| 1. |
- 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
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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 80 years, 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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| 2. |
- Makitie, RE, et al.
(författare)
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A Novel IFITM5 Variant Associated with Phenotype of Osteoporosis with Calvarial Doughnut Lesions: A Case Report
- 2021
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 109:6, s. 626-632
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) and other decreased bone density disorders comprise a heterogeneous group of heritable diseases with skeletal fragility. Recently, it was discovered that mutations in SGMS2, encoding sphingomyelin synthetase 2, result in aberrant sphingomyelin metabolism and lead to a novel form of OI termed osteoporosis with calvarial doughnut lesions (OP-CDL) with moderate to severe skeletal fragility and variable cranial hyperostotic lesions. This study describes a Japanese family with the skeletal phenotype of OP-CDL. The affected individuals have moderately severe, childhood-onset skeletal fragility with multiple long-bone fractures, scoliosis and bone deformities. In addition, they exhibit multiple CDLs or calvarial bumps with central radiolucency and peripheral radiopacity. However, SGMS2 sequencing was normal. Instead, whole-exome sequencing identified a novel IFITM5 missense mutation c.143A>G (p.N48S) (classified as a VUS by ACMG). IFITM5 encodes an osteoblast-restricted protein BRIL and a recurrent c.-14C>T mutation in its 5' UTR region results in OI type V, a distinctive subtype of OI associated with hyperplastic callus formation and ossification of the interosseous membranes. The patients described here have a phenotype clearly different from OI type V and with hyperostotic cranial lesions, feature previously unreported in association with IFITM5. Our findings expand the genetic spectrum of OP-CDL, indicate diverse phenotypic consequences of pathogenic IFITM5 variants, and imply an important role for BRIL in cranial skeletogenesis.
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| 3. |
- Malmgren, B, et al.
(författare)
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Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta
- 2021
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 109:2, s. 121-131
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with intravenous bisphosphonate (BP) in children and adolescents with osteogenesis imperfecta (OI) started in Sweden in 1991. No human studies on the role of BP therapy in development of disturbances in tooth mineralization or tooth morphology have been published. The study cohort comprised 219 individuals who were divided into four groups: group 1, BP treatment onset before 2 years of age (n = 22); group 2, BP treatment onset between 2 and 6 years of age (n = 20); group 3, BP treatment onset between 6 and 10 years of age (n = 13); and a control group of patients with OI who had not received BP therapy (n = 164). The chi-square test was used in between-group comparisons of the prevalence of tooth agenesis. The prevalence of tooth agenesis was significantly higher in children who began BP treatment before the age of 2 years (group 1; 59%,) compared to the controls (10%; p < 0.001) and to children who had begun BP therapy between ages 2 and 6 years (group 2; 10%; p = 0.009) or between ages 6 and 10 years (group 3; 8%; p = 0.003). Different types of disturbances in the enamel formation were seen in 52 premolars, where 51 were seen in those who began BP treatment before the age of 2 years. To conclude, starting BP treatment before the age of 2 years increases the risk of abnormalities in tooth formation manifesting as morphological aberrations, tooth agenesis, and enamel defects.
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| 4. |
- Malmgren, B, et al.
(författare)
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Bisphosphonate Therapy and Tooth Development in Children and Adolescents with Osteogenesis Imperfecta
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 107:2, s. 143-150
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Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by repeated fractures and skeletal disorders. At present, bisphosphonate (BP) therapy is the gold standard for OI treatment. The present retrospective study evaluated the effect of BP therapy on tooth development and eruption of permanent teeth in a cohort of children receiving pamidronate. Three groups were studied: patients with OI who were treated with BPs (n = 45), patients with OI who were not treated with BPs (n = 117), and age- and gender-matched healthy controls (n = 121). Dental age, dental maturity, and tooth eruption were assessed on panoramic radiographs using the methods of Demirjian et al. (Hum Biol 45(2):211–227, 1973) and Haavikko (Suom Hammaslaak Toim 66(3):103–170, 1970) and were evaluated using the t-test, Chi-square test, and the Mann–Whitney U test. Dental age in the study group was significantly (p < 0.05) lower than chronological age compared with both control groups. Dental maturity and the eruption of permanent teeth were also significantly (p < 0.05) delayed in the study group in relation to the two control groups. The dental age was significantly lower (p < 0.001) in patients with OI type III treated with BPs compared with healthy controls and the dental maturation was significantly delayed in patients with OI type IV treated with BPs compared with those not treated. In conclusion, BP therapy in OI patients seems to lower the dental age, delay the dental maturity, and tooth eruption. BP administration before 2 years of age might be a contributing factor.
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| 5. |
- Matthews, BG, et al.
