| 1. |
- Bornefalk, Eva, et al.
(författare)
-
Age-dependent effect of oral glucocorticoids on markers of bone resorption in patients with acute asthma
- 1998
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 63:1, s. 9-13
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally accepted that bone formation is depressed during corticosteroid treatment, but the effects of glucocorticoids on bone resorption are less well characterized. We have investigated the effects of short-term treatment with high-dose oral glucocorticoids on biochemical markers of bone turnover in 20 consecutive patients with asthma who sought help for acute respiratory obstruction in our emergency department. Serum concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP), reflecting bone formation, were measured by radioimmunoassay. Changes of the circulating levels of the bone resorption marker 1CTP after treatment were age dependent with a significant negative correlation (r = -0.54, P = 0.01). The dependency on age remained when correcting, in a multiple linear regression analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose of inhaled glucocorticoids. Circulating levels of P1CP were suppressed in the whole group 1 week after initiation of glucocorticoid therapy, from 123.3 +/- 10.2 ng/ml at admission to 88.1 +/- 6.3 ng/ml after 1 week (P < 0.01). The changes in P1CP levels were not related to age. Our data indicate that bone formation is suppressed by glucocorticoids in all age groups, whereas the effect of glucocorticoids on markers of bone resorption is dependent on age.
|
|
| 2. |
- Brahm, Helena, et al.
(författare)
-
Relationships between bone mass measurements and lifetime physical activity in a Swedish population
- 1998
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 62:5, s. 400-412
-
Tidskriftsartikel (refereegranskat)abstract
- Lifetime occupational and leisure time activities were assessed by a questionnaire in order to evaluate their relationship to bone mass measurements and biochemical markers of bone metabolism in a population of 61 women and 61 men, randomly selected from a Swedish population register, to represent ages between 22 and 85 years. We also considered possible confounders by using questions about smoking habits, milk consumption, hormone replacement therapy (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck, trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In addition, both DXA and SXA provided information on bone area. Quantitative ultrasound measurements (QUS) at the heel were performed to assess the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples were analyzed for biochemical markers of bone metabolism as well as parathyroid hormone (PTH) and total serum calcium. After adjustment for confounding factors, neither BMD nor QUS measurements were consistently related to lifetime leisure time or occupational activities; nor were there any consistent patterns relating biochemical markers of bone metabolism to bone mass measurements. However, physical activity seemed to influence bone mass, area, and width more than density. In men, high levels of leisure time activity were associated with raised values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck area (5.5%) compared with their low activity counterpart. Men exposed to high levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and area (5.3%) than men with low activity levels. Within an unselected Swedish population, estimation of lifetime occupational and sport activities as well as bedrest, using a questionnaire, demonstrated no major effects on bone density. However, the association between high levels of lifetime activity and raised values for bone mass, area, and width indicate that geometrical changes in bone may provide better estimations of mechanically induced bone strength than bone density, at least in men.
|
|
| 3. |
- Kharazmi, Mohammad, et al.
(författare)
-
A Genome-Wide Association Study of Bisphosphonate-Associated Atypical Femoral Fracture
- 2019
-
Ingår i: Calcified Tissue International. - : SPRINGER. - 0171-967X .- 1432-0827. ; 105:1, s. 51-67
-
Tidskriftsartikel (refereegranskat)abstract
- Atypical femoral fracture is a well-documented adverse reaction to bisphosphonates. It is strongly related to duration of bisphosphonate use, and the risk declines rapidly after drug withdrawal. The mechanism behind bisphosphonate-associated atypical femoral fracture is unclear, but a genetic predisposition has been suggested. With the aim to identify common genetic variants that could be used for preemptive genetic testing, we performed a genome-wide association study. Cases were recruited mainly through reports of adverse drug reactions sent to the Swedish Medical Products Agency on a nation-wide basis. We compared atypical femoral fracture cases (n=51) with population-based controls (n=4891), and to reduce the possibility of confounding by indication, we also compared with bisphosphonate-treated controls without a current diagnosis of cancer (n=324). The total number of single-nucleotide polymorphisms after imputation was 7,585,874. A genome-wide significance threshold of p<5x10(-8) was used to correct for multiple testing. In addition, we performed candidate gene analyses for a panel of 29 genes previously implicated in atypical femoral fractures (significance threshold of p<5.7x10(-6)). Compared with population controls, bisphosphonate-associated atypical femoral fracture was associated with four isolated, uncommon single-nucleotide polymorphisms. When cases were compared with bisphosphonate-treated controls, no statistically significant genome-wide association remained. We conclude that the detected associations were either false positives or related to the underlying disease, i.e., treatment indication. Furthermore, there was no significant association with single-nucleotide polymorphisms in the 29 candidate genes. In conclusion, this study found no evidence of a common genetic predisposition for bisphosphonate-associated atypical femoral fracture. Further studies of larger sample size to identify possible weakly associated genetic traits, as well as whole exome or whole-genome sequencing studies to identify possible rare genetic variation conferring a risk are warranted.
|
|
| 4. |
- Michaëlsson, Karl, 1959-, et al.
