| 1. |
- Ahlborg, Henrik, et al.
(författare)
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Incidence and risk factors for low trauma fractures in men with prostate cancer.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 43, s. 556-560
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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)
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Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
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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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| 3. |
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| 4. |
- Binkley, Neil, et al.
(författare)
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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
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:4, s. 639-647
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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)
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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
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:1, s. 72-83
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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)
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Automated osteoporosis risk assessment by dentists : a new pathway to diagnosis
- 2007
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 40:4, s. 835-842
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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)
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Bone mass, size and previous fractures as predictors of prospective fractures in an osteoporotic referral population.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 45:4, s. 808-813
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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)
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The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12
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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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| 9. |
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| 10. |
- Geraets, Wil G, et al.
(författare)
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Prediction of bone mineral density with dental radiographs
- 2007
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 40:5, s. 1217-1221
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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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| 11. |
- Goldhahn, Jörg, et al.
(författare)
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Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:2, s. 343-347
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Tidskriftsartikel (refereegranskat)abstract
- Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. © 2008 Elsevier Inc. All rights reserved.
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| 12. |
- Halling Linder, Cecilia, et al.
(författare)
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Glycosylation differences contribute to distinct catalytic properties among bone alkaline phosphatase isoforms.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:5, s. 987-993
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Tidskriftsartikel (refereegranskat)abstract
- Three circulating human bone alkaline phosphatase (BALP) isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue. The present study was designed to correlate differing glycosylation patterns of each BALP isoform with their catalytic activity towards presumptive physiological substrates and to compare those properties with two recombinant isoforms of the tissue-nonspecific ALP (TNALP) isozyme, i.e., TNALP-flag, used extensively for mutation analysis of hypophosphatasia mutations and sALP-FcD(10), a chimeric enzyme recently used as therapeutic drug in a mouse model of infantile hypophosphatasia. The BALP isoforms were prepared from human osteosarcoma (SaOS-2) cells and the kinetic properties were evaluated using the synthetic substrate p-nitrophenylphosphate (pNPP) at pH 7.4 and 9.8, and the three suggested endogenous physiological substrates, i.e., inorganic pyrophosphate (PP(i)), pyridoxal 5'-phosphate (PLP), and phosphoethanolamine (PEA) at pH 7.4. Qualitative glycosylation differences were also assessed by lectin binding and precipitation. The k(cat)/K(M) was higher for B2 for all the investigated substrates. The catalytic activity towards PEA was essentially undetectable. The kinetic activity for TNALP-flag and sALP-FcD(10) was similar to the activity of the human BALP isoforms. The BALP isoforms differed in their lectin binding properties and dose-dependent lectin precipitation, which also demonstrated differences between native and denatured BALP isoforms. The observed differences in lectin specificity were attributed to N-linked carbohydrates. In conclusion, we demonstrate significantly different catalytic properties among the BALP isoforms due to structural differences in posttranslational glycosylation. Our data also suggests that PEA is not an endogenous substrate for the BALP isoforms or for the recombinant TNALP isoforms. The TNALP-flag and the sALP-FcD(10) isoforms faithfully mimic the biological properties of the human BALP isoforms in vivo validating the use of these recombinant enzymes in studies aimed at dissecting the pathophysiology and treating hypophosphatasia.
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| 13. |
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| 14. |
- Hollberg, Karin, et al.
