| 1. |
|
|
| 2. |
- Bergström, I., et al.
(author)
-
Prednisolone treatment reduces the osteogenic effects of loading in mice
- 2018
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 112, s. 10-18
-
Journal article (peer-reviewed)abstract
- Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone. Three-month-old female C57BL/6 mice were treated with high-dose prednisolone (15 mg/60 day pellets/mouse) or vehicle for two weeks. During the treatment, right tibiae were subjected to short periods of cyclic compressive loading three times weekly, while left tibiae were used as physiologically loaded controls. The bones were analyzed using peripheral quantitative computed tomography, histomorphometry, real-time PCR, three-point bending and Fourier transform infrared micro-spectroscopy. Loading alone increased trabecular volumetric bone mineral density (vBMD), cortical thickness, cortical area, osteoblast-associated gene expression, osteocyte- and osteoclast number, and bone strength. Prednisolone alone decreased cortical area and thickness and osteoblast-associated gene expression. Importantly, prednisolone treatment decreased the load-induced increase in trabecular vBMD by 57% (p < 0.001) and expression of osteoblast-associated genes, while completely abolishing the load-induced increase in cortical area, cortical thickness, number of osteocytes and osteoclasts, and bone strength. When combined, loading and prednisolone decreased the collagen content. In conclusion, high-dose prednisolone treatment strongly inhibits the loading-induced increase in trabecular BMD, and abolishes the loading-induced increase in cortical bone mass. This phenomenon could be due to prednisolone inhibition of osteoblast differentiation and function.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Conaway, H. H., et al.
(author)
-
Activation of dimeric glucocorticoid receptors in osteoclast progenitors potentiates RANKL induced mature osteoclast bone resorbing activity
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 93, s. 43-54
-
Journal article (peer-reviewed)abstract
- Glucocorticoid (GC) therapy is the greatest risk factor for secondary osteoporosis. Pathogenic mechanisms involve an initial increase in bone resorption followed by decreased bone formation. To gain a better understanding of the resorptive activity of GCs, we have used mouse bone marrow macrophages (BMM) to determine if GCs can directly modulate RANKL stimulated osteoclast formation and/or activity. In agreement with previous studies, experiments performed in plastic wells showed that GCs (dexamethasone, hydrocortisone, and prednisolone) inhibited osteoclast number and size during the initial phases of RANKL stimulated osteoclastogenesis; however, in prolonged cultures, decreased apoptosis was observed and escape from GC induced inhibition occurred with an enhanced number of osteoclasts formed, many with an increased area. When BMM cells were seeded on bone slices, GCs robustly enhanced RANKL stimulated formation of resorption pits and release of CTX without affecting the number or size of osteoclasts formed and with no effect on apoptosis. Stimulation of pit formation was not associated with increased life span of osteoclasts or an effect on mRNA expression of several osteoclastic or osteoclastogenic genes. The potentiation of RANKL induced CTX release by dexamethasone was significantly less in BMM cells from mice with conditional knockout of the osteoclastic glucocorticoid receptor and completely absent in cells from GRdim mice, which carry a point mutation in one dimerizing interface of the GC receptor. These data suggest that: 1. Plastic is a poor medium to use for studying direct effects of GCs on osteoclasts 2. GCs can enhance bone resorption without decreasing apoptosis, and 3. A direct enhancement of RANKL mediated resorption is stimulated by the dimeric GC-receptor. © 2016 Elsevier Inc.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Gustafsson, Anna, et al.
(author)
-
Strains caused by daily loading might be responsible for delayed healing of an incomplete atypical femoral fracture
- 2016
-
In: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 88, s. 125-130
-
Journal article (peer-reviewed)abstract
- Atypical femoral fractures are insufficiency fractures in the lateral femoral diaphysis or subtrochanteric region that mainly affect older patients on bisphosphonate therapy. Delayed healing is often seen in patients with incomplete fractures (cracks), and histology of bone biopsies shows mainly necrotic material inside the crack. We hypothesized that the magnitude of the strains produced in the soft tissue inside the crack during normal walk exceeds the limit for new bone formation, and thereby inhibit healink. A patient specific finite element model was developed, based on clinical CT images and high resolution CT images of a biopsy from the crack site. Strain distributions in the femur and inside the crack were calculated for load cases representing normal walk. The models predicted large strains inside the crack, with strain levels above 10% in more than three quarters of the crack volume. According to two different tissue differentiation theories, bone would only form in less than 1-5% cif the crack volume. This can explain the impaired healing generally seen in incomplete atypical fractures. Furthermore, the microgeometry of the crack highly influenced the strain distributions. Hence, a realistic microgeometry needs to be considered when modeling the crack. Histology of the biopsy showed signs of remodeling in the bone tissue adjacent to the fracture line, while the crack itself contained mainly necrotic material and signs of healing only in portions that seemed to have been widened by resorption. In conclusion, the poor healing capacity of incomplete atypical femoral fractures can be explained by biomechanical factors, and daily low impact activities are enough to cause strain magnitudes that prohibit bone formation. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 9. |
- Hantikainen, Essi, et al.
