BACKGROUND & AIMS: :Strontium (Sr)-doped calcium sulfate hemihydrate (SrCSH) bioactive materials have been demonstrated to promote osteoporotic bone repair, being associated with the stimulation of bone formation and a reduction in bone resorption. However, the rapid degradation and absorption of SrCSH affects its clinical value. In order to delay the degradation time of SrCSH and improve the utilization of Sr2+, chitosan (CS)-coated SrCSH microspheres (CS-SrCSH) are prepared by electrostatic interaction between CS and SrCSH. X-ray diffraction analysis verifies that SrCSH coated by CS does not alter the phase composition of the SrCSH. It was observed that CS-SrCSH microspheres have uniform particle size. More importantly, the in vivo and in vitro degradation time of CS-SrCSH microspheres is significantly longer than that of SrCSH, and the release rate of Sr2+ is stable, achieving a sustained release effect. Furthermore, CS-SrCSH-based cement is used to repair critical-sized OVX rat tibial defects. The in vivo results reveal that CS-SrCSH exhibits a long-term capability for osteogenesis, angiogenesis and bone metabolism inhibition. In conclusion, the controllable degradation of CS-SrCSH-based cements described here could be beneficial for the repair of bone defects, especially in the osteoporotic bone.

背景与目标： : 掺锶 (Sr) 的半水硫酸钙 (SrCSH) 生物活性材料已被证明可促进骨质疏松的骨修复，与刺激骨形成和减少骨吸收有关。然而，SrCSH的快速降解和吸收影响了其临床价值。为了延缓SrCSH的降解时间并提高Sr2的利用率，通过CS和SrCSH之间的静电相互作用制备了壳聚糖 (CS) 包覆的SrCSH微球 (CS-SrCSH)。X射线衍射分析验证了用CS涂覆的SrCSH不会改变SrCSH的相组成。观察到CS-SrCSH微球具有均匀的粒径。更重要的是，cs-srcsh微球的体内外降解时间明显长于SrCSH，且Sr2 + 的释放速率稳定，达到了缓释效果。此外，基于cs-srcsh的水泥用于修复临界尺寸的OVX大鼠胫骨缺损。体内结果表明，cs-srcsh具有长期的成骨，血管生成和骨代谢抑制能力。总之，本文所述的基于cs-srcsh的水泥的可控降解可能有利于骨缺损的修复，尤其是在骨质疏松的骨中。

BACKGROUND & AIMS: :Osteoporosis is an important skeletal disease characterized by bone weakness and high risk of fracture in postmenopausal women. Tea consumption is known to play an important role in the prevention or alleviation of osteoporosis. However, the therapeutic effects of aqueous extracts of white tea (WT) have not been evaluated in osteoporosis rat models. The aim of this study was to investigate the potential anti-osteoporotic role of WT in ovariectomized (OVX) rats. WT was given orally at 0.5% w/v doses for 12 weeks in OVX rats. Biochemical parameters in blood samples, bone tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type 1 collagen (CTX) and estradiol levels were evaluated. Bone mineral density and bone mineral content values were measured in the left femur. In addition to histopathological examination, osteolcalcin, osteopontin and TUNEL levels were determined. OVX group data demonstrated that bone loss occurred by thinning of the metaphyseal growth plates of the femur. Similarly, the levels of TRAP and CTX, markers of osteoclastic activity, were found to be high concurrently with a decrease in femoral bone mineral density. In addition, increased osteolcalcin and osteopontin levels were present in the metaphyseal growth zones. On the other hand, while TRAP and CTX levels were suppressed in the OVX-WT group, bone mineral content increased. In ad-dition, TUNEL, osteocalcin and osteopontin positivity decreased in the right femoral metaphysis growth zones, proliferating zone and resting zone cells. These results showed that chronic WT consumption has a protective effect by reducing bone resorption in OVX-induced osteoporotic rats.

