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1.
J Oncol Pharm Pract ; 25(8): 1846-1852, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31694497

RESUMEN

OBJECTIVE: To identify the incidence of hypercalcemia and hypocalcemia in zoledronic acid and denosumab groups. Secondary objective was to determine the correlation between calcium supplement and calcium level control. METHODS: An observational retrospective cohort study was conducted by reviewing patient electronic records, laboratory results, and medication charts from 1 August 2015 to 31 July 2016. Adult cancer patients who were diagnosed with bone metastasis secondary to a solid tumor or multiple myeloma and who received either zoledronic acid or denosumab were included. Other indications for bone targeting agents were excluded. Data of bone targeting agents administration encounters were collected, evaluated, and analyzed. RESULTS: A total of 1141 encounters (for 271 patients) were included. The incidence of hypocalcemia was higher in denosumab compared to zoledronic acid group (5.5% vs. 3.1%, OR = 0.55, 95% CI [0.3-1.0]; P = 0.05). Hypercalcemia incidence was also higher in denosumab group (8.5% vs. 3.1%, OR = 2.9, 95% CI [1.68-5.03]; P < 0.0001). Breast cancer was the most common malignancy associated with hypocalcemia (27.3%) followed by ovarian cancer (25%) and multiple myeloma (22.7%). The risk of developing hypocalcemia was reduced by 16% in patients receiving calcium supplementation (RR = 0.84, 95% CI [0.55-1.20]; P = 0.39). CONCLUSION: Denosumab use was associated with higher rates of both hypercalcemia and hypocalcemia compared to zoledronic acid. Adequate supplementation with calcium substantially reduced the risk of hypocalcemia. Our results highlight the importance of taking preventative measures upon bone targeting agents initiation and during treatment including regular monitoring of calcium levels and providing supplements accordingly.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Denosumab/administración & dosificación , Ácido Zoledrónico/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/secundario , Calcio/metabolismo , Estudios de Cohortes , Denosumab/efectos adversos , Femenino , Humanos , Hipercalcemia/inducido químicamente , Hipocalcemia/inducido químicamente , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ácido Zoledrónico/efectos adversos
2.
Medicine (Baltimore) ; 98(46): e17778, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31725619

RESUMEN

INTRODUCTION: Giant cell tumor of bone with pulmonary and bone metastases is exceedingly rare in adolescents. Furthermore, Denosumab and Sunitinib in the treatment of giant cell tumor of bone has never been reported. PATIENT CONCERNS: A 16-year-old boy complained of fever, chest tightness, and shortness of breath and back pain for 5 days. DIAGNOSIS: Giant cell tumor of bone with pulmonary and bone metastases. INTERVENTIONS: The patient underwent 2 surgeries for giant cell tumor of bone located in the spine and received Denosumab to reduce local recurrence and control the metastases. Then Sunitinib was added into treatment strategies after the progressing of metastases. OUTCOMES: Within 5 months of Denosumab and Sunitinib, lung metastases were shrinking (stable disease, response evaluation criteria in solid tumors version 1.1). Until now about 4 years into treatment the patient is still survival. Pulmonary and bone metastases are stable. CONCLUSIONS: This is a case of multi-center giant cell tumor of bone, it does not only provide a reference to the treatment of similar cases of the clinic but also reflects the limitations of the application of Denosumab in the real world.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Sunitinib/uso terapéutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/secundario , Denosumab/administración & dosificación , Tumor Óseo de Células Gigantes/patología , Tumor Óseo de Células Gigantes/cirugía , Humanos , Neoplasias Pulmonares/secundario , Masculino , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Sunitinib/administración & dosificación
3.
Medicine (Baltimore) ; 98(48): e18161, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31770261

