RESUMEN
A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity. INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. The characteristics of APR may differ by compound. The aim of the present study was to evaluate the characteristics of APR (rates, signs and symptoms, severity), in the absence of any preventive measure, after a first IV application of ZOL or IBN in patients naïve or previously exposed to BP in a real-world clinical setting. METHODS: This is an open-label prospective exploratory study with two cohorts of consecutive postmenopausal women with osteoporosis treated with either IV ZOL or IBN at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. RESULTS: Intravenous BP was administered to 725 women (411 ZOL and 314 IBN). Prior oral or IV BP use was less frequent in the ZOL group (61.8 vs. 71.7%, p = 0.005). In total, 301 women (41.5%) reported the presence of one or more signs or symptoms of APR with rates for ZOL and IBN of 47.7 and 33.4%, respectively (p < 0.001). Corresponding APR rates in the subgroup of BP-naïve patients were 55.6 and 32.4%, respectively (p < 0.001). The leading APR clinical sign was the presence of post-dose myalgia or arthralgia (68.1%). Prior BP exposure was predictive of both APR risk and severity, and lower serum 25-hydroxy vitamin D (25(OH)D) levels were possibly predictive of severity. CONCLUSIONS: In a real-world setting, APR rates with ZOL and IBN may be higher than reported in randomised controlled trials and may differ by compound, prior BP exposure, and serum 25(OH)D levels.
Asunto(s)
Reacción de Fase Aguda/inducido químicamente , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Anciano , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/administración & dosificación , Difosfonatos/uso terapéutico , Femenino , Humanos , Ácido Ibandrónico , Imidazoles/administración & dosificación , Imidazoles/uso terapéutico , Infusiones Intravenosas , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ácido ZoledrónicoRESUMEN
UNLABELLED: Rebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone. INTRODUCTION: The purposes of this study are to characterize rebound-associated vertebral fractures following the discontinuation of a highly potent reversible antiresorptive therapy based on clinical observation and propose a pathophysiological rationale. METHODS: This study is a case report of multiple vertebral fractures early after discontinuation of denosumab therapy in a patient with hormone receptor-positive non-metastatic breast cancer treated with an aromatase inhibitor. RESULTS: Discontinuation of highly potent reversible bone antiresorptives such as denosumab may expose patients to an increased fracture risk due to the joined effects of absent microdamage repair during therapy followed by synchronous excess activation of multiple bone remodelling units at the time of loss-of-effect. We suggest the term rebound-associated vertebral fractures (RVF) for this phenomenon characterized by the presence of multiple new clinical vertebral fractures, associated with either no or low trauma, in a context consistent with the presence of high bone turnover and rapid loss of lumbar spine bone mineral density (BMD) occurring within 3 to 12 months after discontinuation (loss-of-effect) of a reversible antiresorptive therapy in the absence of secondary causes of bone loss or fractures. Unlike atypical femoral fractures that emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, RVF originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of highly potent reversible antiresorptives. CONCLUSIONS: Studies are urgently needed to i) prove the underlying pathophysiological processes suggested above, ii) establish the predictive criteria exposing patients to an increased risk of RVF, and iii) determine appropriate treatment regimens to be applied in such patients.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Denosumab/administración & dosificación , Fracturas Osteoporóticas/etiología , Fracturas de la Columna Vertebral/etiología , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/inducido químicamente , Enfermedades Óseas Metabólicas/prevención & control , Neoplasias de la Mama/tratamiento farmacológico , Denosumab/uso terapéutico , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Privación de TratamientoRESUMEN
End caps are intended to prevent nail migration (push-out) in elastic stable intramedullary nailing. The aim of this study was to investigate the force at failure with and without end caps, and whether different insertion angles of nails and end caps would alter that force at failure. Simulated oblique fractures of the diaphysis were created in 15 artificial paediatric femurs. Titanium Elastic Nails with end caps were inserted at angles of 45°, 55° and 65° in five specimens for each angle to create three study groups. Biomechanical testing was performed with axial compression until failure. An identical fracture was created in four small adult cadaveric femurs harvested from two donors (both female, aged 81 and 85 years, height 149 cm and 156 cm, respectively). All femurs were tested without and subsequently with end caps inserted at 45°. In the artificial femurs, maximum force was not significantly different between the three groups (p = 0.613). Push-out force was significantly higher in the cadaveric specimens with the use of end caps by an up to sixfold load increase (830 N, standard deviation (SD) 280 vs 150 N, SD 120, respectively; p = 0.007). These results indicate that the nail and end cap insertion angle can be varied within 20° without altering construct stability and that the risk of elastic stable intramedullary nailing push-out can be effectively reduced by the use of end caps.