(författare)
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Osteoclast polarization is not required for degradation of bone matrix in rachitic FGF23 transgenic mice
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:6, s. 1111-1121
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Tidskriftsartikel (refereegranskat)abstract
- Hypophosphatemic transgenic (tg) mice overexpressing FGF23 in osteoblasts display disorganized growth plates and reduced bone mineral density characteristic of rickets/osteomalacia. These FGF23 tg mice were used as an in vivo model to examine the relation between osteoclast polarization, secretion of proteolytic enzymes and resorptive activity. Tg mice had increased mRNA expression levels of the ostcoblast differentiation marker Runx2 and mineralization-promoting proteins alkaline phosphatase and bone sialoprotein in the long bones compared to wild type (wt) mice. In contrast, expression of alpha 1 (1) collagen, osteocalcin, dentin matrix protein 1 and osteopontin was unchanged, indicating selective activation of osteoblasts promoting mineralization. The number of osteoclasts was unchanged in tg compared to wt mice, as determined by histomorphometry, serum levels of TRAP 5b activity as well as mRNA expression levels of TRAP and cathepsin K. However, tg mice displayed elevated serum concentrations of C-terminal telopeptide of collagen I (CTX) indicative of increased bone matrix degradation. The majority of osteoclasts in FGF23 tg mice lacked ultrastructural morphological signs of proper polarization. However, they secreted both cathepsin K and MMP-9 at levels comparable to osteoclasts with ruffled borders. Mineralization of bone matrix thus appears essential for inducing osteoclast polarization but not for secretion of osteoclast proteases. Finally, release of CTX by freshly isolated osteoclasts was increased on demineralized compared to mineralized bovine bone slices, indicating that the mineral component limits collagen degradation. We conclude that ruffled borders are implicated in acidification and subsequent demineralization of the bone matrix, however not required for matrix degradation. The data collectively provide evidence that osteoclasts, despite absence of ruffled borders, effectively participate in the degradation of hypomineralized bone matrix in rachitic FGF23 tg mice.
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| 15. |
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| 16. |
- Kanis, John A, et al.
(författare)
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Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 44:6, s. 1049-54
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Bazedoxifene has been shown to significantly decrease the risk of vertebral fractures in postmenopausal women. No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture. AIMS: The aim of this study was to re-evaluate the efficacy of bazedoxifene on fracture outcomes avoiding subgroup analysis by examining the efficacy of intervention as a function of fracture risk. METHODS: The phase III study was a double-blind, randomised, placebo- and raloxifene-controlled randomised 3-year multinational study that enrolled 7492 osteoporotic women aged 55 years or more (mean age=66 years). For the present analysis, women taking raloxifene were excluded (n=1849), and we compared the effects of two doses of bazedoxifene (20 and 40 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture. The risk of a major osteoporotic fracture was assessed using region specific FRAX algorithms, and the relationship between pre hoc 10-year fracture probabilities and efficacy examined by Poisson regression. RESULTS: Overall, bazedoxifene was associated with a significant 39% decrease in incident morphometric vertebral fractures (hazard ratio HR=0.61; 95% CI=0.43-0.86; p=0.005) and a non-statistically significant 16% decrease in all clinical fractures (hazard ratio HR=0.84; 95% CI=0.67-1.06; p=0.14) compared to placebo. Hazard ratios for the effect of bazedoxifene on all clinical fractures decreased with increasing fracture probability. In patients with 10-year fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the risk of all clinical fractures. The 16% probability threshold corresponded to the 80th percentile of the study population. Hazard ratios for the effect of bazedoxifene on morphometric vertebral fractures also decreased with increasing fracture probability. In patients with 10-year fracture probabilities above 6.9% (corresponding to the 41st percentile), bazedoxifene was associated with a significant decrease in the risk of morphometric vertebral fractures. At equivalent fracture probability percentiles, the treatment effect of bazedoxifene was greater on vertebral fracture risk than on the risk of all clinical fractures. For example, at the 90th percentile of FRAX probability, bazedoxifene was associated with a relative risk reduction of 33% (95% CI=7-51%) for all clinical fractures and 51% reduction (95% CI=21-69%) for morphometric vertebral fractures. The findings were robust to several sensitivity analyses. CONCLUSION: Bazedoxifene (20 and 40 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX based fracture probability threshold. These results, consistent with the previous subgroup analysis, suggest that bazedoxifene should be targeted preferentially to women at high fracture risk.
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| 17. |
- Kanis, John A, et al.
(författare)
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FRAX and its applications to clinical practice
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:5, s. 734-43
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the WHO FRAX algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. FRAX integrates the influence of several well validated risk factors for fracture with or without the use of BMD. Its use in fracture risk prediction poses challenges for patient assessment, the development of practice guidelines, the evaluation of drug efficacy and reimbursement, as well as for health economics which are the topics outlined in this review.
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| 18. |
- Kanis, JA, et al.