RESUMEN

RATIONALE: Epithelioid hemangioma (EH) of bone is an intermediate vascular tumor that can be locally aggressive. The optimum management of multifocal EH of bone is not well delineated. We described our experience treating one patient with multifocal EH of bone in an effort to document the effect of bisphosphonates in bone EH. PATIENT CONCERNS: In this report, a 53-year old male patient presented with back pain which was initially been diagnosed of multiple bone metastatic carcinoma by 18F-FDG PET/CT scan and bone scintigraphy. DIAGNOSIS: CT-guided bone biopsy of ilium indicated that puncture tissue had irregular hyperplasia of thick and thin-walled blood vessels, immunohistochemistry revealed positive staining for CD31 and CD34, negative for CAMTA-1, PCK and EMA, which confirmed the diagnosis of multiple EH. INTERVENTIONS: The patient was treated with 4 times of intravenous Zometa (zoledronate, 4 mg each time) with average three-month interval. Bone metabolic markers including serum bone specific alkaline phosphatase (BALP) and type I collagen cross-linked C-terminal telopeptide (CTX) levels were closely monitored before and after use of bisphosphonates each time. OUTCOME: BALP and CTX were significantly lowered following intravenous Zometa and the back pain improved with integrated therapy including bone graft fusion internal fixation surgery and vertebroplasty. CONCLUSIONS: EH of multiple bones responded favorably to intravenous Zometa with improvement of bone metabolic markers. After 1 year on follow-up, the patient was doing well with no significant pain. We suggest that bisphosphonates should be considered in the treatment of multifocal osteolytic EH of bone.


Asunto(s)
Neoplasias Óseas , Huesos , Hemangioendotelioma Epitelioide , Inmunohistoquímica/métodos , Metástasis de la Neoplasia/diagnóstico , Procedimientos Ortopédicos/métodos , Ácido Zoledrónico/administración & dosificación , Biopsia/métodos , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Remodelación Ósea/efectos de los fármacos , Huesos/diagnóstico por imagen , Huesos/metabolismo , Huesos/patología , Terapia Combinada , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Monitoreo de Drogas/métodos , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/metabolismo , Hemangioendotelioma Epitelioide/patología , Hemangioendotelioma Epitelioide/terapia , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
4.
G Ital Nefrol ; 36(5)2019 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-31580546

RESUMEN

Calcific uremic arteriolopathy (CUA) is a highly morbid condition usually found in ESRD patients that has rarely been reported after renal transplantation and renal function restoration. Furthermore, little is known about the optimal management of CUA in this setting. Herein, we report on the clinical case of AB, a 70-year-old woman who developed CUA after renal transplantation and renal function restoration. However, other risk factors for CUA such as diabetes and warfarin treatment, due to mechanical aortic valve implantation, were present. Thirty-eight months after renal transplantation she developed erythema and livedo reticularis in both legs and a gradually enlarging skin ulcer in the right leg. A skin biopsy of the ulcer showed features compatible with the CUA, such as sub-intimal calcification and luminal obstruction of the small dermal arterioles, tissue ischemia and signs of adipocytes degeneration. A multidisciplinary approach was adopted, including medical and non-medical treatments such as surgical debridement and vacuum-assisted closure therapy. Medical treatments included a five weeks course of once a week intravenous infusion of pamidronate and intravenous sodium thiosulfate (STS) at increasing doses. Four months after beginning the therapy with STS, a complete healing of the ulcer on the right leg and the disappearance of the livedo reticularis on the left leg was noted. In conclusion, although rare CUA may develop also in renal transplanted patients, a timely and combined therapeutic approach is essential for its resolutive treatment. Sodium thiosulfate therapy has proven to be effective and tolerated.


Asunto(s)
Calcifilaxia/terapia , Trasplante de Riñón/efectos adversos , Úlcera de la Pierna/terapia , Enfermedades Raras/terapia , Anciano , Anticoagulantes/uso terapéutico , Conservadores de la Densidad Ósea/administración & dosificación , Calcifilaxia/etiología , Quelantes/administración & dosificación , Terapia Combinada/métodos , Diabetes Mellitus , Femenino , Humanos , Úlcera de la Pierna/etiología , Livedo Reticularis/etiología , Livedo Reticularis/terapia , Pamidronato/administración & dosificación , Enfermedades Raras/etiología , Factores de Riesgo , Tiosulfatos/administración & dosificación , Warfarina/uso terapéutico
5.
BMC Cancer ; 19(1): 980, 2019 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-31640606

RESUMEN

BACKGROUND: While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy. METHODS: To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions. RESULTS: The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF. CONCLUSIONS: We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Denosumab/uso terapéutico , Fracturas del Fémur/epidemiología , Fracturas del Fémur/patología , Osteoporosis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Denosumab/administración & dosificación , Denosumab/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Ácido Zoledrónico/efectos adversos , Ácido Zoledrónico/uso terapéutico
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1045-1051, 2019 Sep 30.
Artículo en Chino | MEDLINE | ID: mdl-31640962