背景与目标： : 骨质疏松症是一种重要的骨骼疾病，其特征是绝经后妇女的骨骼无力和高骨折风险。众所周知，饮茶在预防或减轻骨质疏松症中起着重要作用。然而，尚未在骨质疏松症大鼠模型中评估白茶 (WT) 水提取物的治疗作用。这项研究的目的是研究WT在去卵巢 (OVX) 大鼠中的潜在抗骨质疏松作用。在OVX大鼠中以0.5% w/v剂量口服WT 12周。评估血液样本中的生化参数，抗骨酒石酸酸性磷酸酶 (TRAP)，1型胶原蛋白的C末端肽 (CTX) 和雌二醇水平。测量左股骨的骨矿物质密度和骨矿物质含量值。除组织病理学检查外，还确定了骨钙素，骨桥蛋白和TUNEL水平。OVX组数据表明，股骨干phy端生长板变薄会导致骨质流失。同样，发现破骨细胞活性标志物TRAP和CTX的水平很高，同时股骨骨矿物质密度降低。此外，在干phy端生长区域中存在骨钙素和骨桥蛋白水平升高。另一方面，尽管OVX-WT组的TRAP和CTX水平受到抑制，但骨矿物质含量增加。另外，TUNEL，骨钙素和骨桥蛋白阳性在右股骨干端生长区，增殖区和静息区细胞中降低。这些结果表明，长期消耗WT通过减少OVX诱导的骨质疏松大鼠的骨吸收而具有保护作用。

BACKGROUND & AIMS: :Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.

背景与目标： : 已证明双膦酸盐可增加已确定的骨质疏松症患者以及骨质减少的患者的骨矿物质密度。证据最终表明，使用更有效的含氮二膦酸盐的患者骨折率降低。实际上，仅经过1年的治疗，就已证明椎体骨折率显着降低。第二代双膦酸盐阿仑膦酸盐和第三代双膦酸盐利塞膦酸盐是治疗骨质疏松症的一线药物，因为它们在预防椎骨和非椎骨骨折方面均具有功效。有证据表明，间歇性的周期性治疗可以预防椎体骨折。已显示所有这三个都增加了脊柱的骨矿物质密度，阿仑膦酸盐和利塞膦酸盐显着增加了髋部骨密度。降钙素已证明能够以最小的骨密度变化降低椎体骨折率。降钙素在减轻与骨折相关的骨痛方面也是有益的。

BACKGROUND & AIMS: OBJECTIVE:To investigate the effects of age, body mass index (BMI), bone mineral density (BMD), and levels of serum 25-hydroxyvitamin D (25OHD) on hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis. METHODS:A total of 252 postmenopausal women patients, whose bone density had reached the threshold of osteoporosis and age ≥50 years (50-98 years), collected from the Second Affiliated Hospital of Fujian Medical University from January 2015 to December 2018, were performed by retrospective analysis. According to whether or not they had a hip fracture, including femoral neck fracture or intertrochanteric fracture, the patients were divided into two groups, including 117 cases (50-84 years old) in the non-hip fracture group and 135 cases (57-98 years old) in the hip fracture group. BMD was measured by Hologic Discovery A DXA bone mineral densitometer. Levels of serum 25OHD were detected by ROCHE detection instrument. Comparisons of age, BMI, bone density of femoral neck, and levels of serum 25OHD between the two groups were performed by using the Student's t-test. Furthermore, the statistically significant factors were analyzed by multiple regression analysis to investigate the independent risk factors of hip fracture. RESULTS:The group without hip fracture: 117 cases; average age: 67.4 ± 8.5 years; BMI: 22.3 ± 3.2 kg/m2 ; bone density of femoral neck: (0.504 ± 0.067) g/cm2 ; T-value of femoral neck: -3.1 ± 0.6; levels of serum 25OHD: (24.9 ± 8.5) ng/mL. The group with brittle hip fracture: 135 cases; average age: 80.7 ± 7.6 years; BMI: 20.3 ± 3.5 kg/m2 ; bone density of femoral neck: (0.426 ± 0.077) g/cm2 ; T-value of femoral neck: -3.8 ± 0.7; levels of serum 25OHD: (15.9 ± 8.9) ng/mL. Age, BMI, bone density of femoral neck, and 25OHD level of the group without hip fracture were markedly lower than hip fracture group (P < 0.05). The results of logistic regression analysis suggested that age, bone density of femoral neck, and levels of serum 25OHD were independent risk factors for fragile hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis. CONCLUSION:Higher age, lower levels of bone density and 25OHD are the main risk factors of hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis.