(författare)
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Intervention thresholds for osteoporosis in the UK
- 2005
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 36:1, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in women based on data from the UK. We modelled the effects of an intervention costing pound350 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect (offset time) for a further 5 years. Sensitivity analyses included a range of treatment duration (3-10 years), intervention costs (pound300-400/year) and offset times (0-15 years). Data on costs and risks were from the UK. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of pound30,000/QALY gained was used. With the base case (pound350 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.1% at the age of 50 years to 9.0% at the age of 85 years. Intervention thresholds were sensitive to the assumed costs and offset time. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. Cost-effective scenarios were found for women at the threshold for osteoporosis from the age of 60 years. Treatment of established osteoporosis was cost-effective irrespective of age. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age and that available treatments can be targeted cost-effectively to individuals from the UK at moderately increased fracture risk.
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| 19. |
- Karayianni, Kety, et al.
(författare)
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Accuracy in osteoporosis diagnosis of a combination of mandibular cortical width measurement on dental panoramic radiographs and a clinical risk index (OSIRIS) : the OSTEODENT project
- 2007
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 40:1, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- Clinical questionnaires and dental radiographic findings have both been suggested as methods of identifying women at risk of having osteoporosis and who might benefit from bone densitometry. The aim of this study was to measure the diagnostic accuracy of a combination of mandibular cortical width (MCW) measured from dental panoramic radiographs (DPRs) and the osteoporosis index of risk (OSIRIS) in the diagnosis of osteoporosis. 653 women (age range 45-70 years, mean age 54.95 years) in four European centres underwent standardised dual X-ray energy absorptiometry (DXA) to provide reference data on osteoporosis status. Each subject was interviewed to derive OSIRIS scores and underwent DPR examination. MCW was measured directly by five observers. Receiver Operating Characteristic (ROC) curve analysis was used to calculate sensitivities and specificities of the clinical and radiographic tests for the diagnosis of osteoporosis. 512 (78.4%) of the study population were classified as having normal BMD and 141 (21.6%) as having osteoporosis. Using ROC analysis, OSIRIS gave a ROC curve area (A(z)) of 0.838, with a sensitivity of 70.9% and a specificity of 79.5% at a diagnostic threshold of
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| 20. |
- Lind, T, et al.
(författare)
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The hyalectan degrading ADAMTS-1 enzyme is expressed by osteoblasts and up-regulated at regions of new bone formation.
- 2005
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 36:3, s. 408-17
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Tidskriftsartikel (refereegranskat)abstract
- During bone formation, there are numerous pivotal changes in the interrelationships between osteoblasts and molecules of the extracellular matrix (ECM). Consequently, the mechanisms that underlie the temporal and spatial distribution of ECM molecules in bone are of considerable interest in understanding its formation. A subfamily of a disintegrin and metalloproteinase (ADAMs) has been identified, which contain thrombospondin-like motifs (ADAMTS), and can break down several ECM molecules. Using reversed transcribed PCR, we identified ADAMTS-1, -4 and -5 mRNA expression in cultures of rat osteoblasts treated with ascorbic acid, beta-glycerophosphate and dexamethasone, molecules known to drive osteoblast differentiation. Of these, ADAMTS-1 followed most closely the osteogenic marker osteocalcin during in vitro mineralisation. Consequently, we studied, in detail, protein expression of ADAMTS-1 during in vitro osteogenesis together with ADAMTS-1 immunohistochemistry staining of sections from 2- and 10-day-old rat femur. Western analysis of osteoblast proteins showed ADAMTS-1 products that correspond well with both full-length and furin-processed species. In the ECM laid down by osteoblasts, only the mature secreted protein (approximately 90 kDa) and its accumulation during the later stages of osteogenesis in vitro were noticed. Furthermore, immunostaining with an antibody recognising ADAMTS-1 demonstrated strong expression around mineralised nodules and intense focal staining of putative new areas of nodule formation in vitro. Finally, immunohistochemistry of 2- and 10-day-old rat femur localised ADAMTS-1 protein to regions associated with osteogenesis. These data show that ADAMTS-1 protein accumulates in osteoblast ECM during differentiation. Furthermore, the focalised expression of ADAMTS-1 in regions of osteogenesis, both in vitro and in vivo, implicates this multifunctional protein to be involved in mineralised nodule and bone formation.
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| 21. |
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| 22. |
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| 24. |
- Michaëlsson, Karl, et al.
