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- Aspenberg, Per, et al.
(author)
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Teriparatide for Acceleration of Fracture Repair in Humans: A Prospective, Randomized, Double-Blind Study of 102 Postmenopausal Women With Distal Radial Fractures
- 2010
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In: JOURNAL OF BONE AND MINERAL RESEARCH. - : Wiley. - 0884-0431 .- 1523-4681. ; 25:2, s. 404-414
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Journal article (peer-reviewed)abstract
- Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 mu g dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 mu g (n = 34) or teriparatide 40 mu g (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparaticle 40 mu g versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparaticle 20 1 and 40 mu g, respectively (overall p = .015). There was no significant difference between the teriparaticle 40 mu g versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparaticle 40 1 versus 20 mu g (p = .053); however, the time to healing was shorter in teriparaticle 20 mu g than placebo (p = .006). The primary hypothesis that teriparatide 40 jug would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparaticle 20 mu g compared with placebo still may suggest that fracture repair can be accelerated by teriparaticle, but this result should be interpreted with caution and warrants further study.
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- Boonen, Steven, et al.
(author)
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Balloon Kyphoplasty for the Treatment of Acute Vertebral Compression Fractures: 2-Year Results From a Randomized Trial
- 2011
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 26:7, s. 1627-1637
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Journal article (peer-reviewed)abstract
- Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). Quality of life, function, disability, and pain were assessed over 24 months. Kyphoplasty was associated with greater improvements in Short-Form 36 (SF-36) Physical Component Summary (PCS) scores when averaged across the 24-month follow-up period compared with nonsurgical therapy [overall treatment effect 3.24 points, 95% confidence interval (CI) 1.47-5.01, p = .0004]; the treatment difference remained statistically significant at 6 months (3.39 points, 95% CI 1.13-5.64, p = .003) but not at 12 months (1.70 points, 95% CI -0.59 to 3.98, p = .15) or 24 months (1.68 points, 95% CI -0.63 to 3.99, p = .15). Greater improvement in back pain was observed over 24 months for kyphoplasty (overall treatment effect -1.49 points, 95% CI -1.88 to -1.10, p<.0001); the difference between groups remained statistically significant at 24 months (-0.80 points, 95% CI -1.39 to -0.20, p = .009). There were two device-related serious adverse events in the second year that occurred at index vertebrae (a spondylitis and an anterior cement migration). There was no statistically significant difference between groups in the number of patients (47.5% for kyphoplasty, 44.1% for control) with new radiographic vertebral fractures; fewer fractures occurred (similar to 18%) within the second year. Compared with nonsurgical management, kyphoplasty rapidly reduces pain and improves function, disability, and quality of life without increasing the risk of additional vertebral fractures. The differences from nonsurgical management are statistically significant when averaged across 24 months. Most outcomes are not statistically different at 24 months, but the reduction in back pain remains statistically significant at all time points. (C) 2011 American Society for Bone and Mineral Research.
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| 6. |
- Buttazzoni, Christian, et al.
(author)
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Does a childhood fracture predict low bone mass in young adulthood? - A 27-year prospective controlled study.
- 2013
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:2, s. 351-359
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Journal article (peer-reviewed)abstract
- BACKGROUND: A fracture in childhood is associated with low bone mineral density (BMD), but it is debated whether a fracture at growth also predicts low BMD in young adulthood. PURPOSE: To gender-specifically evaluate whether children with a fracture are at increased risk of low BMD in young adulthood. METHODS: Distal forearm BMD (g/cm(2) ) was measured with single photon absorptiometry (SPA) in 47 boys and 26 girls (mean age 10 years, range 3-16) with an index fracture and in 41 boys and 43 girls (mean age 10 years, range 4-16) with no fracture. BMD was re-measured mean 27 years later with the same SPA apparatus and with dual energy absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral computed tomography (pQCT). Individual Z-scores were calculated using the control cohort as reference population. Data are presented as means with 95% confidence intervals (95% CI) within brackets and correlation with Pearson's correlation coefficient RESULTS: Boys with an index fracture had at fracture event a distal forearm BMD Z-score of -0.4 (-0.7, -0.1) and at follow-up -0.4 (-0.7, -0.1). Corresponding values in girls were -0.2 (-0.5, 0.1) and -0.3 (-0.7, 0.1). The deficit in absolute bone mass was driven by men with index fractures in childhood due to low rather than moderate or high energy. There were no changes in BMD Z-score during the follow-up period. The BMD deficit at follow-up was in boys with an index fracture verified with all advocated techniques CONCLUSIONS: A childhood fracture in men was associated with low BMD and smaller bone size in young adulthood while the deficit in women did not reach statistical significance. © 2012 American Society for Bone and Mineral Research.
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| 7. |
- Byberg, Liisa, et al.
(author)
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Birth Weight is not Associated with Risk of Fracture : Results From Two Swedish Cohort Studies
- 2014
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 29:10, s. 2152-2160
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Journal article (peer-reviewed)abstract
- Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1,334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2,796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 (95% confidence interval [CI], 0.94-1.09) for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 82-year-old men in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43 to 126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.
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| 8. |
- Byberg, Liisa, et al.
(author)
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Prediction of fracture risk in men : A cohort study
- 2012
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 27:4, s. 797-807
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Journal article (peer-reviewed)abstract
- FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture.
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| 9. |
- Börjesson, Anna E, et al.
(author)
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The role of activation functions 1 and 2 of estrogen receptor-alpha for the effects of estradiol and selective estrogen receptor modulators in male mice
- 2013
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In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 28:5, s. 1117-1126
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Journal article (peer-reviewed)abstract
- Estradiol (E2) is important for male skeletal health and the effect of E2 is mediated via estrogen receptor (ER)-. This was demonstrated by the findings that men with an inactivating mutation in aromatase or a nonfunctional ER had osteopenia and continued longitudinal growth after sexual maturation. The aim of the present study was to evaluate the role of different domains of ER for the effects of E2 and selective estrogen receptor modulators (SERMs) on bone mass in males. Three mouse models lacking either ERAF-1 (ERAF-10), ERAF-2 (ERAF-20), or the total ER (ER/) were orchidectomized (orx) and treated with E2 or placebo. E2 treatment increased the trabecular and cortical bone mass and bone strength, whereas it reduced the thymus weight and bone marrow cellularity in orx wild type (WT) mice. These parameters did not respond to E2 treatment in orx ER/ or ERAF-20 mirx ERAF-10 mice were tissue-dependent, with a clear response in cortical bone parameters and bone marrow cellularity, but no response in trabecular bone. To determine the role of ERAF-1 for the effects of SERMs, we treated orx WT and ERAF-10 mice with raloxifene (Ral), lasofoxifene (Las), bazedoxifene (Bza), or vehicle. These SERMs increased total body areal bone mineral density (BMD) and trabecular volumetric BMD to a similar extent in orx WT mice. Furthermore, only Las increased cortical thickness significantly and only Bza increased bone strength significantly. However, all SERMs showed a tendency toward increased cortical bone parameters. Importantly, all SERM effects were absent in the orx ERAF-10 mice. In conclusion, ERAF-2 is required for the estrogenic effects on all evaluated parameters, whereas the role of ERAF-1 is tissue-specific. All evaluated effects of Ral, Las and Bza are dependent on a functional ERAF-1. Our findings might contribute to the development of bone-specific SERMs in males. (c) 2013 American Society for Bone and Mineral Research.
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| 10. |
- Börjesson, Anna E, et al.
(author)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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In: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Journal article (peer-reviewed)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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