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1.
J Clin Densitom ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31378452

RESUMO

Bone mineral density (BMD) can be measured at multiple skeletal sites using various technologies to aid clinical decision-making in bone and mineral disorders. BMD by dual-energy X-ray absorptiometry (DXA) has a critical role in predicting risk of fracture, diagnosis of osteoporosis, and monitoring patients. In clinical practice, DXA remains the most available and best validated tool for monitoring patients. A quality baseline DXA scan is essential for comparison with all subsequent scans. Monitoring patients with serial measurements requires technical expertise and knowledge of the least significant change in order to determine when follow-up scans should be repeated. Prior ISCD Official Positions have clarified how and when repeat DXA is useful as well as the interpretation of results. The 2019 ISCD Official Positions considered new evidence and clarifies if and when BMD should be repeated. There is good evidence showing that repeat BMD measurement can identify people who experience bone loss, which is an independent predictor of fracture risk. There is good evidence showing that the reduction in spine and hip fractures with osteoporosis medication is proportional to the change in BMD with treatment. There is evidence that measuring BMD is useful following discontinuation of osteoporosis treatment. There is less documentation addressing the effectiveness of monitoring BMD to improve medication adherence, whether monitoring of BMD reduces the risk of fracture, or effectively discriminates patients who should and should not recommence treatment following an interruption of medication. Further research is needed in all of these areas.

2.
Arch Osteoporos ; 14(1): 67, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243557

RESUMO

The main objective of this study was to explore whether vertebral fracture characteristics or posture is independently associated with physical performance. Posture was significantly associated with physical performance but fracture characteristics were not, suggesting posture should be the focus of physical performance variance. PURPOSE: The main objective of this study was to explore whether vertebral fracture characteristics (number, severity, location) or occiput-to-wall distance (OWD) is independently associated with physical performance. METHODS: This was a secondary data analysis using baseline data from a randomized controlled trial, of community-dwelling women aged 65 years and older with a suspected vertebral fragility fracture. Lateral thoracic and lumbar spine radiographs were used to determine the number, location, and severity of fracture. The dependent variables were timed up and go (TUG), five times sit-to-stand, four-meter walk, and step test. The independent variables were number, severity, location of fracture, and OWD. Pain during movement and age were covariates. Multivariable regression analyses determined the association between each of the dependent and independent variables. RESULTS: Participants' (n = 158) mean (standard deviation [SD]) age was 75.9 (6.5) years. They had a mean (SD) BMI, OWD, and number of fractures of 26.7 (5.3) kg/m2, 5.7 (4.6) cm, and 2.2 (1.8), respectively. OWD was independently associated with TUG (estimated coefficient [B] = 0.29, 95% confidence interval [CI] = 0.16, 0.42), five times sit-to-stand (B = 0.33, 95% CI = 0.12, 0.55), four-meter walk (B = 0.09, 95% CI = 0.05, 0.13), and step test (B = - 0.36, 95% CI = - 0.50, - 0.23) in the unadjusted model. OWD was independently associated with TUG (B = 0.25, 95% CI = 0.12, 0.38), five times sit-to-stand (B = 0.29, 95% CI = 0.07, 0.50), four-meter walk (B = 0.08, 95% CI = 0.03, 0.12), and step test (B = - 0.22, 95% CI = - 0.47, - 0.19) in the adjusted model. CONCLUSION: OWD was significantly associated with physical performance but fracture characteristics were not. These analyses were exploratory and require replication in future studies.

3.
Am J Med ; 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31152714

RESUMO

Patients often start treatment to reduce fracture risk because of a bone mineral density T-score consistent with osteoporosis (≤ -2.5). Others with a T-score above -2.5 may be treated when there is a history of fragility fracture or when a fracture risk algorithm categorizes them as having a high risk for fracture. It is common to initiate therapy with a generic oral bisphosphonate, unless contraindicated, and continue therapy if the patient is responding as assessed by stability or an increase in bone mineral density. However, some patients may respond well to an oral bisphosphonate, yet remain with an unacceptably high risk for fracture. Recognition of this occurrence has led to the development of an alternative strategy: treat-to-target. This involves identifying a biological marker (treatment target) that represents an acceptable fracture risk and then initiating treatment with an agent likely to reach this target. If the patient is on a path to reaching the target with initial therapy, treatment is continued. If it appears the target will not be reached with initial therapy, treatment is changed to an agent more likely to achieve the goal.

