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Suresh E.,Alexandra Hospital Jurong Health | Abrahamsen B.,University of Southern Denmark | Abrahamsen B.,Research Center for Ageing and Osteoporosis
Cleveland Clinic Journal of Medicine | Year: 2015

Denosumab is a novel antiresorptive drug that has been approved for use as a first-line drug for primary and secondary prevention of osteoporotic fractures. The authors discuss the mechanism of action of denosumab, review the evidence for its efficacy and safety in patients with osteoporosis, and offer recommendations for its use in clinical practice.

Abrahamsen B.,Research Center for Ageing and Osteoporosis | Abrahamsen B.,University of Southern Denmark | Osmond C.,University of Southampton | Cooper C.,University of Southampton
Journal of Bone and Mineral Research | Year: 2015

Osteoporosis is a chronic disease, carrying an elevated risk of fractures, morbidity, and death. Long-term treatment may be required, but the long-term risks with osteoporosis drugs remain incompletely understood. The competing risk of death may be a barrier to treating the oldest, yet this may not be rational if the risk of death is reduced by treatment. It is difficult to devise goal-directed long-term strategies for managing osteoporosis without firm information about residual life expectancy in treated patients. We conducted an observational study in Danish national registries tracking prescriptions for osteoporosis drugs, comorbid conditions, and deaths. We included 58,637 patients and 225,084 age- and sex-matched control subjects. Information on deaths until the end of 2013 was retrieved, providing a follow-up period of 10 to 17 years. In men younger than 80 years and women younger than 60 years, the relative risk of dying declined from being strongly increased in the first year to a stable but elevated level in subsequent years. In women older than 65 to 70 years, there was only a small elevation in risk in the first year of treatment followed by lower than background population mortality. The residual life expectancy of a 50-year-old man beginning osteoporosis treatment was estimated to be 18.2 years and that of a 75-year-old man was 7.5 years. Estimates in women were 26.4 years and 13.5 years, respectively. This study shows an excess mortality in men and in women younger than 70 years who are treated for osteoporosis compared with the background population. This excess risk is more pronounced in the first few years on treatment. The average life expectancy of osteoporosis patients is in excess of 15 years in women younger than 75 years and in men younger than 60 years, highlighting the importance of developing tools for long-term management. © 2015 American Society for Bone and Mineral Research.

Abrahamsen B.,University of Southern Denmark | Abrahamsen B.,Research Center for Ageing and Osteoporosis | Jorgensen N.R.,Research Center for Ageing and Osteoporosis | Jorgensen N.R.,Copenhagen University | And 2 more authors.
Osteoporosis International | Year: 2014

Summary: National epidemiological studies of forearm fractures are scarce. We examined in- and outpatient rates in Denmark, including anatomical location, surgery, hospitalization ratio, recurrent fractures, and ratio of forearm to hip fractures. This may be useful for triangulation in countries with less detailed information. Rates were higher than previously estimated.Introduction: Despite a significant contribution to the overall burden of osteoporotic, nonvertebral fractures, relatively little information is available about age- and gender-specific incidence rates for many countries including Denmark.Methods: We used national individual patient data on inpatient and outpatient treatment to calculate rates of forearm fractures, taking readmissions into account, with subtables for distal and proximal fractures. We also calculated ratios of forearm to hip fractures that may be useful when imputing forearm fracture rates from other administrative sources. In addition, we report the rates of hospital admission and the rates of surgical treatment, allowing readers to extrapolate from the number of admissions or surgical procedures to incidence rates, should their data sources be less comprehensive.Results: Forearm fracture rates were 278 per 100,000 patient years in men aged 50+ and 1,110 per 100,000 in women aged 50+. The female to male incidence rate ratio was 4.0 for the age group 50+ but close to unity in persons aged 40 or under. Two thirds of patients were treated on an outpatient basis with little difference across age and gender strata. Four out of five fractures were treated conservatively. The rate of forearm fractures in Denmark was somewhat higher in both genders than recently imputed from hip fracture rates and were close to the rates previously reported in studies from Norway and Sweden.Conclusion: The rates of forearm fracture in Denmark are higher than previously estimated and very similar to the high risk reported from studies in Norway and Sweden. © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.