(författare)
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αSMA Osteoprogenitor Cells Contribute to the Increase in Osteoblast Numbers in Response to Mechanical Loading
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 106:2, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- Bone is a dynamic tissue that site-specifically adapts to the load that it experiences. In response to increasing load, the cortical bone area is increased, mainly through enhanced periosteal bone formation. This increase in area is associated with an increase in the number of bone-forming osteoblasts; however, the origin of the cells involved remains unclear. Alpha-smooth muscle actin (αSMA) is a marker of early osteoprogenitor cells in the periosteum, and we hypothesized that the new osteoblasts that are activated by loading could originate from αSMA-expressing cells. Therefore, we used an in vivo fate-mapping approach in an established axial loading model to investigate the role of αSMA-expressing cells in the load-induced increase in osteoblasts. Histomorphometric analysis was applied to measure the number of cells of different origin on the periosteal surface in the most load-responsive region of the mouse tibia. A single loading session failed to increase the number of periosteal αSMA-expressing cells and osteoblasts. However, in response to multiple episodes of loading, the caudal, but not the cranial, periosteal surface was lined with an increased number of osteoblasts originating from αSMA-expressing cells 5 days after the initial loading session. The proportion of osteoblasts derived from αSMA-labeled progenitors increased by 70% (p < 0.05), and the proportion of αSMA-labeled cells that had differentiated into osteoblasts was doubled. We conclude that αSMA-expressing osteoprogenitors can differentiate and contribute to the increase in periosteal osteoblasts induced by mechanical loading in a site-specific manner.
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| 6. |
- 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
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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 6 weeks. 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-peptide had 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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| 7. |
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| 8. |
- Mira-Pascual, L, et al.
(författare)
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A Novel Sandwich ELISA for Tartrate-Resistant Acid Phosphatase 5a and 5b Protein Reveals that Both Isoforms are Secreted by Differentiating Osteoclasts and Correlate to the Type I Collagen Degradation Marker CTX-I In Vivo and In Vitro
- 2020
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Ingår i: Calcified tissue international. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 106:2, s. 194-207
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Tidskriftsartikel (refereegranskat)abstract
- Tartrate-resistant acid phosphatase type 5 (TRAP) exists as two isoforms, 5a and 5b. 5b is a marker of osteoclast number and 5a of chronic inflammation; however, its association with bone resorption is unknown. In this study, a double-TRAP 5a/5b sandwich ELISA measuring 5a and 5b protein in the same sample was developed. TRAP 5a and 5b protein levels were evaluated as osteoclast differentiation/activity markers in serum and in culture, and their correlation to the resorption marker CTX-I was examined. Serum TRAP 5a and 5b concentrations in healthy men were 4.4 ± 0.6 ng/ml and 1.3 ± 0.2 ng/ml, respectively, and they correlated moderately to each other suggesting that their secretion is coupled under healthy conditions. A correlation was also observed between serum TRAP 5a and 5b with CTX-I, suggesting that both TRAP isoforms associate with osteoclast number. During osteoclast differentiation on plastic/bone, predominantly 5b increased in media/lysate from M-CSF/RANKL-stimulated CD14+ PBMCs. However, substantial levels of 5a were detected at later stages suggesting that both isoforms are secreted from differentiating OCs. More TRAP 5b was released on bone indicating a connection to osteoclast resorptive activity, and a peak in TRAP 5b/5a-ratio coincided with rapid CTX-I release. At the end of the culture period of M-CSF + RANKL-stimulated CD14+ PBMCs, there was a correlation between the secretion of TRAP 5a and 5b proteins with CTX-I. The correlation of not only 5b but also 5a with collagen degradation, both in serum and osteoclast cultures indicates that a considerable proportion of the TRAP 5a originates from osteoclasts and may reflect a hitherto undisclosed regulatory mechanism during bone resorption and bone remodeling.
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| 9. |
- Padidela, Raja, et al.
(författare)
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Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia
- 2021
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Ingår i: Calcified Tissue International. - : Springer. - 0171-967X .- 1432-0827. ; 108, s. 622-633
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Tidskriftsartikel (refereegranskat)abstract
- Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline.
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| 10. |
- Rosengren, Björn E., et al.
(författare)
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Musculoskeletal Benefits from a Physical Activity Program in Primary School are Retained 4 Years after the Program is Terminated
- 2021
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 109:4, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- Daily school physical activity (PA) improves musculoskeletal traits. This study evaluates whether the benefits remain 4 years after the intervention. We followed 45 boys and 36 girls who had had 40 min PA/school day during the nine compulsory school years and 21 boys and 22 girls who had had 60 min PA/school week (reference), with measurements at baseline and 4 years after the program terminated. Bone mineral content (BMC; g) and bone mineral density (BMD; g/cm2) were measured by dual-energy X-ray absorptiometry and knee flexion peak torque relative to total body weight (PTflexTBW) at a speed of 180 degrees/second with a computerized dynamometer. Group differences are presented as mean differences (adjusted for sex and duration of follow-up period) with 95% confidence intervals. The total gain bone mass [mean difference in spine BMC +32.0 g (14.6, 49.4) and in arms BMD of +0.06 g/cm2 (0.02, 0.09)] and gain in muscle strength [mean difference in PTflex180TBW +12.1 (2.0, 22.2)] were greater in the intervention than in the control group. There are still 4 years after the intervention indications of benefits in both bone mass and muscle strength gain. Daily school PA may counteract low bone mass and inferior muscle strength in adult life. ClinicalTrials.gov.NCT000633828 retrospectively registered 2008-11-03
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