Asunto(s)
Clavos Ortopédicos , Fracturas del Fémur/cirugía , Migración de Cuerpo Extraño/prevención & control , Fijación Intramedular de Fracturas/instrumentación , Anciano de 80 o más Años , Fenómenos Biomecánicos , Clavos Ortopédicos/efectos adversos , Cadáver , Niño , Femenino , Fracturas del Fémur/fisiopatología , Migración de Cuerpo Extraño/etiología , Fijación Intramedular de Fracturas/efectos adversos , Humanos , Masculino , Modelos Anatómicos , Falla de PrótesisRESUMEN
UNLABELLED: Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION: The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS: Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS: Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS: In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.
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Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Teriparatido/uso terapéutico , Absorciometría de Fotón/métodos , Anciano , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Evaluación de Medicamentos/métodos , Femenino , Humanos , Ácido Ibandrónico , Inyecciones Intravenosas , Inyecciones Subcutáneas , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Estudios Retrospectivos , Teriparatido/farmacología , Resultado del TratamientoRESUMEN
BACKGROUND: In postmenopausal women, yearly intravenous zoledronate (ZOL) compared to placebo (PLB) significantly increased bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN), and total hip (TH) and decreased fracture risk. The effects of ZOL on BMD at the tibial epiphysis (T-EPI) and diaphysis (T-DIA) are unknown. METHODS: A randomized controlled ancillary study of the HORIZON trial was conducted at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. Women with ≥1 follow-up DXA measurement who had received ≥1 dose of either ZOL (n=55) or PLB (n=55) were included. BMD was measured at LS, FN, TH, T-EPI, and T-DIA at baseline, 6, 12, 24, and 36 months. Morphometric vertebral fractures were assessed. Incident clinical fractures were recorded as adverse events. RESULTS: Baseline characteristics were comparable with those in HORIZON and between groups. After 36 months, BMD was significantly higher in women treated with ZOL vs. PLB at LS, FN, TH, and T-EPI (+7.6%, +3.7%, +5.6%, and +5.5%, respectively, p<0.01 for all) but not T-DIA (+1.1%). The number of patients with ≥1 incident non-vertebral or morphometric fracture did not differ between groups (9 ZOL/11 PLB). Mean changes in BMD did not differ between groups with and without incident fracture, except that women with an incident non-vertebral fracture had significantly higher bone loss at predominantly cortical T-DIA (p=0.005). CONCLUSION: ZOL was significantly superior to PLB at T-EPI but not at T-DIA. Women with an incident non-vertebral fracture experienced bone loss at T-DIA.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Fracturas Óseas , Imidazoles/uso terapéutico , Osteoporosis Posmenopáusica , Tibia/metabolismo , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Femenino , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Humanos , Imidazoles/farmacología , Incidencia , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/metabolismo , Ácido ZoledrónicoRESUMEN
UNLABELLED: In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase). INTRODUCTION: The purpose of this study was to compare the trends and epidemiological characteristics of hospitalizations for MOF and other frequent diseases between years 2000 and 2008 in Switzerland. METHODS: Trends in the number, age-standardized incidence, mean LOS, and cost of hospitalized MOF and MCE (acute myocardial infarction, stroke, and heart failure) were compared in women and men aged ≥ 45 years, based on data from the Swiss Federal Statistical Office. RESULTS: Between 2000 and 2008, the incidence of acute hospitalizations for MOF increased by 3.4% in women and 0.3% in men. In both sexes, a significant decrease in hip fractures (-15.0% and -11.0%) was compensated by a concomitant, significant increase in nonhip fractures (+24.8% and +13.8%). Similarly, the incidence of acute hospitalizations for MCE increased by 4.4% in women and 8.2% in men, as an aggregated result from significantly increasing acute myocardial infarctions and significantly decreasing strokes. While the mean LOS in the acute inpatient setting decreased almost linearly between years 2000 and 2008 in all indications, the inpatient costs increased significantly (p < 0.001) for MOF (+30.1% and +42.7%) and MCE (+22.6% and +47.1%) in women and men, respectively. CONCLUSIONS: Between years 2000 and 2008, the burden of hospitalized osteoporotic fractures to the Swiss healthcare system has continued to increase in both sexes. In women, this burden was significantly higher than that of MCE and the gap widened over time.