(author)
-
Prospective study of dietary Non Enzymatic Antioxidant Capacity on the risk of hip fracture in the elderly
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 90, s. 31-36
-
Journal article (peer-reviewed)abstract
- Background: Dietary antioxidants may play an important role in the prevention of bone loss and associated fractures by reducing levels of oxidative stress. We prospectively investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC) and the risk of hip fracture and whether this effect was modified by smoking. Method: In the Swedish National March Cohort 13,409 men and women over the age of 55 who had not experienced cancer, cardiovascular disease or hip fracture, were followed through record-linkages from 1997 through 2010. NEAC was assessed by a validated food frequency questionnaire collected at baseline. We categorized the distribution of NEAC into sex-specific quartiles and used multivariable adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CI). Results: During a mean follow-up time of 12.4 years, we identified 491 incident cases of first hip fracture. Subjects in the highest quartile of dietary NEAC had a 39% lower risk of incident hip fracture compared to those in the lowest quartile (HR: 0.61; 95% CI: 0.44-0.85). The association was non-linear (p for non-linearity: 0.004) with a potential threshold between the first and the second quartile and no further risk reduction at higher levels of dietary NEAC. Due to a low smoking prevalence in our study population, we had limited power to detect effect modification between dietary NEAC and smoking on a multiplicative or additive scale. Conclusion: Higher dietary NEAC intake is associated with lower risk of hip fracture in the elderly.
|
|
| 10. |
|
|
| 11. |
- Jiang, X, et al.
(author)
-
The genetics of vitamin D
- 2019
-
In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 126, s. 59-77
-
Journal article (peer-reviewed)
|
|
| 12. |
- Johansson, Jonas, 1984-, et al.
(author)
-
Objectively measured physical activity is associated with parameters of bone in 70-year-old men and women
- 2015
-
In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 81, s. 72-79
-
Journal article (peer-reviewed)abstract
- As the world's population ages, the occurrence of osteoporosis-related fractures is projected to increase. Low areal bone mineral density (aBMD), a well-known risk factor for fractures, may be influenced by physical activity (PA). In this cross-sectional study, we aimed to investigate potential associations between objective measures of PA and bone properties, in a population-based cohort of 1228 70-year-old men and women. We measured volumetric BMD (vBMD, mg/cm3) together with cross-sectional area (CSA, mm2) by peripheral quantitative computed tomography at sites located 4% and 66% in the distal–proximal trajectory at the tibia and radius. We also measured aBMD (g/cm2) by dual energy X-ray absorptiometry at the femoral neck, lumbar spine (L1–L4) and radius. Participants wore triaxial accelerometers for 7 consecutive days to obtain objective estimates of PA. The intensity of the objective PA was divided into light (100–1951 counts/min [CPM]), moderate (1952– 5724 cpm) and vigorous (≥5725 cpm). Maximal accelerations for the anterior–posterior (z), medio-lateral (x), and vertical (y) axes were also separately assessed. Associations were investigated using bivariate correlations and multiple linear regression, adjusted for height, weight and sex. Vigorous PA showed the strongest association with femoral neck aBMD (β = 0.09, p b 0.001), while both moderate and vigorous PAs were associated with cor- tical area and trabecular vBMD in the weight-bearing tibia (all p b 0.05). Peak vertical accelerations were associated significantly with cortical area (β = 0.09, p b 0.001) and trabecular vBMD (β = 0.09, p = 0.001) of the tibia, whereas peak anterior–posterior accelerations showed no correlation with these properties. No positive association was found between objectively measured PA and bone parameters of the radius. In conclusion, vertical accelerations and moderate to vigorous PA independently predict bone properties, especially in the weight-bearing tibia, in 70-year-old men and women.
|
|
| 13. |
- Kamal, Bushra, et al.
(author)
-
Biomechanical properties of bone in a mouse model of Rett syndrome.
- 2015
-
In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 71, s. 106-114
-
Journal article (peer-reviewed)abstract
- Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2(stop/y) male mice in which Mecp2 is silenced in all cells and female Mecp2(stop/+) mice in which Mecp2 is silenced in ~50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.
|
|
| 14. |
- Karampampa, Korinna, et al.
(author)
-
Declining incidence trends for hip fractures have not been accompanied by improvements in lifetime risk or post-fracture survival - A nationwide study of the Swedish population 60 years and older
- 2015
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 78, s. 55-61
-
Journal article (peer-reviewed)abstract
- Background: Hip fracture is a common cause of disability and mortality among the elderly. Declining incidence trends have been observed in Sweden. Still, this condition remains a significant public health problem since Sweden has one of the highest incidences worldwide. Yet, no Swedish lifetime risk or survival trends have been presented. By examining how hip fracture incidence, post-fracture survival, as well as lifetime risk have developed between 1995 and 2010 in Sweden, this study aims to establish how the burden hip fractures pose on the elderly changed over time, in order to inform initiatives for improvements of their health. Material and Methods: The entire Swedish population 60 years-old and above was followed between 1987 and 2010 in the National Patient Register and the Cause of Death Register. Annual age-specific hip fracture cumulative incidence was estimated using hospital admissions for hip fractures. Three-month and one-year survival after the first hip fracture were also estimated. Period life table was used to assess lifetime risk of hip fractures occuring from age 60 and above, and the expected mean age of the first hip fracture. Results: The age-specific hip fracture incidence decreased between 1995 and 2010 in all ages up to 94 years, on average by 1% per year. The lifetime risk remained almost stable, between 9% and 11% for men, and between 18% and 20% for women. The expected mean age of a first hip fracture increased by 2.5 years for men and by 2.2 years for women. No improvements over time were observed for the 3-month survival for men, while for women a 1% decrease per year was observed. The 1-year survival slightly increased over time for men (0.4% per year) while no improvement was observed for women. Conclusions: The age-specific hip fracture incidence has decreased overtime. Yet the lifetime risk of a hip fracture has not decreased because life expectancy in the population has increased in parallel. Overall, survival after hip fracture has not improved.
