| 1. |
- Brage, M, et al.
(författare)
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Different cysteine proteinases involved in bone resorption and osteoclast formation.
- 2005
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 76:6, s. 439-47
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Tidskriftsartikel (refereegranskat)abstract
- Cysteine proteinases, especially cathepsin K, play an important role in osteoclastic degradation of bone matrix proteins and the process can, consequently, be significantly inhibited by cysteine proteinase inhibitors. We have recently reported that cystatin C and other cysteine proteinase inhibitors also reduce osteoclast formation. However, it is not known which cysteine proteinase(s) are involved in osteoclast differentiation. In the present study, we compared the relative potencies of cystatins C and D as inhibitors of bone resorption in cultured mouse calvariae, osteoclastogenesis in mouse bone marrow cultures, and cathepsin K activity. Inhibition of cathepsin K activity was assessed by determining equilibrium constants for inhibitor complexes in fluorogenic substrate assays. The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity. A recombinant human cystatin C variant with Gly substitutions for residues Arg8, Leu9, Val10, and Trp106 did not inhibit bone resorption, had 1,000-fold decreased inhibitory effect on cathepsin K activity compared to wildtype cystatin C, but was equipotent with wildtype cystatin C as an inhibitor of osteoclastogenesis. It is concluded that (i) different cysteine proteinases are likely to be involved in bone resorption and osteoclast formation, (ii) cathepsin K may not be an exclusive target enzyme in any of the two systems, and (iii) the enzyme(s) involved in osteoclastogenesis might not be a typical papain-like cysteine proteinase.
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| 2. |
- Cronin, O., et al.
(författare)
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Role of the Microbiome in Regulating Bone Metabolism and Susceptibility to Osteoporosis
- 2022
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 110:3, s. 273-284
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Tidskriftsartikel (refereegranskat)abstract
- The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.
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| 3. |
- den Bussche, K., et al.
(författare)
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Influence of Birth Weight on Calcaneal Bone Stiffness in Belgian Preadolescent Children
- 2012
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 91:4, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the relation between birth weight and calcaneal bone stiffness in a large sample of Belgian, healthy, preadolescent children. Participants were 827 children (3.6-11.2 years, 51.6 % boys) from the Belgian cohort of the IDEFICS study. Birth weight was obtained using a parental questionnaire, and quantitative ultrasound (QUS) measurements were performed to determine calcaneal broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) using the Lunar Achilles device. Average birth weights were 3435.7 +/- A 512.0 g for boys and 3256.9 +/- A 471.1 g for girls. Average calcaneal QUS measurements were 89.6 +/- A 24.0 (23.3-153.9) dB/MHz for BUA, 1621.4 +/- A 49.6 (1516.3-1776.5) m/s for SOS, and 92.8 +/- A 15.6 (49.0-163.0) for SI. Birth weight was positively associated with BUA (r = 0.13, p = 0.002) and SOS (r = -0.16, p < 0.001). The associations remained after correcting for age and sex in multiple regression analyses but disappeared after correcting for anthropometric covariates. Our findings suggest that birth weight, as a rough proxy indicator for genetic and environmental influences during intrauterine life, is associated with BUA and SOS in preadolescent children and may therefore influence the risk of osteoporosis later in life. Further studies using QUS are needed to investigate the consistency of the results of this study.
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| 4. |
- Johansson, Peter, et al.
(författare)
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Increased Risk of Hip Fracture in Patients with Lymphoma, a Swedish Population Study of 37,236 Lymphoma Patients.
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 106, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Increased bone loss has been noted in lymphoma patients; however, the incidence of hip fracture is not known. The aim of our study was to explore the risk for hip fracture in patients with lymphoma compared with the entire Swedish population. The risk of hip fracture was determined in a retrospective population cohort study of adult Swedish lymphoma patients (n=37,236), diagnosed 1995-2015 and compared with the entire Swedish population during the same period. The incidence of hip fracture in lymphoma patients was higher in women than in men, increased by age, and decreased by calendar year as also demonstrated in the total population. 2.2% of the men and 4.7% of women with lymphoma sustained a hip fracture. For the total group of females, the hazard ratio (HR) was 1.19 (95% CI 1.11-1.28) and for men, the hazard ratio was 1.06 (95% CI 0.97-1.17) compared with the Swedish population. The HR for hip fracture (2016) was 2.80 (95% CI 1.20-6.53), 2.04 (95% CI 1.30-3.20), 1.56 (95% CI 1.21-2.01), 1.08 (95% CI 0.89-1.30), and 1.07 (95% CI 0.92-1.25) in females aged 40, 50, 60, 70, and 80years, respectively. Corresponding figures for men were not significant in 2016. Unmarried men with lymphoma had a two times higher risk for hip fracture (HR 2.02 95% CI 1.63-2.50) compared with married men. Patients with lymphoma had an increased risk of hip fracture, especially younger women and unmarried men. The incidence of hip fracture is decreased by calendar year in the lymphoma patients and the entire Swedish population.