背景与目标：

BACKGROUND & AIMS: UNLABELLED:We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION:Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS:Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS:Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS:In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

背景与目标：

BACKGROUND & AIMS: :Liver transplantation provides an important, often life-saving treatment for end-stage liver disease. Osteoporosis post-liver transplantation has been described in adults; however, this has not been described in the pediatric population to date. We present a case of a 13-year-old female patient who underwent an orthotopic liver transplant for cryptogenic liver cirrhosis. Her immunosuppressants were tacrolimus and prednisone. Four months posttransplant, she started complaining of bilateral lower limb pain and limping while walking, progressing to a point where she was almost immobile. Magnetic resonance imagining of the pelvis showed bilateral avascular necrosis involving the weight-bearing surfaces of both femoral heads, in addition to the extensive edema involving both hip joints. Bone mineral densitometry was below normal for her age at the hip and forearm. She was started on high-dose calcium and vitamin D supplement, as well as zoledronic acid with a remarkable symptomatic and functional improvement.

背景与目标： : 肝移植为终末期肝病提供了重要的，通常挽救生命的治疗方法。已在成年人中描述了肝移植后的骨质疏松症; 但是，迄今为止，尚未在儿科人群中描述。我们介绍了一例13岁的女性患者，该患者因隐源性肝硬化接受了原位肝移植。她的免疫抑制剂是他克莫司和泼尼松。移植后四个月，她开始抱怨双侧下肢疼痛和走路时跛行，进展到几乎不动的地步。骨盆的磁共振成像显示双侧缺血性坏死涉及两个股骨头的承重表面，此外还涉及两个髋关节的广泛水肿。在臀部和前臂的年龄，骨矿物质密度低于正常水平。她开始服用大剂量钙和维生素d补充剂，以及唑来膦酸，症状和功能明显改善。

BACKGROUND & AIMS: OBJECTIVE:To analyse the distribution of polymorphism of the collagen type Ialpha1 gene (COL1A1) and its relationship with bone metabolism and bone turnover in men with idiopathic osteoporosis. METHODS:A total of 35 male patients with idiopathic osteoporosis, aged 50.4 +/- 10.3 yr, and 60 healthy males (controls), aged 47 +/- 17 yr, were included in the study. Serum osteocalcin, 25-hydroxyvitamin D and parathyroid hormone were determined in all patients. The COL1A1 Sp1 genotypes (SS, SS:, ss) were assessed by restriction enzyme digestion (BAL:1) of DNA amplified by the polymerase chain reaction. RESULTS:Patients with idiopathic osteoporosis had a higher frequency of the s allele than men in the control group (29 vs 11%, P: = 0.003) and a higher frequency of the SS: genotype (patients, 48% SS, 46% SS:, 6% ss; controls, 80% SS, 18% SS:, 2% ss; P: = 0.003). No significant differences between genotypes were observed in serum concentrations of osteocalcin, vitamin D or parathyroid hormone among either the patients or the controls. CONCLUSION:This study suggests that, in men with idiopathic osteoporosis, there is a high prevalence of the s allele and the SS: genotype that is unrelated to other parameters of bone metabolism.

背景与目标：

BACKGROUND & AIMS: :Women who have significant bone loss or a new fracture on monotherapy are considered for combination therapy. Combination therapies increase bone density more than monotherapy by targeting different parts of the osteoclast pathway.In early postmenopausal women who are symptomatic, the use of combination antiresorptives should include hormone therapy with a bisphosphonate or with bazodoxifene. In women who initially receive a weaker antiresorptive such as the SERM raloxifene, a combination with bisphosphonates and calcium supplementation is necessary to prevent bone loss. In older women over 65 years of age who often have impaired calcium absorption, the combination of calcitriol with bisphosphonates has been shown to increase bone density more than monotherapy.

背景与目标： : 接受单药治疗有明显骨质流失或新骨折的女性被考虑联合治疗。联合疗法通过针对破骨细胞途径的不同部位，比单一疗法增加骨密度。对于有症状的绝经后早期妇女，联合抗吸收剂的使用应包括使用双膦酸盐或巴佐多昔芬的激素治疗。在最初接受较弱的抗吸收性 (例如SERM雷洛昔芬) 的女性中，必须与双膦酸盐和钙补充剂联合使用以防止骨质流失。在通常钙吸收受损的65岁以上的老年妇女中，骨化三醇与双膦酸盐的组合已被证明比单一疗法更能增加骨密度。

