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1.
  • Ahlborg, Henrik, et al. (författare)
  • Incidence and risk factors for low trauma fractures in men with prostate cancer.
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 43, s. 556-560
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. METHODS: In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer; among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. RESULTS: Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p=0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0-3.4) and increased rate of bone loss (HR 2.3, 1.2-4.6). CONCLUSIONS: Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these.
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2.
  • Atroshi, Isam, et al. (författare)
  • Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
  • 2009
  • Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.
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4.
  • Binkley, Neil, et al. (författare)
  • Alendronate/vitamin D3 70 mg/2800 IU with and without additional 2800 IU vitamin D3 for osteoporosis : results from the 24-week extension of a 15-week randomized, controlled trial
  • 2009
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:4, s. 639-647
  • Tidskriftsartikel (refereegranskat)abstract
    • Although vitamin D supplementation is a fundamental part of osteoporosis treatment, many patients do not regularly take adequate amounts. A once-weekly (OW) alendronate (ALN) preparation that includes 2800 IU of vitamin D3 in a single combination tablet (ALN+D2800) is available for treating patients and ensuring intake of vitamin D that is consistent with existing guidelines. This randomized, double-blind study extension was conducted to evaluate the safety and tolerability of ALN+D2800 and ALN+D2800 plus an additional 2800 IU vitamin D3 single tablet supplement (ALN+D5600) administered for 24 weeks in men and postmenopausal women with osteoporosis previously treated OW for 15 weeks with either ALN or ALN+D2800. The primary endpoint was the proportion of participants who developed hypercalciuria (defined as a 24-hour urine calcium >300 mg in women or >350 mg in men and an increase of >25% versus randomization baseline) at week 39. The key secondary endpoint was the proportion of participants with vitamin D insufficiency (serum 25(OH)D <15 ng/mL [37.4 nmol/L]) at the end of the study. Hypercalciuria incidence (4.2% [ALN+D5600] vs. 2.8% [ALN+D2800]), did not differ between groups (p = 0.354). No participants developed hypercalcemia. Among the participants with vitamin D insufficiency at the week 0 baseline, the prevalence of insufficiency at the end of the study was reduced by 92% in the ALN+D5600 group and by 86% in the ALN+D2800 group. The incidences of clinical adverse experiences, including drug-related adverse experiences, were similar in both groups. In subjects previously treated with ALN+D2800 for 15 weeks, the addition of 2800 IU D3 for 24 weeks did not produce hypercalcemia nor increase the risk of hypercalciuria.
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5.
  • Brechter, Anna Bernhold, et al. (författare)
  • Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. Effects dependent on activation of NF-kappaB and MAP kinases.
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:1, s. 72-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Pro-inflammatory mediators formed by the kallikrein-kinin system can stimulate bone resorption and synergistically potentiate bone resorption induced by IL-1 and TNF-alpha. We have shown that the effect is associated with synergistically enhanced RANKL expression and enhanced prostaglandin biosynthesis, due to increased cyclooxygenase-2 expression. In the present study, the effects of osteotropic cytokines and different kinins on the expression of receptor subtypes for bradykinin (BK), des-Arg10-Lys-BK (DALBK), IL-1beta and TNF-alpha have been investigated. IL-1beta and TNF-alpha enhanced kinin B1 and B2 receptor binding in the human osteoblastic cell line MG-63 and the mRNA expression of B1 and B2 receptors in MG-63 cells, human gingival fibroblasts and intact mouse calvarial bones. Kinins did not affect mRNA expression of IL-1 or TNF receptors. EMSA showed that IL-1beta and TNF-alpha activated NF-kappaB and AP-1 in MG-63 cells. IL-1beta stimulated NF-kappaB via a non-canonical pathway (p52/p65) and TNF-alpha via the canonical pathway (p50/p65). Activation of AP-1 involved c-Jun in both IL-1beta and TNF-alpha stimulated cells, but c-Fos only in TNF-alpha stimulated cells. Phospho-ELISA and Western blots showed that IL-1beta activated JNK and p38, but not ERK 1/2 MAP kinase. Pharmacological inhibitors showed that NF-kappaB, p38 and JNK were important for IL-1beta induced stimulation of B1 receptors, and NF-kappaB and p38 for B2 receptors. p38 and JNK were important for TNF-alpha induced stimulation of B1 receptors, whereas NF-kappaB, p38 and JNK were involved in TNF-alpha induced expression of B2 receptors. These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. The enhanced kinin receptor expression induced by the pro-inflammatory cytokines IL-1beta and TNF-alpha might be one important mechanism involved in the synergistic enhancement of prostaglandin formation caused by co-treatment with kinins and one of the two cytokines. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis.
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6.
