Particular features of steroid-induced osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is characterized by disturbed bone remodelling with consequent reduced bone mass and abnormally low quality of the bone tissue, resulting in an elevated risk of fracture. Glucocorticoids (GC) inhibit processes of bone formation and accelerate bone degradation, all of which must be taken into account especially in the case of long-term treatment with GC. Appropriate diagnostic procedures must be implemented early in the treatment and throughout the course, as must any preventive (improvement of general condition, calcium, vitamin D) and curative treatment required. When indications are carefully observed and the dosage is constantly checked and adjusted as needed, however, GC are not only helpful and beneficial in the treatment of the basic illnesses they are prescribed for, but on balance can even have a positive effect on bone in phases of high inflammatory activity.     

New developments in the surgical treatment of renovascular arterial hypertension.

Surgery of the renal artery and its branches has not developed at the same rate as the progress made in arterial hypertension renovascular studies. Therefore, the percentage of cure is still low, the mortality rate high and the complications frequent. Based on the experiences in renal allo- and autotransplants, on the progress achieved in different fields, such as extracorporeal kidney surgery, on a new way of approach to the spleen's hilus, on the development of microsurgery and on a better knowledge of the biopathology of vascular grafts, new orientations for this type of surgery are supported. No matter which technique is followed, renal hypothermia by arterial perfusion, elimination of the diseased arterial segment, placement of the kidney in the continuity of another arterial system (auto-or splenorenal transplants), substitution of the transperitoneal approach by the retroperitoneal one, and, in complicated cases, the practice of ex situ arterial reconstruction surgery, is considered fundamental. Statistics, following these guidelines, are presented, which indicates that there were no deaths and that the percentage of success is higher than with classic revascularization surgery.     

New treatment targets in osteoporosis

Postmenopausal osteoporosis is characterized by bone remodeling alterations with an imbalance between excessive bone resorption and inadequate bone formation. At present, osteoporosis treatment rests on bone resorption inhibitors and, more specifically, on bisphosphonates. However, the introduction of anabolic agents such as parathyroid hormone that stimulate bone formation has expanded the range of treatment options. New treatment targets have been identified via improved knowledge on bone pathophysiology, bone remodeling, bone cells and intracellular signaling pathways. RANKL inhibition by anti-RANKL antibodies is undergoing considerable development as a treatment for osteoporosis. Also under development are anti-catabolic drugs that target the molecular mechanisms involved in bone resorption, including cathepsin K inhibitors and integrin α_vβ₃ antagonists. The identification of new pathways involved in bone formation is directing clinical research efforts toward the development of anabolic agents. The signaling pathways involved in bone formation, most notably the Wnt-pathway, hold considerable promise as treatment targets in conditions characterized by insufficient bone formation. Current focuses of interest include antibodies against naturally occurring Wnt-pathway antagonists (e.g., sclerostin and Dkk1) and modulators of parathyroid hormone production (calcilytic agents). Thus, active research is ongoing to improve the treatment of osteoporosis, a disease whose high prevalence and considerable functional and socioeconomic impact will raise formidable challenges in the near future.     

The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis

The effects of steroids on a cloned pluripotential cell from bone marrow stroma were examined in vitro in culture and in vivo after the cells were transfected with a traceable gene and transplanted into host mice. Bipedal chickens were treated with steroids to establish a model for osteonecrosis. The effects of a lipid lowering agent, lovastatin, on the prevention of steroid induced adipogenesis in vitro in cell culture, and on adipogenesis and osteonecrosis in vivo in chickens, were evaluated. On treatment with dexamethasone, cloned pluripotential cells began to differentiate into adipocytes and expressed a fat specific gene, whereas the expression of Type I collagen and osteocalcin messenger ribonucleic acid decreased. Addition of lovastatin in culture inhibited steroid induced fat gene expression and counteracted the inhibitory effect of steroids on osteoblastic gene expression. Cloned pluripotential cells were transduced with a traceable retrovirus vector encoding the beta-galactosidase and neomycin resistance genes. The transfected cells were administered to mice either by tail vein or by direct intramedullary injection. Half of the animals in each group were treated with steroids. Histologic sections showed the appearance of transplanted cells in the marrow. Analysis of marrow blowouts by flow cytometry revealed that steroid treatment produced adipogenesis in transplanted cells. Evidence of osteonecrosis was observed in steroid treated chickens, whereas sections from animals treated with steroids and lovastatin showed less adipogenesis and no bone death. The results indicate that steroid induced adipogenesis in the marrow may contribute to osteonecrosis and that lovastatin may be helpful in preventing the development of steroid induced osteonecrosis.     

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

原发性甲状旁腺功能亢进性骨质疏松症的中医病机及防治思路

原发性甲状旁腺功能亢进症是引起骨质疏松症的较常见病因,原发性甲状旁腺功能亢进症是由一个或多个甲状旁腺病理性(肿瘤或增生)过量分泌甲状旁腺激素所造成.随着血钙测定和甲状旁腺素测定在临床上的广泛运用,甲状旁腺功能亢进性骨质疏松的患病率也随之上升,目前我国原发性甲状旁腺功能亢进症多为骨型和肾型.治疗方面,主要以手术治疗和药物...     