RESUMEN

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) via a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; n=6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of ß-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice (P < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice (P < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of ß-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS: Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Densidad Ósea , Huesos/metabolismo , Osteoclastos/efectos de los fármacos , Ovariectomía , Teriparatido/administración & dosificación , Animales , Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/tratamiento farmacológico , Huesos/efectos de los fármacos , Femenino , Placa de Crecimiento/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ligando RANK/metabolismo , Teriparatido/farmacología , beta Catenina/metabolismo
7.
BMJ Case Rep ; 12(9)2019 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-31537587

RESUMEN

We describe an 11-year prospective clinical and radiologic course of a 6-year-old boy with bilateral Legg-Calvé-Perthes disease, who was treated with intravenous pamidronate (IV-PAM). His baseline radiographs showed grade IV avascular necrosis/Catterall stage IV, and at worst he progressed to lateral pillar/Herring stage C bilaterally. His disease initially was extremely functionally limiting with expected poor outcome with eventual joint replacement. Because IV-PAM stops bone breakdown and allows for ongoing bone formation while revascularisation of bone occurs, we hypothesised that IV-PAM could act as an adjunct to traditional treatment to help heal the femoral heads. Our patient received nine once monthly doses of IV-PAM (1 mg/kg/dose) over 13 months, along with Petrie/broomstick casts and physiotherapy. Remarkably, over time, his femoral heads healed. Now, at 11-year follow-up, he has excellent functional and radiologic outcome with congruence between femoral head and acetabulum, no residual osteonecrosis and minimal loss of femoral head sphericity.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Enfermedad de Legg-Calve-Perthes/tratamiento farmacológico , Pamidronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Moldes Quirúrgicos , Niño , Cabeza Femoral/efectos de los fármacos , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Humanos , Enfermedad de Legg-Calve-Perthes/rehabilitación , Enfermedad de Legg-Calve-Perthes/cirugía , Masculino , Pamidronato/administración & dosificación , Tenotomía/métodos , Resultado del Tratamiento
8.
BMC Musculoskelet Disord ; 20(1): 399, 2019 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-31472671

RESUMEN

BACKGROUND: Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials. METHODS: Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence. RESULTS: Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p = 0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p < 0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p < 0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p < 0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p < 0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p < 0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p < 0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p < 0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p = 0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p = 0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p < 0.0001). CONCLUSION: Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Fracturas por Compresión/prevención & control , Osteoporosis/complicaciones , Fracturas Osteoporóticas/prevención & control , Fracturas de la Columna Vertebral/prevención & control , Conservadores de la Densidad Ósea/efectos adversos , Fracturas por Compresión/epidemiología , Fracturas por Compresión/etiología , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , Humanos , Oligopéptidos , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , Privación de Tratamiento/estadística & datos numéricos
9.
Clin Orthop Surg ; 11(3): 352-360, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31475058

RESUMEN

Background: Giant-cell tumor of bone (GCTB) is a locally aggressive primary benign tumor presenting as an expansile osteolytic lesion affecting the epiphysis of long bones. Denosumab halts the osteolysis by giant cells thereby downstaging the tumor, helping in performing less morbid procedures to remove the tumor. Our aim was to report the incidence of local recurrence (LR) in patients operated following neoadjuvant denosumab, to investigate factors associated with LR following extended curettage for GCTB, and to compare the postoperative functional and oncological outcome of patients operated with and without neoadjuvant denosumab. Methods: A total of 123 patients with a mean age of 29.6 years undergoing extended curettage for GCTB were retrospectively divided into group 1 receiving neoadjuvant denosumab and group 2 operated without denosumab. The mean follow-up period was 35 months. The perioperative characteristics and outcome were compared between the two groups and the factors for LR of GCTB were analyzed. Results: The incidence of LR among patients operated after neoadjuvant denosumab therapy was 42.8% and was significantly high compared to that in patients without denosumab (p < 0.001). On multivariate logistic regression analysis, use of denosumab as a neoadjuvant was the only factor independently associated with LR following surgery (p = 0.002). Patients treated with denosumab had a lower LR-free survival rate (log-rank, p = 0.018). Conclusions: Denosumab was independently associated with increased LR following surgery for GCTB. Denosumab has to be used cautiously in patients in whom the burden of downstaging the disease outweighs the possible chance of LR.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Denosumab/efectos adversos , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Recurrencia Local de Neoplasia/inducido químicamente , Osteólisis/prevención & control , Adolescente , Adulto , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/cirugía , Legrado , Denosumab/administración & dosificación , Femenino , Tumor Óseo de Células Gigantes/cirugía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Osteólisis/etiología , Estudios Retrospectivos , Adulto Joven
10.
Expert Opin Drug Saf ; 18(10): 1001-1008, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31394044

