| 1. |
- Banefelt, Jonas, et al.
(författare)
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Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting
- 2022
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:1, s. 52-58
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9–6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5–9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score −1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (−3.0 to –0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD–fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis.
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| 2. |
- Conley, R. B., et al.
(författare)
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Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:1, s. 36-52
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
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| 3. |
- Gerdhem, Paul, et al.
(författare)
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Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women
- 2007
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:1, s. 127-134
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Tidskriftsartikel (refereegranskat)abstract
- Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.
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| 4. |
- Ivaska, Kaisa, et al.
(författare)
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Bone Turnover Markers and Prediction of Fracture: A Prospective Follow-Up Study of 1040 Elderly Women for a Mean of 9 Years
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:2, s. 393-403
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is characterized by compromised bone mass and strength, predisposing to an increased risk of fracture. Increased bone metabolism has been suggested to be a risk factor for fracture. The aim of this study was to evaluate whether baseline bone turnover markers are associated with long-term incidence of fracture in a population-based sample of 1040 women who were 75 years old (Malmo OPRA study). Seven bone markers (S-TRACP5b, S-CTX-1, S-OC[1-49], S-TotaIOC, S-cOC, S-boneALP, and urinary osteocalcin) were measured at baseline and 1-year follow-up visit. During the mean follow-up of 9.0 years (range 7.4-10.9), 363 women sustained at least one fracture of any type, including 116 hip fractures and 103 clinical vertebral fractures. High S-TRACP5b and S-CTX-1 levels were associated with increased risk of any fracture with hazard ratios [HRs (95% confidence interval)] of 1.16 (1.04-1.29) and 1.13 (1.01-1.27) per SD increase, respectively. They also were associated with increased risk of clinical vertebral fracture with HRs of 1.22 (1.01-1.48) and 1.32 (1.05-1.67), respectively. Markers were not associated with risk for hip fracture. Results were similar when we used resorption markers, including urinary osteocalcin, measured at the 1-year visit or an average of the two measurements. The HRs were highest for any fracture in the beginning of the follow-up period, 2.5 years from baseline. For vertebral fractures, the association was more pronounced and lasted for a longer period of time, at least for 5 years. In conclusion, elevated levels of S-TRACP5b, S-CTX-1, and urinary osteocalcin are associated with increased fracture risk for up to a decade in elderly women. (C) 2010 American Society for Bone and Mineral Research.
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| 5. |
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| 6. |
- Koller, Daniel L., et al.
(författare)
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Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women
- 2013
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 28:3, s. 547-558
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n=4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, age- and weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p=1.7x109) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p=1.3x108) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n=5597 for femoral neck; n=4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p=1.3x1011; ESR1/C6orf97 joint p=1.4x1010). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p<1x105). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. (c) 2013 American Society for Bone and Mineral Research.
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| 7. |
- McGuigan, Fiona, et al.
(författare)
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Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification.
- 2010
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; Apr 7, s. 1392-1399
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a major health problem affecting more than 75 million people throughout Europe, USA and Japan. Epidemiological studies have determined that both genetic and environmental factors contribute to the pathogenesis of osteoporosis. We have investigated the association between polymorphisms at the osteocalcin locus and variables linked to bone health. Osteocalcin provides a link between bone and energy metabolism, hence its potential importance as an osteoporosis candidate gene. In this study, we included a total of 996 women (all aged 75 years) from the OPRA cohort. We sequenced the osteocalcin gene along with flanking region to search for novel coding polymorphisms. We also analyzed four polymorphisms selected from within and flanking regions of the osteocalcin gene to study their association with serum total osteocalcin levels (S-TotalOC), total body (TB) bone mineral density (BMD), fracture, TB fat mass and BMI. The promoter polymorphism rs1800247 was significantly associated with S-TotalOC (p = 0.012) after controlling for BMI and TB BMD. The polymorphism rs1543297 was significantly associated with prospectively occurring fractures (p = 0.008). In a model taking into account rs1543297 and rs1800247 along with TB BMD, BMI, smoking and S-TotalOC, the polymorphisms together were able to identify an additional 6% of women who sustained a fracture (p = 0.02). We found no association between the polymorphisms and TB BMD, BMI or TB fat mass. In conclusion, polymorphisms in and around the osteocalcin locus are significantly associated with S-TotalOC and fracture. Genotyping at the osteocalcin locus could add valuable information in the identification of women at risk of osteoporosis. (c) 2010 American Society for Bone and Mineral Research.
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| 8. |
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| 9. |
- Obrant, Karl, et al.
(författare)
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The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects
- 1999
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 14:4, s. 555-560
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.
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| 10. |
- Toth, Emese, et al.
(författare)
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History of Previous Fracture and Imminent Fracture Risk in Swedish Women Aged 55 to 90 Years Presenting With a Fragility Fracture
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 35:5, s. 861-868
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Tidskriftsartikel (refereegranskat)abstract
- The term “fracture cascade” refers to the sequence of fragility fractures resulting from the increased fracture risk that occurs with aging and following fractures. Here, we evaluate the sequence of previous fractures in women aged 55 to 90 years presenting with a fragility fracture and subsequent (12 to 24 months) fracture incidence. In this retrospective, observational study, women aged 55 to 90 years with an “index” fragility fracture in 2013 were identified from Swedish national registries. A history of previous fractures (2001 to 2012) and osteoporosis treatment was used to characterize fracture cascade patterns. Cumulative incidence of new fractures within 12 to 24 months following the index fracture, based on index fracture type and age, were used to describe the risk of subsequent fractures. A total of 35,146 women with a mean age of 73.8 years were included (7180 hip, 2786 clinical vertebral, and 25,180 nonhip/nonvertebral [NHNV] index fractures); 38% of women with hip, 38% with clinical vertebral, and 25% with NHNV index fractures had one or more previous fractures. Across all index fracture types, the proportion of women with any previous fracture increased with age; 34% to 46% of index hip or clinical vertebral fractures in women ≥70 years were not their first fracture. Following any index fracture, cumulative incidence of a new fracture over 24 months was over 11% (index clinical vertebral 18%; index hip 14%). Osteoporosis treatment rates were low both in patients with (27%) and without (18%) a previous fracture. These descriptive data demonstrate that almost one-third of women aged 55 to 90 years suffering a new fracture have had a previous fragility fracture. Fracture location influences incidence and type of subsequent fracture during the 24 months following a fragility fracture, with clinical vertebral fractures carrying the greatest imminent fracture risk. These data highlight the clinical impact and need for early, effective treatment soon after any fragility fracture.
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