(författare)
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The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor
- 2006
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 39:6, s. 1343-1351
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Few studies have considered the dietary influence of vitamin D intake on bone mineral density (BMD). Numerous studies have examined the association between VDR polymorphism and BMD, but no previous study has examined the joint influence of dietary vitamin D intake and VDR polymorphism on BMD. METHODS: We therefore conducted a study in 230 men aged 41-76 years of age. BMD was measured with DXA. A second bone scan was performed on average 2.7 years after the first investigation. Dietary habits were assessed by 14 dietary 24-h recall interviews. The polyadenosine (A) VDR genotypes were determined. RESULTS: Dietary vitamin D intake was associated with BMD at all sites, also after multivariate adjustment. Those in the highest quintile of intake had 9% higher femoral neck BMD (p = 0.004), 6% higher BMD at the lumbar spine (p = 0.06) and 5% higher total body BMD (p = 0.003) compared to men in the lowest quintile of dietary vitamin D intake. However, the positive association between vitamin D intake and BMD was especially apparent among those with the L/L polyadenosine (A) VDR genotype explaining between 10 and 15% of the variability in BMD depending on site (p < 0.004). There was furthermore a trend, in the lumbar spine, of less reduction in BMD with increasing vitamin D intake (p = 0.07) but not at the other sites. Calcium intake conferred no association with BMD. CONCLUSIONS: Our results indicate that the extent of positive association between dietary vitamin D intake and BMD in men is dependent on VDR polymorphism, a novel conceivable important gene-environmental interaction.
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| 25. |
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| 26. |
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| 27. |
- Persson, Emma, et al.
(författare)
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Increased expression of interleukin-6 by vasoactive intestinal peptide is associated with regulation of CREB, AP-1 and C/EBP, but not NF-kappaB, in mouse calvarial osteoblasts.
- 2005
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 37:4, s. 513-29
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL-6), and the related cytokines IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM), are potent stimulators of osteoclastic bone resorption. In the present study, we have addressed the possibility that the neuropeptide vasoactive intestinal peptide (VIP) may regulate the production of and/or sensitivity to the IL-6 family of cytokines in mouse calvarial osteoblasts. VIP stimulated IL-6 mRNA expression and protein release in a time- and concentration-dependent manner, whereas mRNA expression of the IL-6 receptor, as well as mRNA expressions of IL-11, LIF, OSM and their cognate receptors, were unaffected by VIP. In cells transfected with the IL-6 promoter coupled to luciferase, VIP increased transcriptional activity. The effects of VIP were shared by the related neuropeptide PACAP-38, belonging to the same superfamily of neuropeptides, whereas secretin did not have any effect, indicating that the effects were mediated by VPAC2 receptors. The effects of VIP were potentiated by the cyclic AMP phosphodiesterase inhibitor rolipram and mimicked by forskolin, indicating the involvement of the cyclic AMP/protein kinase A pathway. This was further demonstrated by the facts that the stimulatory effect of VIP on luciferase activity could be reversed by the PKA inhibitors H-89 and KT5720 and was mimicked by cyclic AMP analogues selective for PKA, but not by those selective for Epac. In addition, VIP enhanced the phosphorylation of CREB, as assessed by both immunocytochemical analysis and Western blot. The DNA binding activity of nuclear extracts to C/EBP was increased by VIP, whereas binding to AP-1 was decreased. In contrast, DNA binding to NF-kappaB, as well as nuclear translocation of NF-kappaB and C/EBP, were unaffected by VIP. The mRNA expressions of C/EBPbeta, C/EBPdelta, C/EBPgamma, c-Jun, JunB, c-Fos, Fra-1 and IkappaBalpha and protein level of IkappaBalpha were all unaffected by VIP. These observations, together, demonstrate that VIP stimulates IL-6 production in osteoblasts by a mechanism likely to be mediated by VPAC2 receptors and dependent on cyclic AMP/protein kinase A/CREB activation and also involving the transcription factors C/EBP and AP-1.
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| 28. |
- Rehn, Anders P, et al.
(författare)
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ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing.