RESUMEN

Objectives: Bazedoxifene was found to be effective and well tolerated for the treatment and prevention of osteoporosis in postmenopausal women. This post-marketing surveillance study (PMSS) examined the safety of bazedoxifene in postmenopausal Korean women with osteoporosis, in a real-world setting. Methods: This PMSS was conducted from 2013 to 2017. A total of 3,423 subjects from 68 centers were enrolled and monitored for about 3 months (± 2 weeks). Bazedoxifene was prescribed at a dose of 20 mg/day. The safety of bazedoxifene was evaluated based on the number and nature of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and serious ADRs (SADRs) in routine medical practice. Results: The mean age of study subjects was 69.51 years. The incidence of AEs and ADRs was 6.11% and 3.86%, respectively, and significantly decreased with increasing age (p= 0.0007). AE and ADR rates with bazedoxifene treatment of 3 months or more were significantly lower than those of less than 3 months (AE, 3.64% vs 30.00%, p < 0.0001; ADR, 1.74% vs 24.38%, p < 0.0001). Conclusion: In this study, bazedoxifene was well tolerated in the management of postmenopausal osteoporosis in Korean women, including those aged 70 years or more.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Indoles/administración & dosificación , Osteoporosis Posmenopáusica/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/efectos adversos , Femenino , Humanos , Incidencia , Indoles/efectos adversos , Persona de Mediana Edad , Vigilancia de Productos Comercializados , República de Corea , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Factores de Tiempo
11.
Dtsch Med Wochenschr ; 144(16): 1120-1124, 2019 08.
Artículo en Alemán | MEDLINE | ID: mdl-31416103

RESUMEN

Adequate intake of vitamin D and calcium are fundamental for the treatment of osteoporosis. A normal vitamin D status is required for optimal intestinal calcium absorption. However, general calcium and vitamin D supplementation is not sufficient for prevention of osteoporotic fractures in persons older than 50 years. Nevertheless, vitamin D deficiency should be avoided and corrected. In particular, parts of the population with increased risk for vitamin D deficiency (immobilized or older individuals, swarthy, migrants) should be tested. Secondary causes of vitamin D deficiency should be identified and treated.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis , Vitamina D , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Calcio/administración & dosificación , Calcio/uso terapéutico , Suplementos Dietéticos , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/fisiopatología , Vitamina D/administración & dosificación , Vitamina D/uso terapéutico , Deficiencia de Vitamina D
12.
Breast Cancer Res ; 21(1): 97, 2019 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-31455425

RESUMEN

BACKGROUND: Adjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS). PATIENTS AND METHODS: Patients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes. RESULTS: Two hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226-0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371-1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176-1.222, P = 0.120; HR 0.539, 95% CI 0.228-1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369-1.725, P = 0.565; HR 0.456, 95% CI 0.156-1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005-1.045, P = 0.014). CONCLUSIONS: Our results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01099436 , April 2010.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Ácido Zoledrónico/uso terapéutico , Adulto , Anciano , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ensayos Clínicos Fase III como Asunto , Femenino , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Menopausia , Persona de Mediana Edad , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Receptor IGF Tipo 1/metabolismo , Análisis de Supervivencia , Ácido Zoledrónico/administración & dosificación
13.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-31289164

RESUMEN

A 56-year-old man was referred with left-sided hip pain. MRI scans demonstrated an undisplaced stress fracture in the femoral neck and subchondral oedema within the femoral head. Bone densitometry showed T-scores of -2.0 at the spine, -3.5 at the femoral neck and -2.4 for the total hip. Laboratory tests revealed 25-hydroxyvitamin D <10 nmol/L. He was prescribed a 10-day course of calciferol 1.25 mg (50 000 IU)/day and started on calcium carbonate 1.25 g twice daily. Following the correction of vitamin D deficiency, his symptoms resolved. A striking feature of this patient was the complete reversal of 'osteoporosis' within 14 months with vitamin D and calcium supplementation. Bone mineral densities (BMDs) increased by 19.5% and 33.4% at the spine and hip, respectively. Such changes are never seen with conventional pharmacological management of osteoporosis. Vitamin D deficiency should be considered as a cause for reduced BMD in people with risk factors.