|
|
| 15. |
- Kälvesten, Johan, et al.
(author)
-
Digital X-ray radiogrammetry in the study of osteoporotic fractures: Comparison to dual energy X-ray absorptiometry and FRAX
- 2016
-
In: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 86, s. 30-35
-
Journal article (peer-reviewed)abstract
- Osteoporosis is often underdiagnosed and undertreated. Screening of post -menopausal women for clinical risk factors and/or low bone mineral density (BMD) has been proposed to overcome this. Digital X-ray radiogrammetry (DXR) estimates hand BMD from standard hand X-ray images and have shown to predict fractures and osteoporosis. Recently, digital radiology and the internet have opened up the possibility of conducting automated opportunistic screening with DXR in post -fracture care or in combination with mammography. This study compared the performance of DXR with FRAX (R) and DXA in discriminating major osteoporotic fracture (MOF) (hip, clinical spine, forearm or shoulder), hip fracture and femoral neck osteoporosis. This prospective cohort study was conducted on 5278 women 65 years and older in the Study of Osteoporotic Fractures (SOF) cohort Baseline hand X-ray images were analyzed and fractures were ascertained during 10 years of follow up. Age -adjusted area under receiver operating characteristic curve (AUC) for MOF and hip fracture and for femoral neck osteoporosis (DXA FN BMD T -score <= -2.5) was used to compare the methods. Sensitivity to femoral neck osteoporosis at equal selection rates was tabulated for FRAX and DXR. DXR-BMD, FRAX (no BMD) and lumbar spine DXA BMD were all similar in fracture discriminative performance with an AUC around 0.65 for MOF and 0.70 for hip fractures for all three methods. As expected femoral neck DXA provided fracture discrimination superior both to other BMD measurements and to FRAX. AUC for selection of patients with femoral neck osteoporosis was higher with DXR-BMD, 0.76 (0.74-0.77), than with FRAX, 0.69 (0.67-0.71), (p < 0.0001). In conclusion, DXR-BMD discriminates incident fractures to a similar degree as FRAX and predicts femoral neck osteoporosis to a larger degree than FRAX. DXR shows promise as a method to automatically flag individuals who might benefit from an osteoporosis assessment (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 16. |
- Larsson, Susanna C, et al.
(author)
-
Mendelian randomization in the bone field
- 2019
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 126, s. 51-58
-
Journal article (peer-reviewed)abstract
- Identification of causative risk factors amenable for modification is essential for the prevention and treatment of osteoporosis. Observational studies have identified associations between several potentially modifiable risk factors and osteoporosis. However, observational studies are susceptible to confounding, reverse causation bias, and measurement error, all of which limit their ability to provide causal estimates of the effect of exposures on outcomes, thereby reducing their ability to inform prevention and treatment strategies against bone loss and fractures. In addition, not all risk factors are suitable for an analysis in a randomized clinical trial. Mendelian randomization is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable exposures (e.g., biomarkers, adiposity measures, dietary factors, and behaviors) to determine the causal relationships between exposures and health outcomes. This technique has been used to provide evidence of causal associations of serum estradiol concentrations, smoking, body mass index, and type 2 diabetes with bone mineral density and the lack of associations of serum thyroid stimulating hormone, urate, C-reactive protein, and 25‑hydroxyvitamin D concentrations with bone mineral density in generally healthy populations. This review will briefly explain the concept of Mendelian randomization, the advantages and potential limitations of this study design, and give examples of how Mendelian randomization has been used to investigate questions relevant to osteoporosis.
|
|
| 17. |
- Laxman, Navya, et al.