4.
J Clin Endocrinol Metab ; 104(8): 3450-3461, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125092

RESUMO

CONTEXT: Evidence for further nonvertebral fracture (NVF) reductions with long-term antiresorptive therapy in osteoporosis is lacking. OBJECTIVE: To evaluate NVF risk reduction in subjects receiving ≤10 years of denosumab treatment. DESIGN: Phase 3, randomized, placebo-controlled, 3-year Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (NCT00089791) and its open-label 7-year extension (NCT00523341). SETTING: One hundred seventy-two study centers worldwide. PATIENTS: Women 60 to 90 years, lumbar spine or total hip bone mineral density T-scores <-2.5 (≥-4.0 at both). INTERVENTIONS: Subjects randomly assigned 1:1 denosumab 60 mg SC Q6M (long-term) or placebo (crossover) in FREEDOM; eligible subjects could enroll in the extension to receive denosumab 60 mg SC Q6M. MAIN OUTCOME MEASURES: NVF Exposure-adjusted subject incidence (per 100 subject-years) during denosumab treatment years 1 to 3 and 4 to 7 (all subjects) and years 4 to 10 (long-term only), and rate ratios (RRs) for years 4 to 7 or 4 to 10 vs 1 to 3. RESULTS: Among 4074 subjects (2343 long-term, 1731 crossover), NVF rates (95% CI) in all subjects were 2.15 (1.90 to 2.43) during years 1 to 3 and 1.53 (1.34 to 1.75) during years 4 to 7 of denosumab treatment [RR (95% CI) = 0.72 (0.61 to 0.86); P < 0.001]; in long-term only were 1.98 (1.67 to 2.34) during years 1 to 3 and 1.44 (1.24 to 1.66) during years 4 to 10 [RR = 0.74 (0.60 to 0.93); P = 0.008]. combined osteonecrosis of the jaw and atypical femoral fracture rate was 0.06. CONCLUSIONS: Long-term denosumab treatment, >3 and ≤10 years, was associated with further reductions in NVF rates compared with the first 3 years.

5.
Arch Osteoporos ; 14(1): 27, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30820733

RESUMO

This study of women with a suspected vertebral fracture determined the association between vertebral fracture characteristics and posture. The number of fractures was associated with posture. Severity of fracture was associated with posture when adjusting for pain. Fracture characteristics explain some variability in posture in women with a suspected vertebral fracture. PURPOSE: Osteoporotic vertebral fractures are associated with increased morbidity and mortality. An accumulation of vertebral fractures may lead to forward head posture, which has been independently associated with mortality. It is unclear how fracture characteristics, including the number, severity, and location of fracture, contribute to occiput-to-wall distance (OWD). METHODS: This was a cross-sectional secondary data analysis using baseline data from a randomized controlled trial, in community-dwelling women aged 65 years and older with a suspected vertebral fragility fracture. Lateral thoracic and lumbar spine radiographs were used to determine the number, location, and severity of fracture. Occiput-to-wall distance (OWD) was used to assess forward head posture. Pain during movement (0-10 scale) and age were considered as confounding variables. Multivariable regression models were used to evaluate relationships between fracture variables and OWD. RESULTS: Participants (n = 158) were of mean age 75.9 (SD 6.5) years with a mean (SD) BMI = 26.7 (5.3) kg/m2, OWD = 5.7 (4.6) cm, and number of fractures = 2.4 (2.4). In unadjusted analyses, the number of fractures (B = 0.82, 95% CI = 0.04, 1.59) was associated with OWD. When adjusting for pain, severity of fractures (B = 1.08, 95% CI = 0.001, 2.15) was independently associated with OWD. Location was not associated with OWD in any of the models. CONCLUSIONS: The number of fractures was significantly associated with OWD in the unadjusted model, explaining more of the variability in OWD than other fracture characteristics. Severity of fracture was associated with OWD in the adjusted model. However, pain may confound the relationship between OWD and fracture characteristics.