BACKGROUND & AIMS: STUDY DESIGN:Case report of a patient who underwent a new surgical procedure for paraplegia after vertebral collapse due to osteoporosis. OBJECTIVES:To propose a new approach to posterior spinal fusion surgery for osteoporotic patients. SUMMARY OF BACKGROUND DATA:Surgical treatment was performed on a paraplegic patient after vertebral collapse due to osteoporosis. However, the surgery was difficult because implants such as hooks and screws often dislodged during the treatment. The poor holding power of these implants to the osteoporotic spine is a challenging problem in this treatment. METHODS:When a fractured vertebra is shortened by resecting the posterior part of the spine and the application of a compression force, a short vertebra is produced. As a result, the thoracic kyphosis decreases and the force pushing the upper thoracic spine inferio-ventrally also decreases. RESULTS:A 74-year-old woman with T12 vertebral collapse was treated with this new method. Lateral Cobb angle (T10-L2) was reduced from 26 to 4 degrees after surgery. The shortened vertebral body united, and after 33 months, the implant had not dislodged and no loss of correction was seen. CONCLUSION:The posterior spinal shortening can be a choice for treating delayed paraplegia after osteoporotic vertebral fracture.

背景与目标：

BACKGROUND & AIMS: PURPOSE OF REVIEW:The purpose of this review is to provide an update on osteoporosis epidemiology. The focus is on fractures because fractures are the most important clinical consequence of osteoporosis. Studies published over the past 18 months are identified and reviewed. Finally, the clinical impact of these new findings is discussed. RECENT FINDINGS:Important research in 2015-2016 include analyses of screening and rescreening in younger women and older men, risk factors for hip fractures in older men, obesity and weight loss/gain, and risk of fracture. Several dietary factors, including adherence to a Mediterranean diet and a diet rich in protein, fruits, and vegetables and maintenance of physical function with increasing age represent modifiable nonpharmacologic risk factors that improve bone health. Sarcopenia may have a more important role in fracture in men than women. Important biomarkers for fracture include low 25-hydroxyvitamin D and hemoglobin A1c. SUMMARY:Updated literature on fracture epidemiology have identified important risk factors for fracture.

背景与目标：

BACKGROUND & AIMS: :Bone homeostasis requires continuous remodeling of bone matrix to maintain structural integrity. This involves extensive communication between bone-forming osteoblasts and bone-resorbing osteoclasts to orchestrate balanced progenitor cell recruitment and activation. Only a few mediators controlling progenitor activation are known to date and have been targeted for intervention of bone disorders such as osteoporosis. To identify druggable pathways, we generated a medaka (Oryzias latipes) osteoporosis model, where inducible expression of receptor-activator of nuclear factor kappa-Β ligand (Rankl) leads to ectopic formation of osteoclasts and excessive bone resorption, which can be assessed by live imaging. Here we show that upon Rankl induction, osteoblast progenitors up-regulate expression of the chemokine ligand Cxcl9l. Ectopic expression of Cxcl9l recruits mpeg1-positive macrophages to bone matrix and triggers their differentiation into osteoclasts. We also demonstrate that the chemokine receptor Cxcr3.2 is expressed in a distinct subset of macrophages in the aorta-gonad-mesonephros (AGM). Live imaging revealed that upon Rankl induction, Cxcr3.2-positive macrophages get activated, migrate to bone matrix, and differentiate into osteoclasts. Importantly, mutations in cxcr3.2 prevent macrophage recruitment and osteoclast differentiation. Furthermore, Cxcr3.2 inhibition by the chemical antagonists AMG487 and NBI-74330 also reduced osteoclast recruitment and protected bone integrity against osteoporotic insult. Our data identify a mechanism for progenitor recruitment to bone resorption sites and Cxcl9l and Cxcr3.2 as potential druggable regulators of bone homeostasis and osteoporosis.