- 2007
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 41:2, s. 231-8
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Tidskriftsartikel (refereegranskat)abstract
- The multi-domain neutral endopeptidase, ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin repeats) is induced by parathyroid hormone (PTH) in rat osteoblasts and has therefore been suggested to be involved in initiation of bone remodeling. However, its function(s) in bone cells have not been studied. Here, we first establish that ADAMTS-1 protein is rapidly and transiently produced by human primary osteoblasts in response to PTH (1-34). We also show that ADAMTS-1 is specifically in close proximity to collagen fibrils in bone tissue using ultrastructural immunolabeling. To study the consequence(s) of ADAMTS-1 metalloprotease production in osteoblastic cells, human osteosarcoma cells (SaOS-2), were forced to express either wild-type (wtATS) or a point-mutated (pmATS) metalloprotease dead ADAMTS-1. SaOS-2 cells expressing wtATS had a growth advantage and increased collagenolytic activity when seeded inside a collagen type I gel but exhibited a reduced migration in a scratch wound assay. Immunolabeling of moving cells shows ADAMTS-1 to be located towards the direction of cellular migration. Finally, Western analysis demonstrated excess accumulation of mature collagen type I alpha1 species in the extracellular matrix together with increased release of distinct small collagen fragments into the conditioned media, by cultures of wtATS cells compared to pmATS cells. These results show that ADAMTS-1 has both the opportunity in bone and capability in vitro to induce collagen type I processing, together with a positive influence on osteoblastic three-dimensional growth. Although it is not clear at present if ADAMTS-1 promotes collagen degradation directly or indirectly, it shows that ADAMTS-1 activity can have a profound influence on the osteoblast phenotype, inhibiting migration on a planar substrate but enhancing growth in a collagen scaffold. These findings further establish ADAMTS-1 as a potentially important protein in PTH induced bone remodeling.
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| 29. |
- Rittweger, Jörn, et al.
(författare)
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Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment
- 2009
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 44:4, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Immobilization-induced bone loss is usually greater in the epiphyses than in the diaphyses. The larger fraction of trabecular bone in the epiphyses than in the diaphyses offers an intuitive explanation to account for this phenomenon. However, recent evidence contradicts this notion and suggests that immobilization-induced bone loss from the distal tibia epiphysis is mainly from the cortical compartment. The aim of this study was to establish whether this pattern of bone loss was a general rule during immobilization. We monitored various skeletal sites with different tissue composition during 5 weeks of immobilization. Ten healthy male volunteers with mean age of 24.3 years (SD 2.6 years) underwent strict horizontal bed rest. Bone scans were obtained during baseline data collection, at the end of bed rest and after 14 days of recovery by peripheral Quantitative Computed Tomography (pQCT). Sectional images were obtained from the distal tibia epiphysis (at 4% of the tibia's length), from the diaphysis (at 38%), from the proximal metaphysis (at 93%) and from the proximal epiphysis (at 98%), as well as from the distal femur epiphysis (at 4% of the femur's length) and from the patella. Relative bone losses were largest at the patella, where they amounted to -3.2% (SD 1.8%, p<0.001) of the baseline values, and smallest at the tibia diaphysis, where they amounted to -0.7% (SD 1.0%, p=0.019). The relative losses were generally larger from cortical than from trabecular compartments (p=0.004), and whilst all skeletal sites depicted such cortical losses, substantial trabecular losses were found only from the proximal tibia epiphysis. Results confirm that the differential losses from the various skeletal sites cannot be explained on the basis of trabecular vs. cortical tissue composition differences, but that endocortical circumference can account for the different amounts of bone loss in the tibia. The present study therefore supports the suggestion of the subendocortical layer as a transitional zone, which can readily be transformed into trabecular bone in response to immobilization. The latter will lead to cortical thinning, a factor that has been associated with the risk of fracture and with osteoarthritis.
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| 30. |
- Rittweger, Jörn, et al.
(författare)
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Muscle atrophy and bone loss after 90 days bed rest and the effects of flywheel resistive exercise and Pamidronate: Results from the LTBR study.