6.
Arch Osteoporos ; 14(1): 10, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659410

RESUMO

PURPOSE: Using data from the 2-year, randomized, double-dummy VERO trial, we examined the changes in 25-hydroxy-vitamin D (25[OH]D) concentrations over time, and whether the fracture risk reduction of teriparatide versus risedronate varies by baseline 25(OH)D sufficiency category. METHODS: Postmenopausal women with established osteoporosis received subcutaneous daily teriparatide 20 µg or oral weekly risedronate 35 mg, with concomitant 500-1000 mg of elemental calcium and 400-800 IU/day of vitamin D supplements. Fracture endpoints were analyzed by predefined subgroups of 25(OH)D insufficient and sufficient patients. Heterogeneity of the treatment effect on fractures was investigated by logistic and Cox proportional hazards regression models. RESULTS: At baseline, mean serum 25(OH)D was 31.9 ng/mL in the teriparatide group and 31.5 ng/mL in the risedronate group, and 16.8% and 17.9% of patients, respectively, were 25(OH)D insufficient. At month 6, the mean serum 25(OH)D concentration decreased in teriparatide-treated patients to 24.5 ng/mL (by approximately 23%) but remained relatively constant in risedronate-treated patients (32.2 ng/mL) (p < 0.001). Proportions of 25(OH)D insufficient patients at month 6 were 26.7% and 5.6%, respectively (p < 0.001). The risk reduction with teriparatide versus risedronate for any of the fracture endpoints did not significantly differ between subgroups by 25(OH)D sufficiency status at baseline, with nonsignificant (p > 0.1) treatment-by-25(OH)D interactions in all fracture analyses. CONCLUSIONS: Serum 25(OH)D concentration decreases during teriparatide treatment. Fracture risk reduction with teriparatide versus risedronate did not significantly differ between the two groups of patients defined by baseline 25(OH)D. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.

7.
Bone ; 120: 1-8, 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30268814

RESUMO

In randomized clinical trials (RCTs) with teriparatide, the number of patients with incident hip fractures was small and insufficiently powered to show statistically significant differences between groups. We, therefore, conducted a systematic review and meta-analysis of the efficacy of teriparatide in the reduction of hip and upper limb fractures in women and men with osteoporosis. A comprehensive search of databases until 22 November 2017 was conducted for RCTs of at least 6-month duration that reported non-spine fractures (hip, humerus, forearm, wrist), either as an efficacy or safety endpoint. Only RCTs that included patients with the approved treatment indications and dose for use of teriparatide were included; trials with off-label use of teriparatide were excluded. Two independent reviewers performed study selection and data extraction. Statistical procedures included Peto's method and Mantel-Haenszel with empirical correction, as most of the RCTs reported zero events in at least one of the treatment arms. Study results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Publication bias and heterogeneity were evaluated with standard statistical tests. Twenty-three RCTs were included, 19 with an active-controlled arm (representing 64.9% of the patients included in the control group) and 11 double-blind, representing data on 8644 subjects, 3893 of them treated with teriparatide. Mean age (SD) was 67.0 (4.5) years, median treatment duration 18 months (range: 6 to 24 months). A total of 34 incident hip, 31 humerus, 31 forearm, and 62 wrist fractures were included. Meta-analysis results showed an OR (95% CI) for hip fractures of 0.44 (0.22-0.87; p = 0.019) in patients treated with teriparatide compared with controls. The effects on the risk of humerus [1.02 (0.50-2.08)], forearm [0.53 (0.26-1.08)] and wrist fractures [1.21 (0.72-2.04)] were not statistically significant (p > 0.05). This meta-analysis provides evidence of efficacy of teriparatide in reducing hip fractures by 56% in patients with osteoporosis.

9.
J Bone Miner Res ; 33(5): 783-794, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29329484

RESUMO

The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.c. daily teriparatide 20 µg or oral weekly risedronate 35 mg. As previously reported, the risk of new VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced with teriparatide compared with risedronate. Here we present the prospectively planned subgroup analyses of fracture data across subgroups, which were predefined by the following baseline characteristics: age, number and severity of prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before study entry, and baseline BMD. Heterogeneity of the treatment effect on the primary endpoint (new VFx), and the four key secondary endpoints (including clinical fractures and NVFFx) were investigated by logistic and Cox proportional hazards regression models. A total of 1360 women were randomized and treated (680 per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had a prior major NVFx, 43.2% were osteoporosis drug-naïve, 39.3% were recent bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone-equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of teriparatide versus risedronate did not significantly differ in any of the subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most subgroups mirroring results from the total study population. In conclusion, in postmenopausal women with severe osteoporosis, the antifracture efficacy of teriparatide compared with risedronate was consistent in a wide range of patient settings, including treatment-naïve and previously treated patients. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