Asunto(s)
Cuello Femoral/diagnóstico por imagen , Osteomalacia/diagnóstico , Vitamina D/análogos & derivados , Anciano , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Calcifediol/administración & dosificación , Calcifediol/uso terapéutico , Cuello Femoral/patología , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Osteomalacia/sangre , Osteomalacia/tratamiento farmacológico , Osteomalacia/etiología , Resultado del Tratamiento , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones
14.
J Orthop Res ; 37(11): 2278-2286, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31283054

RESUMEN

Bone allografts are inferior to autografts for the repair of critical-sized defects. Prior studies have suggested that bone morphogenetic protein-2 (BMP-2) can be combined with allografts to produce superior healing. We created a bioactive coating on bone allografts using polycondensed deoxyribose isobutyrate ester (PDIB) polymer to deliver BMP-2 ± the bisphosphonate zoledronic acid (ZA) and tested its ability to enhance the functional utility of allografts in preclinical Wistar rat models. One ex vivo and two in vivo proof-of-concept studies were performed. First, PDIB was shown to be able to coat bone grafts (BGs). Second, PDIB was used to coat structural allogenic corticocancellous BG with BMP-2 ± ZA ± hydroxyapatite (HA) microparticles and compared with PDIB-coated grafts in a rat muscle pouch model. Next, a rat critical defect model was performed with treatment groups including (i) empty defect, (ii) BG, (iii) collagen sponge + BMP-2, (iv) BG + PDIB/BMP-2, and (v) BG + PDIB/BMP-2/ZA. Key outcome measures included detection of fluorescent bone labels, microcomputed tomography (CT) quantification of bone, and radiographic healing. In the muscle pouch study, BMP-2 did not increase net bone volume measured by microCT, however, fluorescent labeling showed large amounts of new bone. Addition of ZA increased BV by sevenfold (p < 0.01). In the critical defect model, allografts were insufficient to promote reliable union, however, union was achieved in collagen/BMP-2 and all BG/BMP-2 groups. Statement of clinical significance: These data support the concept that PDIB is a viable delivery method for BMP-2 and ZA delivery to enhance the bone forming potential of allografts. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2278-2286, 2019.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Proteína Morfogenética Ósea 2/administración & dosificación , Trasplante Óseo , Ácido Zoledrónico/administración & dosificación , Aloinjertos , Animales , Desoxirribosa/química , Sistemas de Liberación de Medicamentos , Evaluación Preclínica de Medicamentos , Isobutiratos/química , Masculino , Polímeros/química , Ratas Wistar
15.
Osteoporos Int ; 30(9): 1865-1872, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31317248

RESUMEN

We studied 46,797 older adults who initiated denosumab in Ontario, Canada. Patient characteristics remained relatively stable over time and aligned with public reimbursement restrictions. Almost half of patients persisted with therapy for at least 3 years. Fifty-nine percent of patients who discontinued denosumab returned to treatment within 3.6 years. INTRODUCTION: The purpose of this study was to describe the characteristics of patients who initiated denosumab and estimate persistence with therapy. METHODS: We identified older adults (aged ≥ 66 years) in Ontario who initiated denosumab between 2012/02 and 2015/03 and followed them to 2016/03. Patient characteristics were summarized using medical and pharmacy claims in the year before starting denosumab and osteoporosis drug use considered since 1996/10. Persistence with denosumab and return after discontinuation (> 90-day gap) were estimated using Kaplan-Meier curves. Analyses were stratified by community and long-term care (LTC) residence. RESULTS: We identified 46,797 patients (monthly mean = 1263, SD = 187); 97% female, 13% LTC. Community-dwelling patients had a higher prevalence of bone mineral density testing (62% vs. 5%), yet were younger (mean age 78.5 vs. 86.6 years) and had lower prevalence of hip fractures (3% vs. 10%) compared to LTC patients. Eighty-two percent of patients had used osteoporosis medications in the past; 99% of whom took an oral bisphosphonate. Persistence was similar between community-dwelling and LTC patients: 59% persisted ≥ 2 years, 48% ≥ 3 years, and 38% ≥ 4 years, yet a larger proportion of LTC patients returned to denosumab after discontinuation (76% vs. 57%). CONCLUSIONS: Denosumab utilization is increasing at a steady rate in Ontario. However, persistence remains a concern given the highly reversible pharmacokinetic profile of denosumab that results in a rapid increased fracture risk following discontinuation. Over 80% of patients had a history of oral bisphosphonate therapy, which may persist in bone despite discontinuing denosumab. Consequently, better understanding of denosumab safety and effectiveness among real-world users is important.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Bases de Datos Factuales , Denosumab/administración & dosificación , Esquema de Medicación , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Fracturas de Cadera/prevención & control , Humanos , Estimación de Kaplan-Meier , Masculino , Ontario/epidemiología , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/fisiopatología , Fracturas Osteoporóticas/prevención & control , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos
16.
Osteoporos Int ; 30(9): 1837-1844, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31321446