(author)
-
Second generation sequencing of microRNA in Human Bone Cells treated with Parathyroid Hormone or Dexamethasone
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 84, s. 181-188
-
Journal article (peer-reviewed)abstract
- We investigated the impact of treatment with parathyroid hormone (PTH) and dexamethasone (DEX) for 2 and 24 h by RNA sequencing of miRNAs in primary human bone (HOB) cells. A total of 207 million reads were obtained, and normalized absolute expression retrieved for 373 most abundant miRNAs. In naive control cells, 7 miRNAs were differentially expressed (FDR < 0.05) between the two time points. Ten miRNAs exhibited differential expression (FDR < 0.05) across two time points and treatments after adjusting for expression in controls and were selected for downstream analyses. Results show significant effects on miRNA expression when comparing PTH with DEX at 2 h with even more pronounced effects at 24 h. Interestingly, several miRNAs exhibiting differences in expression are predicted to target genes involved in bone metabolism e.g. miR-30c2, miR-203 and miR-205 targeting RUNX2, and miR-320 targeting beta-catenin (CTNNB1) mRNA expression. CTNNB1 and RUNX2 levels were decreased after DEX treatment and increased after PTH treatment. Our analysis also identified 2 putative novel miRNAs in PTH and DEX treated cells at 24 h. RNA sequencing showed that PTH and DEX treatment affect miRNA expression in HOB cells and that regulated miRNAs in turn are correlated with expression levels of key genes involved in bone metabolism.
|
|
| 18. |
- Lewerin, Catharina, 1961, et al.
(author)
-
Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study
- 2017
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 98, s. 1-8
-
Journal article (peer-reviewed)abstract
- Background: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods: The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69-81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results: TS<15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 mu rnol/L vs. 41.9 mu mol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = -0.17, p < 0.001), TS (r = -0.16, p < 0.001) and serum ferritin (r = -0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C > 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = -0.15, p < 0.001) and TS (r = -0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized beta-values: -0.10, p <0.001; 0.10, p <0.001; and -0.05, p = 0.062, respectively). Conclusion: Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation. (C) 2017 Elsevier Inc. All rights reserved.
|
|
| 19. |
- Lindahl, Katarina, et al.
(author)
-
Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 87, s. 11-18
-
Journal article (peer-reviewed)abstract
- Background: Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe 01; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated.Materials and methods: COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n = 33, type III n = 25 and type IV n = 21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non vertebral and vertebral fractures were collected prior to, and at several time points during treatment.Results: An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to A LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p < 0.0003, < 0.0001 and 0.0003 for all 01 types 1, III and IV respectively). The reduced fracture rate was maintained for types I and IV, while an additional decrease was observed over time for type III. The fracture rate was reduced also in individuals with continued low BMD after >4 yrs Pamidronate. Twice as many boys as girls with 01 type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p = 0.0236). Greater Delta LS BMD, but smaller Delta fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11 years of age at treatment initiation. (p < 0.0001).Conclusion: Pamidronate treatment in children with all types of 01 increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type.
|
|
| 20. |
- Lindahl, Katarina, et al.
(author)
-
Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
- 2018
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 114, s. 268-277
-
Journal article (peer-reviewed)abstract
- Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Pekkinen, M., et al.
(author)
-
FGF23 gene variation and its association with phosphate homeostasis and bone mineral density in Finnish children and adolescents
- 2015
-
In: Bone. - : Elsevier BV. - 1873-2763 .- 1873-2763 .- 8756-3282. ; 71, s. 124-30
-
Journal article (peer-reviewed)abstract
- Fibroblast growth factor 23 (FGF23), a bone-derived hormone, participates in the hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25-dihydroxyvitamin D, plasma phosphate (Pi), and diet. Inappropriately high serum FGF23, seen in certain genetic and acquired disorders, results in urinary phosphate wasting and impaired bone mineralization. This study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health. The study included 183 children and adolescents (110 girls) aged 7-19 years (median 13.2years). Urine and blood parameters of calcium and phosphate homeostasis were analyzed. Bone characteristics were quantified by DXA and peripheral quantitative computed tomography (pQCT). Genetic FGF23 variation was assessed by direct sequencing of coding exons and flanking intronic regions. Nine FGF23 polymorphisms were detected; three of them were common: rs3832879 (c.212-37insC), rs7955866 (c.716C>T, p.T239M) and rs11063112 (c.2185A>T). Four different haplotypes and six different diplotypes were observed among these three polymorphisms. The variations in FGF23 significantly associated with plasma PTH and urinary Pi excretion, even after adjusting for relevant covariates. FGF23 variations independently associated with total hip BMD Z-score, but not with other bone outcomes. In instrument analysis, genetic variance in FGF23 was considered a weak instrument as it only induced small variations in circulating FGF23, PTH and Pi concentrations (F statistic less than 10). The observed associations between FGF23 variations and circulating PTH, and Pi excretion and total hip BMD Z-scores suggest that FGF23 polymorphisms may play a role in mineral homeostasis and bone metabolism.
|
|
| 24. |
- Rittweger, Joern, et al.
(author)
-
On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism : Results from the PlanHab study
- 2016
-
In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 91, s. 130-138
-
Journal article (peer-reviewed)abstract
- Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000 m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P = 0.69) and P1NP serum levels decreased (P = 0.0035) with likewise no difference between NBR and HBR (P = 0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05 mM) to 0.091 mM (day D21, P < 0.001), with no additional effect by hypoxia during bed rest (P = 0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.
|
|
| 25. |
- Sandberg, Olof, et al.