10.
J Bone Miner Res ; 33(2): 298-306, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29024120

RESUMO

There has been renewed interest of late in the role of modeling-based formation (MBF) during osteoporosis therapy. Here we describe early effects of an established anabolic (teriparatide) versus antiresorptive (denosumab) agent on remodeling-based formation (RBF), MBF, and overflow MBF (oMBF) in human transiliac bone biopsies. Postmenopausal women with osteoporosis received subcutaneous teriparatide (n = 33, 20 µg/d) or denosumab (n = 36, 60 mg once/6 months), open-label for 6 months at 7 US and Canadian sites. Subjects received double fluorochrome labeling at baseline and before biopsy at 3 months. Sites of bone formation were designated as MBF if the underlying cement line was smooth, RBF if scalloped, and oMBF if formed over smooth cement lines adjacent to scalloped reversal lines. At baseline, mean RBF/bone surface (BS), MBF/BS, and oMBF/BS were similar between the teriparatide and denosumab groups in each bone envelope assessed (cancellous, endocortical, periosteal). All types of formation significantly increased from baseline in the cancellous and endocortical envelopes (differences p < 0.001) with teriparatide (range of changes 2.9- to 21.9-fold), as did MBF in the periosteum (p < 0.001). In contrast, all types of formation were decreased or not significantly changed with denosumab, except MBF/BS in the cancellous envelope, which increased 2.5-fold (difference p = 0.048). These data highlight mechanistic differences between these agents: all 3 types of bone formation increased significantly with teriparatide, whereas formation was predominantly decreased or not significantly changed with denosumab, except for a slight increase in MBF/BS in the cancellous envelope. © 2017 American Society for Bone and Mineral Research.

11.
Lancet ; 391(10117): 230-240, 2018 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-29129436

RESUMO

BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 µg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Teriparatida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Américas/epidemiologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Radiografia , Ácido Risedrônico/efeitos adversos , Teriparatida/efeitos adversos
12.
J Geriatr Phys Ther ; 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29210932

RESUMO

BACKGROUND AND PURPOSE: We sought to evaluate the Balance Outcome Measure for Elder Rehabilitation (BOOMER) in community-dwelling women 65 years and older with vertebral fracture and to describe score distributions and potential ceiling and floor effects. METHODS: This was a secondary data analysis of baseline data from the Build Better Bones with Exercise randomized controlled trial using the BOOMER. A total of 141 women with osteoporosis and radiographically confirmed vertebral fracture were included. Concurrent validity and internal consistency were assessed in comparison to the Short Physical Performance Battery (SPPB). Normality and ceiling/floor effects of total BOOMER scores and component test items were also assessed. Exploratory analyses of assistive aid use and falls history were performed. RESULTS AND DISCUSSION: Tests for concurrent validity demonstrated moderate correlation between total BOOMER and SPPB scores. The BOOMER component tests showed modest internal consistency. Substantial ceiling effect and nonnormal score distributions were present among overall sample and those not using assistive aids for total BOOMER scores, although scores were normally distributed for those using assistive aids. The static standing with eyes closed test demonstrated the greatest ceiling effects of the component tests, with 92% of participants achieving a maximal score. CONCLUSIONS: While the BOOMER compares well with the SPPB in community-dwelling women with vertebral fractures, researchers or clinicians considering using the BOOMER in similar or higher-functioning populations should be aware of the potential for ceiling effects.

13.
Lancet Diabetes Endocrinol ; 5(7): 513-523, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28546097

RESUMO

BACKGROUND: Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis. METHODS: In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both registered with ClinicalTrials.gov. FINDINGS: Between Aug 3, 2004, and June 1, 2005, 7808 women were enrolled in the FREEDOM study. 5928 (76%) women were eligible for enrolment in the extension, and of these, 4550 (77%) were enrolled (2343 long-term, 2207 crossover) between Aug 7, 2007, and June 20, 2008. 2626 women (1343 long-term; 1283 crossover) completed the extension. The yearly exposure-adjusted participant incidence of adverse events for all individuals receiving denosumab decreased from 165·3 to 95·9 per 100 participant-years over the course of 10 years. Serious adverse event rates were generally stable over time, varying between 11·5 and 14·4 per 100 participant-years. One atypical femoral fracture occurred in each group during the extension. Seven cases of osteonecrosis of the jaw were reported in the long-term group and six cases in the crossover group. The yearly incidence of new vertebral fractures (ranging from 0·90% to 1·86%) and non-vertebral fractures (ranging from 0·84% to 2·55%) remained low during the extension, similar to rates observed in the denosumab group during the first three years of the FREEDOM study, and lower than rates projected for a virtual long-term placebo cohort. In the long-term group, BMD increased from FREEDOM baseline by 21·7% at the lumbar spine, 9·2% at total hip, 9·0% at femoral neck, and 2·7% at the one-third radius. In the crossover group, BMD increased from extension baseline by 16·5% at the lumbar spine, 7·4% at total hip, 7·1% at femoral neck, and 2·3% at one-third radius. INTERPRETATION: Denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. FUNDING: Amgen.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Denosumab/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo
14.
Am J Med ; 130(7): 862.e1-862.e7, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28359721