Shanbhogue V.V.,University of Southern Denmark | Hansen S.,University of Southern Denmark | Frost M.,University of Southern Denmark | Jorgensen N.R.,University of Southern Denmark | And 4 more authors.
Journal of Bone and Mineral Research | Year: 2015

The primary goal of this cross-sectional in vivo study was to assess peripheral bone microarchitecture, bone strength, and bone remodeling in adult type 1 diabetes (T1D) patients with and without diabetic microvascular disease (MVD+ and MVD-, respectively) and to compare them with age-, gender-, and height-matched healthy control subjects (CoMVD+ and CoMVD-, respectively). The secondary goal was to assess differences in MVD- and MVD+ patients. Fifty-five patients with T1DM (MVD+ group: n = 29) were recruited from the Funen Diabetes Database. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal radius and tibia, and biochemical markers of bone turnover were performed in all participants. There were no significant differences in HR-pQCT parameters between MVD- and CoMVD- subjects. In contrast, MVD+ patients had larger total and trabecular bone areas (p = 0.04 and p = 0.02, respectively), lower total, trabecular, and cortical volumetric bone mineral density (vBMD) (p < 0.01, p < 0.04, and p < 0.02, respectively), and thinner cortex (p = 0.03) at the radius, and lower total and trabecular vBMD (p = 0.01 and p = 0.02, respectively) at the tibia in comparison to CoMVD+. MVD+ patients also exhibited lower total and trabecular vBMD (radius p = 0.01, tibia p < 0.01), trabecular thickness (radius p = 0.01), estimated bone strength, and greater trabecular separation (radius p = 0.01, tibia p < 0.01) and network inhomogeneity (radius p = 0.01, tibia p < 0.01) in comparison to MVD- patients. These differences remained significant after adjustment for age, body mass index, gender, disease duration, and glycemic control (average glycated hemoglobin over the previous 3 years). Although biochemical markers of bone turnover were significantly lower in MVD+ and MVD- groups in comparison to controls, they were similar between the MVD+ and MVD- groups. The results of our study suggest that the presence of MVD was associated with deficits in cortical and trabecular bone vBMD and microarchitecture that could partly explain the excess skeletal fragility observed in these patients. © 2015 American Society for Bone and Mineral Research.

Abrahamsen B.,University of Southern Denmark | Abrahamsen B.,Research Center for Ageing and Osteoporosis | Jorgensen H.L.,Bispebjerg Hospital | Laulund A.S.,University of Southern Denmark | And 4 more authors.
Journal of Bone and Mineral Research | Year: 2015

The long-term relationship between hypothyroidism and fracture risk is challenging to dissect because of the modifying influence of subsequent thyroxine replacement with the potential for excessive replacement doses. We studied changes in serum thyrotropin concentration (TSH) over time and association with fracture risk in real-world patients presenting with elevated TSH. All TSH determinations were done in the same laboratory, which served all hospitals and general practices. The study population consisted of all adults with a first measurement of TSH >4.0 mIU/L (n = 8414) or normal TSH (n = 222,138; comparator). We used a Cox proportional hazards analysis incorporating additional time-dependent covariates to represent initiation of thyroxine replacement and cumulative number of periods with high versus low TSH after index date with a mean follow-up of 7.2 years. Elevated baseline TSH was not associated with an increased risk of hip fracture (HR 0.90; 95% CI, 0.80 to 1.02) or major osteoporotic fractures (HR 0.97; 95% CI, 0.90 to 1.05), nor was subsequent thyroxine prescription predictive of increased risk of fractures. The number of subsequent 6-month periods with low TSH - suggesting excessive thyroxine dosing - was significantly associated with increased risk of both hip fracture (HR 1.09; 95% CI, 1.04 to 1.15) and major osteoporotic fracture (HR 1.10; 95% CI, 1.06 to 1.14). When gender- and age-stratified analyses for major osteoporotic fractures were undertaken, hyperthyroid time was identified as a predictor of fracture risk in postmenopausal women whereas hypothyroid time predicted increased fracture risk in men below age 75 years. In conclusion, among patients who present with an elevated TSH, the long-term risk of hip and other osteoporotic fractures is strongly related to the cumulative duration of periods with low TSH - likely from excessive replacement. An independent effect of elevated TSH could only be observed in young and middle-aged men, suggesting gender-discrepant consequences on risk. © 2015 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research.

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