- 2005
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 36:6, s. 1019-1029
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Tidskriftsartikel (refereegranskat)abstract
- Muscle atrophy and bone loss pose substantial problems for long-term space flight and in clinical immobilization. We therefore tested the efficacy of flywheel resistive exercise and pamidronate to counteract such losses. Twenty five young healthy males underwent strict bed rest with 68 head-down tilt for 90 days. Subjects were randomized into an exercise group that practiced resistive exercise with a dflywheelT (FW) device every 2–3 days, a pamidronate group (Pam) that received 60 mg pamidronate i.v. 14 days prior to bed rest and a control group (Ctrl) that received none of these countermeasures. During the study, Ca++ and protein intake were controlled. Peripheral quantitative computed tomography (pQCT) was used to assess bone mineral content (BMC) and muscle cross sectional area (mCSA) of calf and forearm. Measurements were taken twice during baseline data collection, after 28 and after 89 days bed rest, and after 14 days recovery. On the same days, urinary Pyridinoline excretion and serum levels of alkaline phosphatase, Ca++ and PTH were measured. Pre-study exercise habits were assessed through the Freiburg questionnaire. Losses in calf mCSA were significantly reduced in FW (Ctrl: 25.6% F 2.5% Pam: 25.6% F 3.7%, FW: 17.3% F 2.7%), but not in the forearm mCSA (Ctrl: 6.4% F 4.33%, Pam: 7.7% F 4.1%, FW: 7.6% F 3.3%). Both diaphyseal and epiphyseal BMC losses of the tibia were mitigated in Pam and FW as compared to Ctrl, although this was significant only at the diaphysis. Inter-individual variability was significantly greater for changes in BMC than in mCSA, and correlation of BMC losses was poor among different locations of the tibia. A significant positive correlation was found between change in tibia epiphyseal BMC and serum cortisol levels. These findings suggest that both countermeasures are only partly effective to preserve BMC (FW and Pam) and mCSA (FW) of the lower leg during bed rest. The partial efficacy of flywheel exercise as well as the bones’ response to unloading per se underlines the importance of mechanical stimuli. The huge variability of BMC changes, however, suggests that other factors affect changes in whole-bone strength following acute mechanical disuse.
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| 31. |
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| 32. |
- Stevens, H Y, et al.
(författare)
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COX-2 is necessary for venous ligation-mediated bone adaptation in mice
- 2006
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 38:1, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- In osteoblasts, cyclooxygenase 2 (COX-2) is the major isozyme responsible for production of prostaglandins. Prostaglandins are local mediators of bone resorption and formation and are known to be involved in bone's adaptive response to fluid shear stress (FSS). We have previously described a model of trabecular bone loss in hindlimb-suspended mice and rats and demonstrated partial protection from osteopenia by ligation of the femoral vein. The increased FSS resulting from this ligation drove bone adaptation in the absence of mechanical loading. In this study, we investigated the role of COX-2 in this adaptive response to FSS by use of COX-2 knockout mice. COX-2 knockout ("KO"), COX-2 heterozygote ("HET"), and COX-2 wild-type ("WT") animals all lost comparable amounts of trabecular bone from sham-operated limbs as a result of suspension. In WT mice, loss of trabecular BMD in the venous-ligated limb was significantly less than that of the sham-operated limb; this effect, however, was not seen in KO or HET mice. Percentage gain in femoral periosteal circumference was greater in the ligated limb than the sham-operated limb for WT mice. KO and HET mice already possess femora of larger periosteal circumference than their WT littermates and ligation in these bones did not result in an increase in perimeter relative to sham. Histomorphometry on embedded bones revealed thinner cortices and less mineralizing perimeter in KO femora than controls. In conclusion, this is the first in vivo study to show that fluid-flow-mediated bone adaptation, independent of mechanical strain, is COX-2 dependent.
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| 33. |
- Tenne, Max, et al.
(författare)
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Genetic variation in the PTH pathway and bone phenotypes in elderly women: Evaluation of PTH, PTHLH, PTHR1 and PTHR2 genes.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 42, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Parathyroid hormone (PTH) is a key regulator of calcium metabolism. Parathyroid hormone-like hormone (PTHrP) contributes to skeletal development through regulation of chondrocyte proliferation and differentiation during early bone growth. Both PTH and PTHrP act through the same receptor (PTHR1). A second receptor, PTHR2, has been identified although its function is comparatively unknown. PTH hyper-secretion induces bone resorption, whereas intermittent injection of PTH increases bone mass. To explore the effects of genetic variation in the PTH pathway, we have analysed variations in PTH, PTHLH, PTHR1 and PTHR2 in relation to bone mass and fracture incidence in elderly women. MATERIALS AND METHODS: This study includes 1044 elderly women, all 75 years old, from the Malmö Osteoporosis Prospective Risk Assessment study (OPRA). Single nucleotide polymorphisms (SNPs) from 4 genes and derived haplotypes in the PTH signaling pathway were analysed in 745-1005 women; 6 SNPs in the PTH gene and 3 SNPs each in the PTHLH, PTHR1 and PTHR2 genes were investigated in relation to BMD (assessed at baseline), fracture (434 prevalent fractures of all types over lifetime, self-reported and 174 incident fractures up to 7 years, X-ray verified) and serum PTH. RESULTS AND CONCLUSION: Individually, SNPs in the 4 loci did not show any significant association with BMD. Neither were PTHLH, PTHR1 and PTHR2 polymorphisms associated with fracture. Three of 5 common haplotypes, accounting for >98% of alleles at the PTH locus, were identified as independent predictors of fracture. Haplotype 9 (19%) was suggestive of an association with fractures of any type sustained during lifetime (p=0.018), with carriers of one or more copies of the haplotype having the lowest incidence (p=0.006). Haplotypes 1 (13%) and 5 (37%) and 9 were suggestive of an association with fractures sustained between 50 and 75 years (p=0.02, p=0.013 and p=0.034). Carriers of haplotypes 1 and 5 were more likely to suffer a fracture (haplotype 1, p=0.045; haplotype 5, p=0.008). We conclude, that while further genotyping across the gene is recommended, in this cohort of elderly Swedish women, polymorphisms in PTH may contribute to the risk of fracture through mechanisms that are independent of BMD.
