. The prevalence of lumbar degenerative changes (L1-L4) was high at baseline (43%) and significantly increasing over time (67% at 5 and 80% at 10 years follow-up). Vertebrae affected with degenerative changes had significantly higher BMD and there was a gradient over L1 to L4 with higher prevalence distally.



Conclusions: Our results indicate that genetic variation within the PTH pathway genes are associated with fracture prevalence and hip strength indices based on skeletal geometry and degenerative changes but not with BMD in elderly women. We can furthermore conclude that if lumbar degenerative changes are taken into consideration when interpreting DXA scans diagnosis of osteoporosis can be more precise. We suggest the use of L1-L2 in elderly women to avoid under-diagnosis and misinterpretation of drug effect. (Less)
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author
supervisor
opponent
  • Professor Nordsletten, Lars, University of Oslo, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
osteoporosis, fracture, parathyroid hormone, gene, polymorphism, dual energy X-ray absorptiometry, bone mineral density, hip strength analysis
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:100
pages
116 pages
publisher
Clinical and Molecular Osteoporosis Research Unit, Clinical Sciences, Malmö.
defense location
Universitetsklinikernas aula, ingång 35, Skånes universitetssjukhus, Malmö
defense date
2011-11-25 09:00
ISSN
1652-8220
ISBN
978-91-86871-50-5
language
English
LU publication?
yes
id
d6783bf3-30be-4a05-84f0-6201badbf5f4 (old id 2201454)
date added to LUP
2011-11-03 12:07:38
date last changed
2016-09-19 08:44:50
@phdthesis{d6783bf3-30be-4a05-84f0-6201badbf5f4,
  abstract     = {Background: Fragility fractures are a major health problem world wide and the numbers are growing due to ageing populations. Early identification of individuals at risk for osteoporosis and fracture, enabling preventive measures and treatment is essential. Bone strength is partly dependent on lifestyle but genetic factors account for approximately 70-80%. Parathyroid hormone (PTH) is the key regulator of calcium homeostasis in the human organism and in addition a powerful skeletal anabolic agent when administered as a drug. Dual energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD) in the hip and lumbar spine. However, at the lumbar spine in the elderly, degenerative changes frequently cause a falsely elevated BMD.<br/><br>
<br/><br>
Aims: To evaluate a hypothesized relationship between variation in PTH pathway genes, BMD, fracture, degenerative changes and bone geometry in elderly women. To evaluate the prevalence and localization of degenerative changes at the lumbar spine in elderly women and its impact on DXA measurements.<br/><br>
<br/><br>
Methods: 1044 women of the Osteoporosis Prospective Risk Assessment Study (OPRA) all 75 years at inclusion were measured by DXA at baseline, 5 and 10 years follow-up. Retrospective and prospective fractures were registered, a questionnaire regarding life style factors was answered and blood samples were obtained for genetic analysis. All lumbar DXA scan images were visually assessed regarding degenerative and other manifestations.<br/><br>
<br/><br>
Results: Association analysis showed a significant relationship between PTH haplotypes and fracture but not BMD. There were also a significant correlation between PTH haplotypes and hip strength analysis (HSA) parameters. PTH receptor 2 gene was related to prevalence of lumbar degenerative changes. The prevalence of lumbar degenerative changes (L1-L4) was high at baseline (43%) and significantly increasing over time (67% at 5 and 80% at 10 years follow-up). Vertebrae affected with degenerative changes had significantly higher BMD and there was a gradient over L1 to L4 with higher prevalence distally.<br/><br>
<br/><br>
Conclusions: Our results indicate that genetic variation within the PTH pathway genes are associated with fracture prevalence and hip strength indices based on skeletal geometry and degenerative changes but not with BMD in elderly women. We can furthermore conclude that if lumbar degenerative changes are taken into consideration when interpreting DXA scans diagnosis of osteoporosis can be more precise. We suggest the use of L1-L2 in elderly women to avoid under-diagnosis and misinterpretation of drug effect.},
  author       = {Tenne, Max},
  isbn         = {978-91-86871-50-5},
  issn         = {1652-8220},
  keyword      = {osteoporosis,fracture,parathyroid hormone,gene,polymorphism,dual energy X-ray absorptiometry,bone mineral density,hip strength analysis},
  language     = {eng},
  pages        = {116},
  publisher    = {Clinical and Molecular Osteoporosis Research Unit, Clinical Sciences, Malmö.},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Osteoporosis in elderly women; Bone traits, fracture and the PTH gene complex},
  volume       = {2011:100},
  year         = {2011},
}