RESUMEN

This study evaluated the 2-year persistence with teriparatide in the Netherlands. Analyses showed that the risk of non-persistence was 28% lower in patients who were followed according to an additional educational and motivational support program. INTRODUCTION: Until recently, teriparatide (TPTD) was a third-line treatment option for severe osteoporosis in the Netherlands, which could only be prescribed by medical specialists based on a specific medical statement. We aimed to determine whether an educational and motivational support program (EMSP) increased 2-year treatment persistence with TPTD in patients with severe osteoporosis. METHODS: We evaluated persistence in 1573 Dutch patients treated with TPTD from January 2013 until January 2018. From January 2013 onwards, all patients received a basic support program (BSP) consisting of an educational home visit to initiate TPTD treatment and phone calls (at 1, 2.5 and 8 weeks). Since May 2015, all patients received the EMSP consisting of the BSP extended with evaluation of medication adherence during phone calls, an additional phone call (at 12 months), and motivational letters at 9 and 14 months. RESULTS: The EMSP showed a statistically significantly higher 2-year persistence (78%) with TPTD as compared with the BSP (72%). Reasons for treatment discontinuation were comparable between groups, except for the proportion of patients who had stopped TPTD administration due to side effects, which was significantly lower in the EMSP group (8% vs. 15% in BSP, p < 0.001). Overall, the risk of non-persistence was 28% lower in the EMSP compared with the BSP group (HR: 0.72; 95% CI: 0.55-0.93). CONCLUSION: The introduction of the EMSP has demonstrated to improve the persistence with TPTD, resulting in 78% of the patients being persistent with TPTD during the 2-year treatment period.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis/tratamiento farmacológico , Educación del Paciente como Asunto/métodos , Teriparatido/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Conservadores de la Densidad Ósea/uso terapéutico , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Persona de Mediana Edad , Motivación , Países Bajos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores Sexuales , Teléfono , Teriparatido/uso terapéutico
17.
Plast Reconstr Surg ; 144(2): 358-370, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31348344

RESUMEN

BACKGROUND: Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds. METHODS: Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 µm of dipyridamole (n = 6), 10,000 µm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test. RESULTS: Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-µm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-µm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 µm versus 10,000 µm dipyridamole; p = 0.104), and rhBMP-2-coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 µm dipyridamole, and p = 0.938 versus 10,000 µm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone. CONCLUSION: Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.


Asunto(s)
Proceso Alveolar/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Proteína Morfogenética Ósea 2/farmacología , Regeneración Ósea/efectos de los fármacos , Dipiridamol/farmacología , Andamios del Tejido , Factor de Crecimiento Transformador beta/farmacología , Proceso Alveolar/lesiones , Animales , Conservadores de la Densidad Ósea/administración & dosificación , Proteína Morfogenética Ósea 2/administración & dosificación , Trasplante Óseo/métodos , Dipiridamol/administración & dosificación , Modelos Animales de Enfermedad , Microscopía Electrónica de Rastreo , Modelos Animales , Osteogénesis/efectos de los fármacos , Impresión Tridimensional , Conejos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Factor de Crecimiento Transformador beta/administración & dosificación , Microtomografía por Rayos X
18.
Acta Reumatol Port ; 44(2): 114-125, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31280276

