RESUMEN
BACKGROUND: Tumor-induced osteomalacia is a rare and fascinating paraneoplastic syndrome usually caused by a small, benign phosphaturic mesenchymal tumor. Most tumors are treated surgically, but we are unaware of any reports that compare the results of curettage and segmental resection for lesions in long bones. METHODS: Seventeen patients (ten male and seven female) with tumor-induced osteomalacia lesions in long bones, who underwent surgical treatment from December 2004 to August 2013 in our hospital, were included in this retrospective study. The mean follow-up (and standard deviation) was 35 ± 27 months (range, twelve to 116 months). The characteristics of the tumor and the effects of different surgical treatments (curettage compared with segmental resection) were evaluated. RESULTS: All patients showed typical clinical characteristics of tumor-induced osteomalacia, including elevated serum fibroblast growth factor-23 (FGF-23); 82% of tumors were in the epiphysis, and 82% grew eccentrically. The mean maximum diameter of the tumors was 2.4 ± 2.0 cm. The complete resection rates were similar for curettage (67%) and segmental resection (80%). However, the recurrence rate after curettage (50%) was higher than that after segmental resection (0%). The complete resection rate for secondary segmental resection (75%) was not different from that for primary segmental resection (83%). All of our cases of tumor-induced osteomalacia were caused by phosphaturic mesenchymal tumors. After successful removal of tumors, serum FGF-23 returned to normal within twenty-four hours and serum phosphorus levels returned to normal at a mean of 6.5 ± 3.5 days. CONCLUSIONS: Most lesions in long bones are located in the epiphysis, so curettage is first suggested to maintain joint function. If curettage is incomplete or there is a recurrence, secondary segmental resection should be considered curative. Changes of serum FGF-23 and phosphorus levels before and after the operation may be of prognostic help.
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Neoplasias Óseas/cirugía , Huesos de la Pierna , Neoplasias de Tejido Conjuntivo/cirugía , Cúbito , Adulto , Neoplasias Óseas/sangre , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/etiología , Legrado , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Tejido Conjuntivo/sangre , Neoplasias de Tejido Conjuntivo/complicaciones , Neoplasias de Tejido Conjuntivo/diagnóstico , Osteomalacia , Osteotomía , Síndromes Paraneoplásicos , Fósforo/sangre , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. METHOD: This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 µg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. RESULTS: A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. CONCLUSION: Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Hidroxicolecalciferoles/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Vitamina K 2/análogos & derivados , Anciano , Fosfatasa Alcalina/sangre , Densidad Ósea/efectos de los fármacos , Calcio/sangre , Método Doble Ciego , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Humanos , Persona de Mediana Edad , Osteocalcina/sangre , Fósforo/sangre , Resultado del Tratamiento , Vitamina K 2/uso terapéuticoRESUMEN
Tumor-induced osteomalacia (TIO) is an acquired form of hypophosphatemia. Tumor resection leads to cure. We investigated the clinical characteristics of TIO, diagnostic methods, and course after tumor resection in Beijing, China, and compared them with 269 previous published reports of TIO. A total of 94 patients with adult-onset hypophosphatemic osteomalacia were seen over a 6-year period (January, 2004 to May, 2010) in Peking Union Medical College Hospital. After physical examination (PE), all patients underwent technetium-99m octreotide scintigraphy ((99) Tc(m) -OCT). Tumors were removed after localization. The results demonstrated that 46 of 94 hypophosphatemic osteomalacia patients had high uptake in (99) Tc(m) -OCT imaging. Forty of them underwent tumor resection with the TIO diagnosis established in 37 patients. In 2 patients, the tumor was discovered on PE but not by (99) Tc(m) -OCT. The gender distribution was equal (M/F = 19/20). Average age was 42 ± 14 years. In 35 patients (90%), the serum phosphorus concentration returned to normal in 5.5 ± 3.0 days after tumor resection. Most of the tumors (85%) were classified as phosphaturic mesenchymal tumor (PMT) or mixed connective tissue variant (PMTMCT). Recurrence of disease was suggested in 3 patients (9%). When combined with the 269 cases reported in the literature, the mean age and sex distribution were similar. The tumors were of bone (40%) and soft tissue (55%) origins, with 42% of the tumors being found in the lower extremities. In summary, TIO is an important cause of adult-onset hypophosphatemia in China. (99) Tc(m) -OCT imaging successfully localized the tumor in the overwhelming majority of patients. Successful removal of tumors leads to cure in most cases, but recurrence should be sought by long-term follow-up.