背景与目标： : 骨内稳态需要不断重塑骨基质以保持结构完整性。这涉及成骨成骨细胞和骨吸收破骨细胞之间的广泛交流，以协调平衡的祖细胞募集和激活。迄今为止，只有少数控制祖细胞激活的介体已知，并且已被靶向干预骨质疏松等骨骼疾病。为了确定可药物治疗的途径，我们建立了一个medaka (Oryzias latipes) 骨质疏松模型，其中核因子 κ-β 配体 (Rankl) 受体激活剂的诱导表达导致破骨细胞异位形成和过度的骨吸收，这可以通过实时成像进行评估。在这里，我们显示在Rankl诱导后，成骨细胞祖细胞上调趋化因子配体Cxcl9l的表达。Cxcl9l的异位表达将mpeg1-positive巨噬细胞募集到骨基质并触发其分化为破骨细胞。我们还证明趋化因子受体Cxcr3.2在主动脉-性腺-中肾 (AGM) 的巨噬细胞的不同子集中表达。实时成像显示，在Rankl诱导后，Cxcr3.2阳性巨噬细胞被激活，迁移到骨基质并分化为破骨细胞。重要的是，cxcr3.2中的突变可防止巨噬细胞募集和破骨细胞分化。此外，化学拮抗剂AMG487和NBI-74330对Cxcr3.2的抑制也减少了破骨细胞的募集，并保护了骨完整性免受骨质疏松损伤。我们的数据确定了将祖细胞募集到骨吸收位点的机制，Cxcl9l和Cxcr3.2是骨稳态和骨质疏松症的潜在可药物调节剂。

BACKGROUND & AIMS: INTRODUCTION:Rheumatoid arthritis (RA) is a chronic disabling disease characterized by a symmetrical articular involvement due to ongoing joint inflammation, if left insufficiently treated. Local and generalized bone loss is one of the main extra-articular complications of RA and leads to an increased risk for fragility fractures, which further impair functional ability, quality of life, and life expectancy. Therefore, there is an urgent need for good fracture risk management in the vulnerable RA patient. AREAS COVERED:The authors review: the epidemiology and pathophysiology (i.e. risk factors) of osteoporosis (OP), fracture, and vertebral fracture risk assessment, the effects of anti-rheumatic drugs on bone loss, pharmacological treatment of OP in RA including both bisphosphonates (BP) and newer drugs including anti-resorptives and osteoanabolic treatment options. EXPERT OPINION:Patients with active RA have elevated bone resorption and local bone loss. Moreover, these patients are at increased risk for generalized bone loss, vertebral and non-vertebral fractures. Since general risk factors (such as low BMI, fall risk) and RA-related factors play a role, optimal fracture prevention in RA patients is based on optimal diagnostics based on both of these factors, and on the use of adequate non-medical and medical treatment options.

背景与目标：

BACKGROUND & AIMS: :Glucocorticoids are the most common cause of drug-induced osteoporosis. Given the widespread use of oral glucocorticoids in the treatment of autoimmune, pulmonary, gastrointestinal disorders and organ transplantation, attention to glucocorticoid-induced osteoporosis has substantially increased. Bone loss occurs rapidly in the first few months of glucocorticoid therapy. Trabecular bone is affected more than cortical bone. Glucocorticoid treatment is associated with a substantially increased risk of fractures, particularly hip and vertebral fractures. The skeletal effects of glucocorticoids are both dose- and duration-dependent. The patophysiology of glucocorticoid-induced osteoporosis is a complex process, several mechanisms are proposed but not yet fully highlighted. Despite several evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis and the availability of effective therapeutic options, the proportion of individuals with appropriate evaluation and treatment remains relatively low.

背景与目标： : 糖皮质激素是药物性骨质疏松症的最常见原因。鉴于口服糖皮质激素在自身免疫、肺、胃肠道疾病和器官移植治疗中的广泛应用，对糖皮质激素引起的骨质疏松症的关注已大大增加。在糖皮质激素治疗的头几个月，骨丢失迅速发生。小梁骨比皮质骨受到的影响更大。糖皮质激素治疗可显著增加骨折的风险，尤其是髋部和椎骨骨折。糖皮质激素的骨骼作用是剂量和持续时间依赖性的。糖皮质激素诱导的骨质疏松是一个复杂的过程，提出了几种机制，但尚未完全阐明。尽管有一些基于证据的预防和治疗糖皮质激素引起的骨质疏松症的指南以及有效的治疗选择，但接受适当评估和治疗的个体比例仍然相对较低。