(author)
-
Temporal role of macrophages in cancellous bone healing
- 2017
-
In: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 101, s. 129-133
-
Journal article (peer-reviewed)abstract
- Macrophages are important phagocytosing and cytokine producing cells with effects on fracture healing. We used clodronate-containing liposomes to reduce the number of macrophages, in order to study their role in the early phases of cancellous bone healing. Holes were drilled bilaterally into the cancellous bone of the proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in the right tibia. The day of surgery was day 0. Clodronate-containing liposomes were injected intraperitoneally as a single injection either day 4 or 1 (before surgery) or day 1 or 3 (after surgery). A control group underwent surgery as above, but received no clodronate. The mice were killed day 7. The mechanical quality of the new formed cancellous bone holding the screw was evaluated by a pull-out test. The contents of the drill hole in the left tibia was analyzed by microCT. Another set of 20 mice received a drill hole in the metaphysis of the right tibia, and were given either clodronate or saline injections days 3 and 2. The animals were killed day 1 and 3. Flow cytometry was used to analyze the composition of macrophage subpopulations in the regenerating tissue. Flow cytometry showed that clodronate injections day 3 and 2 led to a decrease in mature monocytes day 1 together with an increase in immature monocytes. On day 3 this effect had mostly disappeared, suggesting that the effect of the injections lasted 3 to 5 days. Mechanical testing revealed that the injections prior to surgery decreased the strength of the new formed bone, holding the screw, by about half. Bone density in the drill hole was similarly reduced. In contrast, the injections given day I and 3 had smaller and statistically insignificant effects. Since their depletion at later time points failed to produce a significant effect, it seems that the role of macrophages in cancellous bone is most crucial during the first two days after trauma. (C) 2017 Elsevier Inc. All rights reserved.
|
|
| 26. |
- Scott, David, et al.
(author)
-
Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults : The Healthy Ageing Initiative
- 2019
-
In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 120, s. 446-451
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Lower skeletal muscle density, indicating greater infiltration of adipose tissue into muscles, is associated with higher fracture risk in older adults. We aimed to determine whether mid-calf muscle density is associated with falls risk and bone health in community-dwelling older adults.METHODS: 2214 community-dwelling men and women who participated in the Healthy Ageing Initiative (Sweden) study at age 70 were included in this analysis. Mid-calf muscle density (mg/cm3) at the proximal tibia, and volumetric bone mineral density (vBMD) and architecture at the distal and proximal tibia and radius, were assessed by peripheral quantitative computed tomography. Whole-body lean and fat mass, lumbar spine and total hip areal bone mineral density (aBMD) were assessed by dual-energy X-ray absorptiometry. Participants completed seven-day accelerometer measurements of physical activity intensity, and self-reported falls data were collected 6 and 12 months later.RESULTS: 302 (13.5%) participants reported a fall at the 6- or 12-month interview, and 29 (1.3%) reported a fall at both interviews. After adjustment for confounders, each standard deviation decrease in mid-calf muscle density was associated with a trend towards greater likelihood of experiencing a fall (OR 1.13; 95% CI 1.00, 1.29 per SD lower) and significantly greater likelihood of multiple falls (1.61; 1.16, 2.23). Higher muscle density was not associated with total hip aBMD, and was associated with lower lumbar spine aBMD (B = -0.003; 95% CI -0.005, -0.001 per mg/cm3) and higher proximal cortical vBMD (0.74; 0.20, 1.28) at the radius. At the tibia, muscle density was positively associated with distal total and trabecular vBMD, and proximal total and cortical vBMD, cortical thickness, cortical area and stress-strain index (all P < 0.05). Only moderate/vigorous (%) intensity physical activity, not sedentary time or light activity, was associated with higher mid-calf muscle density (0.086; 0.034, 0.138).CONCLUSIONS: Lower mid-calf muscle density is independently associated with higher likelihood for multiple incident falls and appears to have localised negative effects on bone structure in older adults.
|
|
| 27. |
- Shah, Furqan A., et al.
(author)
-
Extracellular matrix composition during bone regeneration in the human dental alveolar socket
- 2019
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 127, s. 244-249
-
Journal article (peer-reviewed)abstract
- Within the dental alveolar socket, the sequence of events following tooth extraction involves deposition of a provisional connective tissue matrix that is later replaced by woven bone and eventually by lamellar bone. Bone regeneration within the dental alveolar socket is unique since the space occupied by the root(s) of a tooth does not originally contain any bone. However, extracellular matrix composition of the healing alveolar socket has not previously been investigated. Here, alveolar bone biopsies representing early (7-46 months, < 4y) and late (48-60 months; 4-5y) healing periods were investigated using Raman spectroscopy, X-ray micro-computed tomography and backscattered electron scanning electron microscopy. Partially or completely edentulous individuals and those with a smoking habit were not excluded. Between < 4y and 4-5y, mineral crystallinity and bone mineral density increase, phenylalanine, proline/hydroxyproline, and bone surface-to-volume ratio decrease, while the carbonate-to-phosphate ratio, the mineral-to-matrix ratio, and the collagen crosslink ratio remain relatively unchanged. Observed exclusively at 4-5y, hypermineralised osteocyte lacunae contain spherical and rhomboidal mineral nodules. Spearman correlation analysis reveals several significant, high (rho = 0.7-0.9; p <= 0.01) and moderate (rho = 0.5-0.7; p <= 0.01) correlations. Mineral crystallinity and proline/hydroxyproline, the carbonate-to-phosphate ratio and phenylalanine, mineral crystallinity and bone surface-to-volume ratio, the carbonate-to-phosphate ratio and bone surface-to-volume ratio, proline/hydroxyproline and bone mineral density, and bone mineral density and bone surface-to-volume ratio are negatively correlated. Mineral crystallinity and bone mineral density, and proline/hydroxyproline and bone surface-to-volume ratio are positively correlated. Although bone regeneration in the dental alveolar socket follows typical bone healing patterns, the compositional and microstructural patterns reveal mature bone at < 4y with indications of better mechanical competence at 4-5y.
|
|
| 28. |
- Sharp, Christopher, et al.