RESUMO

Osteoporosis is a chronic disease that requires life-long strategies to reduce fracture risk. Few trials have investigated the balance of benefits and risk with long-term use of osteoporosis therapies, and fewer still have investigated the consequences of treatment discontinuation. The best available evidence suggests that up to 10 years of treatment with an oral bisphosphonate maintains the degree of fracture risk reduction observed in the 3-year registration trials. With denosumab, 10 years of therapy appears to provide fracture risk reduction similar to or better than that observed in the 3-year registration trial. Available data suggest an increasing but low risk of fractures with atypical features with increasing duration of bisphosphonate therapy. Published data linking duration of therapy to osteonecrosis of the jaw are lacking for bisphosphonates and denosumab. Other side effects associated with denosumab or bisphosphonates do not appear to be related to therapy duration. The antifracture benefits of long-term therapy with bisphosphonates and denosumab in appropriately selected patients outweigh the low risk of serious side effects.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Esquema de Medicação , Fraturas do Fêmur/induzido quimicamente , Humanos , Fraturas por Osteoporose/prevenção & controle , Medição de Risco
15.
Ann. hepatol ; 16(2): 207-214, Mar.-Apr. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-887224

RESUMO

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

16.
J Bone Miner Res ; 32(7): 1481-1485, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28277603

RESUMO

Denosumab is a fully human monoclonal antibody against receptor activator of NF-κB ligand (RANKL) that decreases osteoclast formation, function and survival, and is approved for the treatment of postmenopausal women with osteoporosis at increased or high risk for fracture, among other indications. During the pivotal 3-year fracture trial FREEDOM, denosumab 60 mg subcutaneously every 6 months significantly reduced new vertebral (68%), hip (40%), and nonvertebral (20%) fractures; increased bone mineral density (BMD); and reduced bone turnover markers compared with placebo in postmenopausal women with osteoporosis. Questions have arisen regarding imbalances of certain low-frequency adverse events (AEs) observed in FREEDOM, as well as the top 5 most frequent adverse reactions listed in the United States prescribing information (USPI; back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis). We examined the incidences of these AEs in women who originally received placebo during FREEDOM and then received denosumab for up to 3 years during the FREEDOM Extension (Crossover Group). This provided a unique opportunity for comparison with the original 3-year denosumab FREEDOM observations. We also examined the incidences of these AEs over 6 years of denosumab treatment (Long-term Group; ie, comparing a second 3 years of treatment with findings in the first 3 years). There was no indication of increasing trends regarding the imbalances of either low-frequency AEs or common AEs observed in FREEDOM. © 2017 American Society for Bone and Mineral Research.


Assuntos
Denosumab/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Denosumab/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Estados Unidos/epidemiologia
17.
Ann Hepatol ; 16(2): 207-214, 2017 March-April.
Artigo em Inglês | MEDLINE | ID: mdl-28233741

RESUMO

BACKGROUND: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (&lt;-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.


Assuntos
Antivirais/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Cálcio/sangue , Fatores de Crescimento de Fibroblastos/sangue , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Fosfatos/sangue , Tenofovir/uso terapêutico , Absorciometria de Fóton , Adulto , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Fraturas Ósseas/induzido quimicamente , Guanina/efeitos adversos , Guanina/uso terapêutico , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tenofovir/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Deficiência de Vitamina D/induzido quimicamente
18.
J Clin Densitom ; 20(1): 8-24, 2017 Jan - Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27956123