Asunto(s)
Hospitalización/tendencias , Fracturas Osteoporóticas/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/epidemiología , Femenino , Fracturas de Cadera/economía , Fracturas de Cadera/epidemiología , Costos de Hospital/estadística & datos numéricos , Costos de Hospital/tendencias , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/economía , Factores Sexuales , Suiza/epidemiologíaRESUMEN
UNLABELLED: In Switzerland, the total number and incidence of hospitalizations for major osteoporotic fractures increased between years 2000 and 2007, while hospitalizations due to hip fracture decreased. The cost impact of shorter hospital stays was offset by the increasing cost per day of hospitalization. INTRODUCTION: The aim of the study was to establish the trends and epidemiological characteristics of hospitalizations for major osteoporotic fractures (MOF) between years 2000 and 2007 in Switzerland. METHODS: Sex- and age-specific trends in the number and crude and age-standardized incidences of hospitalized MOF (hip, clinical spine, distal radius, and proximal humerus) in women and men aged ≥45 years were analyzed, together with the number of hospital days and cost of hospitalization, based on data from the Swiss Federal Statistical Office hospital database and population statistics. RESULTS: Between 2000 and 2007, the absolute number of hospitalizations for MOF increased by 15.9% in women and 20.0% in men, mainly due to an increased number of non-hip fractures (+37.7% in women and +39.7% in men). Hospitalizations for hip fractures were comparatively stable (-1.8% in women and +3.3% in men). In a rapidly aging population, in which the number of individuals aged ≥45 years grew by 11.1% (women) and 14.6% (men) over the study period, the crude and age-standardized incidences of hospitalizations decreased for hip fractures and increased for non-hip MOF, both in women and men. The length of hospital stay decreased for all MOF in women and men, the cost impact of which was offset by an increase in the daily costs of hospitalization. CONCLUSIONS: Between years 2000 and 2007, hospitalizations for MOF continued to increase in Switzerland, driven by an increasing number and incidence of hospitalizations for non-hip fractures, although the incidence of hip fractures has declined.
Asunto(s)
Fracturas de Cadera/epidemiología , Hospitalización/tendencias , Tiempo de Internación/tendencias , Fracturas Osteoporóticas/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Fracturas de Cadera/economía , Costos de Hospital/estadística & datos numéricos , Hospitalización/economía , Humanos , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/economía , Distribución por Sexo , Suiza/epidemiologíaRESUMEN
SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.
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Densidad Ósea , Fracturas Óseas/etiología , Articulación de la Cadera/fisiopatología , Osteoporosis Posmenopáusica/diagnóstico , Tibia/fisiopatología , Absorciometría de Fotón/métodos , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Métodos Epidemiológicos , Femenino , Fracturas Óseas/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/fisiopatologíaRESUMEN
BACKGROUND: Whereas a primary role of interleukin-1beta (IL-1beta) in local bone remodelling and articular inflammation has been well established, the effect of prolonged systemic administration of this cytokine on total skeletal Ca, somatic growth and joint tissue has not yet been investigated. METHODS: Five groups of 14 rats each, aged 7-8 weeks, had miniosmotic pumps (Alzet 200 microl) implanted and primed to release 100, 200, 500, 1,000 and 2,000 ng/kg/24 h of human recombinant IL-1beta (rIL-1beta) daily for 14 days. On days 0 and 14 total skeletal mineral content (BMC) was assessed by means of X-ray absorptiometry and vertebral and tibial growth was measured by computer-assisted radiometry. On the same days, blood was drawn and analyzed for rat growth hormone (rGH), insulin-like growth factor (IGF-1), and osteocalcin. Also 24-hour urine was collected for d-pyridinoline (dpd) determinations. Hind- and forepaw diameter as a parameter of joint inflammation was assessed using a micrometric calliper. Subsequently the animals were sacrificed and one tibia dissected for measurement of trabecular volume by computerized histomorphometry. RESULTS: BMC decreased in a dose-dependent manner reaching significance at 1,000 and 2,000 ng/kg (p < 0.03 and 0.04) in close correlation with tibial trabecular volumes (r = 0.84; p < 0.02). Normal vertebral and tibial growth was recorded at all dosages. There was no evidence of joint involvement. Blood rGH and IGF-1 remained normal as did osteocalcin, the latter reflecting lack of osteoblast activation. In contrast dpd increased in a dose-dependent manner indicating enhanced bone matrix turnover. CONCLUSION: It is concluded that graded infusions of supraphysiological doses of rIL-1beta capable of inducing osteopenia did not affect skeletal growth in the absence of articular reaction. This is in contrast with the experience recorded in experimental arthritis in which growth retardation, in addition to osteopenia, may be caused by factors other than circulating IL-1beta.