(author)
-
Increased bone alkaline phosphatase levels do not necessarily cause hypermineralization per se
- 2016
-
In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 89, s. 83-84
-
Journal article (other academic/artistic)abstract
- Diminished bone health and increased risk of fracture is increasingly recognised as a complication of diabetes mellitus and even as a consequence of its management. We read with interest the recently published review by Starup-Linde and Vestergaard [1] about bone turnover markers (BTMs) in patients with types 1 and 2 diabetes mellitus and their value in assessing bone health in diabetic patients. In brief, 611 eligible studies were identified of which 47 were included: 1 meta-analysis, 29 cross-sectional, 13 randomized controlled trials and 4 longitudinal studies.
|
|
| 29. |
- Swolin-Eide, Diana, 1968, et al.
(author)
-
Variation of bone acquisition during growth hormone treatment in children can be explained by proteomic biomarkers, bone formation markers, body composition and nutritional factors
- 2018
-
In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 116, s. 144-153
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Growth hormone (GH) regulates both longitudinal growth and bone acquisition in children, and has profound metabolic effects. The aim was to investigate the association between proteomic biomarkers, body fat, nutrition and bone formation markers, and longitudinal growth in response to GH during the first year of treatment. The degree to which changes in these factors could explain variations in GH-dependent longitudinal growth and bone mineralization was also assessed. METHODS: The individualized GH dose trial included 128 short prepubertal children with either normal (non-GH-deficient) or reduced levels of GH secretion (GH-deficient) (mean age+/-SD, 8.6+/-2.6years; 90 boys), i.e., with a broad range of GH-secretion and GH-responsiveness, receiving GH treatment (mean 43mug/kg/day). Blood samples were taken and dual-energy X-ray absorptiometry (DXA) measured at baseline and 1year of treatment. Step-wise multiple regression models were constructed including three steps with different independent variables added at each step to explain the variance in outcome variables (heightSDS, bone mineral content (BMC) and bone mineral density (BMD). Independent variables included in Step I were previously identified proteomic markers related to GH treatment response, bone formation markers (intact PINP, bone-specific alkaline phosphatase and osteocalcin), variables at treatment start (GH dose mU/kg/day, GH maximum secretion, and difference between child's current and mid-parental heightSDS). Step II explored the added influence of body composition data (body mass index or DXA). Step III explored the added influence of serum nutritional markers and hormones. RESULTS: Step I variables explained 71% of the variation in first year heightSDS gain, median (minimum-maximum) 0.8 (0.24-1.67); and the proportion explained rose to 73% following inclusion of step II variables and 75% following step III. Corresponding values for total body BMC were 58%, 78%, and 80%, respectively. Proportions fell by approximately 20% when BMC was adjusted for height; 33%, 57%, and 57% for steps I, II, and III, respectively. Corresponding values for total body BMD were 29%, 39%, and 45%, respectively. CONCLUSION: For total BMC, as much as 80% of the variation during the first year of GH treatment could be explained by proteomic biomarkers, body fat, nutrition and bone formation markers, whereas for height-adjusted BMC 57% could be explained. The inclusion of information about either body composition (fat/lean mass) or nutritional markers contributed with approximately 20%. The variation in heightSDS gain could be explained to 75%. Hence, information of fat or nutrition markers was needed for explaining the variation in bone acquisition to the same magnitude as explaining the variation in height response.
|
|
| 30. |
- Tubić, Bojan, 1984, et al.
(author)
-
Different osteocalcin forms, markers of metabolic syndrome and anthropometric measures in children within the IDEFICS cohort
- 2016
-
In: Bone. - : ELSEVIER SCIENCE INC. - 8756-3282 .- 1873-2763. ; 84, s. 230-236
-
Journal article (peer-reviewed)abstract
- Objective: Osteocalcin (OC), an aboundant non-collagenous bone protein, is inversely associated with parameters of glucose metabolism. Interactions between bone tissue and energy metabolism have not been thoroughly investigated during childhood. This study investigated OC, metabolic parameters and anthropometric characteristics in normal weight and overweight/obese children. Methods: This study comprised 108 (46 normal weight/62 overweight/obese) Swedish 2-9 year old children. Anthropometric data, insulin, glucose, glycosylated haemoglobin (HbA1c), HOMA index, vitamin D, adiponectin, total OC, carboxylated OC (cOC) and undercarboxylated OC (ucOC) were analysed. Results: No difference was found for total OC between the normal and overweight/obese groups, with a mean (+/- SD) value of 82.6 ( +/- 2.8) ng/mL and 77.0 ( +/- 2.4) ng/mL, (P = 0.11), respectively. Overweight children had lower cOC levels, mean 69.1 ( +/- 2.2) ng/mL, vs. normal weight children, mean 75.6 ( +/- 2.5) ng/mL (P = 0.03). The mean ucOC levels of 7.9 ( +/- 0.4) ng/mL in overweight children did not differ vs. normal weight children, mean level 7.0 (+/- 0.4) ng/mL, (P = 0.067). None of the three OC forms correlated with any of the measured parameters. Conclusions: The cOC levels were lower in overweight children. There was no correlation between the three OC forms and any of the measured anthropometric or metabolic parameters. OC has been suggested to have a possible metabolic role, but in general the current study in prepubertal children does not support the hypothesis of an association between OC and a positive metabolic profile. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 31. |
|
|
| 32. |
- Bloom, A. C., et al.