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| 5. |
- Kanis, J A, et al.
(författare)
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Epidemiology of osteoporosis and fracture in men.
- 2004
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 75:2, s. 90-9
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Kanis, John A, et al.
(författare)
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FRAX(®) with and without Bone Mineral Density
- 2012
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 90:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The use of FRAX, particularly in the absence of BMD, has been the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high validity as judged from an evidence-based assessment and identify a risk that is responsive to pharmaceutical intervention. Moreover, treatment effects, with the possible exception of alendronate, are not dependent on baseline BMD and strongly suggest that FRAX identifies high-risk patients who respond to pharmaceutical interventions. In addition, the selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where DXA facilities are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Whereas the efficacy for agents to reduce fracture risk has not been tested prospectively in randomized controlled trials in patients selected on the basis of FRAX probabilities, there is compelling evidence that FRAX with or without the use of BMD provides a well-validated instrument for targeting patients most likely to benefit from an intervention.
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| 7. |
- Larsson, Berit A M, et al.
(författare)
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Normal Bone Microstructure and Density But Worse Physical Function in Older Women Treated with Selective Serotonin Reuptake Inhibitors, a Cross-Sectional Population-Based Study.
- 2018
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 103:3, s. 278-288
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Tidskriftsartikel (refereegranskat)abstract
- Depression in the elderly is today often treated with selective serotonin reuptake inhibitors (SSRIs) because of their favorable adverse effect profile. However, treatment with SSRIs is associated with increased risk of fractures. Whether this increased risk depends on reduced bone strength or increased fall risk due to reduced physical function is not certain. The aim was therefore to investigate if treatment with SSRIs is associated with impaired bone microstructure, bone density, or physical function in older women. From an ongoing population-based study, 1057 women (77.7±1.5years) were included. Validated questionnaires were used to assess information regarding medical history, medications, smoking, mental and physical health, and physical activity. Physical function was measured using clinically used tests: timed up and go, walking speed, grip strength, chair stand test, and one leg standing. Bone mineral density (BMD) was measured at the hip and spine with dual-energy X-ray absorptiometry (Hologic Discovery A). Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT). Treatment with SSRIs was associated with higher BMD at the femoral neck, total hip, and lumbar spine, whereas no associations were found for any HR-pQCT-derived measurements. The use of SSRIs was associated with lower grip strength, walking speed, and fewer chair stand rises. These associations were valid also after adjustments for known risk factors for falls. Treatment with SSRIs was, independently of covariates, associated with worse physical function without any signs of inferior bone geometry and microstructure.
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| 8. |
- Maurotti, Samantha, et al.
(författare)
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Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats.
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 107, s. 266-280
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Tidskriftsartikel (refereegranskat)abstract
- C-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6weeks. We performed micro-CT and histological testing to assess several trabecular microarchitectural parameters. At the end, diabetic plus C-peptide rats had a higher serum C-peptide (p=0.02) and calcium (p=0.04) levels and tibia weight (p=0.02) than the diabetic control group. The diabetic plus C-peptide group showed a higher trabecular thickness and cross-sectional thickness than the diabetic control group (p=0.01 and p=0.03). Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison with the diabetic control group (p=0.045 and p=0.034). Diabetic rats receiving C-peptidehad higher quality of trabecular bone than diabetic rats not receiving this treatment. If confirmed, C-peptide could have a role in improving bone quality in diabetes.
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| 9. |
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| 10. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Osteomicrobiology: A New Cross-Disciplinary Research Field.
- 2018
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 102:4, s. 426-432
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Forskningsöversikt (refereegranskat)abstract
- The mutualistic interaction between the gut microbiota (GM) and its host profoundly shapes many aspects of our physiology. The composition and activity of the gut microbiota is modulated by environmental factors such as dietary habits and antibiotic treatments. In rodents, studies demonstrate that the GM is a crucial regulator of bone metabolism and that modulation of the GM composition by probiotic interventions can prevent castration-induced bone loss. Short-term colonization of germ-free mice with GM results in an activation of CD4+T cells, resulting in increased levels of pro-inflammatory cytokines in bone and thereby activation of osteoclastic bone resorption. Besides these immune-mediated effects on bone mass, the GM is involved in nutritional uptake and may, thereby, regulate overall body growth and bone sizes possibly mediated via altered IGF-I levels. We recently introduced a new term "osteomicrobiology" for the rapidly emerging research field of the role of the microbiota in bone health. This research field is aimed to bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology. Future studies will determine if the GM is a novel therapeutic target for osteoporosis and if the GM composition might be used as a biomarker for fracture prediction.
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