  • Devlin, Hugh, et al. (författare)
  • Automated osteoporosis risk assessment by dentists : a new pathway to diagnosis
  • 2007
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 40:4, s. 835-842
  • Tidskriftsartikel (refereegranskat)abstract
    • General dental practitioners use a vast amount of panoramic radiography in their routine clinical work, but valuable information about patients' osteoporotic status is not collected. There are many reasons for this, but one of the prime reasons must be the disruption involved in clinical routine with lengthy manual radiographic assessment. We have developed computer software, based on active shape modeling that will automatically detect the mandibular cortex on panoramic radiographs, and then measure its width. Automatic or semi-automatic measurement of the cortical width will indicate the osteoporotic risk of the patient. The aim of our work was to assess the computer search technique's ability to measure the mandibular cortical width and to assess its potential for detection of osteoporosis of the hip, spine and femoral neck. Mandibular cortical width was measured using the manually initialized (semi-automatic) method and, when assessed for diagnosing osteoporosis at one of the three measurement sites, gave an area under the ROC curve (A(z))=0.816 (95% CI=0.784 to 0.845) and for the automatically initialized searches, A(z)=0.759 (95% CI=0.724 to 0.791). The difference between areas=0.057 (95% Confidence interval=0.025 to 0.089), p<0.0001. For diagnosing osteoporosis at the femoral neck, mandibular cortical width derived from the manually initialized fit gave an area under the ROC curve (A(z))=0.835 (95% CI=0.805 to 0.863) and for the automatically initialized searches A(z)=0.805 (95% CI=0.773 to 0.835). The difference in A(z) values between active shape modeling search methods=0.030 (95% CI=-0.010 to 0.070), and this was not significant, p=0.138. We concluded that measurement of mandibular cortical width using active shape modeling is capable of diagnosing skeletal osteoporosis with good diagnostic ability and repeatability. PMID: 17188590 [PubMed - indexed for MEDLINE]
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7.
  • Eklund, Fredrik, et al. (författare)
  • Bone mass, size and previous fractures as predictors of prospective fractures in an osteoporotic referral population.
  • 2009
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 45:4, s. 808-813
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of bone mass, bone size and previous low energy fractures upon prospective fractures has not been investigated in a referral osteoporotic population. We investigated the association between bone mass, bone size, previous fractures, body constitution, and prospective validated fractures in 5701 women and 1376 men, aged 30 years and older. Bone mass measurements of the femoral neck were collected at a single study center in Sweden. Most of the subjects were measured on suspicion of osteoporosis. Data on validated low energy retrospective and prospective fractures in the cohort were collected from the corresponding health care district. Bone mineral density (BMD, g/cm(2)) and estimated volumetric BMD (vBMD, g/cm(3)) were shown to be good independent predictors for fracture in both women and men (Hazard ratio per standard deviation decrease (HR)=1.27-1.52, p<0.05). Bone size did not predict prospective fractures in either sex (HR=0.91-0.99, p>0.05), and bone size completely explained the higher BMD in men than in women. In women, retrospective low energy fractures (HR=1.78, p<0.001) and height (HR=1.02, p=0.006) were additional independent predictors of osteoporotic fractures after adjusting for age and BMD. In conclusion, we show that in a large osteoporotic referral population, age, BMD and previous fractures are independent predictors of prospective low energy fractures. These results add additional strength to the recent change in focus towards a multivariate analysis when assessing the future risk of fracture.
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8.
  • Eriksson, Anna-Lena, 1971, et al. (författare)
  • The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
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10.
  • Geraets, Wil G, et al. (författare)
  • Prediction of bone mineral density with dental radiographs
  • 2007
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 40:5, s. 1217-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • There is consensus to use the bone mineral density (BMD) for the operational definition of the degree of osteoporosis and the risk of osteoporotic fractures. Dual X-ray absorptiometry (DXA) is the common technique to determine BMD. Because of high costs and limited availability of DXA equipment it is worthwhile to look for alternative diagnostic techniques. As part of a larger study, the Osteodent project, we investigated if the trabecular pattern on dental radiographs can be used to predict BMD and to identify the subjects with osteoporosis and increased risk of osteoporotic fractures. In four clinical centers 671 women with an average age of 55 years were recruited. BMD values were measured by DXA equipment at the femoral neck, total hip, and spine. One panoramic and two intraoral radiographs were made. From 525 women a complete set of BMD values and radiographs was obtained. Four regions of interest on the radiographs were selected manually and then processed automatically. On all regions of interest mean and standard deviation of the gray values were measured and several features describing the shape of the binarized trabecular pattern. Multiple regression was used to predict BMD of total hip and spine by means of the radiographic measurements combined with age. It was found that age accounts for 10% of the variation in total hip BMD and 14% of the variation in spinal BMD. When all measurements on the dental radiographs are used the explained variation increases to 22% and 23%. The areas under the ROC curves are comparable to those of commonly used screening instruments for osteoporosis. It is concluded that prediction of DXA measurements of BMD by means of quantitative analysis of the trabecular pattern on dental radiographs is feasible. PMID: 17317351 [PubMed - indexed for MEDLINE]
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