(author)
-
Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 84, s. 253-261
-
Journal article (peer-reviewed)abstract
- Degenerative joint diseases such as osteoarthritis are characterised by aberrant region-specific bone formation and abnormal bone mineral content. A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis. Since CD59a is the principal regulator of the membrane attack complex in mice, we evaluated the impact of CD59a gene deletion upon maintenance of bone architecture. In vivo bone morphology analysis revealed that male CD59a-deficient mice have increased femur length and cortical bone volume, albeit with reduced bone mineral density. However, this phenomenon was not observed in female mice. Histomorphometric analysis of the trabecular bone showed increased rates of bone homeostasis, with both increased bone resorption and mineral apposition rate in CD59a-deficient male mice. When bone cells were studied in isolation, in vitro osteoclastogenesis was significantly increased in male CD59a-deficient mice, although osteoblast formation was not altered. Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis. CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis. These findings increase our understanding of the role of complement regulation in degenerative arthritis.
|
|
| 33. |
- Cöster, Marcus E., et al.
(author)
-
Effects of an 8-year childhood physical activity intervention on musculoskeletal gains and fracture risk
- 2016
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 93, s. 139-145
-
Journal article (peer-reviewed)abstract
- Background Physical activity (PA) in childhood is associated with musculoskeletal benefits while the effect on fracture risk is yet to be determined. The aim of this study was to evaluate whether extension of a PA intervention leads to improvement in musculoskeletal traits with an accompanied reduced fracture risk. We hypothesized that the PA program would have beneficial effects in both sexes, but more so in girls since they tend to be less physically active than boys during this time frame. Methods In one elementary school we increased physical education (PE) from 60 to 200 min per school week and followed 65 girls and 93 boys from a mean age of 7 years until a mean age of 15 years. Thirty-nine girls and 37 boys in three other schools continued with 60 min of PE per week during the same years and served as controls. We measured bone mineral content (BMC), areal bone mineral density (aBMD), and bone area annually with dual energy X-ray absorptiometry, and leg muscle strength with a computerized dynamometer. In 3534 children within the same PE program (1339 in the intervention and 2195 in the control group) we registered incident fractures during the 8-year study period and estimated annual sex-specific fracture incidence rate ratios (IRRs). Results Girls in the intervention group annually gained more total body less head aBMD, spine aBMD (p < 0.01), femoral neck BMC (p < 0.05), lumbar vertebrae size (p < 0.05), and knee flexion strength (p < 0.05) than girls in the control cohort. In boys we found no group differences. There was an inverse correlation between number of years with extra PE and the annual IRR of sustaining fractures in both girls (r = − 0.90 (95% CI − 0.98 to − 0.51); p < 0.001) and boys (r = − 0.74 (95% CI − 0.94 to − 0.02); p < 0.05). Conclusion In this 8-year pediatric school-based moderate exercise intervention program there is an inverse correlation in both sexes between annual IRR and each additional year of extra PA. A sub-cohort of girls in the intervention group had greater gains in bone mass, bone size, and muscle strength, which could possibly explain the inverse correlation between years within the PA program and fracture risk, while in boys the reason for the inverse correlation remains unknown. It should be noted that differences in unreported factors such as skeletal maturity status, diet, and spare time PA could confound our inferences. That is, true causality cannot be stated.
|
|
| 34. |
- Gatenholm, Birgitta, 1986, et al.
(author)
-
Spatially matching morphometric assessment of cartilage and subchondral bone in osteoarthritic human knee joint with micro-computed tomography
- 2019
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 120, s. 393-402
-
Journal article (peer-reviewed)abstract
- © 2018 Objective: The objective of this study was to develop a reproducible and semi-automatic method based on micro computed tomography (microCT) to analyze cartilage and bone morphology of human osteoarthritic knee joints in spatially matching regions of interest. Materials and methods: Tibial plateaus from randomly selected patients with advanced osteoarthritis (OA) who underwent total knee arthroplasty surgery were microCT scanned once fresh and once after staining with Hexabrix. The articular surface was determined manually in the first scan. Total articular surface, defect surface and cartilage surface were computed by triangulation of the cartilage surface and the spatially corresponding subchondral bone regions were automatically generated and the standard cortical bone and trabecular bone morphometric indices were computed. Results: The method to identify cartilage surface and defects was successfully validated against photographic examinations. The microCT measurements of the cartilage defect were also verified by conventional histopathology using safranin O–stained sections. Cartilage thickness and volume was significantly lower for OA condyle compared with healthy condyle. Bone fraction, bone tissue mineral density, cortical density and trabecular thickness differed significantly depending on the level of cartilage damage. Conclusion: This new microCT imaging workflow can be used for reproducible quantitative evaluation of articular cartilage damage and the associated changes in subchondral bone morphology in osteoarthritic joints with a relatively high throughput compared to manual contouring. This methodology can be applied to gain better understanding of the OA disease progress in large cohorts.
|
|
| 35. |
- Herrmann, D., et al.