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Hipofosfatemia/epidemiología , Hipofosfatemia/etiología , Neoplasias de Tejido Conjuntivo/complicaciones , Adulto , Edad de Inicio , Anciano , China/epidemiología , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Estudios de Seguimiento , Humanos , Hipofosfatemia/sangre , Hipofosfatemia/patología , Masculino , Persona de Mediana Edad , Neoplasias de Tejido Conjuntivo/sangre , Neoplasias de Tejido Conjuntivo/patología , Neoplasias de Tejido Conjuntivo/cirugía , Osteomalacia , Síndromes Paraneoplásicos , Fósforo/sangre , Adulto JovenRESUMEN
Autosomal dominant hypophosphatemic rickets (ADHR; MIM 193100) is a hereditary disorder characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D(3) levels. Recent studies have shown that the fibroblast growth factor 23 (FGF23) gene is responsible for this disease. FGF23 protein is a phosphaturic factor that is elevated in several diseases associated with hypophosphatemia and rickets but varies with disease status in ADHR. In the present study we observed a Chinese family of Han ethnic origin diagnosed with ADHR. The proband is a 30-year-old woman with no history of rickets but with multiple tooth abscesses as a young adult. She presented with progressive painful swelling of the left ankle after a blunt trauma at 26 years of age. She developed back pain, generalized weakness, and fatigue, and she could barely walk at age 27. She was found to have severe hypophosphatemia, low ratio of phosphorus tubule maximum (TmP) to glomerular filtration rate (GFR) (TmP/GFR), and elevated alkaline phosphatase at age 28. Her brother, 26 years old, presented with fatigue at 24 years of age and is normophosphatemic. The parents of this family had no history of rickets or hypophosphatemia. Direct sequence analysis of genomic DNA demonstrated a single heterozygous c.527G>A (p.R176Q) mutation in the FGF23 gene in three family members, including the proband, her brother, and their mother. Intact FGF23 assay of seven time points during the oral phosphate loading test showed no significant relationship between intact FGF23 and serum phosphorus levels of the subject with ADHR and a control. It is probably the first report of a Chinese family with ADHR.
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Pueblo Asiatico/genética , Raquitismo Hipofosfatémico Familiar/genética , Factores de Crecimiento de Fibroblastos/genética , Administración Oral , Adulto , Secuencia de Bases , China , Raquitismo Hipofosfatémico Familiar/sangre , Raquitismo Hipofosfatémico Familiar/diagnóstico por imagen , Familia , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fosfatos/administración & dosificación , Fósforo/sangre , RadiografíaRESUMEN
The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.
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Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Resorción Ósea/sangre , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Anciano , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Estatura , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , China , Colágeno Tipo I/sangre , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Femenino , Fémur/química , Cuello Femoral/química , Humanos , Ácido Ibandrónico , Infusiones Intravenosas , Vértebras Lumbares/química , Persona de Mediana Edad , Enfermedades Musculares/inducido químicamente , Osteoporosis Posmenopáusica/sangre , Dolor/inducido químicamente , Péptidos/sangre , Factores de TiempoRESUMEN
OBJECTIVE: To observe the effects of different doses of human parathyroid hormone fragment (hPTH)1-34 on SaoS cells and to explore the signal pathway and mechanism. METHODS: 5 x 10(4) cells/ml SaoS cells were seeded. Doses of 5, 50, 500 and 5 000 micro g/L hPTH1-34 were supplemented respectively. Total RNA was extracted by Trizol kit. Alkaline phosphatase (ALP), osteocalcin (BGP) and cAMP concentrations were measured by chemical, radioimmunoassay and competitive protein binding methods. c-fos gene expression level was semi-quantified by reverse transcriptase (RT)-PCR. RESULTS: ALP activity was higher in 500 micro g/L dose (P < 0.05 vs. control). BGP level was inhibited in 5 000 micro g/L dose (P < 0.05 vs. control and pretreatment). 50 and 500 micro g/L hPTH1-34 enhanced cAMP level significantly (P < 0.05 vs. control). No obvious increase of cAMP level was found in 5 000 micro g/L and 5 micro g/L dose groups (P > 0.05 vs. control and pretreatment). c-fos expression was higher in 50 and 500 micro g/L group. CONCLUSION: Different doses of hPTH1-34 exert distinct effects on osteoblasts. hPTH1-34 affects ALP and c-fos depending on protein kinase A signal pathway. hPTH1-34 exerts its action via regulation of osteoblasts by c-fos.