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| 34. |
- Tervo, Taru, 1972-, et al.
(författare)
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Reduced physical activity corresponds with greater bone loss at the trabecular than the cortical bone sites in men
- 2009
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 45:6, s. 1073-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has been inconclusive as to whether high peak bone mineral density (BMD, g/cm(2)) resulting from previous physical activity is retained with reduced activity later in life. The aim of this 12-year longitudinal study was to investigate the association between BMD loss and reduced physical activity (h/wk) at trabecular and cortical bone sites in men. Three groups with a mean age of 17 years at baseline were investigated: i) 51 athletes who discontinued their active careers during the follow-up period (former athletes), ii) 16 athletes who were active throughout the follow-up period (active athletes), and iii) 25 controls. BMD loss at the hip, spine, and pelvis (mainly trabecular bone) was compared to BMD loss at femur, humerus, and legs (mainly cortical bone) during a 12-year follow-up period. Across the total follow-up period in the total cohort, reduced physical activity was more strongly associated with changes at trabecular BMD sites, i.e. hip, spine, and pelvis (B=0.008-0.005 g/cm(2) per weekly hour physical activity (h), p<0.001), than at cortical bone sites, i.e. humerus, legs (B=0.002-0.003 g/cm(2)/h, p<0.05), and femur (p>0.05). At the final follow-up, former athletes showed higher BMD than controls only at the cortical bone sites of the humerus, legs, and femur (difference 0.05-0.10 g/cm(2), p<0.05). In conclusion, this study indicates that predominantly trabecular bone is lost with reduced physical activity levels in young men. Benefits were still evident at the more cortical sites eight years after the discontinuation of an active sports career.
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| 37. |
- Wermelin, Karin, 1977-, et al.
(författare)
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Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:2, s. 365-71
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Tidskriftsartikel (refereegranskat)abstract
- Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen. Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n=33) and 8 (n=27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 microm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n=28). At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 microm distance it was more than doubled. At 1 week, coated screws had less implant-bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.
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| 50. |
- Kanis, John A, et al.
(författare)
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A reference standard for the description of osteoporosis.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 42:3, s. 467-75
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Tidskriftsartikel (refereegranskat)abstract
- In 1994, the World Health Organization published diagnostic criteria for osteoporosis. Since then, many new technologies have been developed for the measurement of bone mineral at multiple skeletal sites. The information provided by each assessment will describe the clinical characteristics, fracture risk and epidemiology of osteoporosis differently. Against this background, there is a need for a reference standard for describing osteoporosis. In the absence of a true gold standard, this paper proposes that the reference standard should be based on bone mineral density (BMD) measurement made at the femoral neck with dual-energy X-ray absorptiometry (DXA). This site has been the most extensively validated, and provides a gradient of fracture risk as high as or higher than that of many other techniques. The recommended reference range is the NHANES III reference database for femoral neck measurements in women aged 20-29 years. A similar cut-off value for femoral neck BMD that is used to define osteoporosis in women can be used for the diagnosis of osteoporosis in men - namely, a value for BMD 2.5 SD or more below the average for young adult women. The adoption of DXA as a reference standard provides a platform on which the performance characteristics of less well established and new methodologies can be compared.
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