(författare)
-
Diet, bone mass, and osteocalcin : A cross-sectional study
- 1995
-
Ingår i: Calcified Tissue International. - 0171-967X .- 1432-0827. ; 57:2, s. 86-93
-
Tidskriftsartikel (refereegranskat)abstract
- To determine the relationships among nutrients intake, bone mass, and bone turnover in women we have investigated these issues in a population-based, cross-sectional, observational study in one county in central Sweden. A total of 175 women aged 28-74 at entry to the study were included. Dietary assessment was made by both a semiquantitative food frequency questionnaire and by four 1-week dietary records. Dual energy X-ray absorptiometry was performed at five sites: total body, L2-L4 region of the lumbar spine, and three regions of the proximal femur. Serum concentrations of osteocalcin (an osteoblast-specific protein reflecting bone turnover) were measured by a radioimmunoassay. Linear regression models, with adjustment for possible confounding factors were used for statistical analyses. A weak positive association was found between dietary calcium intake as calculated from the semiquantitative food frequency questionnaire and total body bone mineral density (BMD) among premenopausal women. No association emerged between dietary calcium intake and site-specific bone mass, i.e., lumbar spine and femoral neck, nor was an association found between dietary calcium intake and serum osteocalcin. BMD at some of the measured sites was positively associated with protein and carbohydrates and negatively associated with dietary fat. In no previous studies of diet and bone mass have dietary habits been ascertained so carefully and the results adjusted for possible confounding factors. Neither of the two methods of dietary assessment used in this study revealed any effect of calcium intake on BMD at fracture-relevant sites among these healthy, mostly middle-aged women. A weak positive association was found between calcium intake estimates based on the food frequency questionnaire and total body BMD. In this study population the preventive effect of high dietary calcium on osteoporosis is probably very weak. The independent significance of protein, carbohydrates, and fat is uncertain.
|
|
| 5. |
- Mitchell, Adam, et al.
(författare)
-
Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women : A Cross-Sectional Study
- 2018
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 103:5, s. 501-511
-
Tidskriftsartikel (refereegranskat)abstract
- Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2 and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, - 0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin (- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.
|
|
| 6. |
- Yuan, Shuai, et al.
(författare)
-
Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density : A Mendelian Randomization Study
- 2019
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 105:6, s. 582-588
-
Tidskriftsartikel (refereegranskat)abstract
- The causal associations of smoking and alcohol and coffee intake with fracture and bone mineral density are unknown. We investigated the associations using Mendelian randomization (MR). Summary-level data from UK Biobank for bone fractures (main outcome) (53,184 cases; 373,611 non-cases) and estimated bone mineral density (eBMD) (n = 426,824 individuals) were used. Single-nucleotide polymorphisms associated with smoking initiation (n = 378) and alcohol (n = 99) and coffee (n = 15) intake at the genome-wide significance threshold (P = 5 x 10(-8)) were identified from published genome-wide association studies. Univariable and multivariable inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO methods were used for statistical analyses. Genetic predisposition to smoking initiation was associated with fracture but not eBMD. The odds ratio of fracture per one-unit increase in log odds of smoking was 1.09 (95% confidence interval 1.04, 1.15; P = 8.58 x 10(-4)) after adjustment for alcohol intake in the multivariable MR analysis. The association remained in complementary analyses. Genetically predicted alcohol and coffee intake was not associated with fracture or eBMD. Nevertheless, genetic liability to alcohol dependence, based on variants in the ALD1B gene, was associated with fracture and lower eBMD. The odds ratio was 1.06 (95% confidence interval 1.01, 1.12; P = 0.018) per genetically predicted one-unit higher log odds of liability to alcohol dependence. This MR study strengthens the causal inference on an association between smoking and higher fracture risk but found no linear association of modestly higher alcohol and coffee intake with fracture or BMD. However, alcohol dependence may increase fracture risk.
|
|