RESUMO

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Doenças Periodontais/epidemiologia , Comitês Consultivos , Antibacterianos/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/administração & dosagem , Desbridamento , Denosumab/administração & dosagem , Difosfonatos/administração & dosagem , Relação Dose-Resposta a Droga , Fraturas Ósseas/prevenção & controle , Humanos , Higiene Bucal/métodos , Doenças Periodontais/terapia , Guias de Prática Clínica como Assunto , Fatores de Risco , Teriparatida/uso terapêutico
19.
Menopause ; 23(10): 1083-91, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27404034

RESUMO

OBJECTIVE: Conjugated estrogens/bazedoxifene reduces vasomotor symptoms and prevents postmenopausal bone loss without stimulating the breast and endometrium. We analyzed changes in bone mineral density (BMD) and bone markers using pooled data from two phase-3 trials. METHODS: Selective Estrogens, Menopause, and Response to Therapy (SMART)-1 and SMART-5 were randomized, double-blind, placebo- and active-controlled studies conducted in postmenopausal nonhysterectomized women. BMD and turnover marker data were pooled for women given conjugated estrogens (0.45 or 0.625 mg) plus bazedoxifene 20 mg or placebo over 12 months. Sensitivity analyses were conducted using baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, race, and geographic region. RESULTS: There were 1,172 women, mean age 54.9 years, mean 6.21 years since menopause, mean lumbar spine, and total hip T scores -1.05 and -0.58; 58.8% had a Fracture Risk Assessment Tool score less than 5% indicating low fracture risk. At 12 months, adjusted differences (vs placebo) in BMD change in the groups taking conjugated estrogens 0.45 or 0.625 mg plus bazedoxifene 20 mg were 2.3% and 2.4% for lumbar spine, 1.4% and 1.5% for total hip, and 1.1% and 1.5% for femoral neck (all P < 0.001 vs placebo). These increases were unrelated to baseline Fracture Risk Assessment Tool score, age, years since menopause, body mass index, or geographic region. Both doses reduced bone turnover markers (P < 0.001). CONCLUSIONS: Conjugated estrogens/bazedoxifene significantly improved BMD and turnover in a large population of younger postmenopausal women at low fracture risk and is a promising therapy for preventing postmenopausal bone loss.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Estrogênios Conjugados (USP)/administração & dosagem , Indóis/administração & dosagem , Osteoporose Pós-Menopausa/prevenção & controle , Densidade Óssea , Remodelação Óssea , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
J Bone Miner Res ; 31(10): 1827-1834, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27082709

RESUMO

Hip fractures account for over one-half the morbidity, mortality, and cost associated with osteoporosis. Fragility of the proximal femur is the result of rapid and unbalanced bone remodeling events that excavate more bone than they deposit, producing a porous, thinned, and fragile cortex. We hypothesized that the slowing of remodeling during treatment with denosumab allows refilling of the many cavities excavated before treatment now opposed by excavation of fewer new resorption cavities. The resulting net effect is a reduction in cortical porosity and an increase in proximal femur strength. Images were acquired at baseline and 36 months using multidetector CT in 28 women receiving denosumab and 22 women receiving placebo in a substudy of FREEDOM, a randomized, double-blind, placebo-controlled trial involving women with postmenopausal osteoporosis. Porosity was quantified using StrAx1.0 software. Strength was estimated using finite element analysis. At baseline, the higher the serum resorption marker, CTx, the greater the porosity of the total cortex (r = 0.34, p = 0.02), and the higher the porosity, the lower the hip strength (r = -0.31, p = 0.03). By 36 months, denosumab treatment reduced porosity of the total cortex by 3.6% relative to baseline. Reductions in porosity relative to placebo at 36 months were 5.3% in total cortex, 7.9% in compact-appearing cortex, 5.6% in outer transitional zone, and 1.8% in inner transitional zone (all p < 0.01). The improvement in estimated hip integral strength of 7.9% from baseline (p < 0.0001) was associated with the reduction in total porosity (r = -0.41, p = 0.03). In summary, denosumab reduced cortical porosity of the proximal femoral shaft, resulting in increased mineralized matrix volume and improved strength, changes that may contribute to the reduction in hip and nonvertebral fractures reported with denosumab therapy. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Denosumab/administração & dosagem , Colo do Fêmur , Fraturas do Quadril , Menopausa , Osteoporose Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/metabolismo , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/etiologia , Fraturas do Quadril/metabolismo , Fraturas do Quadril/prevenção & controle , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Porosidade , Tomografia Computadorizada por Raios X
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