BACKGROUND & AIMS: BACKGROUND:Patients on prolonged corticosteroid therapy are at risk of developing osteoporosis. Some patients with severe asthma are difficult to wean off corticosteroids and are therefore at risk of developing bony complications due to steroids. OBJECTIVE:The purpose of this study was to examine the relationship of cumulative steroid dosage and duration of therapy with osteoporosis. METHODS:We obtained bone mineral density studies using dual photon absorptiometry, and radiographs of the lumbar spine of 16 steroid-dependent patients with asthma. Patients with conditions affecting bone metabolism were excluded. RESULTS:We studied 16 male steroid-dependent patients with asthma who received 4 to 41 grams equivalent dose of prednisone over a period of 1 to 15 years. The overall prevalence rate for abnormal age-matched bone mineral density was 50%. Abnormal bone mineral density was more commonly noted in the lumbar spine (38%) than in the femoral neck (19%). The lowest dose of corticosteroid associated with a decrease in bone mineral density was a cumulative steroid dose of 5.6 equivalent grams-prednisone. CONCLUSION:Prolonged corticosteroid therapy can cause significant osteoporosis among male patients with steroid-dependent asthma. Bone loss due to corticosteroid therapy occurs at different rates at different bony sites.

背景与目标：

BACKGROUND & AIMS: :The mechanisms of high turnover bone loss induced by Cyclosporin A (CsA) are not clearly understood. Deficiencies in sex hormones result in high turnover osteoporosis, and not only androgen but also estrogen plays an important role in maintaining bone mass in men. To study whether or not there are any changes in the levels of sex hormones, aromatization, and the expression of estrogen receptors in CsA-induced osteoporosis, we treated 39 rats with vehicle, low-dose CsA (5 mg/kg) and high dose CsA (15 mg/kg) for 28 days, and measured sex hormone levels by radioimmunoassay. Aromatase activities in ROS cells and 3T3-L1 cells were determined by measuring the conversion rate of 3H-androstenedione into 3H-estrone. ER and ER mRNA were measured by competitive RT-PCR in collected marrow cells and ROS cells. The levels of free testosterone in the serum in low-dose CsA-treated rats were unchanged, but the levels were significantly decreased in those treated with high-dose CsA as previously reported. The levels of total estradiol in the serum were significantly increased in the low-dose CsA-treated group (5 mg/kg) and were comparable to levels of the control group in the high-dose CsA-treated group (15 mg/kg). CsA increased the conversion of 3H-androstenedione to 3H-estrone in ROS cells, but not in 3T3-L1 cells. Meanwhile, CsA treatment did not change the rates of ER or ER mRNA expression in ROS cells or in collected bone marrow cells. In conclusion, CsA treatment decreased the level of free testosterone in the serum, but did not decrease the level of serum estradiol by enhancing aromatization. High-turnover osteoporosis induced by clinical dosage CsA treatment may not be caused by lowering the levels of circulating estrogen or by decreasing the expression of estrogen receptors.

背景与目标： : 环孢菌素A (CsA) 诱导的高转换骨丢失的机制尚不清楚。性激素缺乏会导致高更替性骨质疏松症，不仅雄激素而且雌激素在维持男性骨量方面起着重要作用。为了研究CsA诱导的骨质疏松症中性激素水平，芳香化作用和雌激素受体表达是否有任何变化，我们用媒介物，低剂量CsA (5 mg/kg) 和高剂量CsA (15 mg/kg) 治疗了39只大鼠 (28天)，并通过放射免疫测定法测定性激素水平。通过测量3h-雄烯二酮向3h-雌酮的转化率来确定ROS细胞和3T3-L1细胞中的芳香化酶活性。通过竞争性rt-pcr测量收集的骨髓细胞和ROS细胞中的ER和ER mRNA。低剂量CsA处理的大鼠血清中游离睾丸激素的水平没有变化，但如先前报道的那样，高剂量CsA处理的大鼠血清中游离睾丸激素的水平显着降低。在低剂量CsA治疗组 (5 mg/kg) 中，血清中总雌二醇的水平显着增加，与高剂量CsA治疗组 (15 mg/kg) 的对照组水平相当。CsA增加了ROS细胞中3h-雄烯二酮向3h-雌酮的转化，但在3T3-L1细胞中则没有。同时，CsA处理不会改变ROS细胞或收集的骨髓细胞中ER或ER mRNA的表达速率。总之，CsA治疗降低了血清中游离睾丸激素的水平，但并未通过增强芳构化作用降低血清雌二醇的水平。临床剂量CsA治疗引起的高更新性骨质疏松症可能不是由于降低循环雌激素水平或降低雌激素受体的表达而引起的。