骨质疏松症的中医病因病机认识与治疗进展

随着我国骨质疏松症的发病率逐年增加,防治形势变得更加严峻,目前单纯的西医药物防治骨质疏松症尚存在各种不良反应与疗效不确切等问题,这为临床上通过其他方式寻找满意的治疗方法提出了迫切的要求。中医药对骨质疏松症的病因病机有独到的见解,其治疗方法也是多种多样,笔者对近年来与骨质疏松相关的中医药研究概况作一总结,为中医药治疗骨质疏松的研究提供理论及临床依据。     

Prevalence,pathogenesis, and treatment options for mastocytosis-related osteoporosis

Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy.     

New developments in the treatment of systemic lupus erythematosus

A large number of new studies on the treatment of systemic lupus erythematosus (SLE) have recently been or are about to be published. Unfortunately, all these studies have been performed in adult patients and there are no studies in children. There is, however, a strong need for more effective drugs with, if possible, fewer side-effects also in children. We do thus need to carefully asses the studies in adult patients to evaluate which of the new drugs can be tried in children with severe lupus nephritis. Some of the new studies have been largely confirmatory, such as demonstrating the efficacy of mycophenolate mofetil in the treatment of SLE, but others have been surprising, such as the lack of efficacy of rituximab. The debate as to why the rituximab studies got negative results is ongoing. Lastly, there is an emergence of novel medications for the treatment of SLE, mostly monoclonal antibodies targeting various aspects of the immune system: belimumab, an antibody affecting B-cell function, is likely to become the first new drug registered for lupus for many years as several large randomized studies have shown significant (albeit not dramatic) responses to this antibody. Many other drugs are in the pipeline and will hopefully come to the clinical arena. This review aims to give a critical appraisal of the plethora of studies in the context of the clinical reality of a pediatric nephrologist treating patients with SLE.     

绝经后骨质疏松症发病机制的表观遗传学研究进展

表观遗传学修饰是指在DNA序列未变化情况下发生可遗传的基因表达的变化,主要机制包括DNA甲基化、组蛋白修饰、非编码RNAs、染色质修饰等。绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)属于原发性骨质疏松症的一种,主要是由于绝经后女性激素水平改变等原因致使骨代谢失衡,骨微结构破坏,骨量减少。近年来,大量研究证实了表观遗传学参与绝经后骨质疏松症的发生发展,本文将从DNA甲基化、组蛋白修饰和非编码RNAs这三个方面综述绝经后骨质疏松症在表观遗传学方面的发病机制。     

激素性股骨头坏死发病机制的研究进展

股骨头坏死(osteonecrosis of the femeral head,ONFH),多发生于中青年人,发病年龄在30～59岁之间[1].本病发展到后期可导致股骨头塌陷并继发骨关节炎,严重影响患者的正常生活,是一种致残率相当高的疾病.     

Early life factors in the pathogenesis of osteoporosis

Osteoporosis is a major public health burden through associated fragility fractures. Bone mass, a composite of bone size and volumetric density, increases through early life and childhood to a peak in early adulthood. The peak bone mass attained is a strong predictor of future risk of osteoporosis. Evidence is accruing that environmental factors in utero and in early infancy may permanently modify the postnatal pattern of skeletal growth to peak and thus influence risk of osteoporosis in later life. This article describes the latest data in this exciting area of research, including novel epigenetic and translation work, which should help to elucidate the underlying mechanisms and give rise to potential public health interventions to reduce the burden of osteoporotic fracture in future generations.     

绝经后骨质疏松症发病机制研究进展

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是由绝经引起的卵巢衰退,雌激素分泌下降导致的骨质疏松症。由于骨量、骨密度及骨强度均有所降低,使骨的脆性增高,加大了骨折的危险性,严重影响绝经后妇女的生活质量。目前对PMOP的发病机制已经从多方面得到阐释,但仍未完全研究清楚。该文通过查询国内外相关文献,从肠道菌群、铁代谢等多个角度对PMOP的发病机制研究进展进行阐述,以期为进一步科学研究理清思路。     

糖皮质激素诱导骨质疏松发病机制的研究进展

糖皮质激素是由肾上腺皮质束状带产生的甾体类物质,具有调节生长发育、代谢、免疫等功能。过量的糖皮质激素抑制骨形成、增强骨吸收,导致骨量减少、骨微结构破坏,增加骨折风险。既往研究证实,糖皮质激素通过作用于骨细胞的信号通路传导、氧化应激等影响骨重塑。近年来研究发现,糖皮质激素也通过影响细胞自噬、铁死亡、外泌体等诱导骨质疏松发生发展。笔者对近年来糖皮质激素诱导骨质疏松（glucocorticoid-induced osteoporosis,GIOP）的分子机制进行综述,旨在为GIOP的防治提供参考。     

New developments in the treatment of castration resistant prostate cancer

In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer （CRPC） have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRPC, as well as the new drugs and targets, which have evolved from this basic research.