RESUMEN
We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 microg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean +/- SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 +/- 1.48% for teriparatide and 5.25 +/- 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 +/- 3.06% and 9.70 +/- 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 +/- 0.41% in the teriparatide and 4.14 +/- 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino-terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (-14%, p = 0.005) and 6 mo (-19%, p < 0.001) and in serum beta-C-terminal telopeptide of type I collagen (beta-CTX) at 1 and 3 mo (-11%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone-forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/metabolismo , Huesos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Osteoporosis/patología , Posmenopausia , Teriparatido/farmacología , Tiofenos/farmacología , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Densidad Ósea , Huesos/metabolismo , Huesos/patología , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/metabolismoRESUMEN
INTRODUCTION: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 microg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr. METHODS: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n=107), risedronate (n=59), etidronate (n=30), and non-bisphosphonate (n=49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months. RESULTS: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide. CONCLUSIONS: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Resorción Ósea/prevención & control , Osteoporosis Posmenopáusica/tratamiento farmacológico , Teriparatido/uso terapéutico , Anciano , Femenino , Humanos , Persona de Mediana Edad , Osteogénesis , Osteoporosis Posmenopáusica/fisiopatología , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Estudios Prospectivos , Teriparatido/efectos adversosRESUMEN
BACKGROUND: Hypopituitary patients with growth hormone deficiency (GHD) complain of reduced vitality, general fatigue, lack of concentration, irritability and reduced alertness during daytime. It is unclear whether these symptoms are primarily due to GH-deficiency and/or secondary to GHD related sleep impairments. Bi-directional interactions between the somatotropic system and human sleep patterns are well established. However, data on the effect of GH either in subjects without GHD or in patients with GHD under GH replacement therapy on the sleep electroencephalogram (EEG) are controversial. No reports exist about objective measures of daytime sleepiness in GH deficient patients before and during GH-therapy. OBJECTIVE: To assess the effects of GH on nocturnal and daytime sleep in adult patients with GHD before and during recombinant human GH (rhGH, Somatropin) replacement therapy. METHODS: Eighteen adult patients with GHD (4 women and 14 men) participated in the study. Mean age at the beginning of the study was 48.5 years (range 27-64 years). Ten patients were recruited from a double-blind, randomized placebo controlled trial over 6 months, followed by an open treatment period of 6 additional months (Group I). In all patients from this group, only the effects of the first 6 months of GH treatment were assessed. Eight additional patients were treated in an open study design for 6 months (Group II). Nocturnal sleep recordings and daytime sleep EEGs with a multiple sleep latency test were performed at baseline and after 6 months of additional GH replacement therapy. RESULTS: One patient dropped out due to side effects and was not included in sleep analysis. IGF-1 levels were increased in all patients, partially in a supraphysiologic range. Side effects were mainly mild but in one patient (from group II), general muscle pain led to interruption of the study. Therefore sleep analysis was only done in 17 patients. Sleep parameters were comparable to healthy control groups from the literature. GH substitution over 6 months did neither affect total sleep time nor times spent in different sleep stages. REM sleep density was also not changed. Daytime sleep propensity as measured by the multiple sleep latency test was not influenced by GH treatment. CONCLUSIONS: GH replacement does neither affect night sleep nor daytime sleep propensity in GH deficient hypopituitary adults. GH substitution has no sleep disturbing effect.
Asunto(s)
Electroencefalografía , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/psicología , Sueño/fisiología , Adenoma/complicaciones , Adenoma/cirugía , Adulto , Craneofaringioma/complicaciones , Craneofaringioma/cirugía , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electroencefalografía/efectos de los fármacos , Femenino , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/efectos adversos , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/sangre , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Polisomnografía/efectos de los fármacos , Sueño/efectos de los fármacos , Sueño REM/efectos de los fármacosRESUMEN
There is increased evidence that the dopaminergic system plays a major role in the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major inhibitory factor of prolactin release and also influences growth hormone (hGH) secretion. The aim of this study was to measure the endocrine activity of RLS patients, to compare it with that of normal subjects and to detect possibly altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and cortisol plasma levels were measured every 20 min for 24 hours in 10 male never-medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5 years). The blood samples taken during the night were paralleled by polysomnographic recordings including the assessment of periodic leg movements (PLM). Plasma levels as well as frequency and amplitude of the pulses of prolactin, hGH and cortisol were not different between RLS patients and controls. Both groups showed the same rhythms during the night- and daytime for all hormones. Cross correlations resulted in high correlation coefficients for each hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and prolactin, respectively). Concerning sleep parameters, there were no significant differences between the two groups apart from a higher PLMS arousal index in RLS patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It is suggested that a possible dysfunction of the dopaminergic system in RLS does not affect the release of prolactin and hGH from the pituitary gland.