(author)
-
Association between bone stiffness and nutritional biomarkers combined with weight-bearing exercise, physical activity, and sedentary time in preadolescent children. A case-control study
- 2015
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 78, s. 142-149
-
Journal article (peer-reviewed)abstract
- Physical activity (PA) and micronutrients such as calcium (Ca), vitamin D (25OHD), and phosphate (PO) are important determinants of skeletal development. This case-control study examined the association of these nutritional biomarkers and different PA behaviours, such as habitual PA, weight-bearing exercise (WBE) and sedentary time (SED) with bone stiffness (SI) in 1819 2-9-year-old children from the IDEFICS study (2007-2008). SI was measured on the calcaneus using quantitative ultrasound. Serum and urine Ca and PO and serum 25OHD were determined. Children's sports activities were reported by parents using a standardised questionnaire. A subsample of 1089 children had accelerometer-based PA data (counts per minute, cpm). Moderate-to-vigorous PA (MVPA) and SED were estimated. Children with poor SI (below the 15th age-/sex-/height-specific percentile) were defined as cases (N = 603). Randomly selected controls (N = 1216) were matched by age, sex, and country. Odds ratios (OR) for poor SI were calculated by conditional logistic regression for all biomarkers and PA behaviour variables separately and combined (expressed as tertiles and dichotomised variables, respectively). ORs were adjusted for fat-free mass, dairy product consumption, and daylight duration. We observed increased ORs for no sports (OR = 1.39, p < 0.05), PA levels below 524 cpm (OR = 1.85, p < 0.05) and MVPA below 4.2% a day (OR = 1.69, p < 0.05) compared to WBE, high PA levels (< 688 cpm) and high MVPA (6.7%), respectively. SED was not associated with SI. ORs were moderately elevated for low serum Ca and 25OHD. However, biomarkers were not statistically significantly associated with SI and did not modify the association between PA behaviours and SI. Although nutritional biomarkers appear to play a minor role compared to the osteogenic effect of PA and WBE, it is noteworthy that the highest risk for poor SI was observed for no sports or low MVPA combined with lower serum Ca (<2.5 mmol/l) or lower 25OHD (<43.0 nmol/l). (C) 2015 Elsevier Inc. All rights reserved.
|
|
| 36. |
- Isaksson, Hanna, et al.
(author)
-
Neutron tomographic imaging of bone-implant interface : Comparison with X-ray tomography
- 2017
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 103, s. 295-301
-
Journal article (peer-reviewed)abstract
- Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6 weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.
|
|
| 37. |
- Meakin, L. B., et al.
(author)
-
Parathyroid hormone's enhancement of bones' osteogenic response to loading is affected by ageing in a dose- and time-dependent manner
- 2017
-
In: Bone. - : Elsevier BV. - 8756-3282. ; 98, s. 59-67
-
Journal article (peer-reviewed)abstract
- Decreased effectiveness of bones' adaptive response to mechanical loading contributes to age-related bone loss. In young mice, intermittent administration of parathyroid hormone (iPTH) at 20-80 mu g/kg/day interacts synergistically with artificially applied loading to increase bone mass. Here we report investigations on the effect of different doses and duration of iPTH treatment on mice whose osteogenic response to artificial loading is impaired by age. One group of aged, 19-month-old female C57BL/6 mice was given 0, 25, 50 or 100 mu g/kg/day iPTH for 4 weeks. Histological and mu CT analysis of their tibiae revealed potent iPTH dose-related increases in periosteally-enclosed area, cortical area and porosity with decreased cortical thickness. There was practically no effect on trabecular bone. Another group was given a submaximal dose of 50 mu g/kg/day iPTH or vehicle for 2 or 6 weeks with loading of their right tibia three times per week for the final 2 weeks. In the trabecular bone of these mice the loading-related increase in BV/TV was abrogated by iPTH primarily by reduction of the increase in trabecular number. In their cortical bone, iPTH treatment time-dependently increased cortical porosity. Loading partially reduced this effect. The osteogenic effects of iPTH and loading on periosteally-enclosed area and cortical area were additive but not synergistic. Thus in aged, unlike young mice, iPTH and loading appear to have separate effects. iPTH alone causes a marked increase in cortical porosity which loading reduces. Both iPTH and loading have positive effects on cortical periosteal bone formation but these are additive rather than synergistic. (C) 2017 The Authors. Published by Elsevier Inc.
|
|