RESUMEN

BACKGROUND: Osteoporotic fractures are a major cause of morbidity and mortality. It is recognized that persistence with medication is crucial to reach optimal clinical outcomes. We aimed to estimate the persistence level to weekly and monthly oral bisphosphonates (OBP) in women with postmenopausal osteoporosis (PMO) over 24 months from therapy initiation in a population-based setting. METHODS: Prospective observational cohort study of PMO women ≥50 years initiating OBP recruited through community pharmacies. Data were collected at baseline during face-to-face interviews. Follow-up included pharmacy records (refill dates and medication possession; cohort 1) and telephone-surveys for patients who agreed to be interviewed (cohort 2). Patients were classified as persistent if they refilled their prescription within 30 days after exhausting the time covered by their previous supply. Log-rank tests were used to compare Kaplan-Meier curves of time to non-persistence. RESULTS: Of 427 women recruited with a mean age of 65.0 years, 380 (89%) agreed to be interviewed (cohort 2). Over 24-months of follow-up, 3.4% (95% CI: [2.0%; 5.6%]) of all subjects were persistent to OBP based on pharmacy records. Analysis combining both self-reported information and pharmacy records (cohort 2) showed a persistence estimate of 20.0% (95% CI: [16.1%; 24.2%]). Lower persistence was associated with more frequent OBP dosing and living alone. The most common reason for treatment discontinuation was self-reported adverse events (27.6%). CONCLUSIONS: Results indicate a low level of persistence with OBP. Barriers and reasons leading to discontinuation of anti-PMO therapies should be proactively addressed to promote persistence and improve fracture protection.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Administración Oral , Anciano , Análisis de Varianza , Estudios de Cohortes , Bases de Datos Farmacéuticas/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Portugal , Estudios Prospectivos , Autoinforme/estadística & datos numéricos , Factores de Tiempo
20.
Acta Orthop Traumatol Turc ; 53(5): 376-380, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31253385

RESUMEN

OBJECTIVES: The aim of this study was to describe the cohort of patients who have been treated with Denosumab as neoadjuvant therapy prior to surgery for aggressive giant cell tumor of bone in the extremities, to evaluate the radiological responses to Denosumab comparing Choi criteria and a newly described computerized tomography (CT) classification, and to evaluate the risk of local recurrence after intralesional curettage or radical excision. METHODS: We retrospectively evaluated 36 patients (20 females and 16 males; mean age at diagnosis 36 years (range, 18-64)) treated with neoadjuvant Denosumab therapy prior to surgery for aggressive giant cell tumor of bone in the extremities. The radiological responses to Denosumab treatment were analyzed on the preoperative images after the neoadjuvant course with the Choi criteria and with a newly proposed classification based on CT. All these images were independently reviewed by two of the researchers. Surgical intervention methods were noted and local recurrence rates were evaluated. The correlation between radiological response amount and local recurrence were analyzed for both Choi criteria and the new CT classification. RESULTS: Denosumab was administered for a mean of 21 weeks (range 7-133). Five patients also had a short postoperative course. According to Choi criteria there was a radiological response in 32 patients (89%), while the new CT classification identified responses in all the 36 patients (100%). The identification of changes after 7 weeks of treatment was higher using the CT classification compared to Choi criteria (p = 0.043 vs p = 0.462). The surgical interventions after Denosumab comprised curettage in 29 patients (74%) and resection in 7 (26%). Local recurrence was higher in patients managed with intralesional curettage than in those treated with en bloc resection (55.1% vs 0%, p < 0.001). At last follow up 19 patients (53%) required en bloc resections. Good responders to Denosumab (type 2C) had lower risk of local recurrence (p = 0.047) after either resection or curettage. CONCLUSION: The new CT classification evaluated more accurately the response to Denosumab. Our experience suggests that the requirement for radical bone resection remains high despite the use of Denosumab. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.


Asunto(s)
Neoplasias Óseas , Denosumab , Tumor Óseo de Células Gigantes , Recurrencia Local de Neoplasia/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adulto , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Clasificación , Estudios de Cohortes , Denosumab/administración & dosificación , Denosumab/efectos adversos , Femenino , Tumor Óseo de Células Gigantes/patología , Tumor Óseo de Células Gigantes/terapia , Humanos , Masculino , Terapia Neoadyuvante/métodos , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/métodos , Periodo Perioperatorio/métodos , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos
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